Enclomiphene citrate stimulates testosterone production while preventing oligospermia A randomized phase II clinical trial comparing topical testosterone

Treatment with enclomiphene increases serum T, E2, and LH levels similar to those obtained with topical T gel in men with secondary hypogonadism with no lowering of sperm count.

Ronald D. Wiehle, Ph.D., Gregory Fontenot, Ph.D., Jenny Wike, B.S., Kuang Hsu, M.S., Jennifer Nydell, B.S. Larry Lipshultz, M.D.

Volume 102, Issue 3, Pages 720-727


To determine the effect of enclomiphene citrate in men with secondary hypogonadism.

Phase II clinical trial.

Community dwelling men making visits to physician offices.

Men with secondary hypogonadism.

Oral administration of enclomiphene citrate or 1% topical T gel.

Main Outcome Measure(s):
Luteinizing hormone, FSH, T, and semen analysis.

Treatment with enclomiphene citrate resulted in increased morning serum T, E2, and LH levels similar to those obtained with a topical T gel in men with secondary hypogonadism. Follicle-stimulating hormone and LH were increased with enclomiphene, and sperm counts were conserved.

Enclomiphene citrate reverses the two hallmarks of secondary hypogonadism, namely, low serum total T and low or inappropriately normal LH while preserving sperm production.

Clinical Trial Registration Number:
NCT01270841 (ClinicalTrials.gov Identifier NCT01270841).

  • This study adds additional validation to our continued off label use for Clomid for our infertility patients with low counts or low testosterone. Although not seen in this current study, any thoughts on why some patients (approx 10-15%) have a paradoxical response and their sperm counts drop down rather than go up?

    • Gregory Fontenot

      Soon to be published data in a mouse model comparing enclomiphene and zuclomiphene, the two isomers of clomid, demonstrate that zuclomiphene, an isomer with a 2 week half-life leading to high levels with continued clomid use, has detrimental effects on male reproductive tissues, as well as other ill effects. This provides validation for the use of a single isomer and not the continued use of clomid.

  • ranjithrama

    Maintaining semen parameters on enclomiphene citrate is not surprising. What would be interesting is whether men actually have improvement in semen parameters while taking enclomiphene citrate. The literature on effect of clomiphene citrate on semen parameters suffers from lack of controlled studies

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