5 Prescriptions for PMOS (formerly PCOS) You Didn’t Learn About in Med School

Prescription #1 for PMOS/PCOS: Naltrexone (not to be confused with low dose naltrexone/LDN) 

As you may recall from your clinical experience, naltrexone (also known by the brand name Vivitrol, or combined with bupropion in the weight-management medication Contrave) is used primarily to combat opioid and alcohol addiction. You might be wondering what a medication used for drug addiction has to do with PMOS? Well, it turns out that naltrexone has been shown to reduce fasting insulin levels, lower inflammation, and reduce cravings in several studies. A comprehensive review of medical management of metabolic dysfunction in PCOS confirmed that naltrexone reduces appetite and modulates insulin release, and its use in PCOS may reduce hyperinsulinemia.[6] This has direct implications for PMOS, which causes hyperinsulinemia, low-grade inflammation, as well as powerful sugar cravings.

Naltrexone also blocks the opioid receptor, which has recently been implicated in promoting hyperinsulinemia. Research has demonstrated that endogenous opioids are elevated in women with PCOS and may stimulate insulin secretion from the endocrine pancreas—an effect that can be inhibited by opioid antagonists, resulting in decreased circulating insulin levels in response to glucose challenge.[6] A landmark review of the endogenous opioid system in PCOS confirmed that peripherally, opioids are involved in the regulation of pancreatic islet function, hepatic insulin clearance, and glucose metabolism, potentially contributing to the pathogenesis of hyperinsulinemia and insulin resistance in PCOS.[19] Furthermore, evidence suggests that a distinct derangement of opioid tone exists in hyperinsulinemic PCOS patients, with naltrexone reducing both the insulin response to oral glucose tolerance testing and the LH response to GnRH specifically in this subgroup.[19]

Naltrexone takes the edge off cravings for sugary foods by modulating the brain's reward system, leading to weight loss and improvements in insulin sensitivity, especially when combined with bupropion—such as in the weight-loss medication Naltrexone/Buproprion combo. In one study, 50 mg per day for 6 months reduced BMI by nearly 5 points in obese women with PCOS (from approximately 30 to 26 kg/m²), equivalent to an impressive weight loss of approximately 24 pounds, while also improving menstrual cyclicity in 80% of patients and significantly decreasing free testosterone, androstenedione, and DHEA-S levels.[3]

In another study, opioid blockade with naltrexone significantly reduced the insulin response to oral glucose tolerance testing in hyperinsulinemic PCOS patients, with evidence suggesting the mechanism involves both reduced pancreatic secretion and improved hepatic removal of insulin.[4] A separate trial confirmed that long-term naltrexone treatment reduced the exaggerated insulin secretion in hyperinsulinemic PCOS patients without affecting glycemic levels.[5] Additionally, in clomiphene-resistant women with PCOS, naltrexone therapy for 6 months led to significant reductions in BMI, fasting serum insulin, LH, LH/FSH ratio, and testosterone, with 33% of women conceiving during combined naltrexone and clomiphene therapy.[2]

Lastly, naltrexone is affordable for most patients.  It also has very few side effects and is generally well tolerated. All of that makes naltrexone a winning drug for PMOS management when prescribed off-label.

Prescriptions #2&3 for PMOS/PCOS: Metformin + GLP-1 Agonist

This regimen involves a combination of two medications taken together to complement one another. As you likely know, metformin is a weight-neutral, insulin-sensitizer and first-line therapy for both PMOS and type 2 diabetes. The 2023 International PCOS Guideline recommends metformin in adults with PCOS and a BMI ≥ 25 kg/m², primarily for metabolic indications.[11] Metformin works in many ways, including by reducing gluconeogenesis, improving insulin sensitivity, and activating the nutrient sensor AMPK, which increases glucose uptake by cells.[20]

Metformin has been shown to regulate cycles, reduce secondary effects like facial hair, and even improve conception rates.[6] Whether or not it reduces long-term complications like diabetes is iffy at best—especially without lifestyle changes—and it is notorious for unpleasant GI side effects like gas and bloating. For most, these effects are fleeting, but not for everyone—especially when taken at a higher dose (over 1,000 mg per day). It is affordable at least.

Metformin is even more powerful when combined with a GLP-1 receptor agonist (also known by brand names such Wegovy and Ozempic). The 2023 International PCOS Guideline now recommends that anti-obesity medications, including liraglutide and semaglutide, could be considered in addition to active lifestyle intervention for the management of higher weight in adults with PCOS.[11] A 2025 meta-analysis of 19 RCTs encompassing 1,657 women with PCOS found that the combination of liraglutide and metformin provided superior benefits across multiple metabolic and hormonal domains compared with metformin monotherapy, including significant improvements in fasting and postprandial glucose, insulin resistance, BMI, and key hormonal disturbances such as elevated LH and total testosterone.[9] Another comprehensive meta-analysis of 8 RCTs confirmed that GLP-1 receptor agonists combined with metformin resulted in significant reductions in body weight (mean difference −1.37 kg), BMI (−0.88 kg/m²), waist circumference (−2.46 cm), and fasting glucose, with improvements in HOMA-IR and increases in sex hormone-binding globulin compared to metformin alone.[8]

However, GLP-1 receptor agonists have not been adequately studied in pregnancy and should not be taken during gestation when weight gain is essential. The 2023 International PCOS Guideline specifically advises that healthcare professionals should ensure concurrent effective contraception when pregnancy is possible for women taking GLP-1 receptor agonists, as pregnancy safety data are lacking.[11] GLP-1 agonists also bear an extremely expensive price tag.  Like metformin, GLP-1 agonists also cause nausea. In fact, the nausea and resulting lack of appetite is likely why they are so effective for weight loss.

Prescription #5 for PMOS/PCOS: Desiccated Thyroid Extract