Volume 117, Issue 2 p. 344-350
Sexual Medicine

Differential effects of isomers of clomiphene citrate on reproductive tissues in male mice

Gregory K. Fontenot

Corresponding Author

Gregory K. Fontenot

Repros Therapeutics Inc., The Woodlands, TX, USA

Correspondence: Gregory K. Fontenot, Repros Therapeutics Inc., 2408 Timberloch Place, B-7, The Woodlands, TX 77380, USA.

e-mail: [email protected]

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Ronald D. Wiehle

Ronald D. Wiehle

Repros Therapeutics Inc., The Woodlands, TX, USA

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Joseph S. Podolski

Joseph S. Podolski

Repros Therapeutics Inc., The Woodlands, TX, USA

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First published: 27 July 2015
Citations: 14

Abstract

Objectives

To determine, in a chronic dosing study, the oral toxicity potential of the test substances, enclomiphene citrate (ENC) and zuclomiphene citrate (ZUC), when administered to male mice by oral gavage.

Materials and Methods

Mice were divided into five treatment groups. Group I, placebo; Group II, 40 mg/kg body weight/day ENC; Group III, 4 mg/kg/day ENC; Group IV, 40 mg/kg/day ZUC; Group V, 4 mg/kg/day ZUC. Serum samples and tissues were obtained from each mouse for analysis and body weights were measured.

Results

In this chronic dosing study in mice, profound effects on Leydig cells, epididymis, seminal vesicles, and kidneys were seen, as well as effects on serum testosterone, follicle-stimulating hormone and luteinising hormone levels that were associated with ZUC treatment only. Treatment with the isolated enclomiphene isomer had positive effects on testosterone production and no effects on testicular histology.

Conclusions

The present study suggests that an unopposed high dose of zuclomiphene can have pernicious effects on male mammalian reproductive organs. The deleterious effects seen when administering ZUC in male mice, justifies the case for a monoisomeric preparation and the development of ENC for clinical use in human males to increase serum levels of testosterone and maintain sperm counts.