DEFINITION — Ectopic pregnancy occurs when a developing embryo implants at a site other than the inside wall of the uterus. A brief overview of early pregnancy may be helpful in understanding ectopic pregnancy.
Normal pregnancy — A woman's reproductive system includes the uterus, two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are narrow tubes that link the ovaries and uterus (show figure 1). Once a month, an egg is released by one of the ovaries (ovulation) and travels down the fallopian tube to the uterine cavity. In women undergoing treatment for infertility, more than one egg may be released by the ovary. If the egg is fertilized in the fallopian tube by the male's sperm, pregnancy begins.
Once joined, the egg and sperm begin to rapidly develop new cells. This group of cells, called the embryo, normally implants on the inner wall of the uterus, called the endometrium. Once implanted, the embryo continues to grow and also forms the placenta, the organ that provides a blood supply for the developing embryo.
Ectopic pregnancy — In an ectopic pregnancy, the developing embryo does not implant on the endometrial wall, but instead attaches to some other surface. Ninety eight percent of the time, that surface is within fallopian tubes. An ectopic pregnancy in a fallopian tube is sometimes called a tubal pregnancy.
Very rarely, the developing embryo will attach to another site such as the cervix or an ovary. It can also implant at the site where the fallopian tube and uterus join; this is called an interstitial pregnancy, or on the abdominal wall. Rarely in twin pregnancies, one embryo implants in the uterus and the other implants at an ectopic location. This rare event is called a heterotopic pregnancy and occurs more commonly in women undergoing infertility treatments.
Embryos that do not implant in the uterine wall are generally unable to develop normally. In addition, an ectopic pregnancy can cause rupture of the organ on which they are implanted, typically the fallopian tube. Rupture can result in severe internal bleeding, shock, and possibly death of the mother. Fortunately, the ability to diagnose, monitor, and treat ectopic pregnancy reduces the risk of life-threatening complications.
RISK FACTORS — A number of factors increase the risk for ectopic pregnancy. They can be divided into strong, moderate, and weak risk factors.
Strong risk factors Abnormalities of the fallopian tubes — If the fallopian tubes are damaged or abnormal as a result of previous infection or surgery, tumors, or rarely, due to malformations present since birth, there is an increased risk of ectopic pregnancy. Surgery to reconstruct the fallopian tube (to improve a woman's chances of becoming pregnant) can increase the risk of ectopic pregnancy, although preexisting tubal damage poses an even greater risk. Previous ectopic pregnancy — Women who have had one ectopic pregnancy have an increased risk for having another. The underlying tubal disorder that led to the first ectopic, and the effects of treating the first episode increase the risk for another ectopic pregnancy. In-utero diethylstilbestrol (DES) exposure — Women whose mothers took DES while pregnant are more likely to have abnormalities of the fallopian tubes and are at increased risk for an ectopic pregnancy.
Moderate risk factors Previous genital infections — Pelvic infection with gonorrhea or chlamydia is a major cause of tubal problems and increases the risk of ectopic pregnancy. Infertility — The incidence of ectopic pregnancy is higher in the infertility population, mostly due to the increased incidence of tubal abnormalities in these women. Fertility drugs also appear to alter tubal function by their effects on hormones and may be associated with the increased risk in this population. Multiple sexual partners — Having more than one sexual partner is associated with an increased risk of pelvic infection, and therefore an increased risk of ectopic pregnancy.
Weak risk factors Smoking — Cigarette smoking around the time of conception increases the risk of ectopic pregnancy; the risk increases with the number of cigarettes smoked. This risk may be the result of impaired immunity in smokers, which predisposes them to pelvic infection or impaired functioning of the fallopian tubes. Vaginal douching — Regular vaginal douching is associated with increased risk of both pelvic infections and ectopic pregnancy. Douching is never recommended under any circumstance. Age — Having a first sexual encounter at a young age (less than 18) slightly increases the risk of ectopic pregnancy.
Other risk factors In vitro fertilization (IVF) — IVF, a fertility treatment in which a woman's egg is fertilized outside the body and then placed in her uterus, is associated with an increased risk of both ectopic and heterotopic pregnancy. Tubal sterilization — Tubal sterilization is a surgical procedure in which the fallopian tubes are either cut, ligated, or coagulated. It is commonly known as having the "tubes tied," and is performed to prevent future pregnancies. Rarely, tubal sterilization fails and pregnancy can result. Women who become pregnant after tubal sterilization have a higher risk for ectopic pregnancy. Intrauterine contraceptive devices — Women who become pregnant while using an intrauterine contraceptive device (IUD) are at higher risk for ectopic pregnancy than women using other forms of contraception or no contraception.
SYMPTOMS — Symptoms, when they occur, appear early in pregnancy and often before the woman realizes she is pregnant. They include abdominal pain, amenorrhea (absence of a period), and vaginal bleeding, which may be minimal. Symptoms of pregnancy (such as breast tenderness, frequent urination, or nausea) may also be present.
However, over 50 percent of women have no symptoms until rupture occurs. Following rupture of the tube, the woman may experience severe pain and profound hemorrhage (bleeding). Lightheadedness or dizziness may occur first, followed by a drop in blood pressure, fainting, and shock. If there is severe bleeding, shock can progress to death.
Sometimes, the embryo is expelled by the fallopian tube before rupture occurs. This is called a "tubal abortion." Once expelled, the embryonic tissue may degenerate, or it may reimplant in the abdominal cavity or on the ovary. Tubal abortion can be accompanied by severe intra-abdominal bleeding requiring surgical intervention, or by minimal bleeding that does not require treatment.
Ectopic pregnancies can sometimes resolve on their own, but the incidence of spontaneous resolution is not known. Because an ectopic pregnancy poses such great risk to the mother, it should be treated as soon as possible after it is diagnosed.
DIAGNOSIS — Transvaginal ultrasound and a blood test that measures the pregnancy hormone, hCG (human chorionic gonadotropin), are used to diagnose ectopic pregnancy. Ultrasound technology uses sound waves to visualize structures within the body. In a transvaginal ultrasound, the ultrasound transducer is inserted into the woman's vagina allowing clearer visualization of the uterus and other pelvic organs. It can generally detect intrauterine pregnancies that are 5 to 6 weeks along. Ultrasound is most useful for identifying an intrauterine gestation. An extrauterine pregnancy will be visualized in only 16 to 32 percent of women, therefore a negative pelvic ultrasound (that is, no intrauterine or extrauterine gestation is seen) does not exclude the possibility of an ectopic pregnancy. hCG (human chorionic gonadotropin) is a substance secreted by the developing embryo/placenta. The hCG blood level is measured to confirm a pregnancy and can be used to monitor the progress of the early pregnant state.
Ectopic pregnancy is diagnosed if the ultrasound detects a fetal heart beat or an embryo that is outside of the uterus. Since ectopic pregnancies may not be detected by ultrasound, the hCG level is also measured. If the hCG is above a threshold level (usually 1500 mIU/mL), but no pregnancy is seen with ultrasound, an ectopic pregnancy is suspected. A value below this level may indicate either an ectopic pregnancy or early intrauterine pregnancy. When this happens, the ultrasound and hCG are repeated every few days until an ectopic pregnancy can be either confirmed or ruled out.
Women with moderate or strong risk factors for ectopic pregnancy, and those who conceived after IVF, are often monitored with ultrasound and blood testing after their first missed period to ensure early detection and treatment of a potential ectopic pregnancy.
TREATMENT — An ectopic pregnancy must be treated to stop its growth; observation or "watch and wait" treatment is never recommended as the life of the mother is at risk if treatment is delayed. Treatment is started as soon as a diagnosis of ectopic pregnancy is confirmed. Ectopic pregnancy may be treated with medication or surgery.
Medical management — The majority of unruptured ectopic pregnancies are treated with methotrexate, which inhibits the production of new cells and halts further growth of the embryo. It is given in an intramuscular injection. After the injection, the woman may experience abdominal pain or cramps, which can usually be controlled with acetaminophen (Tylenol®). Nonsteroidal antiinflammatory drugs should be avoided due to the risk of an interaction between NSAIDs and methotrexate.
hCG levels are monitored once weekly until the level has fallen to less than 10 mIU/mL. In 20 percent of women, a second dose of methotrexate is necessary; this is recommended if the day 7 hCG level has not fallen by at least 25 percent. In some cases, multiple doses of methotrexate are required.
Methotrexate is most successful in women who have an ectopic pregnancy without symptoms (eg, pain), and whose hCG level and ultrasound results fall within specified limits. When used in appropriate situations, treatment with methotrexate is successful 92 to 98 percent of the time (show table 1). If treatment with methotrexate is unsuccessful, tubal rupture can occur. This complication can be avoided with close monitoring and surgical management, if needed.
Surgical management — Surgery is sometimes recommended as treatment for ectopic pregnancy. Indications include: Ruptured ectopic pregnancy, especially when the woman's blood pressure has fallen and she is unstable. A woman who is unable or unwilling to return for monitoring after methotrexate therapy. A woman who would normally be a candidate for medical treatment, but who could not reach a hospital (due to lack of transportation or distance to an appropriate healthcare facility) in the event of tubal rupture during medical therapy.
Surgery may be performed using a laparoscopic approach or through an abdominal incision. In laparoscopy, special instruments are inserted into the abdomen through a few small incisions. These instruments are used to visualize and remove the ectopic pregnancy and control bleeding. In an abdominal procedure, the surgeon opens the abdomen using a single larger incision and then directly visualizes and removes the ectopic pregnancy.
Surgical management may include removal of the fallopian tube (called total or partial salpingectomy) or may remove the ectopic pregnancy and repair the tube (called salpingostomy). Leaving the tube in place is an option for some women and is preferred if the woman would like to become pregnant in the future. Some conditions require removal of the tube, including uncontrolled bleeding, recurrent ectopic pregnancy in the same tube, a severely damaged tube, or a large tubal pregnancy. It may also be performed in women who have completed childbearing.
In a small number of women treated surgically, embryonic tissue may still be present after surgery and cause the hCG level to remain elevated. A dose of methotrexate may be given if this occurs.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Nemours Foundation
(http://kidshealth.org)
Planned Parenthood Federation of America
(www.plannedparenthood.org)
Mayo Clinic
(www.mayoclinic.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ankum, WM, Mol, BWJ, Van Der Veen, F, Bossuyt, PMM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 1996; 65:1093.
2. Yao, M, Tulandi, T. Current status of surgical and non-surgical treatment of ectopic pregnancy. Fertil Steril 1997; 67:421.
3. Tulandi, T. Current protocol for ectopic pregnancy. Contemp Obstet Gynecol 1999; 44:42.
4. Practical and current management of tubal and nontubal ectopic pregnancy. Curr Probl Obstet Gynecol Fertil 2000; 23:94.
Monday, October 15, 2007
Ectopic (tubal) pregnancy
DEFINITION — Ectopic pregnancy occurs when a developing embryo implants at a site other than the inside wall of the uterus. A brief overview of early pregnancy may be helpful in understanding ectopic pregnancy.
Normal pregnancy — A woman's reproductive system includes the uterus, two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are narrow tubes that link the ovaries and uterus (show figure 1). Once a month, an egg is released by one of the ovaries (ovulation) and travels down the fallopian tube to the uterine cavity. In women undergoing treatment for infertility, more than one egg may be released by the ovary. If the egg is fertilized in the fallopian tube by the male's sperm, pregnancy begins.
Once joined, the egg and sperm begin to rapidly develop new cells. This group of cells, called the embryo, normally implants on the inner wall of the uterus, called the endometrium. Once implanted, the embryo continues to grow and also forms the placenta, the organ that provides a blood supply for the developing embryo.
Ectopic pregnancy — In an ectopic pregnancy, the developing embryo does not implant on the endometrial wall, but instead attaches to some other surface. Ninety eight percent of the time, that surface is within fallopian tubes. An ectopic pregnancy in a fallopian tube is sometimes called a tubal pregnancy.
Very rarely, the developing embryo will attach to another site such as the cervix or an ovary. It can also implant at the site where the fallopian tube and uterus join; this is called an interstitial pregnancy, or on the abdominal wall. Rarely in twin pregnancies, one embryo implants in the uterus and the other implants at an ectopic location. This rare event is called a heterotopic pregnancy and occurs more commonly in women undergoing infertility treatments.
Embryos that do not implant in the uterine wall are generally unable to develop normally. In addition, an ectopic pregnancy can cause rupture of the organ on which they are implanted, typically the fallopian tube. Rupture can result in severe internal bleeding, shock, and possibly death of the mother. Fortunately, the ability to diagnose, monitor, and treat ectopic pregnancy reduces the risk of life-threatening complications.
RISK FACTORS — A number of factors increase the risk for ectopic pregnancy. They can be divided into strong, moderate, and weak risk factors.
Strong risk factors Abnormalities of the fallopian tubes — If the fallopian tubes are damaged or abnormal as a result of previous infection or surgery, tumors, or rarely, due to malformations present since birth, there is an increased risk of ectopic pregnancy. Surgery to reconstruct the fallopian tube (to improve a woman's chances of becoming pregnant) can increase the risk of ectopic pregnancy, although preexisting tubal damage poses an even greater risk. Previous ectopic pregnancy — Women who have had one ectopic pregnancy have an increased risk for having another. The underlying tubal disorder that led to the first ectopic, and the effects of treating the first episode increase the risk for another ectopic pregnancy. In-utero diethylstilbestrol (DES) exposure — Women whose mothers took DES while pregnant are more likely to have abnormalities of the fallopian tubes and are at increased risk for an ectopic pregnancy.
Moderate risk factors Previous genital infections — Pelvic infection with gonorrhea or chlamydia is a major cause of tubal problems and increases the risk of ectopic pregnancy. Infertility — The incidence of ectopic pregnancy is higher in the infertility population, mostly due to the increased incidence of tubal abnormalities in these women. Fertility drugs also appear to alter tubal function by their effects on hormones and may be associated with the increased risk in this population. Multiple sexual partners — Having more than one sexual partner is associated with an increased risk of pelvic infection, and therefore an increased risk of ectopic pregnancy.
Weak risk factors Smoking — Cigarette smoking around the time of conception increases the risk of ectopic pregnancy; the risk increases with the number of cigarettes smoked. This risk may be the result of impaired immunity in smokers, which predisposes them to pelvic infection or impaired functioning of the fallopian tubes. Vaginal douching — Regular vaginal douching is associated with increased risk of both pelvic infections and ectopic pregnancy. Douching is never recommended under any circumstance. Age — Having a first sexual encounter at a young age (less than 18) slightly increases the risk of ectopic pregnancy.
Other risk factors In vitro fertilization (IVF) — IVF, a fertility treatment in which a woman's egg is fertilized outside the body and then placed in her uterus, is associated with an increased risk of both ectopic and heterotopic pregnancy. Tubal sterilization — Tubal sterilization is a surgical procedure in which the fallopian tubes are either cut, ligated, or coagulated. It is commonly known as having the "tubes tied," and is performed to prevent future pregnancies. Rarely, tubal sterilization fails and pregnancy can result. Women who become pregnant after tubal sterilization have a higher risk for ectopic pregnancy. Intrauterine contraceptive devices — Women who become pregnant while using an intrauterine contraceptive device (IUD) are at higher risk for ectopic pregnancy than women using other forms of contraception or no contraception.
SYMPTOMS — Symptoms, when they occur, appear early in pregnancy and often before the woman realizes she is pregnant. They include abdominal pain, amenorrhea (absence of a period), and vaginal bleeding, which may be minimal. Symptoms of pregnancy (such as breast tenderness, frequent urination, or nausea) may also be present.
However, over 50 percent of women have no symptoms until rupture occurs. Following rupture of the tube, the woman may experience severe pain and profound hemorrhage (bleeding). Lightheadedness or dizziness may occur first, followed by a drop in blood pressure, fainting, and shock. If there is severe bleeding, shock can progress to death.
Sometimes, the embryo is expelled by the fallopian tube before rupture occurs. This is called a "tubal abortion." Once expelled, the embryonic tissue may degenerate, or it may reimplant in the abdominal cavity or on the ovary. Tubal abortion can be accompanied by severe intra-abdominal bleeding requiring surgical intervention, or by minimal bleeding that does not require treatment.
Ectopic pregnancies can sometimes resolve on their own, but the incidence of spontaneous resolution is not known. Because an ectopic pregnancy poses such great risk to the mother, it should be treated as soon as possible after it is diagnosed.
DIAGNOSIS — Transvaginal ultrasound and a blood test that measures the pregnancy hormone, hCG (human chorionic gonadotropin), are used to diagnose ectopic pregnancy. Ultrasound technology uses sound waves to visualize structures within the body. In a transvaginal ultrasound, the ultrasound transducer is inserted into the woman's vagina allowing clearer visualization of the uterus and other pelvic organs. It can generally detect intrauterine pregnancies that are 5 to 6 weeks along. Ultrasound is most useful for identifying an intrauterine gestation. An extrauterine pregnancy will be visualized in only 16 to 32 percent of women, therefore a negative pelvic ultrasound (that is, no intrauterine or extrauterine gestation is seen) does not exclude the possibility of an ectopic pregnancy. hCG (human chorionic gonadotropin) is a substance secreted by the developing embryo/placenta. The hCG blood level is measured to confirm a pregnancy and can be used to monitor the progress of the early pregnant state.
Ectopic pregnancy is diagnosed if the ultrasound detects a fetal heart beat or an embryo that is outside of the uterus. Since ectopic pregnancies may not be detected by ultrasound, the hCG level is also measured. If the hCG is above a threshold level (usually 1500 mIU/mL), but no pregnancy is seen with ultrasound, an ectopic pregnancy is suspected. A value below this level may indicate either an ectopic pregnancy or early intrauterine pregnancy. When this happens, the ultrasound and hCG are repeated every few days until an ectopic pregnancy can be either confirmed or ruled out.
Women with moderate or strong risk factors for ectopic pregnancy, and those who conceived after IVF, are often monitored with ultrasound and blood testing after their first missed period to ensure early detection and treatment of a potential ectopic pregnancy.
TREATMENT — An ectopic pregnancy must be treated to stop its growth; observation or "watch and wait" treatment is never recommended as the life of the mother is at risk if treatment is delayed. Treatment is started as soon as a diagnosis of ectopic pregnancy is confirmed. Ectopic pregnancy may be treated with medication or surgery.
Medical management — The majority of unruptured ectopic pregnancies are treated with methotrexate, which inhibits the production of new cells and halts further growth of the embryo. It is given in an intramuscular injection. After the injection, the woman may experience abdominal pain or cramps, which can usually be controlled with acetaminophen (Tylenol®). Nonsteroidal antiinflammatory drugs should be avoided due to the risk of an interaction between NSAIDs and methotrexate.
hCG levels are monitored once weekly until the level has fallen to less than 10 mIU/mL. In 20 percent of women, a second dose of methotrexate is necessary; this is recommended if the day 7 hCG level has not fallen by at least 25 percent. In some cases, multiple doses of methotrexate are required.
Methotrexate is most successful in women who have an ectopic pregnancy without symptoms (eg, pain), and whose hCG level and ultrasound results fall within specified limits. When used in appropriate situations, treatment with methotrexate is successful 92 to 98 percent of the time (show table 1). If treatment with methotrexate is unsuccessful, tubal rupture can occur. This complication can be avoided with close monitoring and surgical management, if needed.
Surgical management — Surgery is sometimes recommended as treatment for ectopic pregnancy. Indications include: Ruptured ectopic pregnancy, especially when the woman's blood pressure has fallen and she is unstable. A woman who is unable or unwilling to return for monitoring after methotrexate therapy. A woman who would normally be a candidate for medical treatment, but who could not reach a hospital (due to lack of transportation or distance to an appropriate healthcare facility) in the event of tubal rupture during medical therapy.
Surgery may be performed using a laparoscopic approach or through an abdominal incision. In laparoscopy, special instruments are inserted into the abdomen through a few small incisions. These instruments are used to visualize and remove the ectopic pregnancy and control bleeding. In an abdominal procedure, the surgeon opens the abdomen using a single larger incision and then directly visualizes and removes the ectopic pregnancy.
Surgical management may include removal of the fallopian tube (called total or partial salpingectomy) or may remove the ectopic pregnancy and repair the tube (called salpingostomy). Leaving the tube in place is an option for some women and is preferred if the woman would like to become pregnant in the future. Some conditions require removal of the tube, including uncontrolled bleeding, recurrent ectopic pregnancy in the same tube, a severely damaged tube, or a large tubal pregnancy. It may also be performed in women who have completed childbearing.
In a small number of women treated surgically, embryonic tissue may still be present after surgery and cause the hCG level to remain elevated. A dose of methotrexate may be given if this occurs.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Nemours Foundation
(http://kidshealth.org)
Planned Parenthood Federation of America
(www.plannedparenthood.org)
Mayo Clinic
(www.mayoclinic.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ankum, WM, Mol, BWJ, Van Der Veen, F, Bossuyt, PMM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 1996; 65:1093.
2. Yao, M, Tulandi, T. Current status of surgical and non-surgical treatment of ectopic pregnancy. Fertil Steril 1997; 67:421.
3. Tulandi, T. Current protocol for ectopic pregnancy. Contemp Obstet Gynecol 1999; 44:42.
4. Practical and current management of tubal and nontubal ectopic pregnancy. Curr Probl Obstet Gynecol Fertil 2000; 23:94.
Normal pregnancy — A woman's reproductive system includes the uterus, two ovaries, two fallopian tubes, and the vagina. The fallopian tubes are narrow tubes that link the ovaries and uterus (show figure 1). Once a month, an egg is released by one of the ovaries (ovulation) and travels down the fallopian tube to the uterine cavity. In women undergoing treatment for infertility, more than one egg may be released by the ovary. If the egg is fertilized in the fallopian tube by the male's sperm, pregnancy begins.
Once joined, the egg and sperm begin to rapidly develop new cells. This group of cells, called the embryo, normally implants on the inner wall of the uterus, called the endometrium. Once implanted, the embryo continues to grow and also forms the placenta, the organ that provides a blood supply for the developing embryo.
Ectopic pregnancy — In an ectopic pregnancy, the developing embryo does not implant on the endometrial wall, but instead attaches to some other surface. Ninety eight percent of the time, that surface is within fallopian tubes. An ectopic pregnancy in a fallopian tube is sometimes called a tubal pregnancy.
Very rarely, the developing embryo will attach to another site such as the cervix or an ovary. It can also implant at the site where the fallopian tube and uterus join; this is called an interstitial pregnancy, or on the abdominal wall. Rarely in twin pregnancies, one embryo implants in the uterus and the other implants at an ectopic location. This rare event is called a heterotopic pregnancy and occurs more commonly in women undergoing infertility treatments.
Embryos that do not implant in the uterine wall are generally unable to develop normally. In addition, an ectopic pregnancy can cause rupture of the organ on which they are implanted, typically the fallopian tube. Rupture can result in severe internal bleeding, shock, and possibly death of the mother. Fortunately, the ability to diagnose, monitor, and treat ectopic pregnancy reduces the risk of life-threatening complications.
RISK FACTORS — A number of factors increase the risk for ectopic pregnancy. They can be divided into strong, moderate, and weak risk factors.
Strong risk factors Abnormalities of the fallopian tubes — If the fallopian tubes are damaged or abnormal as a result of previous infection or surgery, tumors, or rarely, due to malformations present since birth, there is an increased risk of ectopic pregnancy. Surgery to reconstruct the fallopian tube (to improve a woman's chances of becoming pregnant) can increase the risk of ectopic pregnancy, although preexisting tubal damage poses an even greater risk. Previous ectopic pregnancy — Women who have had one ectopic pregnancy have an increased risk for having another. The underlying tubal disorder that led to the first ectopic, and the effects of treating the first episode increase the risk for another ectopic pregnancy. In-utero diethylstilbestrol (DES) exposure — Women whose mothers took DES while pregnant are more likely to have abnormalities of the fallopian tubes and are at increased risk for an ectopic pregnancy.
Moderate risk factors Previous genital infections — Pelvic infection with gonorrhea or chlamydia is a major cause of tubal problems and increases the risk of ectopic pregnancy. Infertility — The incidence of ectopic pregnancy is higher in the infertility population, mostly due to the increased incidence of tubal abnormalities in these women. Fertility drugs also appear to alter tubal function by their effects on hormones and may be associated with the increased risk in this population. Multiple sexual partners — Having more than one sexual partner is associated with an increased risk of pelvic infection, and therefore an increased risk of ectopic pregnancy.
Weak risk factors Smoking — Cigarette smoking around the time of conception increases the risk of ectopic pregnancy; the risk increases with the number of cigarettes smoked. This risk may be the result of impaired immunity in smokers, which predisposes them to pelvic infection or impaired functioning of the fallopian tubes. Vaginal douching — Regular vaginal douching is associated with increased risk of both pelvic infections and ectopic pregnancy. Douching is never recommended under any circumstance. Age — Having a first sexual encounter at a young age (less than 18) slightly increases the risk of ectopic pregnancy.
Other risk factors In vitro fertilization (IVF) — IVF, a fertility treatment in which a woman's egg is fertilized outside the body and then placed in her uterus, is associated with an increased risk of both ectopic and heterotopic pregnancy. Tubal sterilization — Tubal sterilization is a surgical procedure in which the fallopian tubes are either cut, ligated, or coagulated. It is commonly known as having the "tubes tied," and is performed to prevent future pregnancies. Rarely, tubal sterilization fails and pregnancy can result. Women who become pregnant after tubal sterilization have a higher risk for ectopic pregnancy. Intrauterine contraceptive devices — Women who become pregnant while using an intrauterine contraceptive device (IUD) are at higher risk for ectopic pregnancy than women using other forms of contraception or no contraception.
SYMPTOMS — Symptoms, when they occur, appear early in pregnancy and often before the woman realizes she is pregnant. They include abdominal pain, amenorrhea (absence of a period), and vaginal bleeding, which may be minimal. Symptoms of pregnancy (such as breast tenderness, frequent urination, or nausea) may also be present.
However, over 50 percent of women have no symptoms until rupture occurs. Following rupture of the tube, the woman may experience severe pain and profound hemorrhage (bleeding). Lightheadedness or dizziness may occur first, followed by a drop in blood pressure, fainting, and shock. If there is severe bleeding, shock can progress to death.
Sometimes, the embryo is expelled by the fallopian tube before rupture occurs. This is called a "tubal abortion." Once expelled, the embryonic tissue may degenerate, or it may reimplant in the abdominal cavity or on the ovary. Tubal abortion can be accompanied by severe intra-abdominal bleeding requiring surgical intervention, or by minimal bleeding that does not require treatment.
Ectopic pregnancies can sometimes resolve on their own, but the incidence of spontaneous resolution is not known. Because an ectopic pregnancy poses such great risk to the mother, it should be treated as soon as possible after it is diagnosed.
DIAGNOSIS — Transvaginal ultrasound and a blood test that measures the pregnancy hormone, hCG (human chorionic gonadotropin), are used to diagnose ectopic pregnancy. Ultrasound technology uses sound waves to visualize structures within the body. In a transvaginal ultrasound, the ultrasound transducer is inserted into the woman's vagina allowing clearer visualization of the uterus and other pelvic organs. It can generally detect intrauterine pregnancies that are 5 to 6 weeks along. Ultrasound is most useful for identifying an intrauterine gestation. An extrauterine pregnancy will be visualized in only 16 to 32 percent of women, therefore a negative pelvic ultrasound (that is, no intrauterine or extrauterine gestation is seen) does not exclude the possibility of an ectopic pregnancy. hCG (human chorionic gonadotropin) is a substance secreted by the developing embryo/placenta. The hCG blood level is measured to confirm a pregnancy and can be used to monitor the progress of the early pregnant state.
Ectopic pregnancy is diagnosed if the ultrasound detects a fetal heart beat or an embryo that is outside of the uterus. Since ectopic pregnancies may not be detected by ultrasound, the hCG level is also measured. If the hCG is above a threshold level (usually 1500 mIU/mL), but no pregnancy is seen with ultrasound, an ectopic pregnancy is suspected. A value below this level may indicate either an ectopic pregnancy or early intrauterine pregnancy. When this happens, the ultrasound and hCG are repeated every few days until an ectopic pregnancy can be either confirmed or ruled out.
Women with moderate or strong risk factors for ectopic pregnancy, and those who conceived after IVF, are often monitored with ultrasound and blood testing after their first missed period to ensure early detection and treatment of a potential ectopic pregnancy.
TREATMENT — An ectopic pregnancy must be treated to stop its growth; observation or "watch and wait" treatment is never recommended as the life of the mother is at risk if treatment is delayed. Treatment is started as soon as a diagnosis of ectopic pregnancy is confirmed. Ectopic pregnancy may be treated with medication or surgery.
Medical management — The majority of unruptured ectopic pregnancies are treated with methotrexate, which inhibits the production of new cells and halts further growth of the embryo. It is given in an intramuscular injection. After the injection, the woman may experience abdominal pain or cramps, which can usually be controlled with acetaminophen (Tylenol®). Nonsteroidal antiinflammatory drugs should be avoided due to the risk of an interaction between NSAIDs and methotrexate.
hCG levels are monitored once weekly until the level has fallen to less than 10 mIU/mL. In 20 percent of women, a second dose of methotrexate is necessary; this is recommended if the day 7 hCG level has not fallen by at least 25 percent. In some cases, multiple doses of methotrexate are required.
Methotrexate is most successful in women who have an ectopic pregnancy without symptoms (eg, pain), and whose hCG level and ultrasound results fall within specified limits. When used in appropriate situations, treatment with methotrexate is successful 92 to 98 percent of the time (show table 1). If treatment with methotrexate is unsuccessful, tubal rupture can occur. This complication can be avoided with close monitoring and surgical management, if needed.
Surgical management — Surgery is sometimes recommended as treatment for ectopic pregnancy. Indications include: Ruptured ectopic pregnancy, especially when the woman's blood pressure has fallen and she is unstable. A woman who is unable or unwilling to return for monitoring after methotrexate therapy. A woman who would normally be a candidate for medical treatment, but who could not reach a hospital (due to lack of transportation or distance to an appropriate healthcare facility) in the event of tubal rupture during medical therapy.
Surgery may be performed using a laparoscopic approach or through an abdominal incision. In laparoscopy, special instruments are inserted into the abdomen through a few small incisions. These instruments are used to visualize and remove the ectopic pregnancy and control bleeding. In an abdominal procedure, the surgeon opens the abdomen using a single larger incision and then directly visualizes and removes the ectopic pregnancy.
Surgical management may include removal of the fallopian tube (called total or partial salpingectomy) or may remove the ectopic pregnancy and repair the tube (called salpingostomy). Leaving the tube in place is an option for some women and is preferred if the woman would like to become pregnant in the future. Some conditions require removal of the tube, including uncontrolled bleeding, recurrent ectopic pregnancy in the same tube, a severely damaged tube, or a large tubal pregnancy. It may also be performed in women who have completed childbearing.
In a small number of women treated surgically, embryonic tissue may still be present after surgery and cause the hCG level to remain elevated. A dose of methotrexate may be given if this occurs.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Nemours Foundation
(http://kidshealth.org)
Planned Parenthood Federation of America
(www.plannedparenthood.org)
Mayo Clinic
(www.mayoclinic.com)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ankum, WM, Mol, BWJ, Van Der Veen, F, Bossuyt, PMM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 1996; 65:1093.
2. Yao, M, Tulandi, T. Current status of surgical and non-surgical treatment of ectopic pregnancy. Fertil Steril 1997; 67:421.
3. Tulandi, T. Current protocol for ectopic pregnancy. Contemp Obstet Gynecol 1999; 44:42.
4. Practical and current management of tubal and nontubal ectopic pregnancy. Curr Probl Obstet Gynecol Fertil 2000; 23:94.
Dilation and curettage (D&C)
INTRODUCTION — Dilation and curettage (D&C) is a procedure in which material from the inside of the uterus is removed. The "dilation" refers to dilation of the cervix, the lower part of the uterus that opens into the vagina (show figure 1). "Curettage" refers to the scraping or removal of tissue lining the uterine cavity (endometrium) with a surgical instrument called a curette. Some curettes are sharp while others use suction.
REASONS FOR DC — There are a number of reasons a D&C might be performed. In some cases, the procedure is used to gain information about the uterus to diagnose a medical condition (called diagnostic D&C). In other cases, the procedure is used to treat a medical problem or condition (called therapeutic D&C).
Diagnostic DC — The primary reason for a diagnostic D&C is to obtain samples of the endometrium to evaluate abnormal uterine bleeding or abnormal cells found during routine screening for cervical cancer. (See "Patient information: Screening for cervical cancer").
In most cases, a healthcare provider will try to obtain a tissue sample with an office procedure called endometrial biopsy. In some cases, endometrial biopsy is not possible or insufficient tissue is obtained. When this occurs, D&C must be done to obtain an adequate tissue sample.
Diagnostic D&C is usually done with hysteroscopy; this involves dilating the cervix and inserting a small instrument that allows the physician to examine and photograph the inside of the uterus. The images are displayed on a monitor, allowing the physician to visualize the endometrium. This helps the physician to avoid missing small polyps and ensures that the most visibly abnormal areas are sampled. (See "Patient information: Abnormal uterine bleeding").
Examination of the endometrial tissue by a pathologist can help establish certain diagnoses, including endometrial (uterine) cancer, endometrial polyps, or precancerous conditions of the lining of the uterus (endometrial hyperplasia).
Therapeutic DC — Therapeutic D&C is done to remove the contents of the uterus in the following circumstances:
Miscarriage — In some miscarriages, the tissues from a pregnancy are passed completely. In other cases, a D&C is needed to remove this tissue or to ensure that all of it has been passed. (See "Patient information: Miscarriage").
Abortion — A D&C can be done to remove the contents of the uterus when a woman chooses to end a pregnancy.
Treatment of molar pregnancies — A molar pregnancy occurs when a tumor forms in place of normal pregnancy placenta. It is often treated with a D&C.
Prolonged or excessive vaginal bleeding — D&C may be done as a treatment in some cases of prolonged or excessive bleeding that do not respond to medical treatment. (See "Patient information: Abnormal uterine bleeding").
Postpartum hemorrhage — Curettage may be done to manage excessive bleeding after delivery of an infant (postpartum hemorrhage).
PREPARING FOR DC — Some patients will need to have blood testing before D&C (such as a blood count), although this is not always necessary. Patients should not eat or drink anything before the procedure. All patients will need someone to accompany them home because it will not be safe to drive after receiving anesthesia, which causes sedation.
Some patients will need to have a device or medication placed in the cervix the day before their procedure. The purpose is to safely and gradually enlarge the cervical opening, reducing the risk of cervical injury. Devices are used when the cervix must be dilated to a larger size than is typically needed for D&C, such as with pregnancy terminations and some types of hysteroscopy. Some patients will be instructed to insert a medicine in the vagina to soften the cervix prior to the procedure.
After arriving for the procedure, a nurse may place an intravenous (IV) line, which can be used to give fluids and medicine before, during, and after the procedure. The nurse or doctor will review the patient's medical history, list of medications used, and any drug allergies.
PROCEDURE — D&C can be performed in an operating room in a hospital or clinic. Many patients have a D&C performed in an outpatient setting. A woman's blood pressure, pulse, and blood oxygen levels are monitored during the procedure. The procedure takes 15 to 30 minutes to complete.
Anesthesia — The procedure can be done using general, regional, or local (paracervical) block anesthesia. The type of anesthesia chosen depends upon the reason for the procedure as well as the medical history.
General anesthesia — General anesthesia induces sleep and completely relaxes the muscles, which makes it easier for the doctor to perform a pelvic examination.
Regional anesthesia — Reginonal anesthesia uses an injection of an anesthetic into the area around the spinal cord to block pain sensation during surgery. The patient may be sedated with medicine given through an intravenous (IV) line.
Paracervical block — Anesthetic agents are injected directly into and around the cervix, numbing the area. The woman is given a sedative through an intravenous (IV) line.
POST-PROCEDURE CARE — After the procedure, the patient will be cared for in a recovery or post-anesthesia care unit for a few hours. This is necessary to monitor for excessive vaginal bleeding or other complications, and allows time for recovery from the anesthesia. Patients who received general anesthesia occasionally have nausea and vomiting, which can be treated with medications.
Most patients should be able to resume their regular activities within a day or two. Mild cramping and spotting may occur for a few hours or days; cramping can be treated with nonsteroidal antiinflammatory medications such as ibuprofen (Advil®, Motrin®). Patients should not put anything into the vagina (tampons, douches) during this time and should ask when they can safely have sexual intercourse. The next menstrual period usually occurs within 4 to 6 weeks of the procedure.
A woman should call her physician if she develops fever (temperature greater than 100.4ยบ F), cramps lasting longer than 48 hours, increasing rather than decreasing pain, prolonged or heavy bleeding, or foul-smelling vaginal discharge.
COMPLICATIONS — D&C is a commonly performed procedure that is usually very safe. Yet as with any operation, complications occur. Complications of D&C can include:
Uterine perforation — Uterine perforation occurs when one of the surgical instruments makes a hole in the uterus. It is more common when the procedure is done during pregnancy due to softening of the uterine wall.
Fortunately, most uterine perforations heal on their own and do not require any treatment. Two potential problems caused by perforation are bleeding from injury to a blood vessel and injury to other internal organs. A second procedure may be needed to repair these types of injury.
Cervical injury — Injuries to the cervix can occur during dilation or from trauma related to the curettage. Lacerations (cuts) to the cervix are managed with pressure to the area, application of medications that help stop bleeding, or in some cases, stitches in the cervix.
Infection — Infection from D&C is rare.
Intrauterine adhesions — Adhesions (areas of scar tissue) can sometimes form in the uterus following D&C. Adhesion is most common when D&C is performed postpartum or postabortion. In some cases, this can lead to abnormalities in the menstrual cycle, painful menstrual cycles, infertility, or miscarriage. If adhesions are extensive, a woman can be treated with hormones to encourage growth of healthy uterine tissue and the scar tissue can be removed with a surgical procedure.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Mayo Clinic
(www.mayoclinic.com)
[1-3]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. APGO educational series on women's health issues. Clinical management of abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics, May 2002.
2. Chen, SS, Lee, L. Reappraisal of endocervical curettage in predicting cervical involvement by endometrial carcinoma. J Reprod Med 1986; 31:50.
3. Gebauer, G, Hafner, A, Siebzehnrubl, E, Lang, N. Role of hysteroscopy in detection and extraction of endometrial polyps: results of a prospective study. Am J Obstet Gynecol 2001; 184:59.
REASONS FOR DC — There are a number of reasons a D&C might be performed. In some cases, the procedure is used to gain information about the uterus to diagnose a medical condition (called diagnostic D&C). In other cases, the procedure is used to treat a medical problem or condition (called therapeutic D&C).
Diagnostic DC — The primary reason for a diagnostic D&C is to obtain samples of the endometrium to evaluate abnormal uterine bleeding or abnormal cells found during routine screening for cervical cancer. (See "Patient information: Screening for cervical cancer").
In most cases, a healthcare provider will try to obtain a tissue sample with an office procedure called endometrial biopsy. In some cases, endometrial biopsy is not possible or insufficient tissue is obtained. When this occurs, D&C must be done to obtain an adequate tissue sample.
Diagnostic D&C is usually done with hysteroscopy; this involves dilating the cervix and inserting a small instrument that allows the physician to examine and photograph the inside of the uterus. The images are displayed on a monitor, allowing the physician to visualize the endometrium. This helps the physician to avoid missing small polyps and ensures that the most visibly abnormal areas are sampled. (See "Patient information: Abnormal uterine bleeding").
Examination of the endometrial tissue by a pathologist can help establish certain diagnoses, including endometrial (uterine) cancer, endometrial polyps, or precancerous conditions of the lining of the uterus (endometrial hyperplasia).
Therapeutic DC — Therapeutic D&C is done to remove the contents of the uterus in the following circumstances:
Miscarriage — In some miscarriages, the tissues from a pregnancy are passed completely. In other cases, a D&C is needed to remove this tissue or to ensure that all of it has been passed. (See "Patient information: Miscarriage").
Abortion — A D&C can be done to remove the contents of the uterus when a woman chooses to end a pregnancy.
Treatment of molar pregnancies — A molar pregnancy occurs when a tumor forms in place of normal pregnancy placenta. It is often treated with a D&C.
Prolonged or excessive vaginal bleeding — D&C may be done as a treatment in some cases of prolonged or excessive bleeding that do not respond to medical treatment. (See "Patient information: Abnormal uterine bleeding").
Postpartum hemorrhage — Curettage may be done to manage excessive bleeding after delivery of an infant (postpartum hemorrhage).
PREPARING FOR DC — Some patients will need to have blood testing before D&C (such as a blood count), although this is not always necessary. Patients should not eat or drink anything before the procedure. All patients will need someone to accompany them home because it will not be safe to drive after receiving anesthesia, which causes sedation.
Some patients will need to have a device or medication placed in the cervix the day before their procedure. The purpose is to safely and gradually enlarge the cervical opening, reducing the risk of cervical injury. Devices are used when the cervix must be dilated to a larger size than is typically needed for D&C, such as with pregnancy terminations and some types of hysteroscopy. Some patients will be instructed to insert a medicine in the vagina to soften the cervix prior to the procedure.
After arriving for the procedure, a nurse may place an intravenous (IV) line, which can be used to give fluids and medicine before, during, and after the procedure. The nurse or doctor will review the patient's medical history, list of medications used, and any drug allergies.
PROCEDURE — D&C can be performed in an operating room in a hospital or clinic. Many patients have a D&C performed in an outpatient setting. A woman's blood pressure, pulse, and blood oxygen levels are monitored during the procedure. The procedure takes 15 to 30 minutes to complete.
Anesthesia — The procedure can be done using general, regional, or local (paracervical) block anesthesia. The type of anesthesia chosen depends upon the reason for the procedure as well as the medical history.
General anesthesia — General anesthesia induces sleep and completely relaxes the muscles, which makes it easier for the doctor to perform a pelvic examination.
Regional anesthesia — Reginonal anesthesia uses an injection of an anesthetic into the area around the spinal cord to block pain sensation during surgery. The patient may be sedated with medicine given through an intravenous (IV) line.
Paracervical block — Anesthetic agents are injected directly into and around the cervix, numbing the area. The woman is given a sedative through an intravenous (IV) line.
POST-PROCEDURE CARE — After the procedure, the patient will be cared for in a recovery or post-anesthesia care unit for a few hours. This is necessary to monitor for excessive vaginal bleeding or other complications, and allows time for recovery from the anesthesia. Patients who received general anesthesia occasionally have nausea and vomiting, which can be treated with medications.
Most patients should be able to resume their regular activities within a day or two. Mild cramping and spotting may occur for a few hours or days; cramping can be treated with nonsteroidal antiinflammatory medications such as ibuprofen (Advil®, Motrin®). Patients should not put anything into the vagina (tampons, douches) during this time and should ask when they can safely have sexual intercourse. The next menstrual period usually occurs within 4 to 6 weeks of the procedure.
A woman should call her physician if she develops fever (temperature greater than 100.4ยบ F), cramps lasting longer than 48 hours, increasing rather than decreasing pain, prolonged or heavy bleeding, or foul-smelling vaginal discharge.
COMPLICATIONS — D&C is a commonly performed procedure that is usually very safe. Yet as with any operation, complications occur. Complications of D&C can include:
Uterine perforation — Uterine perforation occurs when one of the surgical instruments makes a hole in the uterus. It is more common when the procedure is done during pregnancy due to softening of the uterine wall.
Fortunately, most uterine perforations heal on their own and do not require any treatment. Two potential problems caused by perforation are bleeding from injury to a blood vessel and injury to other internal organs. A second procedure may be needed to repair these types of injury.
Cervical injury — Injuries to the cervix can occur during dilation or from trauma related to the curettage. Lacerations (cuts) to the cervix are managed with pressure to the area, application of medications that help stop bleeding, or in some cases, stitches in the cervix.
Infection — Infection from D&C is rare.
Intrauterine adhesions — Adhesions (areas of scar tissue) can sometimes form in the uterus following D&C. Adhesion is most common when D&C is performed postpartum or postabortion. In some cases, this can lead to abnormalities in the menstrual cycle, painful menstrual cycles, infertility, or miscarriage. If adhesions are extensive, a woman can be treated with hormones to encourage growth of healthy uterine tissue and the scar tissue can be removed with a surgical procedure.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Mayo Clinic
(www.mayoclinic.com)
[1-3]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. APGO educational series on women's health issues. Clinical management of abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics, May 2002.
2. Chen, SS, Lee, L. Reappraisal of endocervical curettage in predicting cervical involvement by endometrial carcinoma. J Reprod Med 1986; 31:50.
3. Gebauer, G, Hafner, A, Siebzehnrubl, E, Lang, N. Role of hysteroscopy in detection and extraction of endometrial polyps: results of a prospective study. Am J Obstet Gynecol 2001; 184:59.
Dilation and curettage (D&C)
INTRODUCTION — Dilation and curettage (D&C) is a procedure in which material from the inside of the uterus is removed. The "dilation" refers to dilation of the cervix, the lower part of the uterus that opens into the vagina (show figure 1). "Curettage" refers to the scraping or removal of tissue lining the uterine cavity (endometrium) with a surgical instrument called a curette. Some curettes are sharp while others use suction.
REASONS FOR DC — There are a number of reasons a D&C might be performed. In some cases, the procedure is used to gain information about the uterus to diagnose a medical condition (called diagnostic D&C). In other cases, the procedure is used to treat a medical problem or condition (called therapeutic D&C).
Diagnostic DC — The primary reason for a diagnostic D&C is to obtain samples of the endometrium to evaluate abnormal uterine bleeding or abnormal cells found during routine screening for cervical cancer. (See "Patient information: Screening for cervical cancer").
In most cases, a healthcare provider will try to obtain a tissue sample with an office procedure called endometrial biopsy. In some cases, endometrial biopsy is not possible or insufficient tissue is obtained. When this occurs, D&C must be done to obtain an adequate tissue sample.
Diagnostic D&C is usually done with hysteroscopy; this involves dilating the cervix and inserting a small instrument that allows the physician to examine and photograph the inside of the uterus. The images are displayed on a monitor, allowing the physician to visualize the endometrium. This helps the physician to avoid missing small polyps and ensures that the most visibly abnormal areas are sampled. (See "Patient information: Abnormal uterine bleeding").
Examination of the endometrial tissue by a pathologist can help establish certain diagnoses, including endometrial (uterine) cancer, endometrial polyps, or precancerous conditions of the lining of the uterus (endometrial hyperplasia).
Therapeutic DC — Therapeutic D&C is done to remove the contents of the uterus in the following circumstances:
Miscarriage — In some miscarriages, the tissues from a pregnancy are passed completely. In other cases, a D&C is needed to remove this tissue or to ensure that all of it has been passed. (See "Patient information: Miscarriage").
Abortion — A D&C can be done to remove the contents of the uterus when a woman chooses to end a pregnancy.
Treatment of molar pregnancies — A molar pregnancy occurs when a tumor forms in place of normal pregnancy placenta. It is often treated with a D&C.
Prolonged or excessive vaginal bleeding — D&C may be done as a treatment in some cases of prolonged or excessive bleeding that do not respond to medical treatment. (See "Patient information: Abnormal uterine bleeding").
Postpartum hemorrhage — Curettage may be done to manage excessive bleeding after delivery of an infant (postpartum hemorrhage).
PREPARING FOR DC — Some patients will need to have blood testing before D&C (such as a blood count), although this is not always necessary. Patients should not eat or drink anything before the procedure. All patients will need someone to accompany them home because it will not be safe to drive after receiving anesthesia, which causes sedation.
Some patients will need to have a device or medication placed in the cervix the day before their procedure. The purpose is to safely and gradually enlarge the cervical opening, reducing the risk of cervical injury. Devices are used when the cervix must be dilated to a larger size than is typically needed for D&C, such as with pregnancy terminations and some types of hysteroscopy. Some patients will be instructed to insert a medicine in the vagina to soften the cervix prior to the procedure.
After arriving for the procedure, a nurse may place an intravenous (IV) line, which can be used to give fluids and medicine before, during, and after the procedure. The nurse or doctor will review the patient's medical history, list of medications used, and any drug allergies.
PROCEDURE — D&C can be performed in an operating room in a hospital or clinic. Many patients have a D&C performed in an outpatient setting. A woman's blood pressure, pulse, and blood oxygen levels are monitored during the procedure. The procedure takes 15 to 30 minutes to complete.
Anesthesia — The procedure can be done using general, regional, or local (paracervical) block anesthesia. The type of anesthesia chosen depends upon the reason for the procedure as well as the medical history.
General anesthesia — General anesthesia induces sleep and completely relaxes the muscles, which makes it easier for the doctor to perform a pelvic examination.
Regional anesthesia — Reginonal anesthesia uses an injection of an anesthetic into the area around the spinal cord to block pain sensation during surgery. The patient may be sedated with medicine given through an intravenous (IV) line.
Paracervical block — Anesthetic agents are injected directly into and around the cervix, numbing the area. The woman is given a sedative through an intravenous (IV) line.
POST-PROCEDURE CARE — After the procedure, the patient will be cared for in a recovery or post-anesthesia care unit for a few hours. This is necessary to monitor for excessive vaginal bleeding or other complications, and allows time for recovery from the anesthesia. Patients who received general anesthesia occasionally have nausea and vomiting, which can be treated with medications.
Most patients should be able to resume their regular activities within a day or two. Mild cramping and spotting may occur for a few hours or days; cramping can be treated with nonsteroidal antiinflammatory medications such as ibuprofen (Advil®, Motrin®). Patients should not put anything into the vagina (tampons, douches) during this time and should ask when they can safely have sexual intercourse. The next menstrual period usually occurs within 4 to 6 weeks of the procedure.
A woman should call her physician if she develops fever (temperature greater than 100.4ยบ F), cramps lasting longer than 48 hours, increasing rather than decreasing pain, prolonged or heavy bleeding, or foul-smelling vaginal discharge.
COMPLICATIONS — D&C is a commonly performed procedure that is usually very safe. Yet as with any operation, complications occur. Complications of D&C can include:
Uterine perforation — Uterine perforation occurs when one of the surgical instruments makes a hole in the uterus. It is more common when the procedure is done during pregnancy due to softening of the uterine wall.
Fortunately, most uterine perforations heal on their own and do not require any treatment. Two potential problems caused by perforation are bleeding from injury to a blood vessel and injury to other internal organs. A second procedure may be needed to repair these types of injury.
Cervical injury — Injuries to the cervix can occur during dilation or from trauma related to the curettage. Lacerations (cuts) to the cervix are managed with pressure to the area, application of medications that help stop bleeding, or in some cases, stitches in the cervix.
Infection — Infection from D&C is rare.
Intrauterine adhesions — Adhesions (areas of scar tissue) can sometimes form in the uterus following D&C. Adhesion is most common when D&C is performed postpartum or postabortion. In some cases, this can lead to abnormalities in the menstrual cycle, painful menstrual cycles, infertility, or miscarriage. If adhesions are extensive, a woman can be treated with hormones to encourage growth of healthy uterine tissue and the scar tissue can be removed with a surgical procedure.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Mayo Clinic
(www.mayoclinic.com)
[1-3]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. APGO educational series on women's health issues. Clinical management of abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics, May 2002.
2. Chen, SS, Lee, L. Reappraisal of endocervical curettage in predicting cervical involvement by endometrial carcinoma. J Reprod Med 1986; 31:50.
3. Gebauer, G, Hafner, A, Siebzehnrubl, E, Lang, N. Role of hysteroscopy in detection and extraction of endometrial polyps: results of a prospective study. Am J Obstet Gynecol 2001; 184:59.
REASONS FOR DC — There are a number of reasons a D&C might be performed. In some cases, the procedure is used to gain information about the uterus to diagnose a medical condition (called diagnostic D&C). In other cases, the procedure is used to treat a medical problem or condition (called therapeutic D&C).
Diagnostic DC — The primary reason for a diagnostic D&C is to obtain samples of the endometrium to evaluate abnormal uterine bleeding or abnormal cells found during routine screening for cervical cancer. (See "Patient information: Screening for cervical cancer").
In most cases, a healthcare provider will try to obtain a tissue sample with an office procedure called endometrial biopsy. In some cases, endometrial biopsy is not possible or insufficient tissue is obtained. When this occurs, D&C must be done to obtain an adequate tissue sample.
Diagnostic D&C is usually done with hysteroscopy; this involves dilating the cervix and inserting a small instrument that allows the physician to examine and photograph the inside of the uterus. The images are displayed on a monitor, allowing the physician to visualize the endometrium. This helps the physician to avoid missing small polyps and ensures that the most visibly abnormal areas are sampled. (See "Patient information: Abnormal uterine bleeding").
Examination of the endometrial tissue by a pathologist can help establish certain diagnoses, including endometrial (uterine) cancer, endometrial polyps, or precancerous conditions of the lining of the uterus (endometrial hyperplasia).
Therapeutic DC — Therapeutic D&C is done to remove the contents of the uterus in the following circumstances:
Miscarriage — In some miscarriages, the tissues from a pregnancy are passed completely. In other cases, a D&C is needed to remove this tissue or to ensure that all of it has been passed. (See "Patient information: Miscarriage").
Abortion — A D&C can be done to remove the contents of the uterus when a woman chooses to end a pregnancy.
Treatment of molar pregnancies — A molar pregnancy occurs when a tumor forms in place of normal pregnancy placenta. It is often treated with a D&C.
Prolonged or excessive vaginal bleeding — D&C may be done as a treatment in some cases of prolonged or excessive bleeding that do not respond to medical treatment. (See "Patient information: Abnormal uterine bleeding").
Postpartum hemorrhage — Curettage may be done to manage excessive bleeding after delivery of an infant (postpartum hemorrhage).
PREPARING FOR DC — Some patients will need to have blood testing before D&C (such as a blood count), although this is not always necessary. Patients should not eat or drink anything before the procedure. All patients will need someone to accompany them home because it will not be safe to drive after receiving anesthesia, which causes sedation.
Some patients will need to have a device or medication placed in the cervix the day before their procedure. The purpose is to safely and gradually enlarge the cervical opening, reducing the risk of cervical injury. Devices are used when the cervix must be dilated to a larger size than is typically needed for D&C, such as with pregnancy terminations and some types of hysteroscopy. Some patients will be instructed to insert a medicine in the vagina to soften the cervix prior to the procedure.
After arriving for the procedure, a nurse may place an intravenous (IV) line, which can be used to give fluids and medicine before, during, and after the procedure. The nurse or doctor will review the patient's medical history, list of medications used, and any drug allergies.
PROCEDURE — D&C can be performed in an operating room in a hospital or clinic. Many patients have a D&C performed in an outpatient setting. A woman's blood pressure, pulse, and blood oxygen levels are monitored during the procedure. The procedure takes 15 to 30 minutes to complete.
Anesthesia — The procedure can be done using general, regional, or local (paracervical) block anesthesia. The type of anesthesia chosen depends upon the reason for the procedure as well as the medical history.
General anesthesia — General anesthesia induces sleep and completely relaxes the muscles, which makes it easier for the doctor to perform a pelvic examination.
Regional anesthesia — Reginonal anesthesia uses an injection of an anesthetic into the area around the spinal cord to block pain sensation during surgery. The patient may be sedated with medicine given through an intravenous (IV) line.
Paracervical block — Anesthetic agents are injected directly into and around the cervix, numbing the area. The woman is given a sedative through an intravenous (IV) line.
POST-PROCEDURE CARE — After the procedure, the patient will be cared for in a recovery or post-anesthesia care unit for a few hours. This is necessary to monitor for excessive vaginal bleeding or other complications, and allows time for recovery from the anesthesia. Patients who received general anesthesia occasionally have nausea and vomiting, which can be treated with medications.
Most patients should be able to resume their regular activities within a day or two. Mild cramping and spotting may occur for a few hours or days; cramping can be treated with nonsteroidal antiinflammatory medications such as ibuprofen (Advil®, Motrin®). Patients should not put anything into the vagina (tampons, douches) during this time and should ask when they can safely have sexual intercourse. The next menstrual period usually occurs within 4 to 6 weeks of the procedure.
A woman should call her physician if she develops fever (temperature greater than 100.4ยบ F), cramps lasting longer than 48 hours, increasing rather than decreasing pain, prolonged or heavy bleeding, or foul-smelling vaginal discharge.
COMPLICATIONS — D&C is a commonly performed procedure that is usually very safe. Yet as with any operation, complications occur. Complications of D&C can include:
Uterine perforation — Uterine perforation occurs when one of the surgical instruments makes a hole in the uterus. It is more common when the procedure is done during pregnancy due to softening of the uterine wall.
Fortunately, most uterine perforations heal on their own and do not require any treatment. Two potential problems caused by perforation are bleeding from injury to a blood vessel and injury to other internal organs. A second procedure may be needed to repair these types of injury.
Cervical injury — Injuries to the cervix can occur during dilation or from trauma related to the curettage. Lacerations (cuts) to the cervix are managed with pressure to the area, application of medications that help stop bleeding, or in some cases, stitches in the cervix.
Infection — Infection from D&C is rare.
Intrauterine adhesions — Adhesions (areas of scar tissue) can sometimes form in the uterus following D&C. Adhesion is most common when D&C is performed postpartum or postabortion. In some cases, this can lead to abnormalities in the menstrual cycle, painful menstrual cycles, infertility, or miscarriage. If adhesions are extensive, a woman can be treated with hormones to encourage growth of healthy uterine tissue and the scar tissue can be removed with a surgical procedure.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
The Mayo Clinic
(www.mayoclinic.com)
[1-3]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. APGO educational series on women's health issues. Clinical management of abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics, May 2002.
2. Chen, SS, Lee, L. Reappraisal of endocervical curettage in predicting cervical involvement by endometrial carcinoma. J Reprod Med 1986; 31:50.
3. Gebauer, G, Hafner, A, Siebzehnrubl, E, Lang, N. Role of hysteroscopy in detection and extraction of endometrial polyps: results of a prospective study. Am J Obstet Gynecol 2001; 184:59.
Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)
INTRODUCTION — Premenstrual syndrome (PMS) refers to a group of physical and behavioral symptoms that occur in a cyclic pattern during the second half of the menstrual cycle. Premenstrual dysphoric disorder (PMDD) is the severe form of PMS. Common symptoms are anger, irritability, and internal tension that are severe enough to interfere with daily activities.
Mild PMS is common, affecting up to 75 percent of women with regular menstrual cycles; PMDD affects only 3 to 8 percent of women. This condition affects women of any socioeconomic, cultural, or ethnic backgrounds.
PMDD is usually a chronic condition that can have a serious impact on a woman's quality of life. Fortunately, a variety of treatments and self-care measures can effectively control the symptoms in most women.
CAUSES — The first day of menstrual bleeding is the first day of a woman's cycle. Following this, levels of the hormones estrogen and progesterone increase until approximately day 21, when they begin to fall. Tissues throughout the body are sensitive to these changing hormone levels. Studies suggest that rising and falling hormone levels may also influence chemicals in the brain, including a substance called serotonin, that affect mood.
However, it is not clear why some women develop PMDD and others do not. Levels of estrogen and progesterone are similar in women with and without PMDD. The most likely explanation, based upon several studies, is that women who develop PMDD are exquisitely sensitive to changes in hormone levels.
SYMPTOMS
Common symptoms — The most common symptoms of PMS and PMDD are fatigue, bloating, irritability, and anxiety. Other symptoms include the following: Feeling sad, hopeless, or worthless Feeling tense, anxious, or "on edge" Variable moods with frequent tearfulness Persistent irritability, anger, and conflict with family, coworkers, or friends Decreased interest in usual activities Difficulty concentrating Feeling fatigued, lethargic, or lacking in energy Changes in appetite, which may include binge eating or craving certain foods Sleeping excessively or difficulty sleeping Feeling overwhelmed or out of control Breast tenderness or swelling, headaches, joint or muscle pain, weight gain
Disorders that mimic PMDD — Other conditions can have similar signs and symptoms, including depression, anxiety disorders, and perimenopause. It is important to distinguish between underlying depression (which often worsens before menses) and true PMDD because the treatments are quite different.
Women with underlying depression often feel better during or after menses, but the symptoms do not resolve completely, whereas the symptoms of PMDD do resolve completely when menses begin. Some women who think they have PMDD actually have depression or an anxiety disorder. (See "Patient information: Depression in adults").
There are other medical disorders that worsen before or during menstruation that have features similar to PMDD, such as migraine, chronic fatigue syndrome, or irritable bowel syndrome. A careful medical history should be able to distinguish among these disorders. It is also possible for a woman to have PMDD in addition to another medical condition. (See "Patient information: Headache causes and diagnosis" and see "Patient information: Irritable bowel syndrome").
DIAGNOSIS — There is no single, definitive test for the diagnosis of PMDD. To be diagnosed with PMS or PMDD a woman must have both physical and behavioral symptoms. The symptoms of PMS/PMDD must occur only during the second half (luteal phase) of the menstrual cycle, most often during the five to seven days before the start of the menstrual period. These symptoms are not present between days 4 through 12 of a 28-day menstrual cycle.
Medical history — During a medical history, a healthcare provider will ask about when symptoms started, if symptoms have worsened or improved, severity of symptoms, and how long symptoms occur with each cycle. The provider will also ask about symptom timing in relation to the menstrual cycle and whether menstrual cycles are regular (every 21 to 35 days). The provider will also ask about factors that improve or worsen the symptoms, about other medical conditions, and about other medications, herbs, or vitamins used.
Physical examination — A general physical examination is done to rule out other possible causes of symptoms.
Blood tests — Blood tests are usually normal in women with PMDD. A routine blood count provides a general screening for other medical conditions that cause fatigue, such as anemia. Thyroid function tests can detect hypothyroidism (underactive thyroid gland) or hyperthyroidism (overactive thyroid gland), which can have signs and symptoms similar to PMS. (See "Patient information: Hypothyroidism" and see "Patient information: Hyperthyroidism").
Recording symptoms — Although a woman's symptoms may suggest PMDD, a clinician may request that she carefully record her symptoms on a daily basis for two full menstrual cycles (show figure 1). Using this calendar, a woman can rate the severity of 10 physical symptoms and 12 behavioral symptoms on a 4-point scale.
TREATMENT — Healthcare providers usually recommend conservative treatment of PMS first, which may include regular exercise, relaxation techniques, and vitamin and mineral supplementation. These therapies relieve symptoms in some women and have few or no side effects. If these therapies do not bring sufficient relief, drug therapy can be considered as a second option.
Drug therapy is generally recommended first for women with PMDD because of the severity of symptoms.
Highly effective treatments — Several drugs have proven effectiveness for relieving the symptoms of PMDD.
Serotonin reuptake inhibitors — There is good evidence that serotonin reuptake inhibitors (SRIs) are highly effective for the symptoms of PMDD. The SRIs include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), and paroxetine (Paxil®). In studies, all of these drugs reduced the symptoms of PMDD much more effectively than placebo. Some women find that they do not have to take the medication every day; taking them only during the second half of the menstrual cycle (ie, beginning on day 14 of the cycle and continuing until the bleeding begins) may be sufficient.
Fluoxetine reduces the symptoms of PMDD in up to 75 percent of women and remains effective for many years. The usual dose is 20 mg/day; higher doses have not been proven to be more beneficial. Some women have sexual side effects while using fluoxetine, including anorgasmia (inability to achieve orgasm). If this occurs, using a lower dose or trying an alternate drug in the same drug class may be helpful.
SRIs should be taken for at least two menstrual cycles to determine their effect on the symptoms of PMDD. About 15 percent of women do not achieve relief with these drugs after two cycles, in which case an alternate treatment is recommended.
Other antidepressants that inhibit serotonin reuptake (but are not SRIs), such as clomipramine (Anafranil®) (which can be taken daily or only during the second half of the cycle). Venlaxafine (Effexor®) selectively inhibits the reuptake of two neurotransmitters, serotonin and norepinephrine, and is also more effective than placebo.
Gonadotropin-releasing hormone agonists — A gonadotropin-releasing hormone (GnRH) agonist is an injectable medication that suppresses the pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). As a result, the ovaries temporarily stop making estrogen and progesterone, causing a temporary menopause. Leuprolide (Lupron®) is a GnRH agonist.
Side effects occur due the loss of estrogen, and include hot flashes, thinning of the bones, and an increased risk of osteoporosis with long-term use. GnRH agonists are effective for relieving the physical symptoms of PMS, but the side effects of these drugs limit their use. Side effects can be treated by adding back small doses of estrogen or medications that protect the bones (See "Patient information: Osteoporosis prevention and treatment").
Danazol — Danazol (Danocrine®) is an injectable medication that works similarly to the GnRH agonists in suppressing ovulation. It can improve the symptoms of PMS, but has side effects similar to those of testosterone (acne and growth of facial hair); its use is generally reserved for women who do not improve with other medications.
Other treatments — The effectiveness of some treatments is not as clear. These treatments may relieve the symptoms of PMS or PMDD in some women, and women may use a short trial of these treatments to determine if they are effective.
Alprazolam — The drug alprazolam (Xanax®) may reduce the symptoms of PMS or PMDD in some women. However, it can be addictive and is therefore reserved as a second-line treatment.
Oral contraceptives — PMDD is equally common among women who take oral contraceptives and women who do not. However, some women with PMDD have relief of their symptoms when they begin taking an oral contraceptive (while other women feel worse). Some providers recommend that the pill be taken continuously by women with PMDD (ie, skipping the placebo week of the pill for several months in a row). By doing this, the woman will not have a menstrual period, and in theory, will not have the usual cyclic changes in hormones that could affect mood. This is not, however, a proven treatment for PMDD.
Exercise and relaxation techniques — Some studies suggest that regular exercise, relaxation, and reflexology can improve the symptoms of PMS. However, these techniques are not recommended as the sole treatment for women with PMDD.
Agnus castus fruit extract — The fruits of Vitex agnus castus (the chasteberry tree) have been used to treat the symptoms of PMS. In one clinical trial of women with PMS, agnus castus (one dry extract tablet daily for 3 cycles) resulted in a significant decrease in irritability, anger, headache, and breast fullness when compared with placebo [1]. No significant side effects were seen. While this appears to be a potential therapy for PMS/PMDD, further study is needed before it is recommended. In addition, consumers should use caution with herbal products because their purity is not regulated.
Vitamin and mineral supplements — Several clinical trials have evaluated the benefit of calcium treatment for women with PMS. The women who took 600 mg of calcium twice daily had fewer symptoms compared to those who took a placebo [2]. This is an inexpensive treatment with few side effects, and a trial should be considered by women with mild to moderate symptoms of PMS.
Some smaller clinical trials have studied the benefit of vitamin B6 (up to 100 mg/day), magnesium (200 to 360 mg up to three times per day), and vitamin E (400 IU per day). There may be modest improvement of PMS symptoms with these supplements.
Ineffective treatments — Several treatments are of no proven benefit in relieving the symptoms of PMS. These treatments include progesterone, diuretics such as spironolactone, other antidepressant drugs (tricyclic antidepressants and monoamine oxidase inhibitors), and lithium. There is also no proven benefit of certain popular dietary supplements, including evening primrose oil, essential free fatty acids, and ginkgo biloba.
SUMMARY Premenstrual syndrome (PMS) causes symptoms one to two weeks before a woman's menstrual period. Common symptoms include feeling tired, bloated, irritable, and anxious. Premenstrual dysphoric disorder (PMDD) is the severe form of PMS. PMDD can cause a woman to feel very sad or nervous, to have trouble with friends or family (eg, disagreements with husband or children), and can cause problems with paying attention to work or school (see "Symptoms" above). The cause of PMS and PMDD is not known. Some women may be very sensitive to changes in hormone levels. Hormone levels normally change before and during the menstrual period (see "Causes" above). Other problems, such as depression and anxiety, are similar to PMDD. The main difference is that PMS and/or PMDD only occur before the period. Depression and anxiety are usually noticeable all the time. The treatments of PMDD and depression are quite different. There is no test for PMS or PMDD. To be diagnosed with PMS or PMDD, a woman must have physical symptoms (eg, breast tenderness, muscle pain) and mood changes (eg, sadness, crying). These symptoms must occur before the menstrual period (not after). (see "Diagnosis" above). Some women are asked to keep a record of their feelings every day for two full menstrual cycles (for example, show figure 1). PMS may be treated with behavior changes (eg, exercise, relaxation) first. These treatments are helpful for some women and have few or no side effects. A medication may be tried if behavior changes are not helpful. A medication is usually the best treatment for women with PMDD (see "Treatment" above). The best medications for PMS or PMDD include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), or paroxetine (Paxil®). Some women take this medication every day. Others take medication for two weeks before their menstrual period (see "Serotonin reuptake inhibitors" above).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. The Hormone Foundation
(www.hormone.org/public/pms.cfm)
National Institutes of Health
(www.nlm.nih.gov/medlineplus/healthtopics.html)
United States Department of Health and Human Services
(www.4woman.gov/faq/pms.htm)
American Academy of Family Physicians
(http://familydoctor.org)
The Mayo Clinic
(www.mayoclinic.com)
[1-9]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Schellenberg, R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ 2001; 322:134.
2. Thys-Jacobs, S, Starkey, P, Bernstein, D, Tian, J. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol 1998; 179:444.
3. American College of Obstetricians and Gynecologists. Premenstrual syndrome. ACOG Practice Bulletin 15. American College of Obstetricians and Gynecologists, Washington, DC 2000.
4. Fontana, AM, Palfai, TG. Psychosocial factors in premenstrual dysphoria: stressors, appraisal, and coping processes. J Psychosom Res 1994; 38:557.
5. Ling, FW. Recognizing and treating premenstrual dysphoric disorder in the obstetric, gynecologic, and primary care practices. J Clin Psychiatry 2000; 61 Suppl 12:9.
6. Bailey, JW, Cohen, LS. Prevalence of mood and anxiety disorders in women who seek treatment for premenstrual syndrome. J Womens Health Gend Based Med 1999; 8:1181.
7. Wyatt, KM, Dimmock, PW, O'Brien, PM. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev 2002; :CD001396.
8. Bedaiwy, MA, Casper, RF. Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain. Fertil Steril 2006; 86:220.
9. Mitwally, MF, Gotlieb, L, Casper, RF. Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Menopause 2002; 9:236.
Mild PMS is common, affecting up to 75 percent of women with regular menstrual cycles; PMDD affects only 3 to 8 percent of women. This condition affects women of any socioeconomic, cultural, or ethnic backgrounds.
PMDD is usually a chronic condition that can have a serious impact on a woman's quality of life. Fortunately, a variety of treatments and self-care measures can effectively control the symptoms in most women.
CAUSES — The first day of menstrual bleeding is the first day of a woman's cycle. Following this, levels of the hormones estrogen and progesterone increase until approximately day 21, when they begin to fall. Tissues throughout the body are sensitive to these changing hormone levels. Studies suggest that rising and falling hormone levels may also influence chemicals in the brain, including a substance called serotonin, that affect mood.
However, it is not clear why some women develop PMDD and others do not. Levels of estrogen and progesterone are similar in women with and without PMDD. The most likely explanation, based upon several studies, is that women who develop PMDD are exquisitely sensitive to changes in hormone levels.
SYMPTOMS
Common symptoms — The most common symptoms of PMS and PMDD are fatigue, bloating, irritability, and anxiety. Other symptoms include the following: Feeling sad, hopeless, or worthless Feeling tense, anxious, or "on edge" Variable moods with frequent tearfulness Persistent irritability, anger, and conflict with family, coworkers, or friends Decreased interest in usual activities Difficulty concentrating Feeling fatigued, lethargic, or lacking in energy Changes in appetite, which may include binge eating or craving certain foods Sleeping excessively or difficulty sleeping Feeling overwhelmed or out of control Breast tenderness or swelling, headaches, joint or muscle pain, weight gain
Disorders that mimic PMDD — Other conditions can have similar signs and symptoms, including depression, anxiety disorders, and perimenopause. It is important to distinguish between underlying depression (which often worsens before menses) and true PMDD because the treatments are quite different.
Women with underlying depression often feel better during or after menses, but the symptoms do not resolve completely, whereas the symptoms of PMDD do resolve completely when menses begin. Some women who think they have PMDD actually have depression or an anxiety disorder. (See "Patient information: Depression in adults").
There are other medical disorders that worsen before or during menstruation that have features similar to PMDD, such as migraine, chronic fatigue syndrome, or irritable bowel syndrome. A careful medical history should be able to distinguish among these disorders. It is also possible for a woman to have PMDD in addition to another medical condition. (See "Patient information: Headache causes and diagnosis" and see "Patient information: Irritable bowel syndrome").
DIAGNOSIS — There is no single, definitive test for the diagnosis of PMDD. To be diagnosed with PMS or PMDD a woman must have both physical and behavioral symptoms. The symptoms of PMS/PMDD must occur only during the second half (luteal phase) of the menstrual cycle, most often during the five to seven days before the start of the menstrual period. These symptoms are not present between days 4 through 12 of a 28-day menstrual cycle.
Medical history — During a medical history, a healthcare provider will ask about when symptoms started, if symptoms have worsened or improved, severity of symptoms, and how long symptoms occur with each cycle. The provider will also ask about symptom timing in relation to the menstrual cycle and whether menstrual cycles are regular (every 21 to 35 days). The provider will also ask about factors that improve or worsen the symptoms, about other medical conditions, and about other medications, herbs, or vitamins used.
Physical examination — A general physical examination is done to rule out other possible causes of symptoms.
Blood tests — Blood tests are usually normal in women with PMDD. A routine blood count provides a general screening for other medical conditions that cause fatigue, such as anemia. Thyroid function tests can detect hypothyroidism (underactive thyroid gland) or hyperthyroidism (overactive thyroid gland), which can have signs and symptoms similar to PMS. (See "Patient information: Hypothyroidism" and see "Patient information: Hyperthyroidism").
Recording symptoms — Although a woman's symptoms may suggest PMDD, a clinician may request that she carefully record her symptoms on a daily basis for two full menstrual cycles (show figure 1). Using this calendar, a woman can rate the severity of 10 physical symptoms and 12 behavioral symptoms on a 4-point scale.
TREATMENT — Healthcare providers usually recommend conservative treatment of PMS first, which may include regular exercise, relaxation techniques, and vitamin and mineral supplementation. These therapies relieve symptoms in some women and have few or no side effects. If these therapies do not bring sufficient relief, drug therapy can be considered as a second option.
Drug therapy is generally recommended first for women with PMDD because of the severity of symptoms.
Highly effective treatments — Several drugs have proven effectiveness for relieving the symptoms of PMDD.
Serotonin reuptake inhibitors — There is good evidence that serotonin reuptake inhibitors (SRIs) are highly effective for the symptoms of PMDD. The SRIs include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), and paroxetine (Paxil®). In studies, all of these drugs reduced the symptoms of PMDD much more effectively than placebo. Some women find that they do not have to take the medication every day; taking them only during the second half of the menstrual cycle (ie, beginning on day 14 of the cycle and continuing until the bleeding begins) may be sufficient.
Fluoxetine reduces the symptoms of PMDD in up to 75 percent of women and remains effective for many years. The usual dose is 20 mg/day; higher doses have not been proven to be more beneficial. Some women have sexual side effects while using fluoxetine, including anorgasmia (inability to achieve orgasm). If this occurs, using a lower dose or trying an alternate drug in the same drug class may be helpful.
SRIs should be taken for at least two menstrual cycles to determine their effect on the symptoms of PMDD. About 15 percent of women do not achieve relief with these drugs after two cycles, in which case an alternate treatment is recommended.
Other antidepressants that inhibit serotonin reuptake (but are not SRIs), such as clomipramine (Anafranil®) (which can be taken daily or only during the second half of the cycle). Venlaxafine (Effexor®) selectively inhibits the reuptake of two neurotransmitters, serotonin and norepinephrine, and is also more effective than placebo.
Gonadotropin-releasing hormone agonists — A gonadotropin-releasing hormone (GnRH) agonist is an injectable medication that suppresses the pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). As a result, the ovaries temporarily stop making estrogen and progesterone, causing a temporary menopause. Leuprolide (Lupron®) is a GnRH agonist.
Side effects occur due the loss of estrogen, and include hot flashes, thinning of the bones, and an increased risk of osteoporosis with long-term use. GnRH agonists are effective for relieving the physical symptoms of PMS, but the side effects of these drugs limit their use. Side effects can be treated by adding back small doses of estrogen or medications that protect the bones (See "Patient information: Osteoporosis prevention and treatment").
Danazol — Danazol (Danocrine®) is an injectable medication that works similarly to the GnRH agonists in suppressing ovulation. It can improve the symptoms of PMS, but has side effects similar to those of testosterone (acne and growth of facial hair); its use is generally reserved for women who do not improve with other medications.
Other treatments — The effectiveness of some treatments is not as clear. These treatments may relieve the symptoms of PMS or PMDD in some women, and women may use a short trial of these treatments to determine if they are effective.
Alprazolam — The drug alprazolam (Xanax®) may reduce the symptoms of PMS or PMDD in some women. However, it can be addictive and is therefore reserved as a second-line treatment.
Oral contraceptives — PMDD is equally common among women who take oral contraceptives and women who do not. However, some women with PMDD have relief of their symptoms when they begin taking an oral contraceptive (while other women feel worse). Some providers recommend that the pill be taken continuously by women with PMDD (ie, skipping the placebo week of the pill for several months in a row). By doing this, the woman will not have a menstrual period, and in theory, will not have the usual cyclic changes in hormones that could affect mood. This is not, however, a proven treatment for PMDD.
Exercise and relaxation techniques — Some studies suggest that regular exercise, relaxation, and reflexology can improve the symptoms of PMS. However, these techniques are not recommended as the sole treatment for women with PMDD.
Agnus castus fruit extract — The fruits of Vitex agnus castus (the chasteberry tree) have been used to treat the symptoms of PMS. In one clinical trial of women with PMS, agnus castus (one dry extract tablet daily for 3 cycles) resulted in a significant decrease in irritability, anger, headache, and breast fullness when compared with placebo [1]. No significant side effects were seen. While this appears to be a potential therapy for PMS/PMDD, further study is needed before it is recommended. In addition, consumers should use caution with herbal products because their purity is not regulated.
Vitamin and mineral supplements — Several clinical trials have evaluated the benefit of calcium treatment for women with PMS. The women who took 600 mg of calcium twice daily had fewer symptoms compared to those who took a placebo [2]. This is an inexpensive treatment with few side effects, and a trial should be considered by women with mild to moderate symptoms of PMS.
Some smaller clinical trials have studied the benefit of vitamin B6 (up to 100 mg/day), magnesium (200 to 360 mg up to three times per day), and vitamin E (400 IU per day). There may be modest improvement of PMS symptoms with these supplements.
Ineffective treatments — Several treatments are of no proven benefit in relieving the symptoms of PMS. These treatments include progesterone, diuretics such as spironolactone, other antidepressant drugs (tricyclic antidepressants and monoamine oxidase inhibitors), and lithium. There is also no proven benefit of certain popular dietary supplements, including evening primrose oil, essential free fatty acids, and ginkgo biloba.
SUMMARY Premenstrual syndrome (PMS) causes symptoms one to two weeks before a woman's menstrual period. Common symptoms include feeling tired, bloated, irritable, and anxious. Premenstrual dysphoric disorder (PMDD) is the severe form of PMS. PMDD can cause a woman to feel very sad or nervous, to have trouble with friends or family (eg, disagreements with husband or children), and can cause problems with paying attention to work or school (see "Symptoms" above). The cause of PMS and PMDD is not known. Some women may be very sensitive to changes in hormone levels. Hormone levels normally change before and during the menstrual period (see "Causes" above). Other problems, such as depression and anxiety, are similar to PMDD. The main difference is that PMS and/or PMDD only occur before the period. Depression and anxiety are usually noticeable all the time. The treatments of PMDD and depression are quite different. There is no test for PMS or PMDD. To be diagnosed with PMS or PMDD, a woman must have physical symptoms (eg, breast tenderness, muscle pain) and mood changes (eg, sadness, crying). These symptoms must occur before the menstrual period (not after). (see "Diagnosis" above). Some women are asked to keep a record of their feelings every day for two full menstrual cycles (for example, show figure 1). PMS may be treated with behavior changes (eg, exercise, relaxation) first. These treatments are helpful for some women and have few or no side effects. A medication may be tried if behavior changes are not helpful. A medication is usually the best treatment for women with PMDD (see "Treatment" above). The best medications for PMS or PMDD include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), or paroxetine (Paxil®). Some women take this medication every day. Others take medication for two weeks before their menstrual period (see "Serotonin reuptake inhibitors" above).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. The Hormone Foundation
(www.hormone.org/public/pms.cfm)
National Institutes of Health
(www.nlm.nih.gov/medlineplus/healthtopics.html)
United States Department of Health and Human Services
(www.4woman.gov/faq/pms.htm)
American Academy of Family Physicians
(http://familydoctor.org)
The Mayo Clinic
(www.mayoclinic.com)
[1-9]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Schellenberg, R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ 2001; 322:134.
2. Thys-Jacobs, S, Starkey, P, Bernstein, D, Tian, J. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol 1998; 179:444.
3. American College of Obstetricians and Gynecologists. Premenstrual syndrome. ACOG Practice Bulletin 15. American College of Obstetricians and Gynecologists, Washington, DC 2000.
4. Fontana, AM, Palfai, TG. Psychosocial factors in premenstrual dysphoria: stressors, appraisal, and coping processes. J Psychosom Res 1994; 38:557.
5. Ling, FW. Recognizing and treating premenstrual dysphoric disorder in the obstetric, gynecologic, and primary care practices. J Clin Psychiatry 2000; 61 Suppl 12:9.
6. Bailey, JW, Cohen, LS. Prevalence of mood and anxiety disorders in women who seek treatment for premenstrual syndrome. J Womens Health Gend Based Med 1999; 8:1181.
7. Wyatt, KM, Dimmock, PW, O'Brien, PM. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev 2002; :CD001396.
8. Bedaiwy, MA, Casper, RF. Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain. Fertil Steril 2006; 86:220.
9. Mitwally, MF, Gotlieb, L, Casper, RF. Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Menopause 2002; 9:236.
Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)
INTRODUCTION — Premenstrual syndrome (PMS) refers to a group of physical and behavioral symptoms that occur in a cyclic pattern during the second half of the menstrual cycle. Premenstrual dysphoric disorder (PMDD) is the severe form of PMS. Common symptoms are anger, irritability, and internal tension that are severe enough to interfere with daily activities.
Mild PMS is common, affecting up to 75 percent of women with regular menstrual cycles; PMDD affects only 3 to 8 percent of women. This condition affects women of any socioeconomic, cultural, or ethnic backgrounds.
PMDD is usually a chronic condition that can have a serious impact on a woman's quality of life. Fortunately, a variety of treatments and self-care measures can effectively control the symptoms in most women.
CAUSES — The first day of menstrual bleeding is the first day of a woman's cycle. Following this, levels of the hormones estrogen and progesterone increase until approximately day 21, when they begin to fall. Tissues throughout the body are sensitive to these changing hormone levels. Studies suggest that rising and falling hormone levels may also influence chemicals in the brain, including a substance called serotonin, that affect mood.
However, it is not clear why some women develop PMDD and others do not. Levels of estrogen and progesterone are similar in women with and without PMDD. The most likely explanation, based upon several studies, is that women who develop PMDD are exquisitely sensitive to changes in hormone levels.
SYMPTOMS
Common symptoms — The most common symptoms of PMS and PMDD are fatigue, bloating, irritability, and anxiety. Other symptoms include the following: Feeling sad, hopeless, or worthless Feeling tense, anxious, or "on edge" Variable moods with frequent tearfulness Persistent irritability, anger, and conflict with family, coworkers, or friends Decreased interest in usual activities Difficulty concentrating Feeling fatigued, lethargic, or lacking in energy Changes in appetite, which may include binge eating or craving certain foods Sleeping excessively or difficulty sleeping Feeling overwhelmed or out of control Breast tenderness or swelling, headaches, joint or muscle pain, weight gain
Disorders that mimic PMDD — Other conditions can have similar signs and symptoms, including depression, anxiety disorders, and perimenopause. It is important to distinguish between underlying depression (which often worsens before menses) and true PMDD because the treatments are quite different.
Women with underlying depression often feel better during or after menses, but the symptoms do not resolve completely, whereas the symptoms of PMDD do resolve completely when menses begin. Some women who think they have PMDD actually have depression or an anxiety disorder. (See "Patient information: Depression in adults").
There are other medical disorders that worsen before or during menstruation that have features similar to PMDD, such as migraine, chronic fatigue syndrome, or irritable bowel syndrome. A careful medical history should be able to distinguish among these disorders. It is also possible for a woman to have PMDD in addition to another medical condition. (See "Patient information: Headache causes and diagnosis" and see "Patient information: Irritable bowel syndrome").
DIAGNOSIS — There is no single, definitive test for the diagnosis of PMDD. To be diagnosed with PMS or PMDD a woman must have both physical and behavioral symptoms. The symptoms of PMS/PMDD must occur only during the second half (luteal phase) of the menstrual cycle, most often during the five to seven days before the start of the menstrual period. These symptoms are not present between days 4 through 12 of a 28-day menstrual cycle.
Medical history — During a medical history, a healthcare provider will ask about when symptoms started, if symptoms have worsened or improved, severity of symptoms, and how long symptoms occur with each cycle. The provider will also ask about symptom timing in relation to the menstrual cycle and whether menstrual cycles are regular (every 21 to 35 days). The provider will also ask about factors that improve or worsen the symptoms, about other medical conditions, and about other medications, herbs, or vitamins used.
Physical examination — A general physical examination is done to rule out other possible causes of symptoms.
Blood tests — Blood tests are usually normal in women with PMDD. A routine blood count provides a general screening for other medical conditions that cause fatigue, such as anemia. Thyroid function tests can detect hypothyroidism (underactive thyroid gland) or hyperthyroidism (overactive thyroid gland), which can have signs and symptoms similar to PMS. (See "Patient information: Hypothyroidism" and see "Patient information: Hyperthyroidism").
Recording symptoms — Although a woman's symptoms may suggest PMDD, a clinician may request that she carefully record her symptoms on a daily basis for two full menstrual cycles (show figure 1). Using this calendar, a woman can rate the severity of 10 physical symptoms and 12 behavioral symptoms on a 4-point scale.
TREATMENT — Healthcare providers usually recommend conservative treatment of PMS first, which may include regular exercise, relaxation techniques, and vitamin and mineral supplementation. These therapies relieve symptoms in some women and have few or no side effects. If these therapies do not bring sufficient relief, drug therapy can be considered as a second option.
Drug therapy is generally recommended first for women with PMDD because of the severity of symptoms.
Highly effective treatments — Several drugs have proven effectiveness for relieving the symptoms of PMDD.
Serotonin reuptake inhibitors — There is good evidence that serotonin reuptake inhibitors (SRIs) are highly effective for the symptoms of PMDD. The SRIs include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), and paroxetine (Paxil®). In studies, all of these drugs reduced the symptoms of PMDD much more effectively than placebo. Some women find that they do not have to take the medication every day; taking them only during the second half of the menstrual cycle (ie, beginning on day 14 of the cycle and continuing until the bleeding begins) may be sufficient.
Fluoxetine reduces the symptoms of PMDD in up to 75 percent of women and remains effective for many years. The usual dose is 20 mg/day; higher doses have not been proven to be more beneficial. Some women have sexual side effects while using fluoxetine, including anorgasmia (inability to achieve orgasm). If this occurs, using a lower dose or trying an alternate drug in the same drug class may be helpful.
SRIs should be taken for at least two menstrual cycles to determine their effect on the symptoms of PMDD. About 15 percent of women do not achieve relief with these drugs after two cycles, in which case an alternate treatment is recommended.
Other antidepressants that inhibit serotonin reuptake (but are not SRIs), such as clomipramine (Anafranil®) (which can be taken daily or only during the second half of the cycle). Venlaxafine (Effexor®) selectively inhibits the reuptake of two neurotransmitters, serotonin and norepinephrine, and is also more effective than placebo.
Gonadotropin-releasing hormone agonists — A gonadotropin-releasing hormone (GnRH) agonist is an injectable medication that suppresses the pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). As a result, the ovaries temporarily stop making estrogen and progesterone, causing a temporary menopause. Leuprolide (Lupron®) is a GnRH agonist.
Side effects occur due the loss of estrogen, and include hot flashes, thinning of the bones, and an increased risk of osteoporosis with long-term use. GnRH agonists are effective for relieving the physical symptoms of PMS, but the side effects of these drugs limit their use. Side effects can be treated by adding back small doses of estrogen or medications that protect the bones (See "Patient information: Osteoporosis prevention and treatment").
Danazol — Danazol (Danocrine®) is an injectable medication that works similarly to the GnRH agonists in suppressing ovulation. It can improve the symptoms of PMS, but has side effects similar to those of testosterone (acne and growth of facial hair); its use is generally reserved for women who do not improve with other medications.
Other treatments — The effectiveness of some treatments is not as clear. These treatments may relieve the symptoms of PMS or PMDD in some women, and women may use a short trial of these treatments to determine if they are effective.
Alprazolam — The drug alprazolam (Xanax®) may reduce the symptoms of PMS or PMDD in some women. However, it can be addictive and is therefore reserved as a second-line treatment.
Oral contraceptives — PMDD is equally common among women who take oral contraceptives and women who do not. However, some women with PMDD have relief of their symptoms when they begin taking an oral contraceptive (while other women feel worse). Some providers recommend that the pill be taken continuously by women with PMDD (ie, skipping the placebo week of the pill for several months in a row). By doing this, the woman will not have a menstrual period, and in theory, will not have the usual cyclic changes in hormones that could affect mood. This is not, however, a proven treatment for PMDD.
Exercise and relaxation techniques — Some studies suggest that regular exercise, relaxation, and reflexology can improve the symptoms of PMS. However, these techniques are not recommended as the sole treatment for women with PMDD.
Agnus castus fruit extract — The fruits of Vitex agnus castus (the chasteberry tree) have been used to treat the symptoms of PMS. In one clinical trial of women with PMS, agnus castus (one dry extract tablet daily for 3 cycles) resulted in a significant decrease in irritability, anger, headache, and breast fullness when compared with placebo [1]. No significant side effects were seen. While this appears to be a potential therapy for PMS/PMDD, further study is needed before it is recommended. In addition, consumers should use caution with herbal products because their purity is not regulated.
Vitamin and mineral supplements — Several clinical trials have evaluated the benefit of calcium treatment for women with PMS. The women who took 600 mg of calcium twice daily had fewer symptoms compared to those who took a placebo [2]. This is an inexpensive treatment with few side effects, and a trial should be considered by women with mild to moderate symptoms of PMS.
Some smaller clinical trials have studied the benefit of vitamin B6 (up to 100 mg/day), magnesium (200 to 360 mg up to three times per day), and vitamin E (400 IU per day). There may be modest improvement of PMS symptoms with these supplements.
Ineffective treatments — Several treatments are of no proven benefit in relieving the symptoms of PMS. These treatments include progesterone, diuretics such as spironolactone, other antidepressant drugs (tricyclic antidepressants and monoamine oxidase inhibitors), and lithium. There is also no proven benefit of certain popular dietary supplements, including evening primrose oil, essential free fatty acids, and ginkgo biloba.
SUMMARY Premenstrual syndrome (PMS) causes symptoms one to two weeks before a woman's menstrual period. Common symptoms include feeling tired, bloated, irritable, and anxious. Premenstrual dysphoric disorder (PMDD) is the severe form of PMS. PMDD can cause a woman to feel very sad or nervous, to have trouble with friends or family (eg, disagreements with husband or children), and can cause problems with paying attention to work or school (see "Symptoms" above). The cause of PMS and PMDD is not known. Some women may be very sensitive to changes in hormone levels. Hormone levels normally change before and during the menstrual period (see "Causes" above). Other problems, such as depression and anxiety, are similar to PMDD. The main difference is that PMS and/or PMDD only occur before the period. Depression and anxiety are usually noticeable all the time. The treatments of PMDD and depression are quite different. There is no test for PMS or PMDD. To be diagnosed with PMS or PMDD, a woman must have physical symptoms (eg, breast tenderness, muscle pain) and mood changes (eg, sadness, crying). These symptoms must occur before the menstrual period (not after). (see "Diagnosis" above). Some women are asked to keep a record of their feelings every day for two full menstrual cycles (for example, show figure 1). PMS may be treated with behavior changes (eg, exercise, relaxation) first. These treatments are helpful for some women and have few or no side effects. A medication may be tried if behavior changes are not helpful. A medication is usually the best treatment for women with PMDD (see "Treatment" above). The best medications for PMS or PMDD include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), or paroxetine (Paxil®). Some women take this medication every day. Others take medication for two weeks before their menstrual period (see "Serotonin reuptake inhibitors" above).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. The Hormone Foundation
(www.hormone.org/public/pms.cfm)
National Institutes of Health
(www.nlm.nih.gov/medlineplus/healthtopics.html)
United States Department of Health and Human Services
(www.4woman.gov/faq/pms.htm)
American Academy of Family Physicians
(http://familydoctor.org)
The Mayo Clinic
(www.mayoclinic.com)
[1-9]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Schellenberg, R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ 2001; 322:134.
2. Thys-Jacobs, S, Starkey, P, Bernstein, D, Tian, J. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol 1998; 179:444.
3. American College of Obstetricians and Gynecologists. Premenstrual syndrome. ACOG Practice Bulletin 15. American College of Obstetricians and Gynecologists, Washington, DC 2000.
4. Fontana, AM, Palfai, TG. Psychosocial factors in premenstrual dysphoria: stressors, appraisal, and coping processes. J Psychosom Res 1994; 38:557.
5. Ling, FW. Recognizing and treating premenstrual dysphoric disorder in the obstetric, gynecologic, and primary care practices. J Clin Psychiatry 2000; 61 Suppl 12:9.
6. Bailey, JW, Cohen, LS. Prevalence of mood and anxiety disorders in women who seek treatment for premenstrual syndrome. J Womens Health Gend Based Med 1999; 8:1181.
7. Wyatt, KM, Dimmock, PW, O'Brien, PM. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev 2002; :CD001396.
8. Bedaiwy, MA, Casper, RF. Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain. Fertil Steril 2006; 86:220.
9. Mitwally, MF, Gotlieb, L, Casper, RF. Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Menopause 2002; 9:236.
Mild PMS is common, affecting up to 75 percent of women with regular menstrual cycles; PMDD affects only 3 to 8 percent of women. This condition affects women of any socioeconomic, cultural, or ethnic backgrounds.
PMDD is usually a chronic condition that can have a serious impact on a woman's quality of life. Fortunately, a variety of treatments and self-care measures can effectively control the symptoms in most women.
CAUSES — The first day of menstrual bleeding is the first day of a woman's cycle. Following this, levels of the hormones estrogen and progesterone increase until approximately day 21, when they begin to fall. Tissues throughout the body are sensitive to these changing hormone levels. Studies suggest that rising and falling hormone levels may also influence chemicals in the brain, including a substance called serotonin, that affect mood.
However, it is not clear why some women develop PMDD and others do not. Levels of estrogen and progesterone are similar in women with and without PMDD. The most likely explanation, based upon several studies, is that women who develop PMDD are exquisitely sensitive to changes in hormone levels.
SYMPTOMS
Common symptoms — The most common symptoms of PMS and PMDD are fatigue, bloating, irritability, and anxiety. Other symptoms include the following: Feeling sad, hopeless, or worthless Feeling tense, anxious, or "on edge" Variable moods with frequent tearfulness Persistent irritability, anger, and conflict with family, coworkers, or friends Decreased interest in usual activities Difficulty concentrating Feeling fatigued, lethargic, or lacking in energy Changes in appetite, which may include binge eating or craving certain foods Sleeping excessively or difficulty sleeping Feeling overwhelmed or out of control Breast tenderness or swelling, headaches, joint or muscle pain, weight gain
Disorders that mimic PMDD — Other conditions can have similar signs and symptoms, including depression, anxiety disorders, and perimenopause. It is important to distinguish between underlying depression (which often worsens before menses) and true PMDD because the treatments are quite different.
Women with underlying depression often feel better during or after menses, but the symptoms do not resolve completely, whereas the symptoms of PMDD do resolve completely when menses begin. Some women who think they have PMDD actually have depression or an anxiety disorder. (See "Patient information: Depression in adults").
There are other medical disorders that worsen before or during menstruation that have features similar to PMDD, such as migraine, chronic fatigue syndrome, or irritable bowel syndrome. A careful medical history should be able to distinguish among these disorders. It is also possible for a woman to have PMDD in addition to another medical condition. (See "Patient information: Headache causes and diagnosis" and see "Patient information: Irritable bowel syndrome").
DIAGNOSIS — There is no single, definitive test for the diagnosis of PMDD. To be diagnosed with PMS or PMDD a woman must have both physical and behavioral symptoms. The symptoms of PMS/PMDD must occur only during the second half (luteal phase) of the menstrual cycle, most often during the five to seven days before the start of the menstrual period. These symptoms are not present between days 4 through 12 of a 28-day menstrual cycle.
Medical history — During a medical history, a healthcare provider will ask about when symptoms started, if symptoms have worsened or improved, severity of symptoms, and how long symptoms occur with each cycle. The provider will also ask about symptom timing in relation to the menstrual cycle and whether menstrual cycles are regular (every 21 to 35 days). The provider will also ask about factors that improve or worsen the symptoms, about other medical conditions, and about other medications, herbs, or vitamins used.
Physical examination — A general physical examination is done to rule out other possible causes of symptoms.
Blood tests — Blood tests are usually normal in women with PMDD. A routine blood count provides a general screening for other medical conditions that cause fatigue, such as anemia. Thyroid function tests can detect hypothyroidism (underactive thyroid gland) or hyperthyroidism (overactive thyroid gland), which can have signs and symptoms similar to PMS. (See "Patient information: Hypothyroidism" and see "Patient information: Hyperthyroidism").
Recording symptoms — Although a woman's symptoms may suggest PMDD, a clinician may request that she carefully record her symptoms on a daily basis for two full menstrual cycles (show figure 1). Using this calendar, a woman can rate the severity of 10 physical symptoms and 12 behavioral symptoms on a 4-point scale.
TREATMENT — Healthcare providers usually recommend conservative treatment of PMS first, which may include regular exercise, relaxation techniques, and vitamin and mineral supplementation. These therapies relieve symptoms in some women and have few or no side effects. If these therapies do not bring sufficient relief, drug therapy can be considered as a second option.
Drug therapy is generally recommended first for women with PMDD because of the severity of symptoms.
Highly effective treatments — Several drugs have proven effectiveness for relieving the symptoms of PMDD.
Serotonin reuptake inhibitors — There is good evidence that serotonin reuptake inhibitors (SRIs) are highly effective for the symptoms of PMDD. The SRIs include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), and paroxetine (Paxil®). In studies, all of these drugs reduced the symptoms of PMDD much more effectively than placebo. Some women find that they do not have to take the medication every day; taking them only during the second half of the menstrual cycle (ie, beginning on day 14 of the cycle and continuing until the bleeding begins) may be sufficient.
Fluoxetine reduces the symptoms of PMDD in up to 75 percent of women and remains effective for many years. The usual dose is 20 mg/day; higher doses have not been proven to be more beneficial. Some women have sexual side effects while using fluoxetine, including anorgasmia (inability to achieve orgasm). If this occurs, using a lower dose or trying an alternate drug in the same drug class may be helpful.
SRIs should be taken for at least two menstrual cycles to determine their effect on the symptoms of PMDD. About 15 percent of women do not achieve relief with these drugs after two cycles, in which case an alternate treatment is recommended.
Other antidepressants that inhibit serotonin reuptake (but are not SRIs), such as clomipramine (Anafranil®) (which can be taken daily or only during the second half of the cycle). Venlaxafine (Effexor®) selectively inhibits the reuptake of two neurotransmitters, serotonin and norepinephrine, and is also more effective than placebo.
Gonadotropin-releasing hormone agonists — A gonadotropin-releasing hormone (GnRH) agonist is an injectable medication that suppresses the pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). As a result, the ovaries temporarily stop making estrogen and progesterone, causing a temporary menopause. Leuprolide (Lupron®) is a GnRH agonist.
Side effects occur due the loss of estrogen, and include hot flashes, thinning of the bones, and an increased risk of osteoporosis with long-term use. GnRH agonists are effective for relieving the physical symptoms of PMS, but the side effects of these drugs limit their use. Side effects can be treated by adding back small doses of estrogen or medications that protect the bones (See "Patient information: Osteoporosis prevention and treatment").
Danazol — Danazol (Danocrine®) is an injectable medication that works similarly to the GnRH agonists in suppressing ovulation. It can improve the symptoms of PMS, but has side effects similar to those of testosterone (acne and growth of facial hair); its use is generally reserved for women who do not improve with other medications.
Other treatments — The effectiveness of some treatments is not as clear. These treatments may relieve the symptoms of PMS or PMDD in some women, and women may use a short trial of these treatments to determine if they are effective.
Alprazolam — The drug alprazolam (Xanax®) may reduce the symptoms of PMS or PMDD in some women. However, it can be addictive and is therefore reserved as a second-line treatment.
Oral contraceptives — PMDD is equally common among women who take oral contraceptives and women who do not. However, some women with PMDD have relief of their symptoms when they begin taking an oral contraceptive (while other women feel worse). Some providers recommend that the pill be taken continuously by women with PMDD (ie, skipping the placebo week of the pill for several months in a row). By doing this, the woman will not have a menstrual period, and in theory, will not have the usual cyclic changes in hormones that could affect mood. This is not, however, a proven treatment for PMDD.
Exercise and relaxation techniques — Some studies suggest that regular exercise, relaxation, and reflexology can improve the symptoms of PMS. However, these techniques are not recommended as the sole treatment for women with PMDD.
Agnus castus fruit extract — The fruits of Vitex agnus castus (the chasteberry tree) have been used to treat the symptoms of PMS. In one clinical trial of women with PMS, agnus castus (one dry extract tablet daily for 3 cycles) resulted in a significant decrease in irritability, anger, headache, and breast fullness when compared with placebo [1]. No significant side effects were seen. While this appears to be a potential therapy for PMS/PMDD, further study is needed before it is recommended. In addition, consumers should use caution with herbal products because their purity is not regulated.
Vitamin and mineral supplements — Several clinical trials have evaluated the benefit of calcium treatment for women with PMS. The women who took 600 mg of calcium twice daily had fewer symptoms compared to those who took a placebo [2]. This is an inexpensive treatment with few side effects, and a trial should be considered by women with mild to moderate symptoms of PMS.
Some smaller clinical trials have studied the benefit of vitamin B6 (up to 100 mg/day), magnesium (200 to 360 mg up to three times per day), and vitamin E (400 IU per day). There may be modest improvement of PMS symptoms with these supplements.
Ineffective treatments — Several treatments are of no proven benefit in relieving the symptoms of PMS. These treatments include progesterone, diuretics such as spironolactone, other antidepressant drugs (tricyclic antidepressants and monoamine oxidase inhibitors), and lithium. There is also no proven benefit of certain popular dietary supplements, including evening primrose oil, essential free fatty acids, and ginkgo biloba.
SUMMARY Premenstrual syndrome (PMS) causes symptoms one to two weeks before a woman's menstrual period. Common symptoms include feeling tired, bloated, irritable, and anxious. Premenstrual dysphoric disorder (PMDD) is the severe form of PMS. PMDD can cause a woman to feel very sad or nervous, to have trouble with friends or family (eg, disagreements with husband or children), and can cause problems with paying attention to work or school (see "Symptoms" above). The cause of PMS and PMDD is not known. Some women may be very sensitive to changes in hormone levels. Hormone levels normally change before and during the menstrual period (see "Causes" above). Other problems, such as depression and anxiety, are similar to PMDD. The main difference is that PMS and/or PMDD only occur before the period. Depression and anxiety are usually noticeable all the time. The treatments of PMDD and depression are quite different. There is no test for PMS or PMDD. To be diagnosed with PMS or PMDD, a woman must have physical symptoms (eg, breast tenderness, muscle pain) and mood changes (eg, sadness, crying). These symptoms must occur before the menstrual period (not after). (see "Diagnosis" above). Some women are asked to keep a record of their feelings every day for two full menstrual cycles (for example, show figure 1). PMS may be treated with behavior changes (eg, exercise, relaxation) first. These treatments are helpful for some women and have few or no side effects. A medication may be tried if behavior changes are not helpful. A medication is usually the best treatment for women with PMDD (see "Treatment" above). The best medications for PMS or PMDD include fluoxetine (Prozac®), sertraline (Zoloft®), citalopram (Celexa®), or paroxetine (Paxil®). Some women take this medication every day. Others take medication for two weeks before their menstrual period (see "Serotonin reuptake inhibitors" above).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. The Hormone Foundation
(www.hormone.org/public/pms.cfm)
National Institutes of Health
(www.nlm.nih.gov/medlineplus/healthtopics.html)
United States Department of Health and Human Services
(www.4woman.gov/faq/pms.htm)
American Academy of Family Physicians
(http://familydoctor.org)
The Mayo Clinic
(www.mayoclinic.com)
[1-9]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Schellenberg, R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ 2001; 322:134.
2. Thys-Jacobs, S, Starkey, P, Bernstein, D, Tian, J. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol 1998; 179:444.
3. American College of Obstetricians and Gynecologists. Premenstrual syndrome. ACOG Practice Bulletin 15. American College of Obstetricians and Gynecologists, Washington, DC 2000.
4. Fontana, AM, Palfai, TG. Psychosocial factors in premenstrual dysphoria: stressors, appraisal, and coping processes. J Psychosom Res 1994; 38:557.
5. Ling, FW. Recognizing and treating premenstrual dysphoric disorder in the obstetric, gynecologic, and primary care practices. J Clin Psychiatry 2000; 61 Suppl 12:9.
6. Bailey, JW, Cohen, LS. Prevalence of mood and anxiety disorders in women who seek treatment for premenstrual syndrome. J Womens Health Gend Based Med 1999; 8:1181.
7. Wyatt, KM, Dimmock, PW, O'Brien, PM. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev 2002; :CD001396.
8. Bedaiwy, MA, Casper, RF. Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain. Fertil Steril 2006; 86:220.
9. Mitwally, MF, Gotlieb, L, Casper, RF. Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Menopause 2002; 9:236.
Menstrual cycle disorders (absent and irregular periods)
INTRODUCTION — Menstrual cycle disorders can cause a woman's periods to be absent or infrequent. Although some women do not mind missing their menstrual period, these changes should always be discussed with a healthcare provider because they can signal underlying medical conditions and have long-term health consequences. A woman who misses more than three menstrual periods (either consecutively or over the course of a year) should see a healthcare provider.
DEFINITIONS
Amenorrhea — Amenorrhea refers to the absence of menstrual periods, and is classified as primary (when menstrual periods have not started by age 16) or secondary (when menstrual periods are absent for more than three to six months in a woman who previously had periods).
Oligomenorrhea — Oligomenorrhea refers to infrequent menstrual periods (fewer than six to eight periods per year).
The causes, evaluation, and treatment of amenorrhea and oligomenorrhea are similar, and will be discussed together.
CAUSES — The brain (including the pituitary gland), ovaries, and uterus normally follow a sequence of events once per month; this sequence helps to prepare the body for pregnancy. Two hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), are made by the pituitary gland. Two other hormones, progesterone and estrogen, are made by the ovaries.
During the first half of the cycle, small increases in FSH stimulate the ovary to develop a follicle (cyst) that contains an egg (oocyte). The follicle produces rising levels of estrogen, which cause the lining of the uterus to thicken and the pituitary to release a very large amount of LH. This midcycle "surge" of LH causes the egg to be released from the ovary (called ovulation, show figure 1).
Menstrual cycle disorders can result from conditions that affect the hypothalamus, pituitary gland, ovaries, uterus, cervix, or vagina.
Primary amenorrhea — Many of the conditions that cause primary amenorrhea are present at birth, but may not be noticed until puberty. These conditions include genetic or chromosomal abnormalities and structural abnormalities (eg, if the uterus is not present or developed abnormally) of the reproductive tract.
Functional hypothalamic amenorrhea can also cause primary amenorrhea. This occurs when the hypothalamus slows or stops releasing GnRH (gonadotropin releasing hormone), a hormone that influences when a woman has a menstrual period. The hypothalamus is sensitive to many factors, including low body weight (defined as weighing 10 percent below ideal body weight, show table 1A-1B), having very little body fat, a very low calorie or fat intake, emotional stress, strenuous exercise, and some medical conditions or illnesses. When GnRH production slows or stops, a woman may stop having regular menstrual periods. For example, a woman who is training to run a marathon may stop menstruating until she is no longer training intensively.
Other causes of primary amenorrhea, such as prolactin-secreting tumors of the pituitary gland, are less common. All of the conditions that lead to secondary amenorrhea can also cause primary amenorrhea.
Secondary amenorrhea — Pregnancy is the most common of secondary amenorrhea. Among nonpregnant women, ovarian conditions are the most common cause of secondary amenorrhea; these conditions include polycystic ovary syndrome and ovarian failure (early menopause).
Functional hypothalamic amenorrhea is also a common cause of secondary amenorrhea (see above).
Prolactin-secreting pituitary tumors are another common cause of secondary amenorrhea. (See "Patient information: Lactotroph adenomas (prolactinomas)").
Oligomenorrhea — Many of the conditions that cause primary or secondary amenorrhea can also cause oligomenorrhea. However, most women who develop infrequent periods have polycystic ovary syndrome (see "Polycystic ovary syndrome" below).
EVALUATION — The approach to evaluating amenorrhea/oligomenorrhea will depend upon a woman's medical history and the results of a physical examination.
History — There are often clues about the cause of amenorrhea in a woman's personal and family medical history. Factors to consider include health during infancy and childhood, sexual development during puberty, as well as the family's growth and puberty patterns. The menstrual history will also be reviewed, including when the first period started (if there was a first period) and how frequently periods have occurred since.
Other important points include the presence of discharge from the breasts, hot flashes, masculine features, and headaches or impaired vision. The clinician will also ask about any medications, herbs, and vitamins used, recent stress, recent gynecologic procedures and events, changes in weight, diet, or exercise patterns, and any illnesses.
Physical examination — A physical examination can provide information about growth and sexual development, hormonal status, reproductive tract anatomy, and the presence of other medical conditions, such as thyroid disease or diabetes (both of which can cause menstrual cycle problems).
During a physical examination, the clinician will note the woman's height, weight, and arm span (measurement of length, when arms are extended, from one side to the other). The clinician will examine the thyroid gland, evaluate breast development, and perform a pelvic examination.
Testing — Depending upon the history and physical examination, the clinician may order laboratory test. Because pregnancy is the most common cause of secondary amenorrhea, a pregnancy test is usually recommended for women whose menstrual periods have stopped, even if the results of a home pregnancy test are negative. Blood tests to measure hormone levels may also be ordered.
In selected cases, magnetic resonance imaging (MRI) may be done to determine if there are hypothalamic or pituitary gland abnormalities. In women with a suspected chromosomal abnormality, a chromosome analysis may be recommended. A pelvic ultrasound is recommended to identify potential structural abnormalities of the uterus, cervix, and vagina.
TREATMENT — The goal of treatment is to correct the underlying condition. For a woman who is trying to become pregnant, returning fertility may be another goal.
The type and result of treatment depends upon the underlying cause of amenorrhea. In some cases, the results of the evaluation are unexpected (such as early menopause) and can be distressing; in these situations, counseling with a social worker or psychotherapist may be of benefit.
Anatomic problems — Surgery is often an effective treatment if amenorrhea is caused by an obstruction of the reproductive tract. Examples of obstructions that cause amenorrhea or oligomenorrhea include an imperforate hymen or vaginal septum. In both cases, corrective surgery is needed.
Imperforate hymen — The hymen is the tissue that surrounds the vaginal opening; some young girls lack an opening in the hymen, which causes menstrual blood to collect in the vagina.
Vaginal septum — A vaginal septum is a band of tissue that divides the vagina, either longitudinally or transversely. A transverse vaginal septum is similar to an imperforate hymen because it blocks the flow of menstrual blood, causing it to collect in the vagina.
In rare cases, evaluation may reveal underdeveloped or completely absent structures of the female reproductive tract (such as the vagina or uterus). These anatomic problems are usually caused by chromosomal abnormalities, and treatment options are limited.
Ovarian failure — Normally, a woman's ovaries stop releasing eggs around the age of 50; this is called menopause. If a woman's ovaries stop releasing eggs before age 40, this is called premature ovarian failure. When the ovaries fail, estrogen production stops, leading to amenorrhea and the symptoms and health risks associated with menopause.
Although the ovarian production of eggs cannot be restored , hormone replacement therapy (HRT) with estrogen and progesterone (or a hormonal contraceptive such as a birth control pill) can help prevent or treat many of the symptoms and long-term health consequences, such as hot flashes, vaginal dryness, and osteoporosis. HRT has risks of its own. However, a young (20 to 50 year old) woman who takes HRT does not have the same risks as a woman who is greater than 50 years old and takes HRT. Women considering this option should discuss the pros and cons with their healthcare provider. (See "Patient information: Postmenopausal hormone therapy and breast cancer").
Turner's syndrome — Women with Turner's syndrome have a chromosomal abnormality that causes ovarian failure at an extremely young age (before puberty). However, hormone replacement that begins at puberty can lead to normal breast development and menstrual cycles (induced by the hormones). Women with Turner's syndrome have a normal uterus.
With most types of ovarian failure, pregnancy can be achieved using donor eggs.
Polycystic ovary syndrome — Polycystic ovary syndrome (PCOS) is a chronic condition that causes infrequent periods and an excess of androgens (male hormones); this often leads to acne and excessive facial hair. Women with PCOS can also have problems with high cholesterol levels and obesity. Most healthcare providers recommend medical treatment to alleviate the symptoms of androgen excess, reestablish normal menstrual cycles, and prevent the long-term complications of this disorder (an increased risk of type 2 diabetes and possibly coronary heart disease). (See "Patient information: Polycystic ovary syndrome (PCOS)").
Functional hypothalamic amenorrhea — Women who have functional hypothalamic amenorrhea may resume having normal menstrual periods with certain lifestyle changes, including increasing caloric and/or fat intake, gaining weight, reducing the intensity or frequency of exercise, and resolving emotional stress. Low body weight and/or nutritional deficiencies — Women with eating disorders such as anorexia nervosa or bulimia often need specialized care. This usually includes nutrition counseling and work with eating disorder specialists. Strenuous exercise — Although exercise offers wonderful health benefits, exercising frequently or excessively can lead to amenorrhea and infertility. Studies suggest that amenorrhea develops when a woman's caloric intake is less than she burns with exercise and other daily activities, or when a woman's percentage of body fat drops below a critical level. Most women with amenorrhea associated with exercise have also lost weight (resulting in a weight less than 10 percent of the ideal body weight, show table 1A-1B).
For women with exercise-associated amenorrhea, the primary treatments include increasing calorie intake and reducing the frequency and/or intensity of exercise. These measures are particularly important if a woman is trying to become pregnant. All exercising women with amenorrhea should be sure they eat 1200 to 1500 mg of calcium daily (or take a calcium supplement) and should take a vitamin D supplement (400 IU daily). (See "Patient information: Calcium for bone health").
Some clinicians recommend estrogen and progestin hormone replacement (or a hormonal contraceptive such as a birth control pill) for women with amenorrhea who do not wish to cut back on exercise or increase caloric intake. Nonhormonal medications may be recommended to minimize potential bone loss. (See "Patient information: Osteoporosis prevention and treatment").
Hypothalamic or pituitary conditions — Some hypothalamic and pituitary gland conditions that cause amenorrhea, such as a congenital deficiency of gonadotropin-releasing hormone (GnRH), are irreversible. However, women with these conditions can have menstrual periods and become pregnant when treated with gonadotropins or gonadotropin-releasing hormone (GnRH). These hormones require a daily injection, and function to induce ovulation.
Hyperprolactinemia — Women with amenorrhea and hyperprolactinemia can usually regain normal menstrual periods and become pregnant when treated with medications called dopamine agonists (bromocriptine and cabergoline are examples).
Endometrial adhesions (Asherman syndrome) — Some gynecologic procedures, such as a dilatation and curettage (D&C), can result in formation of adhesions (a type of scar tissue) which damage the uterine lining. If adhesion formation is so extensive that most or all of the normal endometrium is replaced by adhesions, then menstrual blood loss will be reduced or stop. A clinician may recommend surgery to remove the scarred tissue, which is followed by estrogen treatment to stimulate regrowth of the lining. (See "Patient information: Dilation and curettage (D&C)").
Other medical conditions — Treatment of medical conditions, such as hypothyroidism and diabetes mellitus, may restore normal menstrual periods in women with amenorrhea.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Academy of Family Physicians
(www.familydoctor.org)
The Nemours Foundation
(www.kidshealth.org, search for menstrual)
The Hormone Foundation
(www.hormone.org)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Laufer, MR, Floor, AE, Parsons, KE, et al. Hormone testing in women with adult-onset amenorrhea. Gynecol Obstet Invest 1995; 40:200.
2. Laughlin, GA, Dominguez, CE, Yen, SS. Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1998; 83:25.
3. Loucks, AB, Vaitukaitis, J, Cameron, JL, et al. The reproductive system and exercise in women. Med Sci Sports Exerc 1992; 24:S288.
4. Warren, MP, Voussoughian, F, Geer, EB, et al. Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating. J Clin Endocrinol Metab 1999; 84:873.
DEFINITIONS
Amenorrhea — Amenorrhea refers to the absence of menstrual periods, and is classified as primary (when menstrual periods have not started by age 16) or secondary (when menstrual periods are absent for more than three to six months in a woman who previously had periods).
Oligomenorrhea — Oligomenorrhea refers to infrequent menstrual periods (fewer than six to eight periods per year).
The causes, evaluation, and treatment of amenorrhea and oligomenorrhea are similar, and will be discussed together.
CAUSES — The brain (including the pituitary gland), ovaries, and uterus normally follow a sequence of events once per month; this sequence helps to prepare the body for pregnancy. Two hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), are made by the pituitary gland. Two other hormones, progesterone and estrogen, are made by the ovaries.
During the first half of the cycle, small increases in FSH stimulate the ovary to develop a follicle (cyst) that contains an egg (oocyte). The follicle produces rising levels of estrogen, which cause the lining of the uterus to thicken and the pituitary to release a very large amount of LH. This midcycle "surge" of LH causes the egg to be released from the ovary (called ovulation, show figure 1).
Menstrual cycle disorders can result from conditions that affect the hypothalamus, pituitary gland, ovaries, uterus, cervix, or vagina.
Primary amenorrhea — Many of the conditions that cause primary amenorrhea are present at birth, but may not be noticed until puberty. These conditions include genetic or chromosomal abnormalities and structural abnormalities (eg, if the uterus is not present or developed abnormally) of the reproductive tract.
Functional hypothalamic amenorrhea can also cause primary amenorrhea. This occurs when the hypothalamus slows or stops releasing GnRH (gonadotropin releasing hormone), a hormone that influences when a woman has a menstrual period. The hypothalamus is sensitive to many factors, including low body weight (defined as weighing 10 percent below ideal body weight, show table 1A-1B), having very little body fat, a very low calorie or fat intake, emotional stress, strenuous exercise, and some medical conditions or illnesses. When GnRH production slows or stops, a woman may stop having regular menstrual periods. For example, a woman who is training to run a marathon may stop menstruating until she is no longer training intensively.
Other causes of primary amenorrhea, such as prolactin-secreting tumors of the pituitary gland, are less common. All of the conditions that lead to secondary amenorrhea can also cause primary amenorrhea.
Secondary amenorrhea — Pregnancy is the most common of secondary amenorrhea. Among nonpregnant women, ovarian conditions are the most common cause of secondary amenorrhea; these conditions include polycystic ovary syndrome and ovarian failure (early menopause).
Functional hypothalamic amenorrhea is also a common cause of secondary amenorrhea (see above).
Prolactin-secreting pituitary tumors are another common cause of secondary amenorrhea. (See "Patient information: Lactotroph adenomas (prolactinomas)").
Oligomenorrhea — Many of the conditions that cause primary or secondary amenorrhea can also cause oligomenorrhea. However, most women who develop infrequent periods have polycystic ovary syndrome (see "Polycystic ovary syndrome" below).
EVALUATION — The approach to evaluating amenorrhea/oligomenorrhea will depend upon a woman's medical history and the results of a physical examination.
History — There are often clues about the cause of amenorrhea in a woman's personal and family medical history. Factors to consider include health during infancy and childhood, sexual development during puberty, as well as the family's growth and puberty patterns. The menstrual history will also be reviewed, including when the first period started (if there was a first period) and how frequently periods have occurred since.
Other important points include the presence of discharge from the breasts, hot flashes, masculine features, and headaches or impaired vision. The clinician will also ask about any medications, herbs, and vitamins used, recent stress, recent gynecologic procedures and events, changes in weight, diet, or exercise patterns, and any illnesses.
Physical examination — A physical examination can provide information about growth and sexual development, hormonal status, reproductive tract anatomy, and the presence of other medical conditions, such as thyroid disease or diabetes (both of which can cause menstrual cycle problems).
During a physical examination, the clinician will note the woman's height, weight, and arm span (measurement of length, when arms are extended, from one side to the other). The clinician will examine the thyroid gland, evaluate breast development, and perform a pelvic examination.
Testing — Depending upon the history and physical examination, the clinician may order laboratory test. Because pregnancy is the most common cause of secondary amenorrhea, a pregnancy test is usually recommended for women whose menstrual periods have stopped, even if the results of a home pregnancy test are negative. Blood tests to measure hormone levels may also be ordered.
In selected cases, magnetic resonance imaging (MRI) may be done to determine if there are hypothalamic or pituitary gland abnormalities. In women with a suspected chromosomal abnormality, a chromosome analysis may be recommended. A pelvic ultrasound is recommended to identify potential structural abnormalities of the uterus, cervix, and vagina.
TREATMENT — The goal of treatment is to correct the underlying condition. For a woman who is trying to become pregnant, returning fertility may be another goal.
The type and result of treatment depends upon the underlying cause of amenorrhea. In some cases, the results of the evaluation are unexpected (such as early menopause) and can be distressing; in these situations, counseling with a social worker or psychotherapist may be of benefit.
Anatomic problems — Surgery is often an effective treatment if amenorrhea is caused by an obstruction of the reproductive tract. Examples of obstructions that cause amenorrhea or oligomenorrhea include an imperforate hymen or vaginal septum. In both cases, corrective surgery is needed.
Imperforate hymen — The hymen is the tissue that surrounds the vaginal opening; some young girls lack an opening in the hymen, which causes menstrual blood to collect in the vagina.
Vaginal septum — A vaginal septum is a band of tissue that divides the vagina, either longitudinally or transversely. A transverse vaginal septum is similar to an imperforate hymen because it blocks the flow of menstrual blood, causing it to collect in the vagina.
In rare cases, evaluation may reveal underdeveloped or completely absent structures of the female reproductive tract (such as the vagina or uterus). These anatomic problems are usually caused by chromosomal abnormalities, and treatment options are limited.
Ovarian failure — Normally, a woman's ovaries stop releasing eggs around the age of 50; this is called menopause. If a woman's ovaries stop releasing eggs before age 40, this is called premature ovarian failure. When the ovaries fail, estrogen production stops, leading to amenorrhea and the symptoms and health risks associated with menopause.
Although the ovarian production of eggs cannot be restored , hormone replacement therapy (HRT) with estrogen and progesterone (or a hormonal contraceptive such as a birth control pill) can help prevent or treat many of the symptoms and long-term health consequences, such as hot flashes, vaginal dryness, and osteoporosis. HRT has risks of its own. However, a young (20 to 50 year old) woman who takes HRT does not have the same risks as a woman who is greater than 50 years old and takes HRT. Women considering this option should discuss the pros and cons with their healthcare provider. (See "Patient information: Postmenopausal hormone therapy and breast cancer").
Turner's syndrome — Women with Turner's syndrome have a chromosomal abnormality that causes ovarian failure at an extremely young age (before puberty). However, hormone replacement that begins at puberty can lead to normal breast development and menstrual cycles (induced by the hormones). Women with Turner's syndrome have a normal uterus.
With most types of ovarian failure, pregnancy can be achieved using donor eggs.
Polycystic ovary syndrome — Polycystic ovary syndrome (PCOS) is a chronic condition that causes infrequent periods and an excess of androgens (male hormones); this often leads to acne and excessive facial hair. Women with PCOS can also have problems with high cholesterol levels and obesity. Most healthcare providers recommend medical treatment to alleviate the symptoms of androgen excess, reestablish normal menstrual cycles, and prevent the long-term complications of this disorder (an increased risk of type 2 diabetes and possibly coronary heart disease). (See "Patient information: Polycystic ovary syndrome (PCOS)").
Functional hypothalamic amenorrhea — Women who have functional hypothalamic amenorrhea may resume having normal menstrual periods with certain lifestyle changes, including increasing caloric and/or fat intake, gaining weight, reducing the intensity or frequency of exercise, and resolving emotional stress. Low body weight and/or nutritional deficiencies — Women with eating disorders such as anorexia nervosa or bulimia often need specialized care. This usually includes nutrition counseling and work with eating disorder specialists. Strenuous exercise — Although exercise offers wonderful health benefits, exercising frequently or excessively can lead to amenorrhea and infertility. Studies suggest that amenorrhea develops when a woman's caloric intake is less than she burns with exercise and other daily activities, or when a woman's percentage of body fat drops below a critical level. Most women with amenorrhea associated with exercise have also lost weight (resulting in a weight less than 10 percent of the ideal body weight, show table 1A-1B).
For women with exercise-associated amenorrhea, the primary treatments include increasing calorie intake and reducing the frequency and/or intensity of exercise. These measures are particularly important if a woman is trying to become pregnant. All exercising women with amenorrhea should be sure they eat 1200 to 1500 mg of calcium daily (or take a calcium supplement) and should take a vitamin D supplement (400 IU daily). (See "Patient information: Calcium for bone health").
Some clinicians recommend estrogen and progestin hormone replacement (or a hormonal contraceptive such as a birth control pill) for women with amenorrhea who do not wish to cut back on exercise or increase caloric intake. Nonhormonal medications may be recommended to minimize potential bone loss. (See "Patient information: Osteoporosis prevention and treatment").
Hypothalamic or pituitary conditions — Some hypothalamic and pituitary gland conditions that cause amenorrhea, such as a congenital deficiency of gonadotropin-releasing hormone (GnRH), are irreversible. However, women with these conditions can have menstrual periods and become pregnant when treated with gonadotropins or gonadotropin-releasing hormone (GnRH). These hormones require a daily injection, and function to induce ovulation.
Hyperprolactinemia — Women with amenorrhea and hyperprolactinemia can usually regain normal menstrual periods and become pregnant when treated with medications called dopamine agonists (bromocriptine and cabergoline are examples).
Endometrial adhesions (Asherman syndrome) — Some gynecologic procedures, such as a dilatation and curettage (D&C), can result in formation of adhesions (a type of scar tissue) which damage the uterine lining. If adhesion formation is so extensive that most or all of the normal endometrium is replaced by adhesions, then menstrual blood loss will be reduced or stop. A clinician may recommend surgery to remove the scarred tissue, which is followed by estrogen treatment to stimulate regrowth of the lining. (See "Patient information: Dilation and curettage (D&C)").
Other medical conditions — Treatment of medical conditions, such as hypothyroidism and diabetes mellitus, may restore normal menstrual periods in women with amenorrhea.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Academy of Family Physicians
(www.familydoctor.org)
The Nemours Foundation
(www.kidshealth.org, search for menstrual)
The Hormone Foundation
(www.hormone.org)
[1-4]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Laufer, MR, Floor, AE, Parsons, KE, et al. Hormone testing in women with adult-onset amenorrhea. Gynecol Obstet Invest 1995; 40:200.
2. Laughlin, GA, Dominguez, CE, Yen, SS. Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1998; 83:25.
3. Loucks, AB, Vaitukaitis, J, Cameron, JL, et al. The reproductive system and exercise in women. Med Sci Sports Exerc 1992; 24:S288.
4. Warren, MP, Voussoughian, F, Geer, EB, et al. Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating. J Clin Endocrinol Metab 1999; 84:873.
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