The effect of statins on semen parameters in patients with hypercholesterolemia: A systematic review

Anagnostis, Panagiotis; Papanikolaou, Dimitrios; Ioannidou, Pinelopi; Bosdou, Julia K.; Mikhailidis, Dimitri P.; Hatzimouratidis, Konstantinos; Goulis, Dimitrios G.

doi:10.1111/andr.13039

Cited by 3 publications

(1 citation statement)

References 39 publications

(118 reference statements)

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“…For steroidogenesis to occur, the Leydig cells can absorb cholesterol from the blood via low density lipoprotein-receptors and are also capable of de novo cholesterol synthesis. Upon the initiation of statin metabolism, there is a decrease in the circulating LDL-cholesterol and the total amount of cholesterol transported to the Leydig cells is reduced [ 77 ]. However, the reduction in the amount of cholesterol transported to the Leydig cells does not necessarily infer impaired steroidogenesis.…”

Section: Mechanisms Through Which Statins May Impact Male Reproductionmentioning

confidence: 99%

Statins and Male Fertility: Is There a Cause for Concern?

Omolaoye

Halabi

Mubarak

et al. 2022

Toxics

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The well-known 3-hydroxyl 3-methyl glutaryl-Coenzyme A reductase inhibitors, called statins, have been the main medication used in the treatment of hypercholesterolemia and some cases of cardiovascular diseases. The effectiveness of this drug in controlling cholesterol production is impeccable, however, patients often complain of a variety of side effects, such as myalgia, muscle atrophy, and in some cases, rhabdomyolysis. Not only has the use of statins caused the aforementioned side effects, but they are also shown to cause testicular discomfort, erectile dysfunction, altered semen parameters, and modified steroid hormone production. These reported adverse effects on male fertility are not generally agreed upon, as some have shown the use to be beneficial. Hence, this makes the aftermath effect of statin use on male fertility debatable and controversial. The negative effects have been associated with imbalanced or reduced steroid hormones, which are necessary for proper spermatogenesis and other sexual functions. Meanwhile, the beneficial effects are related to statin’s anti-inflammatory and cardioprotective properties. These contradictory findings are in part due to the different age of users, concentrations of statins, the type and duration of treatment, and the underlying disease and/or comorbidities. Therefore, the current study aims to analyze the literature and gather evidence as to the effects of statin on male sexual health and reproductive parameters, and subsequently give recommendations for the direction of future studies.

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Section: Mechanisms Through Which Statins May Impact Male Reproductionmentioning

confidence: 99%

Statins and Male Fertility: Is There a Cause for Concern?

Omolaoye

Halabi

Mubarak

et al. 2022

Toxics

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A pharmacovigilance study of drug‐reduced male semen quality based on the Food and Drug Administration adverse event reporting system database

Tan,

Luo,

et al. 2024

Andrology

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BackgroundReal‐world big data studies on drug‐reduced male semen quality are few and far between, with most studies based on animal trials, small scale retrospective studies, or a limited number of pre‐market clinical trials.MethodsThis study aimed to identify culprit drugs that reduced male semen quality based on the United States Food and Drug Administration adverse event reporting system. The Medical Dictionary for Regulatory Activities preferred terms and standardized Medical Dictionary for Regulatory Activities queries were used to define reduced male semen quality. Adverse events related to drug‐reduced male semen quality were then analyzed by disproportionality analysis using the United States Food and Drug Administration adverse event reporting system data between 2004 and 2023.ResultsAt the preferred term level, 59 drugs with risk signals were detected to be associated with drug‐reduced male semen quality, with the three most frequently reported second‐level Anatomical Therapeutic Chemical groups being antineoplastic agents (n = 16, 27.12%), psychoanaleptics (n = 9, 15.25%), and psycholeptics (n = 6, 10.17%). At the standardized Medical Dictionary for Regulatory Activities queries level, the five drugs with the greatest number of cases were finasteride (845 cases, IC025 = 7.72), dutasteride (163 cases, IC025 = 7.22), tamsulosin (148 cases, IC025 = 5.99), testosterone (101 cases, IC025 = 4.08), and valproic acid (54 cases, IC025 = 2.44). Additionally, clinical information about drug‐reduced male semen quality is absent from the Summary of Product Characteristics of 41 drugs in our study.ConclusionsUsing the United States Food and Drug Administration adverse event reporting system database, we offer a list of drugs with risk signals for reducing male semen quality. In the future, there is still a need for more studies on drugs whose effects on male semen quality are not fully understood.

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Lipids, lipid-modified drug target genes, and the risk of male infertility: a Mendelian randomization study

Li,

Zha

et al. 2024

Front. Endocrinol.

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BackgroundPrevious observational studies have reported a possible association between circulating lipids and lipid-lowering drugs and male infertility (MIF), as well as the mediating role of circulating vitamin D. Then, due to issues such as bias, reverse causality, and residual confounding, inferring causal relationships from these studies may be challenging. Therefore, this study aims to explore the effects of circulating lipids and lipid-lowering drugs on MIF through Mendelian randomization (MR) analysis and evaluate the mediating role of vitamin D.MethodGenetic variations related to lipid traits and the lipid-lowering effect of lipid modification targets are extracted from the Global Alliance for Lipid Genetics Genome-Wide Association Study. The summary statistics for MIF are from the FinnGen 9th edition. Using quantitative expression feature loci data from relevant organizations to obtain genetic variations related to gene expression level, further to explore the relationship between these target gene expression levels and MIF risk. Two-step MR analysis is used to explore the mediating role of vitamin D. Multiple sensitivity analysis methods (co-localization analysis, Egger intercept test, Cochrane’s Q test, pleiotropy residuals and outliers (MR-PRESSO), and the leave-one-out method) are used to demonstrate the reliability of our results.ResultIn our study, we observed that lipid modification of four lipid-lowering drug targets was associated with MIF risk, the LDLR activator (equivalent to a 1-SD decrease in LDL-C) (OR=1.94, 95% CI 1.14-3.28, FDR=0.040), LPL activator (equivalent to a 1-SD decrease in TG) (OR=1.86, 95% CI 1.25-2.76, FDR=0.022), and CETP inhibitor (equivalent to a 1-SD increase in HDL-C) (OR=1.28, 95% CI 1.07-1.53, FDR=0.035) were associated with a higher risk of MIF. The HMGCR inhibitor (equivalent to a 1-SD decrease in LDL-C) was associated with a lower risk of MIF (OR=0.38, 95% CI 0.17-0.83, FDR=0.39). Lipid-modifying effects of three targets were partially mediated by serum vitamin D levels. Mediation was 0.035 (LDLR activator), 0.012 (LPL activator), and 0.030 (CETP inhibitor), with mediation ratios of 5.34% (LDLR activator), 1.94% (LPL activator), and 12.2% (CETP inhibitor), respectively. In addition, there was no evidence that lipid properties and lipid modification effects of six other lipid-lowering drug targets were associated with MIF risk. Multiple sensitivity analysis methods revealed insignificant evidence of bias arising from pleiotropy or genetic confounding.ConclusionThis study did not support lipid traits (LDL-C, HDL-C, TG, Apo-A1, and Apo-B) as pathogenic risk factors for MIF. It emphasized that LPL, LDLR, CETP, and HMGCR were promising drug targets for improving male fertility.

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The effect of statins on semen parameters in patients with hypercholesterolemia: A systematic review

Cited by 3 publications

References 39 publications

Statins and Male Fertility: Is There a Cause for Concern?

Statins and Male Fertility: Is There a Cause for Concern?

A pharmacovigilance study of drug‐reduced male semen quality based on the Food and Drug Administration adverse event reporting system database

Lipids, lipid-modified drug target genes, and the risk of male infertility: a Mendelian randomization study

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