It should be noted the COI of the corresponding author. RD Wiehle is a RPRX employee (one of about 6) who undoubtedly contributed only to the writing of the article, no more. Further, the very selective data used for the report. In fact, this attempt at selective use of data led to RPRX problems in their current clinical site studies. RPRX asked but was denied by the FDA to exclude data on sperm counts, which were consistent with published data on topical testosterone. RPRX selected use of data on sperm counts is important since this is the endpoint needed for FDA Approval, NOT serum testosterone. Kaminetsky J, Werner M, Fontenot G, Wiehle RD. Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel. The Journal of Sexual Medicine. Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel - Kaminetsky - 2013 - The Journal of Sexual Medicine - Wiley Online Library
Introduction - Clomiphene
citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene
is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism.
Aim - Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone.
Main Outcome Measures - Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 IGF
-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated.
Methods - This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone.
Results - After discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75–334 × 106/mL range. The gel was ineffective in raising sperm counts above 20 × 106/mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts.
Conclusions - Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic–pituitary–testicular axis.
Note: Corresponding Author: Ronald D. Wiehle, PhD, Repros Therapeutics, 2408 Timberloch Place, B-7, The Woodlands, TX 77380, USA. Tel: 281-719-3406; Fax: 281-719-3446; E-mail: