Research indicates clomiphene citrate may be a viable treatment option for male hypogonadism.
By Mary Ann Kuykendall, PharmD Intern, Reviewed By Bruce Biundo, RPh, PCCA Pharmacy Consultant
Male hypogonadism is the condition in which the testes do not produce enough testosterone. There are two major forms: primary hypogonadism is due to testicular dysfunction or failure, and secondary hypogonadism is caused by dysfunction of the hypothalamic-pituitary axis. The secondary form is more common. However, both forms of this condition can cause negative effects leading to unsatisfying changes in libido, sexual function, mood, behavior, lean body mass, and bone density. While hypogonadism can be caused by several factors, increasing age is a common source of decreased androgen production as total testosterone has been shown to decrease at a rate of one percent per year after the age of 40.
The most common treatment for low testosterone traditionally has been testosterone supplementation, for it generally has been rather successful. Since this is the case, there are various dosage forms of testosterone commercially available (IM injection, topical gel, topical solution, implantable pellets, buccal system). Compounded preparations include gels, creams, topical solutions, sublingual drops and sublingual tablets or troches. One form not available is an oral pill. That is because synthetic forms of testosterone, such as methyltestosterone, have been associated with liver toxicities, while bio-identical testosterone has a very high first pass effect, requiring high doses to be effective.
Clomiphene citrate is a nonsteroidal ovulatory drug that has traditionally been used in female infertility. It is classified as a selective estrogen receptor modulator (SERM). Clomiphene competes with estradiol for the estrogen receptors at the hypothalamus and blocks the normal negative feedback of circulating estradiol, preventing estrogen from limiting production of gonadotropin-releasing hormone (GnRH). The increase in GnRH level stimulates the pituitary gland to release more FSH and LH. FSH acts on the testes to increase serum production, while LH acts to increase testosterone production. A downside of testosterone supplementation is that it can cause the negative feedback and affect not only LH, but also FSH. Thus, it can inhibit spermatogenesis. Clomiphene does not do this, so it does not inhibit sperm production. Therefore, clomiphene is becoming a first-line treatment option for patients wishing to maintain fertility.
Another reason for clomiphene’s growing popularity is its availability as an oral tablet. Clomiphene comes in a 50 mg tablet and in bulk powder for compounding. Capsules of varying doses can be prepared easily. However, it has not yet been proven to be effective topically. Doses ranging from 25 milligrams every other day to 100 milligrams daily have been studied in the treatment of male hypogonadism. It also has shown to be a safe and effective treatment in men for long-term use of up to three years.
In clinical studies, this medication has been shown to generate significant increases in testosterone levels, and therefore, improvements in signs and symptoms. No serious adverse events have been reported in studies looking at the use of clomiphene for treatment of this disorder. Clomiphene has proven to be a safe and effective means of restoring testosterone levels. Despite the pros listed above, clomiphene citrate use for the treatment of hypogonadism is not currently approved by the FDA. Further research continues to be conducted in order to support the evidence for its use in treating male hypogonadism.
Clomiphene Monograph. Clinical Pharmacology. Gold Standard, Inc. 2007. Available at: http://www.clinicalpharmacology-ip.com. Accessed: September 19, 2012
Da Ros CT, Averbeck MA. Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency – a prospective study. Int Braz J Urol 2012; 38: 512-18.
Guay AT, Jacobson J, Perez JB, et al. Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit? Int J Impot Res 2003; 15: 156-65.
Moskovic DJ, Katz DJ, Akhavan A, et al. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int 2012. doi: 10.1111/j.1464-410X.2012.10968.x
Shabsigh A, Kang Y, Shabsign R, et al. Clomiphene citrate effects on testosterone/estrogen ration in male hypogonadism. J Sex Med 2005; 2: 716-21.
Tan RS, Vasudevan D. Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse. Fertil Steril 2003; 79: 203-5.
Taylor F, Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost. J Sex Med 2010; 7: 269-76.
Article Courtesy of www.pccarx.com