Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 8687515 · doi:10.1056/NEJM199608293350902
What was done
Twenty-four obese women with polycystic ovary syndrome were randomized to receive either oral metformin (500 mg three times daily) or placebo for four to eight weeks. Investigators evaluated oral glucose-tolerance tests, fasting serum steroid levels, basal luteinizing hormone, sex hormone-binding globulin, and the response of serum 17 alpha-hydroxyprogesterone to leuprolide before and after treatment.
What was found
In the 11 women who received metformin, the mean area under the serum insulin curve during oral glucose administration decreased from 9303 +/- 1603 to 4982 +/- 911 microU/mL/min (P = 0.004). Basal serum 17 alpha-hydroxyprogesterone decreased from 135 +/- 21 to 66 +/- 7 ng/dL (P = 0.01), and leuprolide-stimulated peak 17 alpha-hydroxyprogesterone decreased from 455 +/- 54 to 281 +/- 52 ng/dL (P = 0.01). Basal serum luteinizing hormone decreased from 8.5 +/- 2.2 to 2.8 +/- 0.5 mIU/mL (P = 0.01), serum free testosterone decreased from 0.34 +/- 0.07 to 0.19 +/- 0.05 ng/dL (P = 0.009), and serum sex hormone-binding globulin increased from 0.8 +/- 0.2 to 2.3 +/- 0.6 microgram/dL (P < 0.001). Values increased slightly or did not change significantly in the placebo group.
Why it matters
This study provides evidence that hyperinsulinemia directly stimulates ovarian cytochrome P450c17alpha activity in polycystic ovary syndrome. It shows that reducing insulin with metformin decreases androgen production and circulating free testosterone.
Limits
The sample size is very small, with only 24 total participants and 11 receiving metformin. The trial duration was short (four to eight weeks) and restricted to obese women with polycystic ovary syndrome. Clinical endpoints such as ovulatory frequency, hirsutism progression, or pregnancy rates were not reported.
Cited by
- supports Sex hormone-binding globulin (SHBG) levels increase when insulin levels decrease.