TRT-Induced Azoospermia: Why hCG and Gonadotropin Levels Don’t Predict Sperm Recovery

[madman]

Abstract​

INTRODUCTION AND OBJECTIVES:​

The use of testosterone replacement therapy (TRT) among men is rising leading to an increasing number of men with TRT induced azoospermia from hypothalamic-pituitary-gonadal (HPG) axis suppression. Human chorionic gonadotropin (HCG) is used to mitigate withdrawal and restore spermatogenesis, but its effects on pituitary gonadotropins and relation to sperm recovery are unclear. We aimed to characterize pituitary and spermatogenic recovery with HCG treatment.

METHODS:​

Retrospective review of men with TRT induced infertility treated with HCG. Men with central hypogonadism were excluded. HCG dose, schedule and duration of treatment were recorded. Levels of testosterone, estradiol, luteinizing hormone (LH), and follicle stimulating hormone (FSH), were measured prior to initiation of HCG and at 1, 3 and 6 months. Semen analyses were analyzed at 3 and 6 months.

RESULTS:​

59 men with TRT induced infertility received HCG with doses ranging from 500 to 5000 IU every Monday, Wednesday, and Friday. 59.3% of men were started at the 2000 IU dose. Average baseline LH and FSH levels were 0.84 mIU/mL (SD 1.2) and 1.16 mIU/mL (SD 2.8) respectively. Table A summarizes gonadotropin response to HCG treatment at 1, 3 and 6 months. At 3 and 6 months, 36 and 16 men had a SA respectively. At 3 months, 32 (89%) had spermatogenesis. Of those without SA at 6 months, 18 men had normalized parameters, 1 achieved pregnancy, and 1 was lost to follow up. At 3 and 6 months, average total motile sperm count (TMS) did not differ significantly between men with suppressed and recovered FSH.

CONCLUSIONS:​

No consistent gonadotropin response to HCG occurs after TRT cessation: roughly half of men remain suppressed at 3 and 6 months, yet gonadotropin recovery does not correspond to higher TMS counts. These findings inform counseling of men with TRT-induced azoospermia and question the utility of isolated gonadotropin measurements to guide surgical fertility management—including decisions after vasectomy or with delayed spermatogenic recovery. Higher powered, longitudinal studies are required to better characterize the effect of prolonged HCG treatment on the HPG axis and fertility outcomes.