Challenge for providers: Polycystic ovary syndrome
Weight gain. Excess hair growth. Infrequent periods. What’s your initial diagnosis? Whether you write the term polycystic ovary syndrome (PCOS), Stein-Leventhal syndrome, or hyperandrogenic chronic anovulation in your patient’s chart, you have just begun to touch on a condition estimated to affect 5% to 7% of women.
Diagnosing PCOS may prove challenging if the focus is on textbook characteristics: obesity, hirsutism, oligomenorrhea (where the interval between menses exceeds 35 days but is not long enough to be labeled amenorrhea), and subfertility.1 In reality, many women with PCOS may not be heavy or exhibit excess hair growth. Even the appearance of polycystic ovaries does not mean an automatic diagnosis.
The lack of uniform diagnostic criteria has hampered effective diagnosis and treatment of polycystic ovary syndrome, says Richard Legro, MD, assistant professor of OB/GYN at Pennsylvania State University’s College of Medicine at the Milton S. Hershey Medical Center in Hershey. Over the past 10 years, however, there has been a growing acceptance that the women who are most severely affected tend to have excess androgens and irregular periods due to chronic anovulation.
It is important to make a good diagnosis when anovulation is involved, stresses Sarah Berga, MD, associate professor of OB/GYN and reproductive sciences at the University of Pittsburgh School of Medicine at Magee-Womens Hospital. (See how Berga approaches a diagnosis of polycystic ovary syndrome, p. 54.) "Health consequences are very different, depending on the type of anovulation one has, and the therapies are radically different," she says.
The central problem in PCOS lies in aberrant gonadotropin-releasing hormones (GnRH) and gonadotropin response, which is associated with high serum levels of luteinizing hormone (LH).1 LH stimulates ovarian androgen production. This testosterone adds to the amount of adrenally produced androgens and results in the classical symptoms of excess hair growth and acne. Also, the high androgen level suppresses pituitary production of follicle stimulating hormone (FSH), which affects ovarian cycling and luteal progesterone production. Endometrial proliferation continues, which results in irregular endometrial sloughing.
In dealing with polycystic ovary syndrome, some providers have focused on cosmetic symptoms of the condition or on infertility problems encountered by reproductive-age women. Providers also must consider long-term health consequences, says Legro. A risk of endometrial cancer exists due to infrequent endometrial sloughing. Many women with PCOS are obese and have abnormal lipid profiles, which may place them at risk of developing cardiovascular disease. Perhaps the most important health concern associated with PCOS is the risk of diabetes. In a recently published study, Legro and colleagues at New York City’s Mount Sinai School of Medicine found that women with PCOS have a much higher chance of developing impaired glucose tolerance levels, a risk factor for diabetes.2
Treatment in research
According to Legro, the central problem in PCOS lies in insulin resistance. The condition leads to excess insulin, which stimulates the ovary to produce androgens. That line of reasoning is leading researchers to study the use of insulin sensitizers in women with polycystic ovary syndrome. Those drugs include metformin (Glucophage, Bristol-Myers Squibb, Princeton, NJ) and troglitazone (Rezulin, Parke-Davis, Morris Plains, NJ).
In one small study, almost 90% of women with polycystic ovary syndrome who took metformin for a month ovulated spontaneously or with help from the fertility drug clomiphene citrate.3 Among those taking a placebo, only 12% ovulated even with clomiphene.
The role of insulin sensitizers in the long-term chronic management of PCOS is unknown, say Berga and Legro. More research must be conducted to determine their safety and efficacy in treating the condition.
Other research efforts are examining the use of androgen blockers such as flutamide. Because women with PCOS have high levels of androgens, scientists say flutamide may allow ovulation. A small European study showed that the drug restored ovulation in anovulatory PCOS patients.4 Women with PCOS who have not responded to clomiphene citrate treatment for infertility are participating in a study sponsored by the National Institute of Child Health and Human Development in Bethesda, MD. Results from those and future studies may determine what role androgen blockers play in treatment.
Experts say treatment of PCOS varies, depending on which symptoms are present and which need to be controlled. A healthy diet, weight maintenance, and regular exercise can help improve the body’s sensitivity to insulin and help diminish the chances of developing diabetes, heart attack, or stroke. Levels for LDL, HDL, and triglycerides should be monitored on a regular basis, with fasting glucose levels taken once a year for diabetes detection.
A low-dose oral contraceptive can help lower androgen levels, establish regular menstruation, and provide effective birth control for those who desire it.1
References
1. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology. 17th edition. New York City: Ardent Media; 1998.
2. Legro RS, Kunselman AR, Dodson WC, et al. Preva lence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: A prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999; 84:65-169.
3. Nestler JE, Jakubowicz DJ, Evans WS, et al. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998; 338:1,876-1,880.
4. De Leo V, Lanzetta D, D’Antona D, et al. Hormonal effects of flutamide in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83:99-102.
Resource
• Polycystic Ovarian Syndrome Association, P.O. Box 7007, Rosemont IL 60018-7007. Telephone: (630) 585-3690. E-mail: [email protected]. Web: http://www.pcosupport.org. The organization’s annual conference is scheduled for June 5-7, 1999, in Arlington Heights, IL. More information on the condition is on the Web: www.collmed.psu.edu/obgyn/pcos.htm.
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