‘Simplified’ PCOS diagnostic process can help women receive timely diagnosis, treatment

Key takeaways:

• The updated guideline for polycystic ovary syndrome states anti-Mullerian hormone can replace ultrasound assessment for diagnosis.
• The guidance states PCOS should be considered a risk factor for heart disease.

SAN FRANCISCO — An updated evidence-based guideline for the assessment and management of polycystic ovary syndrome includes new recommendations for a timelier diagnosis and evidence that firmly supports PCOS is a risk factor for CVD.

Women with PCOS often experience a delay in diagnosis and, once diagnosed, may not receive recommended health screenings that could reduce their risks for cardiometabolic conditions, such as hypertension and type 2 diabetes, according to Anuja Dokras, MD, PhD, MCHI, professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania and director of the Penn Polycystic Ovary Syndrome Center.

The 2023 updates to the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome support the Rotterdam criteria for diagnosis, which are now evidence-based. Additionally, an updated algorithm recommends women with PCOS receive screenings for all cardiometabolic risk factors, including cholesterol, with follow-up based on individualized risk level. There is also a renewed emphasis on preconception counseling, as well as other recommendations for women seeking pregnancy.

Healio spoke with Dokras, a co-author of the guideline, about changes to the criteria to diagnose PCOS, how to assess cardiometabolic risk factors and where the science stands on the use of popular GLP-1 receptor agonists like semaglutide (Ozempic, Wegovy, Rybelsus; Novo Nordisk). Dokras delivered the Hale Lecture, titled “Polycystic Ovary Syndrome: No Longer an Enigmatic Syndrome,” at the ACOG Annual Clinical & Scientific Meeting.

Healio: How would you frame the take-home message of your lecture?

Dokras: I am reviewing updates to the international PCOS guideline. The first guideline was published in 2018, and we published a 5-year update in September 2023. I review some of the changes to the guideline and emphasize the salient features. We want to encourage everyone to have a guideline-directed practice, as much as possible. Guidelines are just that — guidelines. They are not mandatory and care needs to be personalized to the patient. But, in general, for the overall care of people with PCOS, both the diagnosis and the treatment should be guidelines directed.

Healio: What do the updated guidelines tell us about diagnosing PCOS?

Dokras: The first step is we use the Rotterdam criteria for diagnosis and none of the old criteria remain. The guideline authors highlighted this in 2018, and we are reemphasizing this with the update. The first criterion is irregular periods; the second is elevated androgen levels or the manifestations, such as hirsutism. The third criterion has changed. Previously, the third criterion was the ultrasound features of PCOS. We have expanded on that to note it can include ultrasound features or an elevated anti-Mullerian hormone level, or AMH level. That is the biggest change. This is exciting because it simplified the diagnosis. It is much easier to make a diagnosis if a provider could order a blood draw and get all the necessary data, rather than ask a patient to stop at a lab and then go to a radiology facility.

Healio: The updated algorithm highlights the importance of addressing cardiometabolic manifestations that are common with PCOS. What screenings are needed when, and why?

Dokras: After making a PCOS diagnosis, the next step is, which screenings are needed at the time of diagnosis? Next, what is needed for that patient during a return visit? Regardless of whether a patient desires fertility or not, we must screen them to assess cardiometabolic risk. It is important to assess BMI, blood pressure and glucose or an HbA1c — those are the three things already listed in the original guideline. However, we have more data now to suggest we should also measure a patient’s lipid levels. We should also screen everyone for depression and anxiety. This is a one-time screening that every patient needs at the time of diagnosis.

Follow-up will depend on whether a clinician found something on the medical history. If the patient has no other cardiometabolic risk factors, a normal-range body weight and no family history of CVD, then follow-up every 3 years might be OK. We do not have follow-up timelines set in stone yet. Our goal is for every provider to conduct a baseline screening for every women diagnosed with PCOS to put them in a category of high risk or low risk and follow them accordingly.

Healio: You mention depression and anxiety. Why is it so important to assess for those conditions in the setting of PCOS?

Dokras: There are very good data that people with PCOS have a high prevalence of depressive symptoms and an even higher prevalence of anxiety symptoms. They coexist. This interferes not only with their own feelings of wellness and quality of life, but also with following all the other guidance. We want patients to engage in lifestyle management. That is very difficult if you do not feel well. The conditions are intertwined. You cannot expect someone to exercise or take medications as prescribed when not feeling well.

The prevalence of these conditions in PCOS is much higher than the background rate, so women with PCOS are a high-risk group. We should screen them for anxiety and depression at the baseline visit, and we noted in the guidlines that we should also discuss disordered eating and body image distress. With issues such as hair growth, acne and weight gain, people can have a negative view of themselves and that ties into depressive symptoms.

We also need to screen for disordered eating, when warranted, because the clinical dietitians and nutritionists should not be giving the same recommendations for every patient. If a person with PCOS has underlying disordered eating and a provider recommends restricting calorie intake, they can put the patient into a vicious cycle of restrictive eating. This all impacts cardiometabolic health. We need a more holistic approach.

Healio: For women with PCOS who hope to achieve a pregnancy, what should they know?

Dokras: Preconception health is key. That means we try to get women with PCOS as healthy as possible prior to pregnancy so they have a healthy uncomplicated pregnancy and a good outcome. We highlight this in the updated guidance. We must invest time talking to women about getting healthier and in screening them before pregnancy.

The algorithm has not changed since 2018 with respect to fertility recommendations. Letrozole remains a recommended first-line therapy, and it could be combined with metformin. Clomid is second-line, with or without metformin. Only a small proportion of patients will progress all the way to IVF.

Again, many people will become pregnant on their own. It is not that women with PCOS do not ovulate at all. They do. They do not always need our help to become pregnant; hence, we need to help them become healthy in the event they become pregnant on their own.

Healio: Are there any other updates to the PCOS guideline that you want to highlight?

Dokras: For the first time, we have enough evidence to state women with PCOS are at higher risk for CVD. By that I mean heart attack and stroke. Previously, we knew that women with PCOS could have elevated cholesterol numbers or BP. We also knew from studies that women with PCOS tended to have more calcium deposits in the heart. What we did not have was hard data on actual heart attack or stroke incidence.

Now, studies in the intervening 5 years allowed us to include for the first time that PCOS should be considered as a risk factor for CVD. That is an important statement because it tells us we should be screening these women for hypercholesterolemia, type 2 diabetes, hypertension and overweight or obesity.

As far as ideal diets, we do not have data suggesting any one diet is better than the other. The same goes for exercise; for example, aerobic vs. weight training. This is more about a holistic approach. If a woman with PCOS has depression, treat it before engaging in any type of lifestyle intervention.

With metformin, consider prescribing it for the metabolic outcomes for someone with PCOS and overweight or obesity; however, it does not manage irregular menses or elevated androgen levels as well as birth control pills. We emphasize that birth control pills remain a first-line treatment, and then metformin.

As for semaglutide and other GLP-1 receptor agonists, the guideline does not currently recommend their use based on limited studies in patients with PCOS, but they can be used based on recommendations in the general population. For many patients, metformin simply does not move the needle on weight as much. I do expect data will show positive weight loss outcomes for women with PCOS using GLP-1 receptor agonists. However, we must caution women to use contraception during any period of weight loss.

For more information:

Anuja Dokras, MD, PhD, can be reached at X (Twitter): @AnujaDokras.