Polycystic Ovary Syndrome May Lead to Diabetes, Cardiovascular Disease

October 07, 2004

Andrew Bowser

Oct. 7, 2004 (New York) — Treating metabolic and cardiovascular risk factors associated with polycystic ovary syndrome (PCOS) could reduce the incidence of serious medical consequences, according to a position statement from the American Association of Clinical Endocrinologists (AACE).

"Physicians should no longer regard PCOS as a cluster of annoying cosmetic complaints, or a condition primarily associated with infertility," but as a condition linked to metabolic disorders "that may be associated with type 2 diabetes mellitus and cardiovascular events," the position paper states.

No large, prospective longitudinal studies definitively link PCOS to diabetes or cardiovascular disease. However, many expert endocrinologists now believe the evidence is finally compelling enough to merit a formal warning.

"Data has been building up for the last 15 years," said Rhoda H. Cobin, MD, chair of the AACE task force on PCOS. "This is the first time anybody has put everything together and come forward to say, 'we need a call to action.' "

Women with PCOS often receive treatment for infertility and non–life-theatening symptoms such as acne and hirsutism. However, many also have an underlying metabolic disorder, characterized by insulin resistance, which often goes untreated, according to experts who drafted the position paper.

Call to Action

The AACE is the first professional society to come out with a statement strongly endorsing the need to recognize underlying medical risks in PCOS, a condition "that heretofore has not been seen as a significant risk factor for illness and death," Dr. Cobin told Medscape.

Today, many PCOS patients receive treatment only for infertility or cosmetic issues, and later in life they develop overt diabetes or coronary disease, she added.

The organization is calling for "widespread case finding" of PCOS, along with screening and treatment for the "hidden risks" of the condition, including myocardial infarction, stroke, and the complications of uncontrolled diabetes, such as retinopathy, kidney failure, and amputation.

Treatment may reduce risk of early death and debilitating complications. The experts recommend lifestyle modification, emphasizing exercise, controlled eating, and tobacco avoidance. Medication to treat diabetes, hypertension, and lipid abnormalities may be considered, depending on the patient.

The antihyperglycemic drug metformin (Glucophage) should be considered in "most women with PCOS as initial therapy" because it can improve metabolic abnormalities and may improve potential for pregnancy. Although metformin is not approved for use in PCOS, "abundant literature" supports its efficacy in this setting, experts said.

Common Condition

Simply identifying PCOS remains a major challenge. Most women see several physicians before receiving a definitive diagnosis. "This is the whole tragedy," said Walter Futterweit, MD, a PCOS expert who wrote the first textbook on the condition in 1984.

"It's getting a little better, as more lectures and literature are coming out, but even some endocrinologists...are still not aware of the intricacies," said Dr. Futterweit, a clinical professor of medicine at Mount Sinai School of Medicine in New York City.

Approximately 10% of reproductive-age women have PCOS, making it the most common metabolic abnormality in young women, according to AACE.

Most experts base the diagnosis of PCOS on a history of irregular menstrual cycles and anovulation, along with the presence of hyperandrogenism, ruling out similar hormonal disorders such as hyperprolactinemia or Cushing's syndrome. At least half of women with PCOS meet obesity criteria.

Insulin resistance with compensatory hyperinsulinemia is a common clinical feature of PCOS, occurring in at least 75% of these patients, recent reports show. Consequently, experts said in the position paper, women with PCOS should be evaluated for components of the insulin resistance syndrome (IRS), a cluster of clinical syndromes and abnormalities such as low levels of high-density lipoprotein cholesterol, increased triglycerides levels, hypertension, and insulin resistance with increased tendency toward type 2 diabetes mellitus.

Since 2001, AACE has recommended that women with PCOS be screened for diabetes by the age of 30 years because multiple investigations have suggested diabetes and its complications may develop at a relatively young age.

Evidence of Harm

In the Nurses' Health Study, which included more than 116,000 women aged 25 to 42 years who were followed for eight years, incidence of type 2 diabetes mellitus was increased by 2.0- to 2.5-fold in women with a history of abnormal or infrequent menstrual cycles. That finding is "highly suggestive" of PCOS as a risk factor for diabetes, because about 80% of women with irregular menstrual cycles have underlying PCOS, according to the authors of the AACE position paper.

Women with PCOS also appear to be prone to hypertension and atherosclerosis, and separate investigations have found these patients may have increased levels of coronary artery calcification and carotid intima media thickness, two "major" surrogate markers for cardiovascular risk factors, the authors stated.

There are no prospective, longitudinal studies assessing cardiovascular outcomes in PCOS patients. A number of retrospective epidemiologic studies have been completed. Most, but not all, of those studies confirmed increased risk of cardiovascular events. Notably, the Nurses' Health Study results suggest a twofold increased risk for nonfatal myocardial infarction in women with irregular menstrual cycles.

"It is likely that a large proportion of these women had PCOS, yielding indirect confirmation of increased adverse cardiovascular outcomes," according to the position paper.

Reviewed by Gary D. Vogin, MD

Andrew Bowser is a freelance writer for Medscape.

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