Letrozole and Infertility Among Males With Spermatogenic Failure: A Randomized Clinical Trial.

Area of Science:

• Reproductive Endocrinology
• Male Infertility Research
• Clinical Trials in Urology

Background:

• Spermatogenic failure (SPGF) presents limited medical treatment options.
• Aromatase inhibitors show promise for SPGF, but high-quality evidence is scarce.

Purpose of the Study:

• To assess the efficacy and safety of letrozole in enhancing sperm concentration categories for men with SPGF.
• To evaluate letrozole's impact on semen parameters and reproductive hormones.

Main Methods:

• A multicenter, open-label, assessor-blinded randomized clinical trial.
• 296 men with SPGF received either letrozole plus vitamins C and E or vitamins C and E alone for 3 months.
• Primary outcome: World Health Organization Sperm Concentration Categories (WHO-SCC) upgrade rate at 3 months.

Main Results:

• Letrozole significantly increased WHO-SCC upgrade rates (14.3% vs 5.4%, P=.01) and odds of achieving better WHO-SCC grades (OR, 2.65; P=.008).
• Higher Dutch Society of Obstetrics and Gynecology Total Motile Sperm Count Categories (NVOG-TMSCC) upgrade rates were observed with letrozole.
• Letrozole increased gonadotropins and testosterone while decreasing estradiol; no significant changes in other semen parameters were noted. Decreased libido was more frequent in the letrozole group.

Conclusions:

• Letrozole effectively improved sperm concentration categories in men with SPGF.
• The treatment was well-tolerated, suggesting its potential role in managing infertility severity.
• Letrozole may offer a viable option for less invasive reproductive strategies.