Effects of simvastatin and oral contraceptive agent on polycystic ovary syndrome: prospective, randomized, crossover trial.
BACKGROUND
Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and cardiovascular risks including dyslipidemia and systemic inflammation. In vitro, statins decrease proliferation and steroidogenesis of ovarian theca-interstitial cells.


OBJECTIVE
The study objective was to compare effects of two treatments of PCOS: simvastatin plus oral contraceptive pill (OCP) vs. OCP alone.


METHODS
In a prospective, crossover trial, 48 women with PCOS were randomized to either simvastatin plus OCP for 12 wk followed by OCP alone for an additional 12 wk, or to OCP alone for 12 wk and, subsequently, simvastatin plus OCP for an additional 12 wk. Evaluations were performed at baseline, after 12 wk (crossover), and after 24 wk. Data were analyzed using a random effects model.


METHODS
The study was conducted in an academic medical center.


METHODS
Serum total testosterone was the primary outcome measure.


RESULTS
Total testosterone decreased by 38% after Statin + OCP, whereas OCP alone led to a 26% decrease; the statin-attributable effect was significant (P < 0.004). Free testosterone declined by 58% after Statin + OCP, significantly more than the 35% decline after OCP alone (P = 0.006). Hirsutism decreased by 8.1% after Statin + OCP, a greater effect than the 4.7% decrease after OCP alone (P = 0.02). Statin decreased LH, but not FSH or prolactin. Statin + OCP decreased total and low-density lipoprotein cholesterol by 7.5% and 20%, respectively. OCP alone led to a 5% increase of total cholesterol without effect on low-density lipoprotein cholesterol. Statin prevented OCP induced increase of triglycerides. C-reactive protein decreased by 45% after Statin + OCP, a significantly different effect (P = 0.006) than a 6% increase after OCP alone. Soluble vascular cell adhesion molecule 1 decreased by 18% after Statin + OCP, a greater decline than the 10% decrease after OCP alone (P = 0.01).


CONCLUSIONS
Simvastatin improved endocrine/clinical aspects of PCOS and had beneficial effects on lipid profile and markers of systemic inflammation.
Banaszewska
Beata
B
Department of Gynecology/Obstetrics, Poznan University of Medical Sciences, Poznan, Poland.
Pawelczyk
Leszek
L
Spaczynski
Robert Z
RZ
Dziura
James
J
Duleba
Antoni J
AJ
D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage*; D018592:Cross-Over Studies; D017135:Desogestrel / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000008:administration & dosage; D004997:Ethinyl Estradiol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D010907:Pituitary Hormones / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage*; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
D003277:Contraceptives, Oral, Combined; D004967:Estrogens; D000960:Hypolipidemic Agents; D010907:Pituitary Hormones; D013739:Testosterone; D004997:Ethinyl Estradiol; D017135:Desogestrel; D019821:Simvastatin