Polycystic ovary syndrome (PCOS)

DEFINITION — Polycystic ovary syndrome (PCOS) is a chronic condition that causes irregular menstrual periods and elevated levels of androgens (male hormones) in women. The elevated androgen levels can sometimes cause excessive facial hair growth, acne, and/or male-pattern hair thinning. The condition occurs in about 5 to 10 percent of women.

Although PCOS is not completely reversible, there are a number of treatments that can reduce or minimize bothersome symptoms. Most women with PCOS are able to lead a normal life without significant complications.

CAUSE — The cause of PCOS is not completely understood. It is believed that abnormal levels of the pituitary hormone LH and high levels of male hormones (androgens) interfere with normal function of the ovaries. To explain how these hormones cause symptoms, it is helpful to understand the normal menstrual cycle.

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).

After ovulation, the ovary produces both estrogen and progesterone, which prepare the uterus for possible implantation and pregnancy. In women with PCOS, multiple follicles (cysts) may develop. The follicles are unable to grow to a size that would trigger ovulation. Therefore, small follicles (4 to 9 mm in diameter) accumulate in the ovary, hence the term polycystic ovaries. None of these small follicles are capable of initiating ovulation nor can they release an egg. As a result, the levels of estrogen, progesterone, LH, and FSH become imbalanced.

Androgens are normally produced by the ovaries, the adrenal gland, and probably from other sources as well. Examples of androgens include testosterone, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S). It is thought that androgens (male-type hormones) become increased in women with PCOS because of the high levels of LH, but also because of high levels of insulin that are usually seen with PCOS (see "Insulin abnormalities" below).

SIGNS AND SYMPTOMS — The changes in hormone levels, described above, cause the classic symptoms of PCOS, including absent or irregular menstrual periods, abnormal hair growth or loss, acne, weight gain, and difficulty becoming pregnant. (See "Patient information: Hair loss in men and women (androgenetic alopecia)").

Signs and symptoms of PCOS usually begin around the time of puberty, although some women do not develop symptoms until adulthood. Because hormonal changes vary from one woman to another, patients with PCOS may have mild to severe acne, facial hair growth, or scalp hair loss.

Menstrual irregularity — If ovulation does not occur, the lining of the uterus (called the endometrium) does not uniformly shed and regrow as in a normal menstrual cycle. Instead, the endometrium becomes thicker and may shed irregularly, which can result in heavy and/or prolonged bleeding. Irregular or absent menstrual periods can increase a woman's risk of endometrial overgrowth (called endometrial hyperplasia) or even endometrial cancer.

Women with PCOS usually have fewer than six to eight menstrual periods per year. Some women have normal cycles during puberty, which may become irregular as weight gain occurs.

Weight gain and obesity — PCOS is associated with gradual weight gain and obesity in about one-half of women. For some women with PCOS, obesity develops at the time of puberty.

Hair growth and acne — Male-pattern hair growth (hirsutism) may be seen on the chin, neck, sideburn area, chest, and upper abdomen. Acne is a skin condition that causes oily skin and blockages in hair follicles, leading to pimples.

Insulin abnormalities — PCOS is associated with elevated levels of insulin in the blood. Insulin is a hormone that is produced by specialized cells within the pancreas; insulin regulates blood glucose levels. When blood glucose levels rise (after eating, for example), these cells produce insulin to help the body use glucose for energy. If glucose levels do not decline in response to normal levels of insulin, the pancreas produces additional insulin. Excess production of insulin is called hyperinsulinemia. When increased levels of insulin are required to maintain normal glucose levels, a person is said to be insulin resistant. When the blood glucose levels are not completely controlled with increased amounts of insulin, the person is said to have impaired glucose tolerance. If blood glucose levels continue to rise despite increased insulin levels, the person is said to have type 2 diabetes.

These conditions are diagnosed with blood tests. (See "Patient information: Diabetes mellitus, type 2").

Insulin resistance and hyperinsulinemia can occur in both normal-weight and overweight women with PCOS. Among women with PCOS, up to 35 percent of obese women develop impaired glucose tolerance by age 40, while up to 10 percent of obese women develop type 2 diabetes. The risk of these conditions is much higher in women with PCOS compared to women without PCOS.

Infertility — If a woman with PCOS has difficulty becoming pregnant after six to 12 months of trying to conceive, an evaluation of both partners is needed to determine the cause of infertility. (See "Patient information: Evaluation of the infertile couple").

Heart disease — Women who are obese and who also have insulin resistance or diabetes have an increased risk of coronary artery disease, the narrowing of the arteries that supply blood to the heart. Both weight loss and treatment of insulin abnormalities can decrease this risk. Other treatments (eg, cholesterol lowering medications, treatments for high blood pressure) may also be recommended. (See "Patient information: High cholesterol and lipids (hyperlipidemia)" and see "Patient information: High blood pressure treatment").

Sleep apnea — Sleep apnea is a condition that causes brief spells where breathing stops (apnea) during sleep. Patients with this problem often experience fatigue and daytime sleepiness. In addition, there is evidence that people with untreated sleep apnea have an increased risk of cardiovascular problems such as high blood pressure, heart attack, abnormal heart rhythms, or stroke. This risk may be due to the wide fluctuations in heart rate and blood pressure that occur in people with sleep apnea.

Sleep apnea may occur in up to 30 percent of women with PCOS. The condition can be diagnosed with a sleep study, and several treatments are available. (See "Patient information: Sleep apnea").

DIAGNOSIS — There is no single test for diagnosing PCOS. A woman may be diagnosed with PCOS based upon her signs and symptoms and blood tests. Expert groups have determined that a woman must have all of the following to be diagnosed with PCOS: Irregular menstrual periods caused by anovulation or irregular ovulation Evidence of elevated androgen levels. The evidence can be based upon signs (hirsutism, acne, or male pattern balding) or blood tests (high serum androgen concentrations) No evidence of other causes of elevated androgen levels or irregular periods (eg, congenital adrenal hyperplasia, androgen-secreting tumors, or hyperprolactinemia)

Blood tests are usually recommended to determine if another condition is the cause of a person's signs and/or symptoms. Blood tests for pregnancy, prolactin level, thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH) may be recommended.

If PCOS is confirmed, the blood glucose level and cholesterol levels are usually measured; these tests are best done before the first meal of the day. Other glucose tests, called oral glucose tolerance testing and hemoglobin A1C, may also be recommended. In women with moderate to severe hirsutism (excess hair growth), blood tests for testosterone and DHEA-S may be recommended.

All women who are diagnosed with PCOS should be monitored by a healthcare provider. Symptoms of PCOS may seem minor and annoying and treatment may seem unnecessary. However, untreated PCOS can increase a woman's risk of other health problems over time.

TREATMENTS

Oral contraceptives — Oral contraceptives (OCs) are the most commonly used treatment for establishing normal menstrual periods in women with PCOS. OCs protect the uterine lining from a precancerous or cancerous condition by inducing a monthly menstrual period, and are also effective for treating hirsutism and acne.

Women with PCOS occasionally ovulate, and oral contraceptives are useful in providing protection from pregnancy. Although an OC allows for bleeding once per month, this does not mean that the PCOS is "cured"; irregular cycles generally return when the OC is stopped. (See "Patient information: Menstrual cycle disorders (Absent and irregular periods)").

Oral contraceptives decrease the body's production of androgens, and anti-androgen drugs (such as spironolactone) decrease the effect of androgens. Both treatments can lessen and slow hair growth. Oral contraceptives and antiandrogens can also reduce acne, although some women should consult a healthcare provider about the need for prescription skin treatments (eg, medicated lotions) or oral antibiotics. (See "Patient information: Acne").

Before prescribing an oral contraceptives, a clinician will perform an examination or a blood test to be certain that a woman is not pregnant. If a woman hasn't had a period for six weeks or longer, her clinician may first prescribe a hormone (eg, Provera®) to induce a menstrual period. Side effects — Some women who take oral contraceptives (not just those with PCOS) may notice amenorrhea (lack of monthly bleeding) or breakthrough bleeding (bleeding that occurs at the irregular time of the month). Breakthrough bleeding usually resolves after a few menstrual cycles.

Many women worry that they will gain weight on the pill. This is not a concern with the currently available low-dose pills. Some women develop nausea, breast tenderness, and bloating after beginning the pill, but these symptoms usually resolve after two or three months.

The pill is safe and effective, although it slightly increases the risk of blood clots in the legs or lungs, although this is a rare complication in young, healthy women who do not smoke. The risk is higher in women older than 35 years and in smokers. (See "Patient information: Hormonal methods of birth control").

Progestin — Another method to treat menstrual irregularity is to take a hormone called progestin (eg, Provera®) for 10 to 14 days every one to three months. This will cause a period in almost all women with PCOS, but it does not help with the cosmetic concerns (hirsutism and acne) and does not prevent pregnancy. It does reduce the risk of uterine cancer.

Hair treatments — Excess hair can be removed by shaving or use of depilatories, electrolysis, or laser therapy. Many women worry that these treatments cause hair to grow faster, although this is not true. (See "Patient information: Causes and treatment of hirsutism"). Hair loss can be treated with medications in some situations, although medications are not usually as effective in women with hormonally-related hair loss as they are in men. Other options include hair replacement and wigs. (See "Patient information: Hair loss in men and women (androgenetic alopecia)").

Weight loss — Weight loss is one of the simplest, yet most effective, approaches for managing insulin abnormalities, menstrual irregularities, and other symptoms of PCOS. For example, many overweight women with PCOS who lose 5 to 10 percent of their body weight notice that their periods become more regular. Weight loss can often be achieved with a program of diet and exercise.

There are a number of options available for obesity. These options are identical to those recommended for women without PCOS, and include diet and exercise, weight loss medications, and weight loss surgery. (See "Patient information: Diet and health" and see "Patient information: Weight loss treatments").

Weight loss surgery may be an option for severely obese women with PCOS. Significant amounts of weight can be lost after surgery, which can restore normal menstrual cycles, reduce high androgen levels and hirsutism, and reduce the risk of type 2 diabetes. (See "Patient information: Weight loss surgery").

Metformin — Metformin (Glucophage®) is medication that improves the effectiveness of insulin produced by the body. It is sometimes used to treat the insulin abnormalities associated with PCOS. This medication can decrease the ovary's production of androgens and reestablish the body's normal hormone balance. The end result is that some signs and symptoms of PCOS improve.

Metformin is usually prescribed for the treatment of diabetes. In preliminary studies, metformin helps restore normal menstrual cycles in approximately 50 percent of women with PCOS. Blood androgen levels sometimes decrease, but there may not be much improvement in hirsutism or acne. In addition, metformin does not prevent pregnancy. In fact, it can stimulate ovulation; another method of pregnancy prevention is recommended to women who do not want to become pregnant.

Metformin may also help with weight loss. Although metformin is not a weight-loss drug, some studies have shown that women with PCOS who are on a low-calorie diet lose more weight when metformin is added. If metformin is used, it is essential that diet and exercise are also part of the recommended regimen because the weight that is lost in the early phase of metformin treatment may be regained over time.

Treatment of infertility — If tests determine that lack of ovulation is the cause of infertility, several treatment options are available, including clomiphene and gonadotropin therapy. These treatments work best in women who are not obese. A summary of treatment options is shown in table 1 (show table 1).

The primary treatment for women who are unable to become pregnant and who have PCOS is weight loss. Even a modest amount of weight loss may cause the woman to begin ovulating normally. In addition, weight loss can improve the effectiveness of other infertility treatments.

Clomiphene is a medication that stimulates the ovaries to release one or more eggs. It triggers ovulation in about 80 percent of women with PCOS, and about 50 percent of these women will become pregnant. (See "Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)").

Several studies have shown that metformin increases the effectiveness of clomiphene in producing ovulation. However, it is unknown if this drug is safe during pregnancy, so the current recommendation is to stop metformin once pregnancy is achieved.

If a woman does not ovulate or is unable to conceive with clomiphene, gonadotropin therapy may be recommended. Gonadotropins are hormones (LH and FSH) that are given as a daily injection under the skin for 7 to 10 days. Ovulation occurs in almost all women with PCOS who use gonadotropin therapy; approximately 60 percent of these women become pregnant.

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.

From UpToDate — 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.

From other sources — 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/polycystic.cfm, available in English and Spanish)
U.S. Department of Health and Human Services

(www.4woman.gov/faq/pcos.htm)
American Academy of Family Physicians

(www.familydoctor.org)
The Nemours Foundation

(http://kidshealth.org/teen/sexual_health/girls/pcos.html)


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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ehrmann, DA, Cavaghan, MK, Barnes, RB, et al. Prevalence of impaired glucose tolerance and diabetes in women with Polycystic Ovary Syndrome. Diabetes Care 1999; 22:141.
2. Adams, J, Polson, DW, Franks, S. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. BMJ 1986; 293:355.
3. Huber-Buchholz, MM, Carey, DG, Norman, RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: Role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab 1999; 84:1470.
4. Nestler, JE, Jakubowicz, DJ, Evans, WS, Pasquali, R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998; 338:1876.