AT 2016 ASRM

SALT LAKE CITY (FRONTLINE MEDICAL NEWS)Resveratrol significantly decreased androgen levels and insulin resistance among women with polycystic ovary syndrome (PCOS), according to a first-in-kind randomized, double-blind placebo-controlled trial of 30 patients.

After 3 months of daily oral treatment with 1.5 g of the antioxidant polyphenol, testosterone levels fell an average of 23%, dehydroepiandrosterone sulfate (DHEAS) levels dropped 22%, fasting insulin levels decreased by 32%, and insulin sensitivity improved by 66%, Antoni Duleba, MD, said at the annual meeting of the American Society for Reproductive Medicine. No such improvements occurred in the placebo group, he and his coinvestigators reported simultaneously in the Journal of Clinical Endocrinology & Metabolism ( doi: 10.1210/jc.2016-1858 ).

Resveratrol is derived from certain plant products, most famously red wine grapes, but “depending on whether it is a Tuscan wine, or a Malbec from Argentina, it would take anywhere from 100-200 L of red wine a day to achieve the effect we found in this study,” noted Dr. Duleba of the University of California, San Diego.

Past work has found that resveratrol inhibits mRNA expression of Cyp17a1 and reduces androgen production by ovarian theca-interstitial cells. To build on those findings, Dr. Duleba worked with researchers at Poznan (Poland) University of Medical Sciences to enroll 30 women with PCOS based on the Rotterdam criteria. Treatment and placebo groups resembled each other at baseline in terms of age, body mass index, androgen levels, lipid profiles, and levels of follicle-stimulating hormone, luteinizing hormone, prolactin, sex hormone–binding globulin, fasting glucose, and insulin, as well as scores on an insulin sensitivity index.

For the primary outcome measure – total testosterone level – the resveratrol group averaged 0.53 ng/mL at baseline and 0.41 ng/mL at 3-month follow-up, a statistically significant decrease (P = .01). In contrast, testosterone levels in the placebo group remained essentially unchanged, averaging 0.48 ng/mL at baseline and 0.49 ng/mL at follow-up. The difference in effect between the resveratrol and placebo groups was statistically significant (P = .04).

Similarly, average DHEAS levels dropped from 8.1 to 6.3 micromol/L in the resveratrol group (a 22% decline), but increased by 10% in the placebo group.

Resveratrol did not significantly affect progesterone levels, which is consistent with prior findings, Dr. Duleba said. Nor was resveratrol associated with significant changes in body mass index, lipid profile, markers of inflammation or endothelial function, ovarian volume, or gonadotropins.

“We were disappointed that we didn’t see gross changes in ovarian morphology on ultrasound,” he added. Whether those changes might occur with longer treatment is unknown, but for now, “we can only be sure of declining androgen and insulin levels, and improvements in insulin sensitivity.”

The study won a Scientific Congress Prize from ASRM.

RevGenetics provided the resveratrol for the study. Dr. Duleba reported having no relevant financial disclosures.