Compensated Hypospermatogenesis: Elevated Follicle-stimulating Hormone Predicts Decline in Semen Parameters Among Men With Normal Index Semen Analysis

Abstract

ObjectiveTo determine whether men with elevated follicle-stimulating hormone (FSH) and normal semen analysis (SA) are more likely to experience a decline in semen parameters over time compared to men with normal FSH. MethodsMen presenting for fertility evaluation between 2002 and 2020 with normal initial SA were dichotomized according to baseline FSH as normal (<7.6 IU/mL) vs elevated (≥7.6 IU/mL). Primary outcomes included the development of abnormal sperm concentration (<15 million/mL) and total motile sperm count <9 million. Secondary outcomes included abnormal sperm motility (<40%), morphology (<4%), and total number of SA abnormalities. ResultsThe final sample consisted of 858 men; 776 had normal FSH, and 82 had elevated FSH at presentation. Compared to men with normal FSH, men with elevated FSH had lower total motile sperm count (64.1 vs 107.3, P < .001) and higher testosterone levels (339 ng/dL vs 309 ng/dL, P = .03). At each follow-up timepoint, more men with elevated FSH had oligospermia compared to men with normal FSH. Men with elevated FSH were more likely to experience a decline in total motile sperm count below the intrauterine insemination threshold of 9 million and more likely to develop SA abnormalities over time. ConclusionIn men presenting for fertility evaluation with normal index SA, elevated FSH was associated with subsequent decline in semen parameters over time. Men with elevated FSH and normal SA, a condition we have termed compensated hypospermatogenesis, represent an at-risk population for whom close follow-up is warranted.