Do 5α-Reductase Inhibitors Raise Circulating Serum Testosterone Levels? A Comprehensive Review and Meta-Analysis to Explaining Paradoxical Results

Abstract

Introduction: Many studies have reported that 5α-reductase inhibitors (finasteride and dutasteride) raise serum testosterone (T) levels, yet there is lack of consistency among studies on this point.

Aim: To review and meta-analyze available studies reporting changes in serum T concentrations in men treated with 5α-reductase inhibitors (5α-RIs).

Methods: A Medline search using PubMed and EMBASE was performed including the following key words: "finasteride," "dutasteride," "testosterone and 5α-reductases."

Main outcome measure: Relevant studies were extracted, evaluated, and analyzed. Of these, 40 studies were analyzed qualitatively and 11 were included in the meta-analysis. A random effects model was used to conduct the meta-analysis.

Results: In 11 studies comprising 1,784 patients with age ranging between 18 and 83 years and average treatment follow-up of 17 months, meta-analytic estimate of the mean baseline change was 27 (95% confidence interval 1-54). The meta-analysis did not demonstrate unequivocal significant increase in serum T levels. The increase was not uniform among all studies reported. Sensitivity analysis showed that no single study contributed decisively to the outcome or could be attributed to drug action. The reported increases in T levels with finasteride or dutasteride in men with low baseline serum T may be attributed, in part, to increased trapping of T by unsaturated sex hormone binding globulin (SHBG) due to dissociation of 5α-dihydrotestosterone. In men with high baseline T levels, there appears to be no change in serum T levels. 10 studies reported luteinizing hormone, follicle-stimulating hormone, SHBG, and estradiol values and none reported significant changes in their levels, suggesting that observed changes in serum T levels are unlikely mediated by gonadotropins levels or peripheral conversion of T to estradiol.

Conclusion: 5α-RI therapy is not associated with consistent and significant increases in serum T levels. Traish AM, Krakowsky Y, Doros G, et al. Do 5α-reductase inhibitors raise circulating serum testosterone levels? A comprehensive review and meta-analysis to explaining paradoxical results. Sex Med Rev 2019;7:95-114.

Keywords: 5α-Dihydrotestosterone; Dutasteride; Finasteride; Follicle-Stimulating Hormone; Luteinizing Hormone; Testosterone.