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

Int J Mol Sci. 2020 Dec 22;22(1):21. doi: 10.3390/ijms22010021.


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.

Publication types

  • Review

MeSH terms

  • Androgens / blood
  • Androgens / therapeutic use
  • Clomiphene / therapeutic use
  • Fertility / drug effects
  • Hormone Replacement Therapy / methods*
  • Humans
  • Hypogonadism / drug therapy*
  • Male
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Testosterone / blood
  • Testosterone / therapeutic use*
  • Treatment Outcome


  • Androgens
  • Selective Estrogen Receptor Modulators
  • Clomiphene
  • Testosterone