Effects of Metformin Plus Simvastatin on Polycystic Ovarian Syndrome (PCOS): A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

Summary

Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting 6.5%-6.7% of women in reproductive age, and is commonly associated with obesity, menstrual irregularity, insulin resistance (IR), infertility, and clinical hyperandrogenism and/or hyperandrogenemia (1,2). PCOS is also associated with increased risk of abnormal lipoproteins and hypertension, as well as cardiovascular or cerebrovascular morbidity (3). The lipid and lipoprotein profile in androgenized women with poly cystic ovaries is similar to the made pattern with higher levels of cholesterol, low-density lipoprotein (LDL), and lower levels of high-density lipoprotein (HDL), and this abnormal pattern is independent of body weight (4). Insulin resistance is associated with reproductive abnormalities in women with PCOS. Improving insulin sensitivity through both lifestyle and pharmacological intervention can ameliorate these abnormalities. Insulin resistance in women with PCOS is common (up to 50%), both in obese and nonobese women (5), and disordered insulin action precedes the increase in androgen.

Treatment for PCOS subjects typically includes, implementation of lifestyle changes especially weight loss and adjuvant pharmaceutical intervention including oral contraceptives, anti-androgen therapy and insulin-lowering drugs (such as, metformin) (6). Metformin is a biguanide used extensively in type 2 diabetes. It inhibits hepatic glucose production and increases peripheral insulin sensitivity, but dose not cause hypoglycemia. Several studies have shown an increase in insulin sensitivity and pregnancy rate accompanied by decreased insulin and androgen levels in PCOS patients taking metformin (7).

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase inhibitors (statins) are the rate-limiting step in cholesterol biosynthesis, and inhibition of this enzyme decreases cholesterol synthesis and a compensatory increase in the expression of LDL receptors in the liver. Statins reduce plasma triglycerides in dose-dependent fashion and also have a modest HDL-raising effect which is not dose-dependent (8,9). Furthermore, statins pose other cardio-protective properties, including antioxidant and anti-inflammatory actions (10,11).

Some studies have reported that simvastatin decreases serum androgen levels in women with PCOS (12,13) by inhibiting proliferation and steroidogenesis of ovarian theca-interstitial cells (14). According to these previous findings, we hypothesized that combination therapy with simvastatin and metformin will result in lower androgen levels and cardiovascular risk factors in women with PCOS.

Conditions

• Polycystic Ovary Syndrome

Interventions

DRUG

Metformin plus Placebo

PCOS patients(n=42) will be assigned to the placebo (once/day) plus metformin (500mg three times a day, n=42; group 2)

DRUG

Metfomin plus Simvastatin

Sponsors & Collaborators

• Shiraz University of Medical Sciences

  collaborator OTHER

• Fasa University of Medical Sciences

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

16 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-01-31

Primary Completion

2009-03-31

Completion

2009-11-30

Countries

• Iran

Study Locations