PCOS Guideline Cites Need to Screen Younger Women, Follow Women Longer

The International PCOS Network cites need for screening for polycystic ovary syndrome in adolescent girls to improve long-term outcomes including diabetes, depression, and cardiovascular disease

With Nanette Santoro, MD, and Ricardo Azziz, MD, MPH, MBA

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in adult women, generally characterized by infertility, irregular menses, acne, hirsutism, and obesity.1 Of particular clinical concern is the increased risk for cardiometabolic risk factors, with an elevated risk of developing type 2 diabetes (T2D), cardiovascular disease (CVD), and endometrial cancer.2

“Diagnosis remains controversial, and the assessment and management are inconsistent,” according to the International PCOS Network writing group,3 in issuing of these evidence-based recommendations to advance the clinical care of women with polycystic ovary syndrome.

Complications of PCOS linger after menopause, requiring long-term care. Younger women with PCOS require screening for cardiovascular disease and diabetes to improve outcomes in older age.

As published in the journal Fertility and Sterility,3 these recommendations were issued in an attempt to enhance, and perhaps hasten, earlier response to and more focused attention to patient care. In preparing the guideline, the International PCOS Network evaluated existing evidence in order to update recommendations, in two categories:

  • High-quality evidence within the past five years adapted for country-specific use
  • Evidence deemed of high quality completed more than five years ago 

The working group reviewed and organized the best available evidence, clinical expertise, and consumer preference in developing the recommendations.3 In fact, “rather than there being anything ‘new’ per se, in the guideline, rather the recommendations urge a greater consideration in what is known and actions to be taken.”

What Is the Impact of the New Guideline in Clinical Practice?

PCOS is understood to be a lifelong disorder that may arise as precocious puberty and continue to influence medical and psychiatric health long after menopause.1-3 

“Diagnosing PCOS in young women is especially challenging, and the document spends a fair amount of time and space describing how to do this,” said Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics and Gynecology at the University of Colorado School of Medicine in Aurora.

“It’s another important area that requires clarity because it is almost impossible to diagnose adolescents. But failure to do so in a timely manner can be very costly to the patient,” said Dr. Santoro, because undiagnosed and unmonitored PCOS may lead to a variety of adverse effects including hirsutism, acne, substantial weight gain and even endometrial hyperplasia.

“Even though it has been shown that women with PCOS are at higher risk for type 2 diabetes,4,5 there is evidence that routine screening is not being performed aggressively,” she said. In fact, a team of Danish investigators ”found that the risk of developing diabetes is four times greater and that diabetes is diagnosed four years earlier in women with PCOS compared to controls.”

“This document strongly supports the practice of initial screening tests [for diabetes risk] at diagnosis,” Dr. Santoro told EndocrineWeb. “I personally prefer doing an oral glucose tolerance test even though it is less convenient, and then follow-up every 2-3 years. This follow-up is critical and supported by the American Diabetes Association which now includes PCOS as a diagnosis that should be considered high risk for diabetes.[ADA] to assure that we make the diagnosis early and treat patients properly to help prevent complications of the disease later in life.”

Cardiometabolic Consequences, Mood Disorders Persist  Long-Term

Although many symptoms of PCOS may diminish with age and lessen with the cessation of ovulation, the metabolic, cardiovascular, and affective consequences of PCOS persist long-term.2,3

However, “it is not yet fully known whether the risk of heart disease, diabetes, or other disorders is greater in women with PCOS compared with those without PCOS,” said Ricardo Azziz, MD, MPH, MBA, professor of medicine and chief officer for Academic Health and Hospital Affairs for the State University of New York (SUNY) System Administration in Albany New York, who is a member of the International PCOS Network.

Dr. Santoro stressed that the medical evidence concerning mood disorders in women with PCOS is an emerging consequence, requiring greater clinical attention.2 In particular, women with PCOS have an increased prevalence of depressive symptoms, independent of age or obesity,6 along with eating disorders.7

As such, its good news that the guideline recognizes the increased prevalence of affective comorbidities and/or consequences of PCOS and emphasizes the need for routine screening and treatment for depression, anxiety, and eating disorders,3,6 she said.

“Clinicians need to be alert to this possibility and have the necessary resources available for their patients,” said Dr. Santoro. While it is not yet clear if treating insulin resistance and/or hyperandrogenism will reduce depression in women with PCOS, the guideline offers numerous recommendations for lifestyle interventions and modifications, including guidance to work with patients to address diet, exercise, weight loss, and smoking cessation.3

Dr. Azziz agreed: “The need for weight loss in overweight or obese women with PCOS–whether through lifestyle interventions, pharmacotherapy or surgery if necessary.” He also said that not all women with PCOS are overweight/obese–in fact, women with PCOS who are of normal weight often don’t seek medical care until other bothersome manifestations present, delaying diagnosis and treatment.

Revolving and Evolving Criteria to Establish Diagnosis of PCOS

The table of recommendations for assessing and actively managing PCOS covers 31 evidence-based recommendations, 59 clinical consensus recommendations, and 76 clinical practice points.3 Undeniably, these recommendations represent a significant piece of work involving an international effort spearheaded by the Australian government, according to Dr. Azziz.

Understandably, Nanette Santoro, MD, told EndocrineWeb, "at first glance, this guideline appears to be a “lengthy laundry list of things to do.”3  While many clinicians may find the guideline is sufficiently comprehensive as to be overwhelming, “overall, the recommendations are reasonable."

This guideline endorses the Rotterdam PCOS Diagnostic Criteria in adults,which require women to meet two of the following 3 criteria:

  • Oligo- and/or anovulation
  • Clinical and/or biochemical signs of hyperandrogenism
  • Polycystic ovaries

The original NIH criteria (1990) required confirmation of both chronic anovulation and clinical and/or biochemical signs of hyperandrogenism, whereas the AE-PCOS Society guidelines required both clinical and/or biochemical signs of hyperandrogenism and ovarian dysfunction (oligo-anovulation and/or polycystic ovarian morphology).9

In 2012, the NIH sponsored the Evidence-based Methodology Workshop on Polycystic Ovary Syndrome, which endorsed the Rotterdam diagnostic criteria and recommended the use of the following four phenotypes: (1) Androgen excess + ovulatory dysfunction; (2) androgen excess + polycystic ovarian morphology; (3) ovulatory dysfunction + polycystic ovarian morphology; and (4) androgen excess + ovulatory dysfunction + polycystic ovarian morphology.

Informing Clinical Practice Now While Awaiting Better Data 

According to Dr. Azziz, we understand that these phenotypes influence risk and morbidity, particularly with regard to insulin resistance and metabolic dysfunction, and may help inform management of PCOS so women receive clinical attention sooner rather than later.

The guideline writing group introduced their recommendations as presenting “considerable refinement of individual diagnostic criteria with a focus on improving the accuracy of diagnosis,” and reducing unnecessary testing.3

For example, the guideline establishes a strict ultrasound threshold on either ovary of >20 follicles per ovary and/or an ovarian volume >10 ml on either ovary.3 In addition, there is a recommendation supporting the measurement of anti-müllerian hormone (AMH) as useful, although it is not yet clear where and how it will be most applicable in the diagnosis of PCOS.

Dr. Santoro summed up the recommendations: “what is new here is (1) an appreciation that women with PCOS need to have additional and ongoing monitoring once the diagnosis has been made; (2) psychosocial aspects of the disorder deserve attention, and (3) PCOS should not be considered to subside at menopause.”

The International PCOS Network cautioned that the available evidence is generally of “low to moderate quality.” The guideline highlights areas in which continuing research (and funding for research) is needed–notably around the etiology of PCOS, possible genetic underpinnings, and long-term prognosis (among others), Dr. Azziz said. 

Funding was provided by the Australian National Health and Medical Research Council with support from the European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine. Neither of the clinicians indicated any financial conflicts of interest regarding this work.

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