U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Status:
Investigational
Source:
INN:enclomifene [INN]
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



Enclomiphene (Androxal), in development by Repros Therapeutics Inc, is a non-steroidal estrogen receptor antagonist that promotes gonadotropin-dependent testosterone secretion by the testes. Enclomiphene constitutes the trans-stereoisomer of clomiphene citrate, a drug that has been widely prescribed for several decades for the treatment of female ovulatory dysfunction. Because of the antagonistic effects of enclomiphene, the drug has the potential to increase serum testosterone levels in men with secondary hypogonadism by restoring physiological endogenous testosterone secretion while maintaining testicular volume and, potentially, spermatogenesis. In clinical trials conducted to date, enclomiphene demonstrated significant efficacy in the physiological restoration of testosterone levels in males with secondary hypogonadism. The compound also exhibited an unanticipated favorable effect on fasting plasma glucose; this result has been accompanied by rapidly accumulating evidence from other researchers for a bidirectional relationship between low serum testosterone and obesity/metabolic syndrome (syndrome X) in men.
Clomiphene (CLOMID®) is a triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. It is an orally administered, nonsteroidal, ovulatory stimulant. Clomiphene (CLOMID®) is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)] containing between 30% and 50% of the cis-isomer. Clomiphene (CLOMID®) initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event in response to a course of clomiphene therapy is an increase in the release of pituitary gonadotropins. This initiates steroidogenesis and folliculogenesis, resulting in growth of the ovarian follicle and an increase in the circulating level of estradiol. Following ovulation, plasma progesterone and estradiol rise and fall as they would in a normal ovulatory cycle.
Clomiphene (CLOMID®) is a triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. It is an orally administered, nonsteroidal, ovulatory stimulant. Clomiphene (CLOMID®) is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)] containing between 30% and 50% of the cis-isomer. Clomiphene (CLOMID®) initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event in response to a course of clomiphene therapy is an increase in the release of pituitary gonadotropins. This initiates steroidogenesis and folliculogenesis, resulting in growth of the ovarian follicle and an increase in the circulating level of estradiol. Following ovulation, plasma progesterone and estradiol rise and fall as they would in a normal ovulatory cycle.