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Clinical pearls:
- Resveratrol in a dose of 1500 mg/day
reduced the levels of Testosterone and DHES by 23.1% and 22.1% in a small pilot
study of patients with PCOS.
- It also improved the insulin
resistance and decreased serum insulin levels significantly.
Polycystic ovary syndrome (PCOS) is a
complex endocrine disorder and affects 1 in 15 women worldwide with less than 50% of women diagnosed. [1] It
is responsible for 70 percent of infertility issues in women who have
difficulty ovulating, per the PCOS Foundation.[2] It
has been recognized and diagnosed for 75 years. Genetic and environmental factors
play a part in its causation, but the exact etiology remains unknown.
It has a multifactorial etiology that
involves genetic, environmental and hormonal imbalance. Androgen excess is
clearly the culprit but insulin resistance also plays a major role in its
causation.
Although large number of women with obesity have PCOS, not all obese
women have PCOS. Apart from infertility, PCOS is responsible for many chronic
conditions. As per NIH, women with PCOS constitute the largest group at risk
for developing CVD and Type 2 DM. More than half will be diagnosed with
prediabetic or diabetic before the age of 40 years. [3]
Treatment is currently directed at
symptoms rather than treating the pathophysiology which remains largely
unknown. Lifestyle modification, weight loss and metformin have all shown to
decrease androgen, improve insulin sensitivity and bring about ovulation.
Resveratrol is an antioxidant compound
found in many foods like dark chocolate, blueberries, raspberries, including
peanuts and pistachio beside grapes and red wine. It is known to have anti-inflammatory and anti-proliferative
property well known to cause
apoptosis in cancer cells.
In 2010 a
study by researchers at University of California School of Medicine, Department
of Gynecology and Obstetrics, showed that in-vitro animal studies
resveratrol could counteract the negative effect of insulin on ovarian cells
and preventing excess proliferation of the theca interstitial ovarian cells.
The recent study is a randomized,
double-blind, placebo-controlled trial that evaluated the effects of resveratrol
over a period of 3 months at Department of Reproductive Medicine, University of
California, San Diego, La Jolla, CA.
The study included 34 patients diagnosed
with PCOS as per the Rotterdam criteria,[4] each having at least 2 of the following three clinical
or chemical hyperandrogenism; oligo- or amenorrhea; and/or polycystic ovaries
as viewed by transvaginal ultrasound.
All study participants were evaluated at
baseline and after 3 months for BMI, hirsutism, acne score, Insulin levels, OGTT
and other metabolic and endocrine abnormalities.
Participants were then randomly
assigned to receive either placebo or 1500 mg/day of oral micronized transresveratrol.
Over the course of the studies 3 women were lost to follow-up and one became pregnant,
so the final analysis includes 15 women in each arm.
The primary endpoint of the study was changes
in testosterone levels (T).
It was seen that resveratrol was
significantly effective in bringing down the serum testosterone levels in the
study group. Women on resveratrol experienced an average of 23.1% decline of
total T levels (.53 ng/mL at baseline to 0.41 ng/ml) which was significantly
more than what was observed by use of OC pills and metformin (19%) over a 12-month period.[5] For
women in placebo group no change in T levels was seen. Similarly, serum DHES
levels decreased by 22.1% for women taking resveratrol (8.05 μmol/L at baseline
to 6.26 μmol/L after 3 months).
Resveratrol also decreased the serum
fasting insulin levels and exert a positive increase in Insulin Sensitivity
Index of by 66%.
“It is apparent that resveratrol
significantly reduces serum levels of T and DHEAS, suggesting an effect on
ovarian as well as adrenal androgen production” the authors quoted.
In a press releases accompanying the
article, the study’s senior author Dr. Antoni J. Duleba said “Our study is the first clinical trial
to find resveratrol significantly lowers PCOS patients’ levels of testosterone
as well as dehydroepiandrosterone sulfate (DHEAS), another hormone that the body
can convert into testosterone. This nutritional supplement can help moderate
the hormone imbalance that is one of the central features of PCOS.”
He also
stated the need for more studies before a recommendation can be made for its
use in clinical practice.
The authors reported having no
relevant conflicts of interest.
[1] http://www.pcosfoundation.org/what-is-pcos
[2] http://www.pcosfoundation.org/about-pcos
[3] https://prevention.nih.gov/docs/programs/pcos/FinalReport.pdf
[4] Rotterdam
ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on
diagnostic criteria and long-term health risks related to polycystic ovary
syndrome (PCOS). Hum Reprod. 2004;19:41– 47
[5] Glintborg
D, Altinok ML, Mumm H, Hermann AP, Ravn P, Andersen M. Body composition is
improved during 12 months’ treatment with metformin alone or combined with oral
contraceptives compared with treatment with oral contraceptives in polycystic
ovary syndrome. J Clin Endocrinol Metab. 2014;99:2584 –2591
