MONTREAL — The addition of simvastatin to an oral contraceptive regimen significantly reduces hirsutism and elevated levels of total testosterone in women with polycystic ovary syndrome, according to a study conducted by Dr. Antoni J. Duleba of Yale University, New Haven, Conn., and associates.
“This is the first report that simvastatin improves a clinical end point of polycystic ovary syndrome/hirsutism,” Dr. Duleba, the lead investigator, said in an interview.
The data were presented by another investigator in the study, Dr. Beata Banaszewska, at the conjoint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.
Oral contraceptives “do reduce testosterone levels, but in this crossover study, we can appreciate that statins have a greater power to this effect,” said Dr. Banaszewska, of Poznan University of Medical Sciences in Poland.
PCOS affects 5%–10% of women of childbearing age, according to Dr. Duleba. Estimates of the annual cost of evaluation and care in the United States are about $4 billion. “Symptomatic treatments partly improve the situation, and long term, these patients are at increased risk of cardiovascular problems.”
The study randomized 48 PCOS patients (mean age 24 years) into two groups. One received oral contraceptives (OC) (20-mcg ethinyl estradiol and 150-mcg desogestrel) for 12 weeks. Then 20-mg simvastatin was added to their regimen daily for 12 more weeks.
The other group received the combined regimen for 12 weeks then was given OCs alone for 12 weeks. Clinical, endocrine, and metabolic evaluations were performed at baseline, at crossover (12 weeks), and at 24 weeks.
“Simvastatin decreased total testosterone by 18% below the effect of OCs,” Dr. Duleba said. “This effect was paralleled by a 16% decrease of free testosterone below the effect of OCs. We also found that the hirsutism declined, and there was a strong trend toward an improvement in acne, which did not reach statistical significance.”
A simvastatin-attributable decline of hirsutism was modestly but significantly greater than with OC alone; this 4% difference was statistically significant. “Patients were happy. … They did not want to stop therapy,” Dr. Duleba said.
“In PCOS, there is an abnormal hypothalamic-pituitary function characterized by elevated LH. It's usually measured by the ratio of LH to FSH, and we observed that statins also improved this ratio,” he added. Simvastatin, in comparison with OCs, decreased LH by 24% and the LH-FSH ratio by 22%.
Furthermore, simvastatin (as compared with OCs) decreased total cholesterol by 12%, LDL cholesterol by 21%, and triglycerides by 18%—preventing the OC-induced rise in triglycerides.
“So the statin not only normalized androgens, it also normalized hypothalamic-pituitary function. And of course, the statin improved lipid profiles,” Dr. Duleba said.
BMI was not significantly affected.
Kate Johnson contributed to this report.
'The statin not only normalized androgens, it also normalized hypothalamic-pituitary function.' DR. DULEBA