Fontenot GK, Wiehle RD, Podolski JS. Differential Effects of Isomers of Clomiphene Citrate on Reproductive Tissues in Male Mice. BJU Int. http://onlinelibrary.wiley.com/doi/10.1111/bju.13244/abstract
OBJECTIVES: To determine in a chronic dosing study the oral toxicity potential of the test substances Enclomiphene citrate and Zuclomiphene citrate when administered to male mice by oral gavage.
METHODS: A chronic dosing study was conducted utilizing test substances Enclomiphene citrate and Zuclomiphene citrate administered to male mice daily by oral gavage.
Mice were divided into five treatment groups (Group I: Placebo; Group II: 40 MPK (mg/kg body weight)\day Enclomiphene citrate; Group III: 4 MPKday Enclomiphene citrate; Group IV: 40 MPKday Zuclomiphene citrate; Group V: 4 MKP/day Zuclomiphene citrate.
Body weights were measured. Serum samples and tissues were obtained from each animal for analysis.
RESULTS: In a chronic dose study in mice, profound effects on the Leydig cells, epididymis, seminal vesicles and kidneys were seen as well as effects on testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion that were associated with zuclomiphene treatment only. Treatment with the isolated enclomiphene isomer has positive effects on testosterone production and no effects on testicular histology.
CONCLUSIONS: This work suggests that un-opposed high dose of zuclomiphene can have pernicious effects on male mammalian reproductive organs. The deleterious effects seen when administering Zuclomiphene citrate in male mice justifies the case for a monoisomeric preparation and the development of Enclomiphene citrate, for clinical use in human males to increase serum levels of testosterone and maintaining sperm counts.
OBJECTIVES: To determine in a chronic dosing study the oral toxicity potential of the test substances Enclomiphene citrate and Zuclomiphene citrate when administered to male mice by oral gavage.
METHODS: A chronic dosing study was conducted utilizing test substances Enclomiphene citrate and Zuclomiphene citrate administered to male mice daily by oral gavage.
Mice were divided into five treatment groups (Group I: Placebo; Group II: 40 MPK (mg/kg body weight)\day Enclomiphene citrate; Group III: 4 MPKday Enclomiphene citrate; Group IV: 40 MPKday Zuclomiphene citrate; Group V: 4 MKP/day Zuclomiphene citrate.
Body weights were measured. Serum samples and tissues were obtained from each animal for analysis.
RESULTS: In a chronic dose study in mice, profound effects on the Leydig cells, epididymis, seminal vesicles and kidneys were seen as well as effects on testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion that were associated with zuclomiphene treatment only. Treatment with the isolated enclomiphene isomer has positive effects on testosterone production and no effects on testicular histology.
CONCLUSIONS: This work suggests that un-opposed high dose of zuclomiphene can have pernicious effects on male mammalian reproductive organs. The deleterious effects seen when administering Zuclomiphene citrate in male mice justifies the case for a monoisomeric preparation and the development of Enclomiphene citrate, for clinical use in human males to increase serum levels of testosterone and maintaining sperm counts.
