Enclomiphene, A New Treatment for Hypogonadism

Fifteen percent of couples will have difficulty conceiving and a male factor is involved in half of those cases. There are a number of possible underlying causes for male fertility problems. One of them occurs when the testicles have difficulty producing a normal level of testosterone.  It is a condition called hypogonadism.

Hypogonadism is a disorder in its own right, and can occur independent of fertility issues. Hypogonadisim increases in incidence as men age.  Approximately 15% of all men 70 years of age or older will have clinical hypogonadism including symptoms of low sexual desire, lack of energy or easy fatigue, and loss of morning erections.   

Hypogonadism has been traditionally treated with one of several testosterone formulations. One disadvantage of this is that administration of testosterone effectively subordinates the testicle’s role in making testosterone and, by process of an internal feedback loop involving the pituitary gland, the testicles will slow down or halt both their endocrine and their fertility functions; in other words, the testicles will stop or slow their production of both testosterone and sperm.  

About Enclomiphene

Enclomiphene is a new formulation of an older medication called clomiphene. Clomiphene selectively binds to certain receptors in the pituitary, a master endocrine gland that abuts the brain.  Binding to this receptor actually turns on the same feedback loop and leads to more stimulation of the testes, leading to more testosterone production and sometimes, to more sperm production.  

Clomiphene, which is FDA approved for use in female infertility, has been prescribed off label for men for over thirty years. Certain compounds like clomid exist as isomers; that is that they have two forms with the same molecular structure except that the two forms are mirror images of each other, like a right and left hand.   Clomiphene is composed of  two isomers; zuclompiphene and enclomiphene. There is speculation that use of only one isomer, enclomiphene may lead to fewer side effects and make the medication more effective for men.

Enclomiphene Clinical Trail Results

Regardless of possible side effects, an article on the September issue of Fertility and Sterility by Wiehle et al reports on a clinical trial of enclomiphene on seventy-three men.   The men were divided into four groups:  Testosterone gel, enclomiphene 12.5 mg, enclomiphene 25 mg and placebo. Result showed that enclomiphene could achieve a similar testosterone level to the use of testosterone gel. Furthermore, the study showed that the use of Tesosterone gel was associated with a decrease in sperm production whereas  enclomiphene maintained sperm production in hypgonadal men.

Looking towards the future, enclomiphene will almost certainly add to our armamentariaum of medications to treat hypogonadism while maintaining sperm production.  As to whether it will turn out useful specifically in the treatment  of male infertility, it remains to be seen.