Journal Article

Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial

Janny, Laurent, Pereira, Bruno, Pons-Rejraji, Hanae, Marceau, Geoffroy, Grizard, Genevieve, Sion, Benoit, Gremeau, Anne-Sophie, Tauveron, Igor, Maqdasy, Salwan, Gouby, Gerald, Brugnon, Florence, Drevet, Joel

2014

Overview

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. Trial registration ClinicalTrials.gov: NCT02094313 .

• Publisher: BioMed Central,BioMed Central Ltd
• Subject: Acrosome Reaction - drug effects / Adult / Animal biology / Antispermatogenic Agents - adverse effects / Antispermatogenic Agents - pharmacology / Asthenozoospermia - chemically induced / Asthenozoospermia - pathology / Atorvastatin Calcium / Biomarkers - blood / Cellular Biology / Cholesterol / Cholesterol - blood / Development Biology / Down-Regulation - drug effects / Drug therapy / Endocrinology / Endocrinology and metabolism / Epididymis - cytology / Epididymis - drug effects / Epididymis - pathology / Epididymis - secretion / Gonadal Hormones - blood / Gonadal Hormones - secretion / Gynecology and obstetrics / Heptanoic Acids - adverse effects / Heptanoic Acids - pharmacology / Human health and pathology / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects / Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology / Levocarnitine / Life Sciences / Male / Medicine / Medicine & Public Health / Men / Metabolic disorders / Mortality / Phosphatases / Pilot Projects / Prostate - cytology / Prostate - drug effects / Prostate - pathology / Prostate - secretion / Pyrroles - adverse effects / Pyrroles - pharmacology / Reproductive Biology / Reproductive Medicine / Semen - chemistry / Semen - drug effects / Semen - secretion / Spermatogenesis - drug effects / Spermatozoa - cytology / Spermatozoa - drug effects / Spermatozoa - pathology / Testis - cytology / Testis - drug effects / Testis - pathology / Testis - secretion / Young Adult