Therapeutic benefits of gonadotropins in male hypogonadotropic hypogonadism: a focus on spermatogenesis and fertility

Abstract

Male hypogonadotropic hypogonadism is characterized by deficient secretion of luteinizing hormone and follicle-stimulating hormone, leading to low testosterone levels, impaired spermatogenesis, and often infertility. Treatment aims to normalize testosterone and induce spermatogenesis, with gonadotropin therapy as standard. Factors affecting treatment success and optimal duration remain unclear. This single-center retrospective cohort study assessed the outcomes of gonadotropin therapy in men with hypogonadotropic hypogonadism and azoospermia. Men ≥ 18 years were included. The primary outcome was the successful induction of spermatogenesis. Data on demographics, treatment regimens, semen parameters, pregnancy outcomes, and side effects were collected. Regression analyses identified factors associated with treatment success. Thirty-five men were included. Spermatogenesis was achieved in 74% of patients, with higher success rates in those receiving combined human chorionic gonadotropin and follicle-stimulating hormone therapy (78%) versus human chorionic gonadotropin monotherapy (33%). Of those producing sperm, 69% upgraded to a higher WHO semen category, with 29% reaching normospermia. The median maximum sperm concentration achieved during treatment was 8.3 million/mL (IQR: 1.9–36.3). A larger baseline testicular volume was associated with a higher success rate of spermatogenesis and a shorter time to pregnancy. Pregnancy was achieved in 68% of patients, with 39% through spontaneous conception. The median time to first spermatogenesis was 7 months and to pregnancy was 21 months. Mild side effects occurred in 16% of patients. Gonadotropin therapy is effective and well tolerated in inducing spermatogenesis and achieving pregnancy in azoospermic men with HH. These findings, based on a contemporary Western cohort, provide updated evidence that supports personalized counseling and underscore the importance of long-term treatment adherence for successful fertility restoration.