Zanmbeel

Monday, October 15, 2007

Osteoporosis causes, diagnosis, and screening

INTRODUCTION — Osteoporosis is characterized by a progressive decrease in bone density, causing bones to become brittle, weakened, and fracture easily. Osteoporosis and the fractures that result are a major public health concern; more than 1.3 million osteoporotic fractures occur annually in the United States. Early diagnosis of bone loss can reduce or eliminate the risk of fractures.

This topic review discusses the causes, risk factors, signs, and symptoms of osteoporosis, as well as the ways that it can be diagnosed. For information about ways to prevent and treat osteoporosis, see "Patient information: Osteoporosis prevention and treatment".

BONE METABOLISM — To maintain bone density and strength, the body needs a sufficient supply of calcium and phosphorus, normal production of hormones that help to regulate bone cell function (eg, the calcium-regulating hormones, parathyroid hormone, calcitriol, and calcitonin; thyroid hormone; glucocorticoids; the sex hormones estrogen and testosterone), and an adequate supply of vitamin D, which is essential for normal bone formation and calcium absorption.

Bone is constantly being turned over and replaced as a result of cells that break down and remove bone (osteoclasts) and cells that replace and rebuild bone (osteoblasts). The resorption and formation of bone are essential to repair tiny breaks (microfractures) and to "remodel" bone (ie, remove and replace bone) in response to stress, including injury.

Osteoporosis is the result of years of bone loss, due to a "mismatch" between bone formation and resorption. Osteoporosis may also be related to years of inadequate bone formation, especially during the teens and 20s, which are the most important years of bone building. When bone becomes abnormally thin (known as osteopenia) and porous, the risk of fracture increases. Osteopenia is

Cortical bone, the normally dense, compact bone that forms the outer part of skeletal structures, provides strength and protection. Trabecular bone is found inside the long bones, particularly at the ends, and helps to provide mechanical support, particularly within the vertebrae. In patients with osteoporosis, both cortical and trabecular bone may be affected (show figure 1).

The processes of bone resorption and formation vary with age. Although 95 to 100 percent of expected peak bone mass develops by the late teen years, the body continues to form more bone than it breaks down until approximately 30 years of age. Maximum bone density is attained between 20 years (hip) and 30 years of age (spine and forearm). Thereafter, bone mass is slowly lost in the spine and hip; the loss occurs more rapidly during perimenopause.

SIGNS AND SYMPTOMS — Osteoporosis usually causes no symptoms until a fracture occurs, but it can cause back pain or loss of height.

Vertebral fractures — Vertebrae are the bones that make up the spine, and vertebral fractures are the most common sign of osteoporosis. About two-thirds of these fractures occur without symptoms. In these cases, the fracture is found during a chest or abdominal x-ray done for other reasons. In some patients, vertebral fractures may lead to a sudden onset of back pain, usually when performing routine activities, such as bending or lifting. This pain usually resolves over several weeks and is replaced by a chronic dull ache or pain. However, the pain may sometimes persist for many months. Successive compression or crush fractures, in which there is collapse of affected bone, may lead to increased curvature of the spine (thoracic kyphosis). As a result, there is typically an abnormal rounding of the upper back, known as a "dowager's hump," and loss of height (show figure 2). Due to vertebral fractures and associated height loss, the abdomen may be compressed, causing it to bulge forward. Such patients may note that their abdomens appear larger than before, their clothes no longer fit, and their waists seem to have "disappeared" even though they have not gained weight. Patients with multiple vertebral compression fractures may also have hip discomfort. The pain may be due to a decrease in the distance between the bottom of the rib cage and the uppermost portion of the pelvis. This change may also result in difficulty breathing or digestive abnormalities, such as constipation or an early feeling of fullness while eating.

Other fractures — Hip fractures are relatively common in patients with osteoporosis, affecting 15 percent of women and 5 percent of men by age 80. Such fractures are a major cause of disability in the elderly and increase the risk of death, although conditions other than the fracture (such as surgical complications) may be responsible for this increase.

Osteoporosis may also lead to fractures near the wrist in the lower end of the radius (the bone on the thumb side of the forearm), causing backward displacement of the wrist and hand. This type of break is known as a Colles' fracture, and often results when the hand is outstretched to stop a fall.

CAUSES — As mentioned above, osteoporosis results from either accelerated bone loss or inadequate bone formation. The imbalance between the rate of new bone formation and breakdown may occur due to several underlying conditions, including the following:

Menopause-related loss of estrogen — Estrogen is a hormone that plays an important role in regulating bone formation. The rate of bone loss increases soon after the menopause, particularly in trabecular bone; this increased rate of loss lasts for approximately 10 years. At this point, the rate of bone loss slows to near the premenopausal rate, but the premenopausal rate of bone formation is absent.

Hyperthyroidism — Hyperthyroidism is a condition in which the thyroid gland is overactive in its production of thyroid hormones. It is associated with increased bone turnover, potentially leading to bone loss. (See "Patient information: Hyperthyroidism").

Hyperparathyroidism — Hyperparathyroidism refers to overactivity of the parathyroid glands. These glands produce parathyroid hormone, which helps to regulate calcium concentrations in the body. Increased secretion of parathyroid hormone increases the removal of calcium from bone, raising blood calcium levels (hypercalcemia) and potentially leading to osteoporosis. (See "Patient information: Primary hyperparathyroidism").

Age-related bone loss — This may result from decreased calcium absorption, which typically begins in the fourth or fifth decade of life. It is associated with a slow loss of cortical and trabecular bone in both women and men.

Hypogonadism — Hypogonadism is a decrease in activity of the ovaries or testes resulting in low amounts of estrogen or testosterone, respectively. This may be a result of aging, but it can also occur in younger men and women due to medications that cause hypogonadism (eg, chemotherapy agents), block estrogen synthesis (aromatase inhibitors), or induce testosterone/estrogen deficiency (GnRH agonists). It may also occur as a result of low body weight, excessive exercise, or pituitary abnormalities.

Men who have low or absent levels of the hormone testosterone are at increased risk of osteoporosis, and women who have a low level of estrogen are also at risk. Symptoms of hypogonadism in men include a decreased sexual drive (libido) or impotence. In young women, signs of hypogonadism include loss of menstrual periods, which may or may not be associated with hot flashes, night sweats, or vaginal dryness.

Medications — Prolonged therapy with certain medications, including glucocorticoids (also called corticosteroids), heparin, certain medications for seizure disorders (eg, phenytoin, carbamazepine, primidone, and phenobarbital), cyclosporine, medroxyprogesterone acetate and vitamin A may result in accelerated bone resorption as well as slowed bone formation, leading to bone loss.

Pregnancy and breastfeeding — Bone loss occurs during pregnancy and breastfeeding, although the loss is temporary and has no long term effect on a woman's bone density. In women who become pregnant and breastfeed, there is no increased risk of fracture after menopause. Using a calcium supplement while breastfeeding has no effect on the amount of bone lost.

Vitamin B12 deficiency — Vitamin B12 deficiency (also known as pernicious anemia) appears to increase the risk of osteoporosis, which can lead to an increased risk of hip and spine fractures.

RISK FACTORS FOR FRACTURE — Several factors are associated with an increased risk of osteoporotic fractures, including the following:

Age — In people aged 90 years or more, approximately one-third of women and 15 percent of men will have a hip fracture.

Sex — Osteoporosis is a serious problem in men, although women are affected more commonly. Women have a lower average peak bone mass and lose more bone after menopause. About 30 percent of women over age 50 have osteoporosis, and this percentage increases with age.

Race — Whites have a considerably higher risk of hip fractures than blacks. Blacks generally have a higher peak bone mass and a lower rate of bone loss after menopause.

Falls — Repeated falling can be a significant problem for older people with osteoporosis. Over 90 percent of hip fractures occur after a fall. Certain factors contribute to the risk of falls, including poor vision, certain medications (eg, tranquilizers, some anxiety medications, sleeping pills), and neurologic disorders such as dementia (confusion).

Other factors — A number of other factors increase the risk of fractures, some of which include the following: Previous fracture between the ages of 20 and 50 years History of fracture in a first degree relative Cigarette smoking (men and women) Inflammatory bowel disease Celiac disease Cystic fibrosis Sedentary life style Drinking large amounts of caffeine Medications for anxiety or seizures Low body weight or weight loss Above average height Type 1 or 2 diabetes mellitus

DIAGNOSIS — Osteoporosis is diagnosed based upon the patient and family history, physical examination, laboratory studies, and bone mineral density (BMD) testing. It is important to exclude other conditions that can cause bone thinning (osteopenia), such as osteomalacia (softening and weakening of bone) as well as other potentially treatable conditions (eg, hyperparathyroidism, hyperthyroidism, kidney disease).

History and physical examination — During a medical history, a healthcare provider will ask about life events (pregnancies, age at first menstrual period and menopause), past or present medical conditions, medications, calcium intake, exercise, and alcohol/tobacco use.

The physical examination will include measurement of height and weight and may include laboratory tests. Such studies may include a complete blood count, measurement of calcium, phosphorus, vitamin D, bicarbonate, creatinine, and hormones such as thyroid-stimulating hormone (TSH). The testosterone level may be measured in men, particularly if the man has decreased libido or impotence. (See "Patient information: Sexual problems in men").

Bone density measurement — Measurement of bone mineral density is the most common method to determine if a person is at risk for or already has osteoporosis. The goal is to recognize people who are at risk before a fracture occurs. Several methods are available to measure bone density.

Dual x-ray absorptiometry (DXA) — DXA testing is the most popular method for measuring BMD because it provides precise measurements at important bone sites (eg, spine, hip, forearm) with minimal radiation.

During DXA, the patient lies on an examination table. An x-ray detector scans a bone region, and the amount of x-rays that pass through bone are measured and displayed as an image that is interpreted by a radiologist. The test causes no discomfort, and usually takes only 5 to 10 minutes. The bone mineral density is then compared with the normal range for the patient's sex and race.

Other Quantitative computerized tomography — This is a type of CT that provides accurate measures of bone density in the spine. Although this test may be a good alternative to DXA, it is seldom used because it is expensive, less precise for following measurements over time, and requires a higher radiation dose. Ultrasonography — Ultrasound can be used to measure the bone density of the heel. This may be useful to determine a person's fracture risk. However, it is used less frequently than DXA because there are no guidelines that use ultrasound measurements to diagnose osteoporosis or predict fracture risk. In areas that do not have access to DXA, ultrasound is an acceptable way to measure bone density.

We recommend DXA of the hip and spine because measurements at these sites are effective for predicting osteoporotic fracture at any site.

Interpreting BMD results — The World Health Organization (WHO) has defined normal bone density as a value within one standard deviation (SD) from average peak bone mass. Standard deviation is a statistical measure that defines how much a patient's result vary from the "average" young adult. Normal bone density — Bone density that is between 0 and 1 standard deviation below the mean is considered to be normal. This may be reported as a T-score of 0 to -1. Treatment is not usually recommended for people with normal bone density, although preventive measures (eg, calcium supplementation, weight-bearing exercise) are recommended to prevent osteopenia and osteoporosis. (See "Patient information: Osteoporosis prevention and treatment"). Osteopenia — Bone density that is between 1 and 2.5 standard deviations below the mean is called osteopenia. This may be reported as a T-score of -1 to -2.4. A person with osteopenia does not yet have osteoporosis, but is at risk to develop it if not treated. Osteoporosis — Osteoporosis is defined as BMD more than 2.5 standard deviations (SD) below the mean of normal young women. This is reported as a T-score of -2.5 or less. The lower the bone density, the greater the risk of fracture.

When to measure BMD — Bone density testing can be used to diagnose osteoporosis, as well as to screen for it. The National Osteoporosis Foundation has issued recommendations for bone density testing that primarily apply to white women after menopause. Bone density should be measured in women: Greater than 65 years of age Under age 65 who have one or more risk factors for osteoporotic fracture in addition to menopause.

In addition to the recommendations above, the International Society for Clinical Densitometry (ISCD) recommends bone density testing for men over 70 years of age and for adults (including premenopausal women): With fragility fracture (a bone fracture that occurs after a fall from standing height or less) With disease associated with low bone mass (Cushing's syndrome, hyperthyroidism, hyperparathyroidism, rheumatoid arthritis, gastrointestinal diseases associated with malabsorption) Taking drugs associated with low bone mass (glucocorticoids, GnRH agonists, some chemotherapy drugs)

PREVENTION AND TREATMENT — All women should be educated about the risk factors for osteoporotic fractures. A provider may recommend certain lifestyle changes that can help to reduce fracture risk, such as stopping smoking, limiting alcohol consumption, and participating in regular weight-bearing and muscle-strengthening exercises. A full discussion of osteoporosis prevention and treatment is available separately. (See "Patient information: Osteoporosis prevention and treatment").

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)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)

Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
(www.osteo.org)
National Osteoporosis Foundation

Phone: (202) 223-2226
(www.nof.org)
International Society for Clinical Densitometry (ISCD)

(www.ISCD.org)
National Women's Health Resource Center (NWHRC)

Toll-free: (877) 986-9472
(www.healthywomen.org)
Osteoporosis Society of Canada

Phone: (416) 696-2663 x 294
(www.osteoporosis.ca/)
The Hormone Foundation

(www.hormone.org/public/osteoporosis.cfm, available in English, Spanish, French, Italian, German, and Portuguese)

[1-4]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Johnell, O, Kanis, JA, Black, DM, et al. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19:764.
2. Raisz, LG. Clinical practice. Screening for osteoporosis. N Engl J Med 2005; 353:164.
3. Marshall, D, Johnell, O, Wedel, H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254.
4. Bainbridge, KE, Sowers, MF, Crutchfield, M, et al. Natural history of bone loss over 6 years among premenopausal and early postmenopausal women. Am J Epidemiol 2002; 156:410.

Osteoporosis causes, diagnosis, and screening

Calcium for bone health

INTRODUCTION — Osteoporosis is a common bone disorder characterized by a progressive decrease in bone density and mass. As a result, bones become thin, weakened, and easily fractured. It is estimated that more than 1.3 million osteoporosis-associated (or "osteoporotic") fractures occur every year in the United States, primarily of bone within the vertebral column, the hip, and the forearm near the wrist. (See "Patient information: Osteoporosis causes, diagnosis, and screening").

Osteoporosis is the result of accelerated bone loss due to an imbalance between the normal breakdown (resorption) and replacement (formation) of bone. In most patients, such bone loss is largely menopause- and/or age-related. Bone mass naturally declines as people age (ie, beginning at about age 35 years); in addition, women are particularly at risk for osteoporosis following menopause due to declining production of the female hormone estrogen, which helps to maintain bone mass.

Multiple therapies are available that may prevent bone loss and treat low bone mass. However, the first step in preventing or treating osteoporosis is to eat the right foods, particularly those that provide calcium, a mineral essential for bone strength, and vitamin D, which aids in calcium break down and absorption. (See "Patient information: Osteoporosis prevention and treatment").

BENEFITS — Good nutrition is important at all ages, from infants to the elderly, to keep the bones healthy. In some studies in postmenopausal women, taking calcium reduced bone loss and decreased the risk of recurrent vertebral fractures.

In addition, consuming calcium during childhood (eg, in milk) can lead to higher bone mass in adulthood. The increase in bone mineral density is important in modifying future fracture risk. The risk for most osteoporotic fractures increases as the bone density decreases. This means, the lower the bone mass, the greater the tendency to fracture. Calcium also has benefits in other body systems by reducing blood pressure and cholesterol levels.

Calcium balance in the body refers to the balance between calcium that is taken in (eaten) and calcium that is excreted (eg, in urine). Not surprisingly, the less calcium an individual takes in, the more negative the calcium balance. By increasing one's calcium intake, calcium balance can become more positive.

Multiple investigations have supported the importance of calcium intake, demonstrating that adequate calcium reduces bone loss in adults. As examples: Two studies demonstrated that postmenopausal women whose calcium intake was less than 400 or 750 mg/day had significant reductions in bone loss when supplemented with calcium as opposed to placebo (an inactive substance). In women over age 60 years with a low calcium intake who had preexisting spinal (vertebral) fractures, calcium supplementation reduced the incidence of additional vertebral fractures compared to placebo and stopped detectable bone loss within the forearm (over four years of follow-up). One study demonstrated that calcium supplementation in postmenopausal women was associated with a small but significant increase in bone density.

Calcium and vitamin D supplements have been shown to help prevent tooth loss in the elderly.

RECOMMENDATIONS — As mentioned above, adequate calcium intake can result in positive calcium balance and a reduction in the rate of bone loss; it is less clear if adequate calcium intake decreases the risk of bone fractures. However, most clinicians recommend calcium supplementation for patients with a low calcium intake since it appears to reduce bone loss.

Daily calcium intake should be at least 1000 mg in premenopausal women and men, and 1500 mg in postmenopausal women who do not take estrogen. The total daily calcium intake should not routinely exceed 2000 mg due to the possibility of adverse effects.

Persons who cannot get enough calcium from dietary sources should speak with their clinician for specific recommendations about the type, dose, and timing of calcium supplementation (show figure 1). The following are general guidelines Calcium carbonate is an effective and inexpensive form of calcium. It is best absorbed with a low-iron meal (such as breakfast). Calcium citrate (eg, Citracal®) may be recommended for elderly people who absorb calcium carbonate less readily (because of less acid in the stomach). Chewable preparations of calcium carbonate (eg, Viactiv®, Tums®) or calcium citrate (Citracal®) are preferred since many natural calcium carbonate preparations (eg, bone meal, oyster shells) do not dissolve well. In addition, these preparations can be contaminated with lead and/or mercury. Calcium supplements should be taken in divided doses. Doses above 500 mg are not absorbed as well as smaller doses. Calcium supplementation is not an alternative to other osteoporosis treatments. Calcium is less effective than other treatments, including hormone replacement, bisphosphonates (eg, risedronate [Actonel®] and alendronate [Fosamax®]), and raloxifene (Evista®) in slowing bone loss in postmenopausal women. Hormone therapy is recommended only for women with certain menopausal symptoms. However, calcium had additive benefits when used along with other treatments. (See "Patient information: Osteoporosis prevention and treatment").

Underlying gastrointestinal diseases — Patients with impaired absorption of nutrients from the gastrointestinal tract (malabsorption) may have higher than normal calcium requirements due to reduced calcium absorption. In such cases, a healthcare provider can help to determine the appropriate level of calcium supplementation.

Medications — Administration of certain medications may influence calcium balance, such as drugs that promote the excretion of urine (diuretics). As an example, so-called "loop diuretics" increase the excretion of calcium; however, thiazide diuretics may lead to reduced levels of calcium in the urine, potentially helping to protect against possible bone loss and kidney stones (see below). Therefore, it is important for patients to tell their physicians and pharmacists about all medications they are taking so that any possible interactions with calcium can be identified.

DETERMINING CURRENT CALCIUM INTAKE — The primary sources of calcium within the diet include milk and other dairy products, such as hard cheese, cottage cheese, or yogurt, as well as green vegetables, such as spinach (show table 1). A simple way to estimate one's daily intake of dietary calcium is to multiply the number of dairy servings consumed each day by 300 mg. One serving equals 8 oz of milk or yogurt, 1 oz of hard cheese, 16 oz of cottage cheese, or 2 cups of broccoli.

Many experts recommend calcium supplementation rather than dietary changes for individuals with inadequate calcium intake. Evidence suggests that calcium is as well absorbed from supplements as from whole milk. In addition, calcium supplements were used in the studies cited above that demonstrated benefits from increased calcium intake. Therefore, it is likely that calcium supplements are just as effective as calcium in dairy products. However, calcium absorption from vegetables (eg, spinach) is less than that from dairy products.

IMPORTANCE OF VITAMIN D — In addition to calcium, vitamin D is important in the prevention and treatment of osteoporosis. Vitamin D is normally synthesized in the skin after exposure to sunlight. It can also be ingested from dietary sources. Vitamin D deficiency occurs as a result of decreased intake or absorption or from reduced exposure to the sun. Vitamin D levels decline with age and with decreased sun exposure, especially in the winter. In temperate areas such as Boston and Edmonton, for example, production of vitamin D by the skin virtually ceases in winter.

Multiple clinical trials have proven that vitamin D decreases bone loss and lowers fracture rates, especially in older men and women. The current recommendation for daily intake of vitamin D in adults is at least 800 International Units (IU). Lower levels of vitamin D are not as effective while doses higher than 2000 IU per day can be toxic. Milk is the best source of dietary vitamin D, with approximately 100 IU per cup.

A vitamin D supplement is recommended for all patients with osteoporosis whose dietary intake of vitamin D is below 400 IU/day. A daily multivitamin is both convenient and economical, and has the added advantage of providing other vitamins. Alternately, patients may take a calcium supplement that contains Vitamin D.

SIDE EFFECTS — Side effects related to calcium include constipation and indigestion (dyspepsia).

Previous data suggested that calcium supplementation might be associated with weight loss, though two large, randomized trials reported no significant effect of calcium supplements (1000 mg/day) on body weight.

Concern that high dietary calcium increases the risk of kidney stones in otherwise healthy patients appears to be unfounded since the incidence of stone formation appears to be reduced in both men and women who consume high amounts of dietary calcium.

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)
Osteoporosis and Related Bone Diseases National Resource Center (ORBD-NRC)

1232 22nd Street, NW
Washington, DC 20037-1292
Phone: (202) 223-0344
Toll-free: (800) 624-BONE (2663)
TTY: (202) 466-4315
E-mail: orbdnrc@nof.org
(www.osteo.org)
National Osteoporosis Foundation

1232 22nd Street NW
Washington, DC 20037-1292
Phone: (202) 223-2226
E-mail: patientinfo@nof.org
(www.nof.org)
Osteoporosis Society of Canada

33 Laird Drive
Toronto, Ontario M4G 3S9
Phone: (800) 463-6842
(www.osteoporosis.ca/)
The Hormone Foundation

(www.hormone.org/public/osteoporosis.cfm, available in English and Spanish)

[1-7]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. NIH Consensus Development Panel on Optimal Calcium Intake. Optimal calcium intake. JAMA 1994; 272:1942.
2. Aloia, JF, Vaswani, A, Yeh, JK, et al. Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss. Ann Intern Med 1994; 120:97.
3. Cook, JD, Dassenko, SA, Whittaker, P. Calcium supplementation: Effect on iron absorption. Am J Clin Nutr 1991; 53:106.
4. Curhan, GC, Willett, WC, Speizer, FE, et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med 1997; 126:497.
5. Dawson-Hughes, B, Harris, SS, Krall, EA, Dallal, GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337:670.
6. Ross, EA, Szabo, NJ, Tebbett, IR. Lead content of calcium supplements. JAMA 2000; 284:1425.
7. Heaney, RP. Lead in calcium supplements: cause for alarm or celebration?. JAMA 2000; 284:1432.

Calcium for bone health

Alternatives to postmenopausal hormone therapy

INTRODUCTION — During a woman's reproductive years, the body produces a variety of hormones, including estrogen. Estrogen is important for normal menstrual periods and fertility, and it promotes bone strength. Estrogen levels fall at the time of menopause, causing well-known symptoms such as hot flashes. This fall in estrogen increases a woman's risk of osteoporosis and heart disease.

Hormone replacement therapy (HRT) is the term used for estrogen or for estrogen plus progestin treatment after menopause. Progestins are drugs that act like the female hormone progesterone, and they are added to the estrogen to prevent uterine cancer (which can occur if estrogen alone is given to women with a uterus). HRT is an effective option for treating the symptoms of menopause, and it helps prevent osteoporosis.

STUDIES OF HORMONE REPLACEMENT — Previously, scientists thought HRT would reduce the risk of heart disease in postmenopausal women. However, data from large studies such as the Women's Health Initiative (WHI) and HERS trials have shown that combined estrogen-progestin therapy does not reduce the risk of heart disease. In fact, estrogen plus progesterone might increase risk slightly [1,2].

More recent studies, however, suggest that HRT might protect against heart disease in younger postmenopausal women (ie, those 50 to 59 years of age). In the WHI trial of estrogen alone, there was no increased risk of heart disease but the risk of stroke was increased.

The WHI also reported an increased risk of breast cancer with combined estrogen-progestin (similar to that seen in previous studies), and an increase in stroke and blood clots (in the leg and lung). On the other hand, a decrease in the risk of colon cancer and fractures (due to osteoporosis) was also seen. However, the investigators concluded that the risks of HRT may outweigh its benefits in many women.

The results of the WHI trial of unopposed estrogen were quite different. While an increase in strokes and blood clots was seen, there was no increase in breast cancer risk. (See "Patient information: Postmenopausal hormone therapy").

Data from the WHI and the HERS trials have led to changes in our recommendations for estrogen therapy. Continuous estrogen-progestin therapy appears to increase the risk of cardiovascular events and breast cancer, while unopposed estrogen appears to increase stroke risk; in addition, other drugs (eg, bisphosphonates, raloxifene) can protect against osteoporosis. As a result, the primary indication for estrogen therapy at present is for control of menopausal symptoms. For long-term prevention of heart disease and osteoporosis, most women need to consider lifestyle interventions and medications other than estrogen.

A number of alternatives are now available to control menopausal symptoms. This is particularly important for women who have had breast cancer, because hormone therapy appears to increase the risk of recurrence. (See "Patient information: Postmenopausal hormone therapy").

PREVENTING AND TREATING OSTEOPOROSIS — When estrogen levels fall, bone density (strength) starts to decline, and, over time, a woman can develop osteoporosis and even fractures. Your doctor may recommend bone mineral density tests (ie, DEXA scan) to monitor for early bone loss. Several alternatives to HRT can help keep bones strong and even partially reverse osteoporosis, but effective treatment for established osteoporosis usually requires the combination of changes in diet, lifestyle, and medication. (See "Patient information: Osteoporosis causes, diagnosis, and screening" and see "Patient information: Osteoporosis prevention and treatment").

Calcium — Calcium is an essential component of bones, and calcium from foods we eat can help strengthen bones. However, calcium alone cannot always prevent osteoporosis. All postmenopausal women need 1500 mg of calcium each day. Most women will need to eat a well-balanced diet and take a daily supplement that contains 1000 mg of calcium, usually in the form of calcium carbonate, calcium citrate, or an equivalent calcium compound. A list of calcium-rich foods and guidelines for choosing calcium supplements (show figure 1). (See "Patient information: Calcium for bone health").

Vitamin D — Vitamin D helps the body absorb calcium and incorporate calcium into bone. It is therefore also important for bone strength. Many older adults, particularly those over 70 years, have vitamin D deficiencies. Postmenopausal women under the age of 70 years should get at least 400 IU of vitamin D each day in their diet or with a vitamin supplement. Women over 70 years should take 800 IU of vitamin D. Some calcium supplements include vitamin D; patients should read the label to know the amount included.

Exercise — Bones remain stronger when they are used in day-to-day activities, and inactivity increases the rate of postmenopausal bone loss. At least 30 minutes of weight-bearing exercise three times a week can reduce this loss. Weight-bearing exercise includes activities such as walking, aerobics, or tennis, but does not include bicycling or swimming.

Medications — Several medications, such as alendronate, risedronate, ibandronate, zoledronic acid, tamoxifen, and raloxifene can help prevent or even reverse osteoporosis by boosting bone density. These medications can even benefit women who have already suffered fractures. Women taking these medications should continue to take calcium and to follow other measures that promote bone strength. A new drug, human parathyroid hormone (Forteo), given by daily injection under the skin, is now available for the treatment of severe osteoporosis.

Alendronate, risedronate, and ibandronate — Alendronate (Fosamax®), risedronate (Actonel®), and ibandronate (Boniva®) are prescribed for the prevention and treatment of osteoporosis in postmenopausal women. They are able to prevent and reverse bone loss as effectively as estrogen. Women need to take these medications with water 30 minutes before eating in the morning and must sit upright or stand for this time period, to prevent pill-associated irritation of the esophagus (the part of the digestive tract between the mouth and stomach). Women who already have esophageal problems such as heartburn or esophagitis should not take these medications. Preparations are now available that allow patients to take alendronate once weekly and ibandronate once monthly.

Tamoxifen and raloxifene — Tamoxifen (Nolvadex®) is usually prescribed for women with breast cancer. Tamoxifen opposes the action of estrogen in breast tissue, but actually has an estrogen-like effect on bone in post-menopausal women. As a result, tamoxifen increases bone mineral density and decreases the number of bone fractures in postmenopausal women. The most bothersome side effect of tamoxifen is hot flashes. Tamoxifen is usually taken once daily, but is not prescribed for more than five years in women who have had breast cancer. Tamoxifen is also used for prevention of breast cancer in women at high risk. (See "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer").

Raloxifene (Evista®) is similar to tamoxifen in that it has an anti-estrogen effect on breast tissue and an estrogen-like effect on bone. In contrast to tamoxifen, it does not cause uterine cancer. It is used for the prevention and treatment of osteoporosis, and has been tested for breast cancer prevention in women who are at high risk. Hot flashes are a side effect in some women who take raloxifene.

PREVENTING CARDIOVASCULAR DISEASE — The fall of estrogen concentrations after menopause is associated with an increased risk of developing and dying from cardiovascular disease. Replacing estrogen does not lower this risk in women over 60 years of age. Alternatives to HRT can effectively reduce some of the risk factors associated with cardiovascular disease, such as high cholesterol levels.

Smoking cessation — Quitting smoking is probably the most important change a woman can make to decrease her risk of developing heart disease. Be sure to ask your doctor about methods for successfully quitting. (See "Patient information: Smoking cessation").

Dietary modification — Before prescribing any medication, your doctor may recommend a trial of a low-fat diet to bring cholesterol levels under control. If this approach is successful, medication may not be necessary. (See "Patient information: Diet and health").

Cholesterol-regulating medication — In postmenopausal women with high serum cholesterol levels, medications such as statins (ie, simvastatin, atorvastatin, lovastatin, fluvastatin, rosuvastatin) lower levels of total and low-density-lipoprotein (LDL) cholesterol ("bad" cholesterol). These medications also decrease a woman's risk of heart disease. HRT does not prevent heart disease while the statin drugs have been shown to have this effect. (See "Patient information: High cholesterol and lipids (hyperlipidemia)").

CONTROLLING HOT FLASHES — New alternatives for the treatment of hot flashes have been tested and shown to be effective. None work nearly as well as estrogen, but relief from these agents is about 70 percent as effective as estrogen. No treatment may be necessary since hot flashes typically subside after one to two years, even without treatment, and may not be particularly severe. Some of the treatments that can give partial relief of hot flashes include:

Antidepressants — Venlafaxine (Effexor®), and paroxetine (Paxil®) have been shown to relieve hot flashes. This type of medication is usually used to treat depression, but more recent studies show them to be effective for hot flashes. Venlafaxine has been more extensively studied than the others. Fluoxetine (Prozac®) is also effective. These medications can be tried first in women who cannot take estrogen who suffer with hot flashes . However, side effects can occur with these medications as well. Women taking tamoxifen should be cautioned that paroxetine and sertraline (Zoloft®) interfere with the action of tamoxifen.

Clonidine — Clonidine, a blood pressure lowering drug, helps relieve hot flashes in some women. Clonidine is administered by transdermal skin patch (Duraclon®), oral medication (Catapres®), or a combination of both. Clonidine seems to work well in some patients and to be completely ineffective in others. Only a trial of medication can identify those women who receive benefit. Side effects can range from dry mouth and constipation to dizziness and sedation.

Gabapentin — Gabapentin (Neurontin®) is a drug that is primarily used for the treatment of seizures. Although it has not been as well studied as the SSRIs, it appears to be moderately effective for hot flushes and is well tolerated. Because its main side effect is drowsiness, gabapentin is most effective in reducing early morning awakening which can accompany hot flashes.

Megestrol acetate — Megestrol acetate (Megace®) is a hormone that is sometimes used for women who have had breast cancer. It is nearly as effective as estrogen, but can only be given short-term (for several months). Prolonged use of megestrol acetate can lead to weight gain and serious effects can occur if the medication is stopped abruptly. For this reason, the SSRI class of drugs is used before trying megestrol acetate. Recent studies also demonstrate benefit of an injectable progestin hormone, medroxyprogesterone acetate (Depo-Provera®). Depo-Provera® can be used long-term, though can also have side effects, including weight gain and loss of bone density.

Plant-derived estrogens — Plant-derived estrogens, also called phytoestrogens, sometimes help relieve hot flashes somewhat. Dietary sources of phystoestrogens include soy products. Other phytoestrogens such as ginseng, dong quai, and black cohosh can be purchased at health-food stores. However, these supplements might increase breast cancer risk because they act like estrogen in some tissues of the body. The efficacy of these supplements for hot flashes has not been rigorously proven. The same precautions should be used for these compounds as with HRT in breast cancer survivors.

TREATING VAGINAL DRYNESS — When estrogen production falls, the lining of the vagina thins, leading to vaginal dryness, and sometimes painful sexual intercourse. Several alternatives to estrogen can help control these symptoms. (See "Patient information: Sexual problems in women").

Moisturizers and lubricants — Regular use of vaginal moisturizing agents, such as Replens® or KY Long Lasting®, can help relieve vaginal dryness and irritation. These agents must be used regularly and at times other than before intercourse since they work by moisturizing the vaginal tissues, but can be irritating on direct contact.

Lubricants can prevent pain during sexual intercourse and are used immediately before intercourse. Water-soluble lubricants, such as Astroglide®, are more effective for intercourse than lubricants such as K-Y jelly. Products such as petroleum jelly or hand and body lotions should not be used to relieve vaginal dryness since they can be irritating to the vaginal tissues.

Vaginal estrogens — Estrogen creams, such as Premarin® or Estrace®, can be applied directly to the vagina. When applied in a very low dose, they improve the health of the vaginal tissues without substantially increasing levels of estrogen in the bloodstream. Vaginal estrogen creams are given every day for two to three weeks, and then only once or twice weekly to maintain the effects. They are more effective than moisturizers and lubricants for relieving vaginal symptoms. The lowest dose which is effective should be used. Vaginal estrogen tablets (Vagifem®) and very low-dose vaginal estrogen rings (Estring®) are similarly effective and may be less messy and more convenient than estrogen creams.

Vaginal ring — The estrogen vaginal ring (Estring®) is inserted into the vagina and releases estrogen in a controlled fashion over three months. Very small amounts are released into the vagina. The estrogen appears to act only on the tissues of the vagina with little to no estrogen absorbed into the bloodstream. Studies show that women using the ring experience very few side effects. Some women prefer the convenience of the ring over vaginal creams. The ring is changed once every three months by the woman or her healthcare provider. These low dose vaginal rings should not be confused with a high dose ring (Femring®) which has a higher dose of estrogen and is absorbed into the bloodstream to relieve hot flashes.

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 Hormone Foundation

(www.hormone.org/public/menopause.cfm, available in English and Spanish)
The Mayo Clinic

(www.mayoclinic.com)
U.S. Department of Health and Human Services

Agency for Healthcare Research and Quality
(www.ahrq.gov)
American Academy of Family Physicians

(www.familydoctor.org)

[1-10]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Loprinzi, CL, Levitt, R, Barton, D, et al. Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: North Central Cancer Treatment Group Trial N99C7. J Clin Oncol 2006; 24:1409.
2. Loprinzi, CL, Kugler, JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 2000; 356:2059.
3. Stearns, V, Beebe, KL, Iyengar, M, Dube, E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA 2003; 289:2827.
4. Loprinzi, CL, Sloan, JA, Perez, EA, et al. Phase III Evaluation of Fluoxetine for Treatment of Hot Flashes. J Clin Oncol 2002; 20:1578.
5. Stearns, V, Slack, R, Greep, N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol 2005; 23:6919.
6. Hsia, J, Langer, RD, Manson, JE, et al. Conjugated Equine Estrogens and Coronary Heart Disease: The Women's Health Initiative. Arch Intern Med 2006; 166:357.
7. Grodstein, F, Manson, JE, Stampfer, MJ. Hormone Therapy and Coronary Heart Disease: The Role of Time since Menopause and Age at Hormone Initiation. J Womens Health (Larchmt) 2006; 15:35.
8. Pinkerton, JV, Santen, R. Alternatives to the use of estrogen in postmenopausal women. Endocr Rev 1999; 20:308.
9. Grady, D, Herrington, D, Bittner, V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002; 288:49.
10. Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.

Alternatives to postmenopausal hormone therapy

Lichen sclerosus

INTRODUCTION — Lichen sclerosus (LS) is a chronic, progressive skin disorder characterized by thin, white, wrinkled skin that is itchy and often painful (show picture 1). LS can develop on any skin surface, but usually is localized to the labia minora and/or labia majora (the inner and outer genital lips) and anal region (show figure 1). In 15 to 20 percent of patients, LS lesions develop on other skin surfaces, such as the thighs, breasts, wrists, shoulders, neck, and even the inside the mouth.

Females are most often affected by LS before puberty and during the peri- or postmenopausal period. Men can also develop LS. Although it is not clear exactly how many people have LS, it is estimated between 1 out of 300 and 1 out of 1000 patients referred to dermatologists have LS.

POTENTIAL CAUSES AND RISK FACTORS — The cause of LS is not clear; healthcare providers suspect that a number of factors may be involved.

Genetic factors — LS seems to be more common in some families. People who are genetically predisposed to LS may develop symptoms after experiencing trauma, injury, or sexual abuse.

Disorders of the immune system — People with LS are at a greater risk of developing autoimmune disorders, which develop when the body's immune system mistakenly attacks and injures normal body tissues. These may include some types of thyroid disease, anemia, diabetes, alopecia areata, and vitiligo.

Infections — Researchers have tried to identify an infectious organism as a cause of LS, but no clear data have shown that there is an infectious source [1]. LS is not contagious.

SIGNS AND SYMPTOMS

Feature of LS in women — Some women with LS feel dull, painful discomfort in the vulva, while other women with LS have no symptoms. Several common symptoms of LS include: Vulvar itching — The most common symptom of LS is itching. It may be so severe that it interferes with sleep. Anal itching, fissures, bleeding, and pain (See "Patient information: Anal fissure") Painful sexual intercourse (dyspareunia) — This can occur as a result of repeated cracking of the skin (fissuring) or from narrowing of the vaginal opening due to scarring.

Typically, women with LS have thin, white, wrinkled skin on the labia minora and/or labia majora, often extending down and around the anus (show figure 1). Purple-colored areas of bruising may be seen. Cracks (also known as fissures) may form in the skin in the area around the anus, the labia, and the clitoris. The vaginal opening may appear yellow and waxy. Relatively minor rubbing or sex may lead to bleeding due to the fragility of the involved skin.

If lichen sclerosus is not treated, it may progress and change the appearance and structure of the genital area as the outer and inner lips of the vulva fuse (stick together) and bury the clitoris (show picture 2). The opening of the vagina can become narrowed, and cracks, fissures, and thickened, scarred skin in the genital and anal area can make sexual intercourse or genital examination painful. LS does not affect the inner reproductive organs, such as the vagina and uterus.

LS may also cause lesions to occur in areas outside the genitals, especially the upper body, breasts, and upper arms. These lesions tend to be white, flat or raised, and are not as itchy as the affected skin of the genitals and anus.

Features of LS in men — In men, lichen sclerosus may appear on the head of the penis. Men who develop lichen sclerosus are usually uncircumcised (they have not had the foreskin of the penis removed), and the foreskin can become tight, shrunken, and scarred over the head of the penis. Men with lichen sclerosus may also have problems pulling back the foreskin and may experience decreased sensation at the tip of the penis, painful erections, and problems with urination [2].

DIAGNOSIS — Providers typically use the following methods to diagnose lichen sclerosus.

History and physical examination — A medical history and examination of the vulvar and anal areas will be done, looking for the signs and symptoms of lichen sclerosus.

Biopsy — To confirm a suspected diagnosis of lichen sclerosus, a biopsy is always recommended. A small piece of the affected skin will be removed and examined with a microscope.

Excluding other conditions — Tests may be done to exclude other conditions that could cause symptoms similar to those of lichen sclerosus, such as: Lichen planus (a skin disease that can also cause itching and fusing of genital skin). Lichen planus can occur together with lichen sclerosus. Low estrogen level (a lack of the hormone estrogen can rarely cause fusing of genital skin but is often the cause of painful intercourse) Vitiligo (a disorder that can cause white skin patches similar to those of lichen sclerosus). Vitiligo can occur together with lichen sclerosus. Pemphigoid (a blistering skin disorder that also causes scarring of the vulva) is extremely rare. Hemorrhoids (which can also cause cracks in the skin of the anus)

LS and cancer — Women with LS affecting the vulva are at increased risk for developing vulvar cancer. In some cases, women may be diagnosed with both LS and cancer at the same time, even though they had no symptoms. For this reason, the skin of patients with vulvar LS should be examined at least yearly, but women should examine themselves regularly for lumps or sores that do not heal. Biopsy should be performed if there are thickened areas that fails to thin with treatment or there are persistently open or nonresolving lesions. LS lesions outside the genital area are not associated with an increased risk of cancer.

Men with LS that affects the skin of the penis have an increased risk of penile cancer.

TREATMENT — The goals of treatment of LS are to relieve bothersome symptoms and to prevent the condition from worsening. A clinician may recommend medication for the physical symptoms, and may refer the patient for support and therapy for other issues associated with the condition, such as problems with sexual functioning.

Most patients with LS, even those without noticeable symptoms, need to use medication on a regular and ongoing basis.

Patients who are diagnosed with LS should talk to their clinician about: The lifelong and potentially progressive nature of LS; appropriate treatment can stop progression Ways to manage the condition The increased risk of vulvar cancer and the need for ongoing monitoring How to keep the genital area healthy and avoid scratching (show table 1)

Depending on the severity of the condition, a healthcare provider may recommend one or more of the following treatments: Topical steroid ointments reduce inflammation and itching. Steroid creams should be avoided because they contain ingredients that irritate the skin. Generic formulations are less desirable due to variations in the ingredients that may be less effective and more irritating. Steroid injections, especially if topical steroids are not effective Short-term retinoid treatments, which are derived from vitamin A, reduce scarring and inflammation, but are reserved for complicated cases. Tacrolimus ointment and/or pimecrolimus cream can be used to reduce itching, inflammation, and redness, but these medications have not been extensively studied and are not proven to stop scarring [3]. Oral or topical tricyclic antidepressants (TCAs) are sometimes recommended for vulvar pain that persists despite topical steroids. When used orally, the dose of TCAs is typically much lower than that used for treating depression. It is believed that these drugs reduce pain perception when used in low doses, but the exact mechanism of their benefit is unknown.

TCAs commonly used for pain managment include amitriptyline, desipramine, and nortriptyline. Patients beginning TCAs commonly experience fatigue; this is not always an undesirable side effect since it can help improve sleep when TCAs are taken in the evening. TCAs are generally started in low doses and inreased gradually. Their full effect may not be seen for weeks to months.

Surgery is not routinely used to treat LS because lichen sclerosus tends to recur after the skin heals. However, patients whose genital tissues have grown together may have surgery to separate the fused tissues. Recurrence of the scarring occurs frequently. Limited local excision (removal of the affected tissues) can cure vulvar cancer if it is detected early when the area is small.

Men who have lichen sclerosus are generally treated with circumcision, which removes the foreskin of the penis. After circumcision, LS does not usually come back.

WHAT PATIENTS CAN EXPECT — The good news for patients who have been diagnosed with lichen sclerosus is that treatments such as topical steroid ointments are very effective. In one study of 377 patients (74 girls and 253 women), 96 percent of patients showed improvement in their LS symptoms, and 66 percent of patients had relief of all LS symptoms. Thus, early treatment of LS with topical steroids could prevent scarring. However, the likelihood of LS symptom improvement depended upon the patient's age; younger patients have a greater chance for relief of symptoms [4,5]. Regardless of age, follow up in necessary throughout the lifetime.

SUMMARY Lichen sclerosus (LS) is a chronic skin disorder that can develop on any skin surface, but most often affects the genital and anal regions. Although the cause of LS is unclear, the disorder seems to be more common in certain families, suggesting a genetic component. LS is not caused by an infection and it is not contagious. (See "Potential causes and risk factors" above). Symptoms of LS in women may include pain or itching in the vulvar and/or anal area, and the development of thin, white, wrinkled skin on and around the labia. Bruising or cracks (fissures) may also appear, and the fragile skin may bleed with rubbing or sexual activity. In men, LS can develop on the head of the penis, and usually affects the foreskin of uncircumcised males. (See "Signs and symptoms" above). If LS is not treated, it may worsen and cause permanent changes to the genitals. To diagnose LS, a healthcare provider conducts a medical history and physical examination; a biopsy can confirm the diagnosis and rule out other conditions that cause similar symptoms. Patients with LS affecting the genitals are at increased risk for developing cancer, and should be examined regularly for changes. (See "Diagnosis" above). The goals of therapy of LS are to reduce symptoms and prevent the condition from progressing; most patients find that their symptoms improve with treatment over time. Steroid ointments or injections can help reduce inflammation and itching; pain may be treated with medication. (See "Treatment" 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. American Academy of Dermatology

(www.aad.org)
American Urological Association

(www.auanet.org)
National Institute of Arthritis and Musculoskeletal and Skin Diseases

(www.niams.nih.gov)
National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Lichen Sclerosus Support Group

(www.lichensclerosus.org)
National Vulvodynia Association

(www.nva.org)

[2-5]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Funaro, D. Lichen sclerosus: a review and practical approach. Dermatol Ther 2004; 17:28.
2. Questions and Answers about Lichen Sclerosus. National Institute of Arthritis and Musculoskeletal and Skin Diseases 2004. www.niams.nih.gov/hi/topics/lichen/lichen.htm (Accessed 8/4/06).
3. Kunstfeld, R, Kirnbauer, R, Stingl, G, Karlhofer, FM. Successful treatment of vulvar lichen sclerosus with topical tacrolimus. Arch Dermatol 2003; 139:850.
4. Cooper, SM, Gao, XH, Powell, JJ, Wojnarowska, F. Does treatment of vulvar lichen sclerosus influence its prognosis?. Arch Dermatol 2004; 140:702.
5. Renaud-Vilmer, C, Cavelier-Balloy, B, Porcher, R, Dubertret, L. Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch Dermatol 2004; 140:709.

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Monday, October 15, 2007