For years, polyendocrine metabolic ovarian syndrome (PMOS) was misunderstood — which partly explains why 70% of those affected remain undiagnosed, according to the World Health Organization.

Until recently, this condition, affecting 10%-13% of women, was considered a “female disease of the ovaries,” said Karen Elkind-Hirsch, PhD, former scientific director of Woman’s Metabolic Health Clinic and Woman’s Health Research Department at Woman’s Hospital in Baton Rouge, Louisiana. Doctors associated PMOS, formerly known as polycystic ovary syndrome (PCOS), with polycystic ovaries, which gave the condition its name.

Gradually, experts realized polycystic ovaries were a red herring. “Instead of just a reproductive disorder, PCOS is much more of a metabolic disorder, characterized by elevated male hormones, insulin resistance, and glucose dysfunction,” said Elkind-Hirsch, now senior clinical scientist at San Diego-based Dexcom, an American medical device company that manufactures continuous glucose monitoring systems.

The driving force of PMOS is elevated levels of insulin, which stimulate the ovaries to produce androgens (male hormones), said Elkind-Hirsch. Excess androgens are associated with insulin resistance and obesity in PMOS, and these conditions can exacerbate each other. The cycle is self-reinforcing: Hormonal dysregulation can cause obesity, and obesity can cause hormonal dysregulation.

Because PMOS is the leading cause of anovulatory infertility in women of reproductive age, doctors have focused on that side effect. Yet not all women aim to have children, and this approach leaves out the more serious health ramifications of the condition. “People don’t realize, in addition to weight gain, half of women with PCOS will develop type 2 diabetes by age 40,” said Lynsey Johnson, DNP, FNP-C, founder and CEO of PCOS (PMOS) Sisters Telehealth Clinic & Wellness Center. “And with PCOS, there’s an increased risk of cardiovascular events, like hypertension, stroke, and heart attack.”

Fortunately, the medical community is wising up. This past May, an article in The Lancet announced a name change: The condition is now called PMOS. The new name reflects how the condition disrupts multiple hormone systems, causes ovulatory disturbances and infertility, and is metabolic in nature. While PMOS cannot be cured, treatments, such as GLP-1 receptor agonists, can alleviate symptoms.

The Road to GLP-1s for PMOS

For many years, PMOS was treated with surgery — ovarian wedge resection. Now doctors prescribe oral contraceptives to suppress production of androgens and regulate the menstrual cycle. Because some progestins can increase androgens, clinical guidelines often favor oral contraceptives containing less androgenic or antiandrogenic progestins when symptoms such as facial hair or acne are a concern.

Once insulin resistance was recognized as a critical aspect of PMOS, doctors began addressing the metabolic issues. Since the late 1990s and early 2000s, the type 2 diabetes medication, metformin, has been studied and shown to improve insulin resistance and sometimes reduce androgen levels. Some doctors prescribe metformin and oral contraceptives together.

While metformin improves insulin resistance and helps with menstrual regularity and androgen levels, it has not been shown to facilitate significant weight loss. With obesity rates rising, Elkind-Hirsch noticed PMOS “rearing its ugly head a lot faster,” she said. “As we saw more obesity [in the population], the presentation of PMOS was exacerbated.”

Hypothesizing that GLP-1s could be an answer, Elkind-Hirsch led two clinical trials assessing these medications for weight loss in women with obesity and PMOS. As she noted in study results published in Fertility and Sterility in 2022, the GLP-1, liraglutide, was superior to the placebo in reducing body weight and cardiovascular and metabolic markers.

The results of another study she led, published in The Journal of Clinical Endocrinology & Metabolism in 2021, assessed two combination treatments: exenatide (a GLP-1) plus dapagliflozin (an SGLT2 inhibitor used to treat type 2 diabetes) and phentermine (a stimulant-like appetite suppressant) plus topiramate (an anticonvulsant that suppresses appetite). Although both combinations improved fasting glucose, testosterone, and blood pressure and significantly reduced weight and total body fat, the combination with the GLP-1 was superior at improving blood glucose and insulin sensitivity.

A third clinical trial, led by Melanie Cree, MD, PhD, at the University of Colorado, Children’s Hospital Colorado, compared Rybelsus (an oral version of semaglutide) with dietary intervention over 4 months in girls with obesity and PMOS who were aged between 12 and 21 years. While the results have not yet been peer-reviewed, they indicate that patients lost more weight with the GLP-1, although both treatments improved metabolic and reproductive measures.

Both Elkind-Hirsch and Johnson recommend metformin and GLP-1s for patients with obesity and PMOS. As Johnson noted, patients on GLP-1s typically lose 10 lb per month (and experience drops in testosterone levels) vs only 1 or 2 lb per month on metformin alone.

Treatments Should Be Individualized

Despite common symptoms, such as obesity and infertility, “PMOS does not look the same for everyone,” said Sasha Ottey, MHA, MLS (ASCP), founder and executive director of PCOS Challenge: The National Polycystic Ovary Syndrome Association. As many as 80% of women with PMOS are overweight or obese, meaning 20% are not. That number includes Johnson, who was diagnosed with PMOS in her twenties. Instead of excess weight, she experienced hair thinning, along with acne and chin hair. Ottey, diagnosed around the same age, said she had irregular periods and skin issues.

Along with varying presentations, patients have different priorities, Ottey pointed out. “It’s important to ask patients, ‘What is important to you?’” Instead, I get so many reports of 16-year-olds being told they will never get pregnant. After leaving the clinic, that comment affects their mental health, body image, and self-worth. “Refer patients appropriately to a dietitian, nutritionist, therapist, or psychiatrist depending on what the patient’s picture looks like,” Ottey said.

These days, “most people [with PMOS] are on birth control, metformin, and/or semaglutide,” said Johnson.

The Bottom Line

The efficacy of GLP-1s for weight loss has been proven. Because 80% of women with PMOS have overweight or obesity, and obesity can worsen PMOS symptoms, GLP-1s should be a go-to treatment for this condition.

Cree reported serving as a consultant for Eli Lilly and Company, Novo Nordisk, Chiesi Farmaceutici, and Roche Neuroscience and receiving research supplies from Abbott. Ottey reported having no conflicts of interest to declare.