Efficacy and safety of letrozole or anastrozole in the treatment of male infertility with low testosterone‐estradiol ratio: A meta‐analysis and systematic review

Abstract

Background: Aromatase inhibitors (AIs) have been used to treat male infertility for decades. However, due to the lack of large-scale randomized controlled studies and basic research, the efficacy and safety of AIs in the treatment of male infertility remain controversial. Therefore, it is necessary to conduct an evidence-based preliminary evaluation of the existing clinical trials of AIs in the treatment of male infertility. Method: A comprehensive literature search was performed in the PubMed, Embase, Cochrane, CNKI, VIP, CBM, and Wanfang databases through August 2021 for all studies. We conducted a systematic review with a meta-analysis of all available studies reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate.Results: A total of 10 studies involving 666 patients were included. Letrozole (LE) or anastrozole (AZ) administration significantly increased sperm concentration, total sperm count, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) levels, and the testosterone-to-estradiol ratio (T/E2), but E2 levels were significantly reduced compared with baseline values. Compared with the control group, which included selective estrogen receptor modulators (SEMRs) or human chorionic gonadotropin (HCG), LE, or AZ did not have any significant effect on sperm concentration, motility, and morphology, except that AIs had less effect on sperm motility than the control group (weighted mean difference [WMD]: −2.55; 95% CI: −4.11 to −1.00; p = 0.001). Conclusion:AIs may be effective in the treatment of male infertility. For infertile male patients planning assisted reproduction, discontinuation of AIs for 2-7 days prior to sperm retrieval may increase the success rate of fertilization. Further studies with larger sample sizes are needed to validate these findings.

In vitro Development of Controlled-Release Nanoniosomes for Improved Delivery and Anticancer Activity of Letrozole for Breast Cancer Treatment

“…8 Accordingly, the recommended dose of letrozole is 2.5 mg/day for postmenopausal women with advanced breast cancer previously treated with antiestrogens. 9,10 Development of targeted drug delivery systems (DDSs) has received extensive attention. 12,13,14,15 The combination of medicine and nanotechnology has modified multifunctional nanocarriers that can be loaded with different drugs.…”

Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study

“…The role of estradiol in spermatogenesis is still a matter of debate. A meta-analysis of 666 men who received either letrozole or anastrozole due to high estradiol levels found that after treatment, FSH, LH, testosterone, and sperm concentration improved significantly [ 26 ]. However, motility was negatively impacted by aromatase inhibitor therapy, leading the authors to recommend a one-week cessation of medical treatment prior to sperm retrieval [ 26 ].…”

“…A meta-analysis of 666 men who received either letrozole or anastrozole due to high estradiol levels found that after treatment, FSH, LH, testosterone, and sperm concentration improved significantly [ 26 ]. However, motility was negatively impacted by aromatase inhibitor therapy, leading the authors to recommend a one-week cessation of medical treatment prior to sperm retrieval [ 26 ]. In our study, we conducted a subset analysis comparing post-treatment semen parameters and hormone levels in men with T/E ratios of <10 versus ≥10, but we did not find any significant differences between the two groups.…”

Pharmacotherapy of male hypogonadism

“…Considering the negative feedback exerted by estrogen on HPT, reducing estrogen formation (ARI) or action (SERM) have been proposed to stimulate testicular function [17,35,36]. In meta-analyses, SERM were indeed able to induce on average a 7 nmol/L increase in total T by stimulating a 5 mU/L increase in Gn levels [37,38].…”