Enclomiphene

Key points

• Developed for secondary hypogonadism in adult men, where the pituitary gland does not signal the testes to make enough testosterone.
• Not approved for that use: the European Medicines Agency refused marketing authorisation for an enclomiphene product (EnCyzix).
• Clomiphene, which contains enclomiphene, carries warnings about visual disturbances and liver disease.

What is enclomiphene?

Clomiphene citrate is a mixture of two geometric isomers, zuclomiphene and enclomiphene. Enclomiphene is the trans isomer on its own. Like clomiphene, it blocks oestrogen receptors, which the brain reads as a signal to release more of the hormones that drive the testes.

What enclomiphene is used for

Enclomiphene was studied for secondary hypogonadism in men: low testosterone because the pituitary does not send the testes enough signal, as distinct from a problem with the testes themselves. It is also used off-label for male infertility, the same way clomiphene sometimes is. Neither use is approved.

Safety overview for enclomiphene

The safety information comes mostly from clomiphene, which contains it. Clomiphene is not used in pregnancy or in people with liver disease, and it can cause visual symptoms such as blurring, spots or flashes, which may last or become permanent at higher doses or with longer use. Anyone with symptoms of low testosterone should see a doctor first: low testosterone has several causes, and testing decides the treatment.

What the sources say

• Enclomiphene is the trans (E) isomer of clomiphene, a mixture of cis (zuclomiphene) and trans (enclomiphene) isomers. (EMA)
• The EMA’s committee issued a negative opinion and did not grant marketing authorisation for EnCyzix (enclomifene citrate). (EMA)
• Clomiphene may cause visual symptoms including blurring, spots or flashes, which may be prolonged or irreversible with increased dose or duration. (FDA)

Further reading

• Clomiphene - StatPearls (NCBI Bookshelf)
• Testosterone - healthdirect