title: Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial.
abstract: BACKGROUND
  Recommendations for cardiovascular disease prevention advocate lowering both cholesterol and low-density lipoprotein cholesterol systemic levels, notably by statin intake. However, statins are the subject of questions concerning their impact on male fertility. This study aimed to evaluate, by a prospective pilot assay, the efficacy and the toxicity of a decrease of cholesterol blood levels, induced by atorvastatin on semen quality and sexual hormone levels of healthy, normocholesterolaemic and normozoospermic men.
  
  
  METHODS
  Atorvastatin (10 mg daily) was administrated orally during 5 months to 17 men with normal plasma lipid and standard semen parameters. Spermatozoa parameters, accessory gland markers, semen lipid levels and blood levels of gonadal hormones were assayed before statin intake, during the treatment, and 3 months after its withdrawal.
  
  
  RESULTS
  Atorvastatin treatment significantly decreased circulating low-density lipoprotein cholesterol (LDL-C) and total cholesterol concentrations by 42% and 24% (p<0.0001) respectively, and reached the efficacy objective of the protocol. During atorvastatin therapy and/or 3 months after its withdrawal numerous semen parameters were significantly modified, such as total number of spermatozoa (-31%, p<0.05), vitality (-9.5%, p<0.05), total motility (+7.5%, p<0.05), morphology (head, neck and midpiece abnormalities, p<0.05), and the kinetics of acrosome reaction (p<0.05). Seminal concentrations of acid phosphatases (p<0.01), α-glucosidase (p<0.05) and L-carnitine (p<0.05) were also decreased during the therapy, indicating an alteration of prostatic and epididymal functions. Moreover, we measured at least one altered semen parameter in 35% of the subjects during atorvastatin treatment, and in 65% of the subjects after withdrawal, which led us to consider that atorvastatin is unsafe in the context of our study.
  
  
  CONCLUSIONS
  Our results show for the first time that atorvastatin significantly affects the sperm parameters and the seminal fluid composition of healthy men.
authors.affiliation: CHU Clermont Ferrand, Laboratoire de BDR: AMP-CECOS, F-63003 Clermont-Ferrand, France. hpons-rejraji@chu-clermontferrand.fr.
authors.forename: Hanae
authors.initials: H
authors.lastname: Pons-Rejraji
authors.forename: Florence
authors.initials: F
authors.lastname: Brugnon
authors.forename: Benoit
authors.initials: B
authors.lastname: Sion
authors.forename: Salwan
authors.initials: S
authors.lastname: Maqdasy
authors.forename: Gerald
authors.initials: G
authors.lastname: Gouby
authors.forename: Bruno
authors.initials: B
authors.lastname: Pereira
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Marceau
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gremeau
authors.forename: Joel
authors.initials: J
authors.lastname: Drevet
authors.forename: Genevieve
authors.initials: G
authors.lastname: Grizard
authors.forename: Laurent
authors.initials: L
authors.lastname: Janny
authors.forename: Igor
authors.initials: I
authors.lastname: Tauveron
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects; D000328:Adult; D000988:Antispermatogenic Agents / Q000009:adverse effects* / Q000494:pharmacology; D053627:Asthenozoospermia / Q000139:chemically induced / Q000473:pathology; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D004822:Epididymis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D042341:Gonadal Hormones / Q000097:blood / Q000378:metabolism; D006538:Heptanoic Acids / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D010865:Pilot Projects; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011758:Pyrroles / Q000009:adverse effects* / Q000494:pharmacology; D012661:Semen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D000988:Antispermatogenic Agents; D015415:Biomarkers; D042341:Gonadal Hormones; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin