title: Lowering low density lipoprotein cholesterol with simvastatin, a hydroxy-3-methylglutaryl-coenzyme a reductase inhibitor, does not affect luteal function in premenopausal women.
abstract: In this double-blind, randomized, placebo-controlled study, normally cycling women (n = 86) with elevated low density lipoprotein cholesterol (LDL-C) levels were studied over six menstrual cycles. At the end of the screening phase, participants received placebo for the second menstrual cycle and subsequently were randomized to receive either placebo or simvastatin (40 mg/d) for the next four cycles. The second and sixth menstrual cycles were considered baseline and treatment cycles, respectively. Participants kept a menstrual diary throughout the study and provided daily first-void urine samples during cycles 2 and 6. Urine samples were assayed for LH and pregnanediol glucuronide (PdG). The primary end point was change in luteal phase duration as defined by the day of the urinary LH peak to the day preceding the onset of menstruation. Treatment with simvastatin (40 mg/d) effectively lowered LDL-C by 34.3% (P < 0.001). Simvastatin was generally well tolerated, and no meaningful difference in adverse event profile was observed between treatment groups. Compared with the placebo group, simvastatin did not have clinically relevant effects on luteal phase duration, peak PdG concentration, or integrated luteal phase PdG concentration. The results of this study demonstrate that treatment of healthy premenopausal women for approximately 4 months with simvastatin (40 mg/d) lowers LDL-C without adversely affecting reproductive gonadal function. Simvastatin should not be used during pregnancy or by nursing mothers.
authors.affiliation: Department of Clinical Research, Endocrinology and Metabolism, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065-0900, USA. diane_plotkin@merck.com
authors.forename: Diane
authors.initials: D
authors.lastname: Plotkin
authors.forename: Sam
authors.initials: S
authors.lastname: Miller
authors.forename: Steven
authors.initials: S
authors.lastname: Nakajima
authors.forename: Edward
authors.initials: E
authors.lastname: Peskin
authors.forename: Ronald
authors.initials: R
authors.lastname: Burkman
authors.forename: David
authors.initials: D
authors.lastname: Richardson
authors.forename: Yale
authors.initials: Y
authors.lastname: Mitchel
authors.forename: Joanne
authors.initials: J
authors.lastname: Waldstreicher
authors.forename: Minzhi
authors.initials: M
authors.lastname: Liu
authors.forename: Deborah
authors.initials: D
authors.lastname: Shapiro
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
mesh_terms: D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood*; D003338:Corpus Luteum / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008183:Luteal Phase / Q000187:drug effects / Q000652:urine; D007986:Luteinizing Hormone / Q000652:urine; D011276:Pregnanediol / Q000031:analogs & derivatives* / Q000652:urine; D017697:Premenopause / Q000502:physiology*; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; C022270:pregnanediol-3 alpha-glucuronide; D007986:Luteinizing Hormone; D019821:Simvastatin; D011276:Pregnanediol