The Use of HCG-Based Combination Therapy for Recovery of Spermatogenesis after Testosterone Use

Abstract

Introduction and Aim: About 3 million men take testosterone in the United States with many reproductive-age men unaware of the negative impact of testosterone supplementation on fertility. Addressing this population, we provide an early report on the use of human chorionic gonadotropin (HCG)-based combination therapy in the treatment of a series of men with likely testosterone-related azoospermia or severe oligospermia. Methods: We retrospectively reviewed charts from two tertiary care infertility clinics to identify men presenting with azoospermia or severe oligospermia (<1 million sperm/mL) while taking exogenous testosterone. All were noted to have been placed on combination therapy, which included 3,000 units HCG subcutaneously every other day supplemented with clomiphene citrate, tamoxifen, anastrozole, or recombinant follicle-stimulating hormone (or combination) according to physician preference. Main Outcome Measure: Clinical outcomes, including hormone values, semen analyses, and clinical pregnancies, were tracked. Results: Forty-nine men were included in this case series. Return of spermatogenesis for azoospermic men or improved counts for men with severe oligospermia was documented in 47 men (95.9%), with one additional man (2.1%) having a documented pregnancy without follow-up semen analysis. The average time to return of spermatogenesis was 4.6 months with a mean first density of 22.6 million/mL. There was no significant difference in recovery by type of testosterone administered or supplemental therapy. No men stopped HCG or supplemental medications because of adverse events. Conclusions: We here provide an early report of the feasibility of using combination therapy with HCG and supplemental medications in treating men with testosterone-related infertility. Future discussion and studies are needed to further characterize this therapeutic approach and document the presumed improved tolerability and speed of recovery compared with unaided withdrawal of exogenous testosterone.