Hypothalamic-Pituitary-Testicular Axis Effects and Urinary Detection Following Clomiphene Administration in Males

Hypothalamic-Pituitary-Testicular Axis Effects and Urinary Detection Following Clomiphene Administration in Males / Geoffrey D. Miller, Chad Moore, Vinod Nair, Brian Hill, Stuart E. Willick, Alan D. Rogol, Daniel Eichner

  • Journal of Clinical Endocrinology & Metabolism 104 (2019) 3 (March), p. 906-914
  • PMID: 30295816
  • DOI: 10.1210/jc.2018-01159


Context: Clomiphene is a performance-enhancing drug commonly abused by males in sport, but the extent to which testosterone increases in healthy males following its use is unknown. In addition, evidence suggests that clomiphene, a mixture of cis- and trans-isomers zuclomiphene and enclomiphene, is detectable in urine for months following use; the isomer-specific urinary detection window has yet to be characterized in a controlled study.

Objective: To determine the effect of once-daily, 30-day clomiphene treatment on serum testosterone and gonadotropin levels in the subject population studied and the urinary clearance and detection window of clomiphene isomers following administration for antidoping purposes.

Participants and design: Twelve healthy males aged 25 to 38 years, representing a recreational athlete population, participated in this open-label, single-arm study.

Intervention: Oral clomiphene citrate (50 mg) was self-administered once daily for 30 days. Serum and urine samples were collected at baseline and at days 7, 14, 21, 28, 30, 32, 35, 37, 44, 51, and 58; urine collections continued periodically up to day 261.

Results: Mean testosterone, LH, and FSH levels increased 146% (SEM, ±23%), 177% (±34%), and 170% (±33%), respectively, during treatment compared with baseline. Serum drug concentrations and urinary excretion were nonuniform among individuals as isomeric concentrations varied. The zuclomiphene urinary detection window ranged from 121 to >261 days.

Conclusions: Clomiphene significantly raised serum testosterone and gonadotropin levels in healthy men and thus can be abused as a performance-enhancing drug. Such abuse is detectable in urine for ≥4 months following short-term use.

Original document


Research / Study
5 October 2018
Eichner, Daniel
Hill, Brian
Miller, Geoffrey D.
Moore, Chad
Nair, Vinod
Rogol, Alan D.
Willick, Stuart E.
United States of America
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University of Utah School of Medicine
University of Virginia School of Medicine (UVA SoM)
Salt Lake City, USA: The Sports Medicine Research and Testing Laboratory (SMRTL)
Doping classes
S4. Hormone And Metabolic Modulators
Selective estrogen receptor modulators (SERMS)
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Health effects
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Scientific article
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Date generated
4 January 2022
Date of last modification
8 January 2022
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