Other uses
Clomifene has also been used with other assisted reproductive technology to increase success rates of these other modalities.Clomifene is sometimes used in the treatment of male hypogonadism as an alternative to testosterone replacement therapy. The medication has been used at a dosage of 20 to 50 mg three times per week to once day for this indication. It has been found to increase testosterone levels by 2- to 2.5-times in hypogonadal men at such dosages. Despite the use of questionnaires in testosterone replacement comparator trials being called into question, clomifenes lower cost, therapeutic benefits, and greater value towards hypogonadism improvement have been noted.Clomifene consists of two stereoisomers in equal proportion: enclomifene and zuclomifene. Zuclomifene has pro-estrogenic properties, whereas enclomifene is pro-androgenic, i.e. it promotes testosterone production through stimulation of the HPG axis. For this reason, purified enclomifene isomer has been found to be twice as effective in boosting testosterone compared to the standard mix of both isomers. Additionally, enclomifene has a half-life of just 10 hours, but zuclomifene has a half-life of 30 days—therefore if the goal is to boost testosterone, taking regular clomifene may produce far longer-lasting pro-estrogenic effects than pro-androgenic effects. Clomifene has been used in the treatment of gynecomastia. It has been found to be useful in the treatment of some cases of gynecomastia but it is not as effective as tamoxifen or raloxifene for this indication. It has shown variable results for gynecomastia (probably because the zuclomifene isomer is estrogenic), and hence is not recommended for treatment of the condition.
In normal men, 50 mg/day clomifene for 8 months has been found to increase testosterone levels by around 870 ng/dL in younger men and by around 490 ng/dL in elderly men. Estradiol levels increased by 62 pg/mL in younger men and by 40 pg/mL in elderly men. These findings suggest that the progonadotropic effects of clomifene are stronger in younger men than in older men. In men with hypogonadism, clomifene has been found to increase testosterone levels by 293 to 362 ng/dL and estradiol levels by 5.5 to 13 pg/mL. In a large clinical study of men with low testosterone levels (<400 ng/dL), 25 mg/day clomifene increased testosterone levels from 309 ng/dL to 642 ng/dL after 3 months of therapy. No significant changes in HDL cholesterol, triglycerides, fasting glucose, or prolactin levels were observed, although total cholesterol levels decreased significantly. Other activities
Clomifene is an inhibitor of the conversion of desmosterol into cholesterol by the enzyme 24-dehydrocholesterol reductase. Concerns about possible induction of desmosterolosis and associated symptoms such as cataracts and ichthyosis with extended exposure precluded the use of clomifene in the treatment of breast cancer. Continuous use of clomifene has been found to increase desmosterol levels by 10% and continuous high doses of clomifene (200 mg/day) have been reported to produce visual disturbances. Pharmacokinetics
Clomifene produces N-desmethylclomifene, clomifenoxide (clomifene N-oxide), 4-hydroxyclomifene, and 4-hydroxy-N-desmethylclomifene as metabolites. Clomifene is a prodrug most importantly of 4-hydroxyclomifene and 4-hydroxy-N-desmethylclomifene, which are the most active of its metabolites.