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

Graphical Abstract: 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. Lay summary: Some men are infertile because their brain does not produce the hormones needed to make sperm. This condition is called hypogonadotropic hypogonadism. These men often have low testosterone and no sperm in their semen. In this study, we looked at whether hormone treatment could help these men produce sperm and have children. We studied 35 men who were given hormone injections at a Dutch university hospital. After treatment, 74% of them started producing sperm. Those who received a combination of two hormones had better results than those who received only one. Almost 70% of men with sperm had better sperm quality, and over a quarter reached normal sperm levels. Two-thirds of men who wanted children became fathers, mostly through natural conception. Our findings show that hormone treatment is safe and often successful. This can offer hope to men with this condition who want to become fathers.