Acknowledging the Understudied Nature of Long-term PCOS Risks

In an article published in Fertility and Sterility, Bart C.J.M. Fauser, MD, PhD, a gynecologist and professor of reproductive medicine at the University of Utrecht, The Netherlands, highlighted the understudied nature of potential later-life implications of polycystic ovary syndrome (PCOS).

PCOS is diagnosed in up to 20% of reproductive-aged women and “represents a notoriously heterogenous common condition,” wrote Fauser. The Rotterdam criteria are currently used to diagnose the condition and includes women with cycle abnormalities and polycystic ovary morphology despite normal androgen levels. In the past, more exclusive criteria were used that mandated hyperandrogenemia must be present for a PCOS diagnosis.

PCOS also frequently coincides with overweight condition, while hyperandrogenemia and obesity are both considered independent risk factors for metabolic abnormalities. Furthermore, gynecologists previously “focused their attention toward the endocrine treatment of PCOS-associated reproductive symptoms like hirsutism, irregular or absent menstrual cycles, and anovulatory infertility,” Fauser said, adding that times and recommended treatments are changing.

In recent years, young women with PCOS have presented with subtle cardiometabolic dysfunction, even with normal body weight, prompting questions as to how these early-age abnormal laboratory findings should be interpreted in clinical practice.

As different societies have generated divergent clinical practice recommendations, women with this syndrome end up receiving mixed advice based on the specialty of the physician with whom they consult (i.e. gynecologist, medical endocrinologist, and others). Because these approaches are not evidence-based, they may not ultimately benefit the patient, Fauser stressed.

“How should women be informed at a young age regarding the presumed long-term health implications of PCOS, what should be screened and how often, and should women be prescribed life-long medication (like insulin sensitizers) without really knowing the natural cause of the disease?” he posited.

Few long-term studies exist assessing long-term disease risks in PCOS, including stroke, myocardial dysfunction, and death. To address this knowledge gap, Fauser proposed implementing prospective well-phenotyped cohort follow-up studies. However, for women with PCOS, these studies pose several hurdles including the fact initial diagnoses are typically made earlier in life while cardiovascular disease in women usually occurs in their 60s or older.

Identifying specific PCOS subgroups that are more likely to develop long-term disease (based on the absence or presence of hyperandrogenemia, obesity, insulin resistance, or other parameters) could also help answer these questions. But “at present, the sample size of studies often is too small to allow for such subgroup analysis,” Fauser said.

One recent cross-sectional study conducted among Swedish participants included a large sample size (more than 50,000 PCOS cases) and confirmed PCOS as an independent risk factor for type 2 diabetes, regardless of body weight.

Fauser hopes that in the future, the database used will allow for the assessment of real-life hard health end points later in the life of women with PCOS. He conceded possible shortcomings do coexist with registry trials.

In addition, the link between later-life cardiovascular disease and reproductive dysfunction is not exclusive to PCOS and has been demonstrated among those with previous preeclampsia and premature ovarian insufficiency, he explained.

“We as gynecologists may have to ask ourselves the question whether we would like to be part (or even in the lead) of a multidisciplinary team guiding women with PCOS or some other reproductive disorders diagnosed at a relatively young age throughout the different phases of life beyond reproductive life,” Fauser concluded.

“This would certainly be in agreement with major shifts in attention in health care from the curative model (which nowadays seems an illusion in most patients with chronic disease) toward the prevention of later-life disease. More data and strategies are urgently needed.”

Reference

Fauser BCJM. Potential later-life health implications of polycystic ovary syndrome are underserved and understudied. Fertil Steril. Published online July 21, 2021. doi:10.1016/j.fertnstert.2021.06.036