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Early Indication That Resveratrol Corrects PCOS Abnormalities

Feb 20, 2017

Supplements of resveratrol may reverse the hyperandrogenemia and hyperinsulinemia associated with polycystic ovary syndrome (PCOS), a new study suggests.

In a small randomized, double-blind trial, women with PCOS who took resveratrol for 3 months had significantly lower total-testosterone (T) and dehydroepiandrosterone-sulfate (DHEAS) levels than women who took a placebo, senior author Antoni J Duleba, MD, and colleagues report in the Journal of Clinical Endocrinology and Metabolism, published online October 18.

The findings suggest that resveratrol has "effects at both the ovarian and adrenal level," without significant changes in body mass index (BMI), lipid profile, or markers of inflammation or endothelial function, they write.

Resveratrol is an antioxidant that occurs naturally in a variety of foods, including peanuts, pistachios, dark chocolate, blueberries, raspberries, and red grapes, and it is thought to contribute to the health benefits of red wine.

However, it may be premature to break out the Bordeaux, Dr Duleba told Medscape Medical News. To obtain the benefits observed in the study, "one would have to drink over 100 bottles of wine per day. Not very practical."

And given the small size of the current study, much larger trials with any supplement will be needed before this can be routinely recommended as a treatment, he noted.

PCOS: Commonest Endocrine Disorder of Reproductive-Age Women

PCOS is the commonest endocrine disorder affecting women of reproductive age and is characterized by hyperplasia of ovarian theca cells, which produce androgens, Dr Duleba, professor and director, division of reproductive endocrinology and infertility, in the department of reproductive medicine, University of California, San Diego School of Medicine, and coauthors write.

There is still no completely satisfactory way to manage the condition: use of antiandrogens and oral contraceptives (OCs) is often considered "clinically unacceptable" because they may cause liver damage and cannot be used in women considering pregnancy.

In an effort to find a better treatment, the authors have been studying the effects of various antioxidants, including resveratrol, in ovarian cell cultures for several years. "We have shown that resveratrol and other antioxidants reduced growth of ovarian theca cells and reduced production of androgens," most likely by inhibiting the expression of one of the enzymes involved in steroidogenesis, Dr Duleba said in an interview.

Based on these observations, he and his colleagues hypothesized that resveratrol might relieve the hyperandrogenism seen in patients with PCOS.

They initially enrolled 34 women with PCOS as defined by the Rotterdam consensus. Each patient had at least two of these criteria: clinical or chemical hyperandrogenism; oligo- or amenorrhea; or polycystic ovaries as shown on transvaginal ultrasonography.

During the 3 months prior to the study they had not used oral contraceptives, other steroid hormones, or any other treatment that might affect ovarian function, insulin sensitivity, or lipid profile.

All of the women were recruited between December 2013 and March 2015. They were randomly assigned to take an oral supplement of micronized trans resveratrol at a dose of 1500 mg/day (RevGenetics) or a placebo for 3 months.

The mean age of the women in both groups was 26.8 years. At baseline, they did not differ significantly with respect to BMI, levels of T, DHEAS, fasting insulin, or fasting glucose. Women in the resveratrol group had a mean total cholesterol of 200.1 mg/dL, compared with 169.1 mg/dL among women in the placebo group (P = .01).

The primary end point was change in total T. Patients and investigators were blinded as to each woman's treatment group. Over the course of the study, two women in the resveratrol group and one in the placebo group were lost to follow-up, and one woman in the placebo group became pregnant. The final analysis included 15 women in each group.

Resveratrol Improves Testosterone, DHEAS, and Insulin Metabolism

Women in the resveratrol group experienced a 23.1% decrease in mean serum total T, from 0.53 ng/mL at baseline to 0.41 ng/ml after 3 months of treatment (P = .01). Among women in the placebo group, total T was 0.48 ng/mL at baseline and 0.49 ng/mL after 3 months (P = .78). Similarly, mean DHEAS went from 8.05 μmol/L at baseline among women taking resveratrol to 6.26 μmol/L after 3 months, a reduction of 22.2% (P = .01). Among women in the placebo group, mean DHEAS was 8.08 μmol/L at baseline and 8.90 μmol/L after 3 months (P = .08).

There was no significant decline in cholesterol levels in the resveratrol group; however, in the placebo group, cholesterol levels increased, so the authors speculate that resveratrol may have prevented an increase that would otherwise have occurred.

Use of resveratrol was associated with a beneficial change in insulin metabolism. At baseline, mean fasting insulin among women in the resveratrol group was 14.5 μU/mL, compared with 9.8 μU/mL at 3 months, a 31.8% decrease (P = .007). In the placebo group, it remained unchanged, from a mean of 13.8 μU/mL at baseline to 13.8 μU/mL at 3 months (P = 1.00). The insulin-sensitivity index increased by 66.3%, from a mean of 3.11 at baseline to 5.12 after 3 months with resveratrol (P = .04), compared with 3.57 at baseline to 3.98 at 3 months in the placebo group (P = .45). Fasting glucose, however, did not change significantly in either group.

"The magnitude of improvement of hyperandrogenemia observed in response to resveratrol is comparable to or greater than that found in response to oral contraceptive pills or metformin, with the exception of preparations containing cypretorone acetate, which are not available in the United States," the authors write.

In a press release about the study, Dr Duleba said that these findings "suggest resveratrol can improve the body's ability to use insulin and potentially lower the risk of developing diabetes. The supplement may be able to help reduce the risk of metabolic problems common in women with PCOS."

However, he told Medscape Medical News, "We need more and larger studies on various doses of resveratrol before we can recommend routine clinical use." Larger trials are, he said, "being considered."


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