Testosterone Versus Clomiphene Citrate

[Michael Scally MD]

[OA] Dadhich P, Ramasamy R, Scovell J, Wilken N, Lipshultz L. Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men. Indian J Urol 2017;33(3):236-40. http://www.indianjurol.com/article.asp?issn=0970-1591;year=2017;volume=33;issue=3;spage=236;epage=240;aulast=Dadhich

INTRODUCTION: Both clomiphene citrate (CC) and testosterone supplementation therapy (TST) are effective treatments for men with hypogonadism. We sought to compare changes in symptoms and treatment efficacy in hypogonadal men before and after receiving CC and TST.

PATIENTS AND METHODS: 52 men who received TST and 23 men who received CC for symptomatic hypogonadism were prospectively followed for change in hormone levels and symptoms after treatment. These men were also compared to eugonadal men who were not on CC or TST during the same period. Comparisons were made between baseline and posttreatment hormone levels and symptoms. Symptoms were evaluated using the androgen deficiency in aging male (ADAM) and quantitative ADAM (qADAM) questionnaires.

RESULTS: Serum total testosterone increased from pretreatment levels in all men (P < 0.05), regardless of therapy type (TST: 281-541 ng/dL, CC: 235.5-438 ng/dL). Men taking TST reported fewer ADAM symptoms after treatment (5-2, P < 0.05). Similarly, men taking CC reported fewer ADAM symptoms after treatment (3.5-1.5, P < 0.05). Conversely, eugonadal men had similar T levels (352 vs. 364 ng/dL) and hypogonadal symptoms (1.5 vs. 1.4) before and after follow-up.

When we evaluated individual symptoms, men treated with TST showed significant increases in qADAM scores in libido, erectile function, and sports performance.

HOWEVER, AMONG THE MEN WHO RECEIVED CC, QADAM SUBSCORE FOR LIBIDO WAS LOWER FOLLOWING TREATMENT (3.75-3.2, P = 0.04), INDICATING THAT CC COULD HAVE AN ADVERSE EFFECT ON LIBIDO IN HYPOGONADAL MEN.

CONCLUSIONS: Both TST and CC are effective medications in treating hypogonadism; however, our study indicates that TST is more effective in raising serum testosterone levels and improving hypogonadal symptoms. CC remains a viable treatment modality for hypogonadal men but its adverse effect on libido warrant further study.

 

[Michael Scally MD]

[OA] Cangiano B, Cacciatore C, Persani L, Bonomi M. Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis. Endocrinol Diabetes Metab Case Rep. 2017. https://www.edmcasereports.com/articles/endocrinology-diabetes-and-metabolism-case-reports/10.1530/EDM-17-0055

We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate.

The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values.

Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume.

Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic-pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion.

LEARNING POINTS: Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.

In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.

In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.

Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal men who wish to remain fertile.