NCT01021579

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

Completed Phase 4 Last updated 27 November 2009

What this trial tests

Phase 4 trial testing Metformin plus Placebo in Polycystic Ovary Syndrome in 84 participants. Completed in 1 November 2009.

Timeline

1 January 2008

Primary endpoint
1 March 2009

1 November 2009

Quick facts

Lead sponsor	Fasa University of Medical Sciences
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	84
Start date	1 January 2008
Primary completion	1 March 2009
Estimated completion	1 November 2009
Sites	1 location across Iran

Drugs / interventions tested

• Metformin plus Placebo — full drug profile →
• Metfomin plus Simvastatin — full drug profile →

Conditions studied

• Polycystic Ovary Syndrome — all drugs for Polycystic Ovary Syndrome →

Sponsor

Fasa University of Medical Sciences

Who can join

Adults 16 to 45, female only, with Polycystic Ovary Syndrome. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Serum total testosterone
  Time frame: 6 weeks

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.