Patient information: Treatment of polycystic ovary syndrome
Authors:
Kathryn A Martin, MD Harvard Medical School
Robert L Barbieri, MD Harvard Medical School
David A Ehrmann, MD University of Chicago
WHAT IS POLYCYSTIC OVARY SYNDROME? — Polycystic ovary syndrome (PCOS) is a chronic condition in women that is characterized by irregular menstrual periods and evidence of excess androgens (male hormones), which can cause excessive facial hair growth, acne, and/or male-pattern baldness.
Signs and symptoms of PCOS often begin around the time of puberty, but for others, symptoms do not develop until adulthood. Women with PCOS usually have fewer than six to eight menstrual periods per year. In addition, they have variable degrees of excess male hormones. A common symptom is hirsutism, which is the growth of coarse body hair in a male pattern; ie, on the chin, neck, sideburn area, chest, and upper abdomen. Other symptoms include acne, and male-pattern baldness (loss of scalp hair in a male pattern). The symptoms are variable; some women have only mild acne, while others have more severe acne, facial hair growth, and scalp hair loss.
Other common features of PCOS are obesity (discussed below), and infertility (difficulty getting pregnant due to lack of ovulation (release of an egg)) on a regular basis. In fact, many women with PCOS may not be able to conceive without medical or surgical treatment.
PCOS is associated with additional conditions that impact on women's health, including insulin resistance and diabetes mellitus, heart disease, endometrial carcinoma, and sleep apnea (see below).
Today, several drugs and lifestyle modifications can help control the signs and symptoms of PCOS. Medical and surgical treatment can also help women who want to become pregnant, but are having difficulty conceiving. Treatment is individualized and depends on each woman's symptoms, reproductive goals, and presence of other medical conditions. Women with PCOS should take an active role in their medical care by learning as much as they can about the condition and by working with their doctor to develop the best treatment plan.
WHY IS TREATMENT OF PCOS IMPORTANT? — All women with PCOS should be monitored by a doctor and should discuss treatment options for their condition. In some women, symptoms of PCOS may be minor and simply annoying, and treatment may seem unnecessary. However, untreated PCOS may increase a woman's risk of other health problems over time.
WHAT ARE THE POSSIBLE HEALTH PROBLEMS ASSOCIATED WITH PCOS? — Although PCOS is primarily a problem of the ovaries, the condition alters hormone levels and affects tissues throughout the body. Most of these effects can be anticipated and thus prevented or promptly treated before they pose significant health problems.
Weight gain and obesity — PCOS is associated with gradual weight gain and obesity in about one-half of the women with this condition. Diet and exercise can help maintain a normal body weight. For some women with PCOS, the obesity develops at the time of puberty.
Insulin abnormalities and diabetes — PCOS is also associated with abnormal blood insulin levels, the hormone that regulates blood sugar levels. These abnormalities may include:
Hyperinsulinemia (excess production of insulin)
Insulin resistance (poor response of body tissues to insulin)
Impaired glucose tolerance (a condition of borderline diabetes mellitus)
Type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus, a condition characterized by elevated blood sugar levels)
Insulin resistance and hyperinsulinemia can occur in both normal-weight and overweight women with PCOS. By age 40, up to 35 percent of obese women with PCOS develop impaired glucose tolerance, and up to 10 percent of obese women with PCOS develop type 2 diabetes. These rates are much higher than expected for normal women at this young age.
Impaired glucose tolerance and diabetes are usually detected by blood tests. Often a fasting blood test is sufficient, but sometimes a glucose tolerance test is needed. Weight loss, exercise, and drugs can help normalize blood sugar levels.
Heart disease — The presence of both obesity and insulin resistance might increase a woman's risk for coronary artery disease, which is the narrowing of the arteries that supply blood to the heart. Both weight loss and treatment of insulin abnormalities can decrease this risk. Women with PCOS should discuss with their doctor other measures for keeping their cardiovascular system healthy.
Uterine cancer — The hormonal imbalance of PCOS can promote persistent growth of the endometrium (the lining of the uterus), increasing a woman's risk of uterine cancer over time. Treatment with oral contraceptives or intermittent progesterone-like drugs can promote normal menstrual bleeding and lessen overgrowth of the endometrium.
Sleep apnea — Sleep apnea has been reported to occur in up to 30 percent of women with PCOS. This is a disorder characterized by excessive snoring at night with brief spells where breathing stops (apnea). Patients with this problem experience fatigue and daytime sleepiness. It can be diagnosed on a sleep study, and there are a variety of treatments available.
HOW IS MENSTRUAL IRREGULARITY TREATED? — Oral contraceptives are the most commonly used treatment for establishing normal menstrual periods in women with PCOS. In addition to protecting the uterine lining by inducing a monthly menstrual period, the oral contraceptive pill is also effective for the treatment of hirsutism and acne. Because women with PCOS can occasionally ovulate, oral contraceptives can provided the added benefit of preventing pregnancy. Although the pill results in monthly menstrual periods, this does not mean that the PCOS is "cured" because irregular cycles return when the pill is stopped.
Before prescribing oral contraceptives, a doctor performs 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 doctor may first prescribe medroxyprogesterone acetate (Provera) to induce a menstrual period.
Another method to treat the menstrual irregularity (and reduce the risk of uterine cancer), is to give medroxyprogesterone acetate for 10 to 14 days every one to two 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 provide contraception.
A modest amount of weight loss can also restore normal periods in some women. For example, many overweight women with PCOS who lose 5 to 10 percent of their body weight notice that their periods become more regular.
The final treatment for irregular menstrual periods is the use of insulin-lowering agents (see below).
What are the possible side effects of oral contraceptives? — Some women who take oral contraceptives (not just those with PCOS) may notice amenorrhea (lack of menstrual periods) or breakthrough bleeding (bleeding that occurs at the wrong time of the month). Often, minor breakthrough bleeding resolves after a few menstrual cycles.
If a woman with PCOS takes oral contraceptives and experiences amenorrhea or moderate breakthrough bleeding, her doctor may order an ultrasound of the uterus to check the status of the endometrium (uterine lining).
If ultrasound shows that the endometrium is very thin and a woman doesn't mind having amenorrhea, her doctor may simply recommend continuing oral contraceptives. If she prefers having menstrual periods, the type and dosage of contraceptives can be changed to produce menstrual periods.
If the ultrasound shows that the endometrium is thick, a woman's doctor will often prescribe a different type and dosage of oral contraceptives to trigger a period.
Many women worry that they will gain weight on the pill. In the early days of the pill, this was a real problem; however, with the low-estrogen-dose pills that are now used, weight gain is very unusual. Nausea and bloating are potential side effects of the pill, but these symptoms almost always go away after two or three months of taking the pill.
While the pill is thought to be very safe and effective, it can occasionally raise blood pressure, as well as cholesterol, blood sugar, and insulin levels. This is rarely a concern in normal, healthy women, but it is sometimes a concern in women with PCOS who are also obese. Therefore, it is important that women be followed closely by a doctor to have blood pressure, blood sugar, and blood cholesterol levels checked.
In addition, blood clots can occur although this is a rare complication in young, healthy women.
HOW ARE HIRSUTISM AND ACNE TREATED? — Hirsutism and acne are common symptoms of PCOS. Excess hair can be removed with local measures such as shaving, use of depilatories, electrolysis, and laser therapy. Many women worry that these local measures make hair grow faster, but this is not true.
Medications are also effective for hirsutism and acne in women with PCOS. Oral contraceptives decrease the body's production of androgens, and antiandrogen 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 in women with PCOS, although some women may also need topical and/or oral antibiotics. Persistent cases of acne may require consultation with a dermatologist.
HOW ARE INSULIN ABNORMALITIES TREATED? — Obesity and insulin abnormalities are common among women with PCOS. Treatment of both conditions can decrease the ovary's production of androgens and reestablish the body's normal hormone balance. The end result is that some symptoms of PCOS improve.
Weight loss — Weight loss is one of the simplest, yet most effective, approaches for managing insulin abnormalities, menstrual irregularities, and other symptoms of PCOS. Weight loss can often be achieved with a program of diet and exercise. However, many women with PCOS find it unusually difficult to lose weight.
Insulin-lowering drugs — Insulin-lowering drugs are another option for treating the insulin abnormalities associated with PCOS. This class of drugs includes metformin (Glucophage), a drug that is prescribed primarily for the treatment of diabetes. There are also other experimental drugs such as D-chiro-inositol that are now being tested in PCOS.
Metformin for women with PCOS has been receiving much attention in magazines, on television, and on the internet. In some women with PCOS, metformin is a reasonable alternative.
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 provide contraception. In fact, it might stimulate ovulation, so women must be careful in their use of this drug if they do not want to become pregnant.
Because metformin often stimulates ovulation, it is sometimes used to help women with PCOS who are trying to conceive (See the section on infertility below).
Metformin may also help with weight loss. Although we do not consider metformin to be 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. The weight that is lost in the early phase of metformin treatment is typically regained as time goes on.
Preliminary studies also suggest that metformin might reduce the risk of early pregnancy loss and the development of gestational diabetes mellitus (diabetes during pregnancy) in women with PCOS. However, we do not yet recommend using metformin for these indications until there are larger studies that confirm these observations.
The long-term safety and effectiveness of metformin and other experimental drugs is unknown.
HOW IS INFERTILITY TREATED? — If a woman with PCOS and her partner are having difficulty getting pregnant, a doctor usually first recommends that both individuals have thorough medical exams to determine the exact cause of infertility. These exams may include tests of the fallopian tubes in the woman and a semen analysis in the man. If tests determine that lack of ovulation due to PCOS is the cause of infertility, three options are available to promote ovulation and pregnancy. It is important to know that all of these options work best for women who are not obese. However, even a modest amount of weight loss can make these treatments more effective.
Clomiphene citrate — The first line of treatment is the fertility drug clomiphene citrate, which stimulates the ovaries to release one or more eggs. Clomiphene triggers ovulation in about 80 percent of women with PCOS, and about 50 percent of these women will actually become pregnant. In women taking clomiphene, ovulation can be confirmed by blood and urine tests or by measurement of body temperature. If the original dose of clomiphene does not trigger ovulation, a woman's doctor may prescribe a higher dose.
Several studies have shown that the insulin-sensitizing drug, metformin, increases the effectiveness of clomiphene in producing ovulation. However, it is unknown if this drug is safe during pregnancy, so we recommend that the drug be stopped once the woman is pregnant. Although there is some very preliminary information that metformin may lower the risk of early pregnancy loss, we do not yet recommend using metformin for this indication, because it requires taking the medication while pregnant.
Gonadotropin therapy — A second, more aggressive medical treatment for PCOS-related infertility is treatment with drugs called gonadotropins (LH and FSH). FSH is used without LH for women with PCOS, and is given as a daily injection under the skin for 7 to 10 days. These drugs trigger ovulation in almost all women with PCOS and can lead to pregnancy in approximately 60 percent. However, these drugs are expensive; they can also overstimulate the ovaries and produce multiple gestations (pregnancy with multiple fetuses).
Ovarian surgery — Surgery is only used as a last measure for the treatment of infertility in women with PCOS, but can be effective in some women who do not respond to medical treatment.
Today, surgery is usually performed through a laparoscope (a thin, lighted tube). Instruments advanced through the laparoscope are used to mechanically or thermally damage the ovary. This damage likely decreases androgen levels in the ovary and alters other hormone levels in the body, triggering the maturation and release of eggs.
Women with PCOS have an 80 percent to 87 percent chance of becoming pregnant after laparoscopic surgery. Furthermore, surgery usually returns normal menstrual cycles for a prolonged period of time.
Women considering surgery should discuss the potential benefits and risks with their doctor. Surgery to induce ovulation is typically less effective in overweight women. The procedure can lead to the formation of adhesions (attachments of abdominal contents to each other or to the abdominal wall), wasting of the ovary, injury to surrounding tissues, and infection. Although the long-term effects of ovarian surgery are still being evaluated, studies suggest that the procedure may also lead to early menopause.
DOES PCOS INCREASE THE RISK OF COMPLICATIONS DURING PREGNANCY? — Studies suggest that pregnant women with PCOS have an increased risk of miscarriage and of developing gestational diabetes (diabetes during pregnancy). Pregnant women with this condition should work with their doctor to minimize these risks.
WHERE TO GET MORE INFORMATION — Your doctor is the best resource for finding out important information related to your particular case. Not all patients with PCOS are alike, and it is important that your situation is evaluated by someone who knows you as a whole person.
This discussion will be updated as needed every four months on our web site (
www.uptodate.com). Additional topics as well as selected discussions written for health care professionals are also available for those who would like more detailed information.
Some of the most pertinent include:
Professional Level Information:
Clinical features and diagnosis of polycystic ovary syndrome in adolescents
http://patients.uptodate.com/frames....=pediendo/8213
Definition and pathogenesis of polycystic ovary syndrome in adolescents
http://patients.uptodate.com/frames....pediendo/10611
Treatment of polycystic ovary syndrome in adolescents
http://patients.uptodate.com/frames....=pediendo/8697
Clinical manifestations of polycystic ovary syndrome in adults
http://patients.uptodate.com/frames....=r_endo_f/5129
Diagnosis and treatment of polycystic ovary syndrome in adults
http://patients.uptodate.com/frames....r_endo_f/11337
Treatment of hirsutism
http://patients.uptodate.com/frames....=r_endo_f/8185
Laparoscopic surgery for ovulation induction in polycystic ovary syndrome
http://patients.uptodate.com/frames....r_endo_f/12577
Steroid hormone metabolism in polycystic ovary syndrome
http://patients.uptodate.com/frames....=r_endo_f/7252
A number of other sites on the internet have information about PCOS. 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 their information is updated is variable.
National Library of Medicine
(
http://www.nlm.nih.gov/medlineplus/)
The Endocrine Society
(
http://www.endo-society.org/)
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.
source:
http://patients.uptodate.com/topic/t...endo_hor/12474
Patient information: Treatment of polycystic ovary syndrome 
