PCOS Raises Risk of Cardiometabolic, Psychological Problems

Miriam E Tucker

February 02, 2015

Women with polycystic ovary syndrome (PCOS) are at elevated risk for a number of long-term adverse cardiovascular, metabolic, psychological, oncologic, and reproductive health consequences, a new Australian study indicates.

The researchers studied medical records of 2566 women over 15 years of age with a PCOS diagnosis from 1980 until they reached a median age of almost 36 years and age-matched them to 25,660 women without PCOS. On average, those with PCOS had twice as many hospital admissions and were twice as likely to die during the study period.

"This is the largest and longest study of its kind to look at the health implications of a PCOS diagnosis in comparison with a non-PCOS control group....The consistency of the results and magnitude of the difference was startling," lead author Roger Hart, MD, Winthrop Professor of Reproductive Medicine, University of Western Australia, Perth, told Medscape Medical News.

Previous studies have suggested that women with PCOS have a variety of health problems in later life, but the studies were generally small and of short duration, he noted.

"Clinicians must emphasize the predisposition of these women to cardiometabolic disease and encourage patients with PCOS to adopt a healthy lifestyle to reduce their lifelong risks of developing these conditions," Dr Hart said.

He also stressed that the "relevance and significance of the predisposition of women with PCOS to mental-health disorder is perhaps underestimated."

Asked to comment, Rhoda Cobin, MD, Clinical Professor of Medicine at Mount Sinai School of Medicine, New York, NY and an expert in PCOS, told Medscape Medical News that the new study "adds something to the literature, because it points out that PCOS is not simply an obstetrical condition and that it can be associated with significant medical morbidity....The doctor needs to look at this person not as somebody he or she is treating for one specific complaint but look at the whole person and realize she's at risk of serious medical issues that can lead to heart attacks, strokes, and diabetes, even at a young age."

She added a caveat, though, that there has been confusion about the diagnostic criteria for PCOS, and definitions that don't require hyperandrogenism probably select for a less severely affected population.

Moreover, she told Medscape Medical News that the women in this study were relatively young, "so the impact on cardiovascular disease and diabetes complications would be expected to be less than that in older women."

"Severe Lifelong Consequences"

Dr Hart, along with coauthor Dorota A Doherty, PhD, of King Edward Memorial Hospital, Perth, published the results from their retrospective analysis of hospital data online December 22, 2014 in the Journal of Clinical Endocrinology & Metabolism.

Patients with PCOS in the study had the diagnosis recorded on admission to a hospital in western Australia. They were compared with women who did not have a PCOS diagnosis identified from voter rolls, and the data were linked through several registries. Over 90% of controls had been hospitalized at least once, mostly for pregnancy-related reasons, Dr Hart explained.

All-cause mortality was higher among women with than without PCOS over the follow-up period, 0.7% vs 0.4%, respectively (hazard ratio [HR], 1.89, P = .016).

As expected, women with PCOS had more menstrual problems than those without PCOS, with 20.5% vs 5.0% having excessive, irregular menstruation that occurred at an earlier age (P < .001). Infertility was more likely to be a hospital diagnosis in those with vs without PCOS (40.9% vs 4.6%, P < .001).

Women with PCOS were more likely to require in vitro fertilization treatment, have a miscarriage or ectopic pregnancy, require surgical intervention for heavy periods, or have a hysterectomy. Women with PCOS were more likely to deliver preterm or have a stillbirth, the authors report.

Women with PCOS were four times more likely to develop diabetes (12.5% vs 3.8%), even after adjustment for obesity, compared with those without PCOS. And, despite their relatively young age, those with PCOS were more likely to be hospitalized for hypertension (3.8% vs 0.7%) and ischemic heart disease (0.8% vs 0.2%).

The PCOS group was also more likely to develop cerebrovascular disease and arterial and venous disease and to be diagnosed with asthma.

Hospitalizations related to mental and behavioral disorders were also more common in the PCOS group, including those related to stress and anxiety (14.0% vs 5.9%), depression (9.8% vs 4.3%), and licit or illicit psychoactive substance abuse (8.8% vs 4.5%). They were also more likely to self-harm and be involved in vehicle accidents.

PCOS was associated with a significantly increased risk of endometrial cancer (0.4% vs 0.02%, HR 22.52), but not other cancers.

Diagnostic Issues

These findings are in line with the Endocrine Society's 2013 clinical practice guideline that recommends screening women and adolescent girls diagnosed with PCOS for heart-disease risk factors and diabetes.

That document endorses the so-called Rotterdam criteria" for diagnosing PCOS, which includes two of the three following conditions: androgen excess, ovulatory dysfunction, or polycystic ovaries. Other PCOS definitions require androgen excess — chemical or clinical — to make the diagnosis.

Indeed, Drs Hart and Doherty note that patients with a more severe clinical picture, including amenorrhea and signs of hyperandrogenism, are even more likely to have long-term health problems.

"It is the more severe phenotype of PCOS that is at increased risk of the lifelong consequences, whereas a woman with a less severe appearance of PCOS is less likely to be labeled as having PCOS....The milder form of the condition may be less predisposed to these severe lifelong consequences."

Dr Cobin is currently coauthoring a comprehensive review of PCOS that will cover diagnostic criteria that select for patients who are more likely to experience lifelong consequences without intervention. Publication is expected in 2015, she told Medscape Medical News.

The study authors and Dr Cobin have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online December 22, 2014. Abstract

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