PCOS: What Women Do Not Know Can Hurt Them

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility and the likely cause of many menstrual disorders. Many women are not even aware that they have this condition. PCOS is associated with increased risk of endometrial and ovarian cancer, cardiovascular disease, hypertension, and type 2 diabetes.

PCOS is an endocrine disorder that occurs in approximately 7% to 10% of premenopausal females and results in the ovarian production of high amounts of androgens (male hormones), in particular testosterone.¹ The increased androgen levels prohibit the follicles of the ovaries from producing a mature oocyte. Lack of oocyte production causes the follicles to form cysts. Because ovulation does not occur, enlargement of ovaries tends to occur. Polycystic ovaries are usually 2 to 5 times larger than normal ovaries. Approximately 50% to 70% of females with PCOS have insulin resistance (IR).²

Diagnosis

In 1990, the National Institutes of Health proposed that the criteria (listed in Table 1) for diagnosing PCOS should be features of hyperandrogenism with chronic anovulation after identifiable causes have been excluded.

It is important to note that having 1 or more of the characteristics of PCOS does not indicate that an individual has PCOS. Various diagnostic tests?such as physical examinations, ultrasonography, and blood tests?are performed to confirm whether the condition exists and to assess the severity of the condition. In some cases, the patients are asymptomatic and discover PCOS upon an attempt to conceive or after seeking medical attention for irregular or missed menstrual cycles. Approximately 5% to 30% of women have some characteristic of PCOS.⁴

Complications

Complications of PCOS include reproductive, cardiovascular, and metabolic complications.³

Reproductive complications include the following:

• Infertility (74 % of all PCOS cases)
• Endometrial hyperplasia
• Increased incidence of miscarriage

Cardiovascular complications are as follows:

• Coronary artery disease
• Hypertension
• Hypercholesterolemia

The following metabolic complications may occur:

• Obesity
• Insulin resistance
• Type 2 diabetes

Treating PCOS

The focus of PCOS treatment is on restoring regular menstrual cycles, relieving symptoms, and preventing or decreasing future complications related to having this disorder, such as cardiovascular disease, diabetes, and cancer. Various treatments are available for treating PCOS, and treatment must be individualized, based on the severity of the condition and its clinical presentation.

Hormonal Agents

Oral Contraceptives. These agents are effective in decreasing the luteinizing-hormone (LH) levels, thus regulating the menstrual cycle. They also assist in reducing acne and hirsutism.

Progestins. Agents such as medroxyprogesterone or norethindrone aid in decreasing serum levels of LH and regulating menstrual cycles.

Antiandrogens

These agents help to decrease elevated androgen levels and to treat hirsutism and alopecia. Spironolactone is the most commonly prescribed antiandrogen for treating hirsutism.

Fertility Agents

For PCOS patients who want to conceive, clomiphene citrate is typically prescribed to stimulate ovulation. If not successful, other fertility agents can be utilized.

Treating Insulin Resistance Associated with PCOS

Insulin-Sensitizing Agents

Insulin-sensitizing agents (Table 2) are typically prescribed to treat non?insulin-dependent diabetes (type 2 diabetes), but these agents have been shown to be beneficial in treating IR, most commonly found in women with PCOS. Although the use of these agents in PCOS is not FDA-approved, studies suggest that in some cases there is a significant decrease in free testosterone levels and in some instances women have ovulated without the use of fertility agents.⁷ These insulin-sensitizing agents aid the body's sensitivity to insulin and therefore help to normalize the hormonal abnormalities associated with PCOS.

In July 1998, the results of a study, published in the New England Journal of Medicine, suggested that women with PCOS had increased rates of ovulation when placed on agents that lower insulin levels.^8,9 Metformin (Bristol-Myers Squibb) was the first agent to be prescribed for IR, and it is commonly used in treating PCOS patients who have insulin resistance. Metformin belongs to the biguanide drug class.

In 1999, 2 new agents were approved: pioglitazone (Takeda) and rosiglitazone (GlaxoSmithKline). These antidiabetic agents are commonly used for IR in PCOS patients, although this indication has not been approved by the FDA. The use of these agents in some patients with PCOS has been shown to result in a return of the ovulation function.

Rosiglitazone is metabolized with no unchanged drug excreted in the urine. Therapy with this agent should not be initiated in patients who have clinical evidence of liver disease or increased serum transaminase levels. This agent can cause edema, which may exacerbate or cause congestive heart failure. Patients should, therefore, be observed for signs of heart failure. This drug may be taken without regard to meals. There are no documented cases of drug interactions.

Combination Therapy

In October 2002, GlaxoSmithKline Pharmaceuticals announced FDA approval of the combination of rosiglitazone maleate and metformin HCl (Avandamet).¹⁰ This drug combines the 2 leading agents currently used for type 2 diabetes in 1 pill. It furnishes 2 distinct but integral mechanisms of action to regulate diabetes. This agent also is not an approved treatment for PCOS, but, like other thiazolidinediones, it may result in ovulation in some premenopausal anovulatory patients. Avandamet should not be prescribed for patients with any type of renal or hepatic abnormalities or congestive heart failure. A small population of patients may develop lactic acidosis. The most common adverse effects include diarrhea, nausea, and mild weight gain.

Conclusion

PCOS is often underdiagnosed, but with the growing trend toward the recognition of this disorder, more women are being diagnosed and treated. It is imperative that all health care professionals (including pharmacists) be aware of this disorder and realize that, if left untreated, PCOS can cause multiple long-term complications for the vast affected patient population.

Ms. Terrie is a clinical pharmacy writer based in Slidell, La.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. D. Ryan, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: dryan@mwc.com.

For More Information and Support:

Polycystic Ovary Syndrome Association: www.pcosupport.org

National Women's Health Information Center: www.4woman.gov/faq/pcos.htm