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The Effectiveness of Clomiphene Citrate Compared to Exogenous Testosterone Therapy in Adult Males

8 August 2015



Low testosterone (T) in men is a common medical condition affecting approximately 5 million men in the United States. Low T caused by primary hypogonadism is treatable with exogenous testosterone in the form of direct injection or topical gels. However, low T due to secondary hypogonadism is amenable to treatment with exogenous testosterone forms, as well as selective estrogen receptor modulators (SERMs), such as clomiphene citrate (Clomid; CC).There are significant side effects and increased cost with exogenous testosterone therapy (mentioned above) compared to clomiphene. Generic clomiphene, used off-label, avoids these side effects and represents a significant cost savings.But what is its efficacy compared to testosterone therapy?


An exhaustive search of available medical literature was conducted utilizing 3 separate, thoroughly vetted search engines, including MEDLINE-Ovid, Web of Science, and CINAHL. Keywords used included: clomiphene, hypogonadotropic hypogonadism, and ADAM or qADAM or quality of life.


Based on the search criteria, 6 articles were identified and reviewed for relevancy. This was narrowed down to 2 articles that met the inclusion and exclusion criteria. These 2 studies were observational, non-randomized studies. One study found that there was no statistical difference between CC, injected testosterone, or testosterone gel replacement therapy (TGRT) in regards to patient satisfaction as measured with the qADAM questionnaire. The second study found that CC was as effective as TGRT at raising serum T levels at a much lower cost without the same risks of side effects associated with TGRT.

The overall quality of both studies was low and further investigation would need to be done to validate these findings. Specifically, randomized, placebo controlled, double blinded, studies with larger cohorts are necessary.


Clomiphene citrate has been used for many years in an off-label manner to treat men with hypogonadism, mostly in specialty centers.There are only 2 studies found in the literature comparing CC to exogenous testosterone treatment and both of are low quality. Despite this limitation, and a lack of FDA approval, CC appears to be a viable option for men with low T due to secondary hypogonadism, demonstrating equal improvement in overall patient satisfaction and quality of life improvements at a lower cost while avoiding the potential side effects of testicular atrophy and reduced spermatogenesis.

Keywords: Clomiphene citrate, hypogonadotropic hypogonadism, ADAM, qADAM, quality of life


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