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Review
. 2020 Dec 22;22(1):21.
doi: 10.3390/ijms22010021.

Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy

Veerle Ide  1 , Dirk Vanderschueren  1   2 , Leen Antonio  1   2
Affiliations
Review

Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy

Veerle Ide et al. Int J Mol Sci. .

Abstract

Central hypogonadism is a clinical condition, characterized by sexual symptoms and low serum testosterone levels, due to an impaired function of the hypothalamus or pituitary gland. Testosterone replacement therapy (TRT) is the standard treatment for hypogonadism, but it has some disadvantages. TRT is not a good option in men wishing to preserve fertility, nor in men with (a high risk of) prostate cancer, polycythemia, thrombophilia and severe cardiovascular disease. In this review, we discuss alternative treatments for central hypogonadism. If reversible causes are present, non-pharmacological interventions can be therapeutic. Gonadotropins are a good alternative to TRT when fertility is desired in the near future though they require frequent injections. Clomiphene citrate and tamoxifen seem to be a safe alternative for the treatment of functional central hypogonadism in men, as several studies reported a significant increase in testosterone levels with these drugs. However, their use is off-label and data supporting the efficacy of clomiphene citrate and tamoxifen on hypogonadal symptoms are insufficient. For this reason, clomiphene citrate and tamoxifen should not be used in routine clinical practice to treat sexual symptoms in men with central hypogonadism.

Keywords: aromatase inhibitors; central hypogonadism; clomiphene citrate; functional hypogonadism; gonadotropins; hypogonadotropic hypogonadism; late-onset hypogonadism; tamoxifen.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the different causes of central hypogonadism. CHH: congenital hypogonadotropic hypogonadism.
Figure 2
Figure 2
Flowchart to guide the choice of treatment for central hypogonadism. The use of clomiphene citrate, tamoxifen and AIs is off-label in male hypogonadism. The effect of these drugs on hypogonadal symptoms has not been proven. TRT: testosterone replacement therapy, GnRH: gonadotropin releasing hormone, CC: clomiphene citrate, AIs: aromatase inhibitors.
See this image and copyright information in PMC

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