Resveratrol Reduces Serum Testosterone in Women With PCOS

Resveratrol significantly reduced serum testosterone and dehydroepiandrosterone sulfate (DHEAS) levels by more than 20% within 3 months of treatment in women with polycystic ovary syndrome (PCOS), according to findings from a prospective randomized trial. This is the first trial to evaluate resveratrol as a potential option for managing ovarian and adrenal androgen production in PCOS.

Antoni Duleba, MD, of the University of California in San Diego, CA, presented results from the trial at the Scientific Congress & Expo of the American Society for Reproductive Medicine (ASRM), held October 15 to 19, 2016, in Salt Lake City, UT. The study was nominated for the ASRM Scientific Congress Prize Paper Award.

PCOS is the most common endocrine disorder among women of reproductive age. The condition is characterized by hyperandrogenism, anovulation, ovarian thecal hyperplasia, excessive CYP17A1 expression, insulin resistance, and compensatory hyperinsulinemia.

Resveratrol is a natural polyphenol with antioxidant and anti-inflammatory effects. In preclinical studies, resveratrol inhibits messenger RNA expression of CYP17A1 and lowers androgen production in ovarian theca-interstitial cells. Treatment with resveratrol also improves insulin sensitivity in patients with type 2 diabetes mellitus. In the current trial, researchers tested the hypothesis that resveratrol may ameliorate hyperandrogenism and insulin resistance in women with PCOS.

The study included 34 women diagnosed with PCOS according to Rotterdam criteria, based on the presence of hyperandrogenism, oligomenorrhea, and polycystic ovaries. Patients were randomly assigned to resveratrol 1.5 g/day or placebo. All baseline demographic, endocrine, and metabolic characteristics were similar in both groups. Laboratory evaluations were conducted at baseline and after 3 months of treatment. The primary end point was change in total testosterone level at 3 months.

Resveratrol resulted in a significant 23.1% reduction in total testosterone levels from baseline to 3 months (P = .01; Table). By comparison, total testosterone levels increased from baseline by 2.9% at 3 months in the placebo group (P = .78). The difference in treatment effect between the resveratrol and placebo groups relative to testosterone was statistically significant (P = .04).

Table. Effects of Resveratrol vs Placebo in Women With PCOS

DHEAS = dehydroepiandrosterone sulfate, HDL = high density lipoprotein, PCOS = polycystic ovary syndrome, QUICKI = quantitative insulin sensitivity check index.

In the analysis of secondary end points, hyperandrogenemia appeared to improve with resveratrol. Between baseline and 3 months, DHEAS levels were reduced by 22.2% in the resveratrol group (P = .01), whereas levels increased by 10.5% in the placebo group (P = .08). The difference in treatment effect on DHEAS levels was also statistically significant between the resveratrol and placebo groups (P = .002).

The beneficial effects of resveratrol on adrenal androgen production may be related to the effects of treatment on insulin resistance and hyperinsulinemia. Resveratrol significantly reduced mean fasting insulin levels (P = .007) and significantly improved measures of insulin sensitivity after 3 months. 

Resveratrol had no significant effect on body mass index, ovarian volume, gonadotropins, lipid profile, or markers of inflammation and endothelial function at 3 months.

In summary, resveratrol appears to significantly improve insulin resistance and hyperinsulinemia in patients with PCOS, with beneficial downstream effects on hyperandrogenism. Future research may focus on whether resveratrol also directly affects thecal hyperplasia and CYP17A1 expression in these patients.

Source: Duleba A, Spaczynski RZ, Pawelczyk L, et al. Effects of resveratrol on polycystic ovary syndrome. Presented at: American Society for Reproductive Medicine 2016 Scientific Congress & Expo; October 15-19, 2016; Salt Lake City, UT. Abstract O-92.