Work

Pituitary Axis Impacts and Effectiveness of Clomiphene and Human Chorionic Gonadotropin in Treating Hypogonadism: Cohort Study

Year: 2026

Type: article

Abstract: PURPOSE: Men with testosterone deficiency (TD) aiming to preserve testicular function can be treated with strategies including testosterone replacement therapy (TRT) combined with human chorionic gonadotropin (hCG) or clomiphene citrate (CC), or CC monotherapy. Evidence regarding these strategies on the pituitary axis and quality of life is limited. MATERIALS AND METHODS: This retrospective cohort study compared the effects of hCG+TRT, CC+TRT, and CC monotherapy on pituitary axis function, testosterone levels and quality of life during TD treatment. Changes in serum luteinising hormone (LH), follicle-stimulating hormone (FSH), total and free testosterone, and quality of life (QADAM scores) from baseline to 6 months were calculated using mixed models. RESULTS: 6,999 adult men were included: 6,364 men (91%) prescribed hCG+TRT, 552 (8%) prescribed CC+TRT, 83 (1%) prescribed CC monotherapy. hCG+TRT suppressed LH and FSH (p<0.05), whereas CC+TRT was associated with reduction in FSH only (p=0.02). At 6 months, CC monotherapy was associated with significant increases in LH and FSH (p<0.001). All treatments were associated with substantial increases in total and free testosterone with rapid attainment of physiological levels (ranging from 23.58 nmol/L to 26.52 nmol/L). Similar changes in QADAM scores were observed across the three approaches (from 7.86 points to 9.50 points, all p<0.001). CONCLUSIONS: This study revealed distinct patterns in the natural history of pituitary hormone levels across different fertility-sparing strategies for TD, while observing comparable benefits in testosterone levels and quality of life. Future studies should prospectively correlate longitudinal trends in pituitary hormones with semen parameters and other fertility outcomes to enable personalised treatment selection.

Source: The World Journal of Men s Health

DOI: 10.5534/wjmh.250422

Authors: Ashley Kieran Clift, Hans Johnson, David R. Huang, Ranjith Ramasamy

Institutions: Menwell Limited, Imperial College London, University of Bristol

Language: English

Topic: Hormonal and reproductive studies

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W7167415443