Review – AndrologyTestosterone Replacement Therapy Versus Clomiphene Citrate in the Young Hypogonadal Male
Section snippets
Young men and hypogonadism—What is the issue?
Over the past two decades, there has been a dramatic rise in testosterone prescriptions in the USA. In September 2014, the Food and Drug Administration expressed their concerns for men initiating testosterone replacement therapy (TRT) strictly due to aging alone. They found that 28% of men who initiated TRT did so without having a prior serum testosterone level drawn. In addition, the same study found that 21% of men who initiated TRT did not have a follow-up serum testosterone level after
Guideline statements
Recent guidelines have addressed the issue of preserving fertility in TRT-naïve patients who present with symptomatic hypogonadism. The 2016 European Association of Urology guidelines support the use of human chorionic gonadotropin (hCG) in men with secondary hypogonadism and who desire future fertility [4]. The AUA 2018 guidelines state that men with testosterone deficiency who are interested in fertility should have a reproductive health evaluation and that the long-term impact of exogenous
TRT
TRT suppresses spermatogenesis by decreasing intratesticular testosterone and follicle-stimulating hormone levels through suppression of the hypothalamic-pituitary-gonadal axis [8]. Conflicting evidence exists for the long-term risk to fertility in men undergoing TRT. Data abstracted from trials which sought to utilize TRT as a contraceptive found that sperm concentrations were suppressed to less than 1 × 106 sperm/ml within 3.5 mo. After discontinuation of testosterone, projected time to
Clomiphene citrate
Clomiphene citrate and the single isomer isolate enclomiphene are well-known selective estrogen receptor modulators which have been used alternatively to treat men with hypogonadism [13], [14], [15]. Clomiphene citrate stimulates endogenous testosterone production by inhibiting the negative feedback at the hypothalamus and pituitary, resulting in an increased gonadotropin-releasing hormone and luteinizing hormone (LH) release. In theory, the mechanism of clomiphene citrate is a seemingly
hCG
hCG is an analog of LH and has been used to stimulate testosterone production. Compared with clomiphene citrate, the data supporting the use of hCG is less developed. A study evaluating the use of hCG or clomiphene citrate in hypogonadal men (n = 282) who wished to preserve fertility found that hCG, clomiphene citrate, and combination therapy improved serum testosterone levels by 245 ng/ml, 304 ng/ml, and 305 ng/ml at 3 mo, respectively [19]. Hypogonadal symptoms improved in both the hCG and
Expert summary
It is essential for practitioners to consider the risks to future fertility when considering TRT as a treatment for patients with symptomatic hypogonadism. We recommend first considering alternative therapies, such as clomiphene citrate or hCG, in young men with mildly decreased testosterone. The use of clomiphene citrate or hCG as an alternative to TRT is effective at raising serum testosterone levels. However, the data supporting hypogonadal symptom relief with these agents is still
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