Enclomifene (INNTooltip International Nonproprietary Name), or enclomiphene (USANTooltip United States Adopted Name), a nonsteroidal selective estrogen receptor modulator of the triphenylethylene group acts by antagonizing the estrogen receptor (ER) in the pituitary gland, which reduces negative feedback by estrogen on the hypothalamic-pituitary-gonadal axis, thereby increasing gonadotropin secretion and hence gonadal production of testosterone.[3] It is one of the two stereoisomers of clomifene, which itself is a mixture of 38% zuclomifene and 62% enclomifene.[3] Enclomifene is the (E)-stereoisomer of clomifene, while zuclomifene is the (Z)-stereoisomer.[4][5] Whereas zuclomifene is more estrogenic, enclomifene is more antiestrogenic.[3] In accordance, unlike enclomifene, zuclomifene is antigonadotropic due to activation of the ER and reduces testosterone levels in men.[3] As such, isomerically pure enclomifene is more favorable than clomifene as a progonadotropin for the treatment of male hypogonadism.[3]
Enclomiphene (former tentative brand names Androxal and EnCyzix), was under development for the treatment of male hypogonadism and type 2 diabetes.[4][5][6][3] By December 2016, it was in preregistration and was under review by the Food and Drug Administration in the United States and the European Medicines Agency in the European Union.[6] In January 2018, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended refusal of marketing authorization for enclomifene for the treatment of secondary hypogonadism.[7] In April 2021, development of enclomifene was discontinued for all indications.[6]
The key difference between enclomiphene citrate and traditional testosterone replacement therapy is that enclomiphene citrate stimulates the body to produce its own testosterone, while traditional testosterone replacement therapy replaces low testosterone levels in men with exogenous, synthetic testosterone.
^Mikkelson TJ, Kroboth PD, Cameron WJ, Dittert LW, Chungi V, Manberg PJ (September 1986). "Single-dose pharmacokinetics of clomiphene citrate in normal volunteers". Fertility and Sterility. 46 (3): 392–396. doi:10.1016/s0015-0282(16)49574-9. PMID 3091405.
^Ghobadi C, Gregory A, Crewe HK, Rostami-Hodjegan A, Lennard MS (2008). "CYP2D6 is primarily responsible for the metabolism of clomiphene". Drug Metabolism and Pharmacokinetics. 23 (2): 101–105. doi:10.2133/dmpk.23.101. PMID 18445989.
^ abcdefHill S, Arutchelvam V, Quinton R (February 2009). "Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men". IDrugs. 12 (2): 109–119. PMID 19204885.
^ abElks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 298–. ISBN 978-1-4757-2085-3.
^ abMorton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 79–. ISBN 978-0-7514-0499-9.
Enclomifene (INNTooltip International Nonproprietary Name), or enclomiphene (USANTooltip United States Adopted Name), a nonsteroidal selective estrogen...
mixture of 38% zuclomifene and 62% enclomifene. Zuclomifene is the (Z)-stereoisomer of clomifene, while enclomifene is the (E)-stereoisomer. Whereas zuclomifene...
stereoisomers in equal proportion: enclomifene and zuclomifene. Zuclomifene has pro-estrogenic properties, whereas enclomifene is pro-androgenic, i.e. it promotes...
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