The world journal of men's health

2287-42084112023JanThe world journal of men's healthWorld J Mens HealthTemporal Changes of Clomiphene on Testosterone Levels and Semen Parameters in Subfertile Men.198203198-20310.5534/wjmh.220010Clomiphene citrate (CC) is prescribed off-label in men to improve testosterone and sperm parameters, but the duration of treatment needed to reach maximal benefit remains unclear. Our objective was to examine temporal effects of CC on total testosterone (TT) and semen analysis (SA) using longitudinal follow-up data in treated men.We analyzed an IRB-approved database of men treated with CC (25 mg q.d. or 50 mg q.o.d.) from January 2016 through May 2021. We identified patients with 3, 6, 9, and 12 month follow-up data for TT and 3, 6, and 9 month follow-up SA. Mean absolute changes in TT and sperm concentration compared to baseline were calculated, along with 95% confidence intervals. Men with prior genitourinary procedures or hormone therapy were excluded. Paired t-tests were used to compare TT and sperm concentration at each time point to baseline (alpha=0.05).One hundered thirty-four men received CC, mean age 37.7 years (SD 6.7, range 24-52). TT at all follow-ups (3, 6, 9, and 12 months) were available for 25 men, and SA at 3, 6, and 9 months for 26 men. Baseline TT was 358±145 ng/dL and sperm concentration was 13±17.2 M/mL. Significant improvement in TT was identified at 3 months (62.7 ng/dL, 95% CI: 0.49-125.0, p=0.048), additional benefit at 6 months (181.8 ng/dL, 95% CI: 114.1-249.5, p<0.01), and plateau at 9 and 12 months. Improvement in sperm concentration was first observed at 9 months (20.7 M/mL, 95% CI: 10.2-31.2, p<0.01). Semen volume and sperm motility did not change.Duration of treatment with clomiphene may impact testosterone and sperm concentration, and the historical 3 month milestone may be insufficient for clinical and research evaluation. Men taking CC may experience plateau in TT at 6 months and first benefit in sperm concentration at 9 months.Copyright © 2023 Korean Society for Sexual Medicine and Andrology.JiangTommyT0000-0002-1199-0615Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.SigalosJohn TJT0000-0001-9458-9626Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.OsadchiyVadimV0000-0003-0492-9987Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.SantamariaAlvaroA0000-0002-7953-4253Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ZhengMichael HMH0000-0001-5760-0486Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ModiriNeilufarN0000-0003-1465-0808Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.RegetsKeith VKV0000-0002-9563-4211Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.MillsJesse NJN0000-0002-7833-7071Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.EleswarapuSriram VSV0000-0003-1852-4833Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Seleswarapu@mednet.ucla.edu.engJournal Article20220613