Acromegaly and male sexual health

Abstract

Acromegaly is a rare pathology characterized by chronic hypersecretion of Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) that causes somatic, metabolic, and systemic changes. The somatotropic axis acts physiologically favoring gonadal function, but when GH is produced in excess it has deleterious effects on many aspects of male sexuality. It is widely demonstrated, in fact, that acromegaly induces hypogonadism through different mechanisms, both through direct mass effect on gonadotropic cells and through increased plasma levels of prolactin. Moreover, hypogonadism is also one of the factors linking acromegaly to erectile dysfunction (ED), but also metabolic complications of acromegaly and, probably, GH itself contribute to the genesis of this disorder. There are few data in the literature on the impact of the disease on fertility and testicular volume. Finally, knowledge of the role of GH hypersecretion on the occurrence of prostatic diseases such as benign prostatic hypertrophy and prostatic cancer appears to be of fundamental clinical importance in the long-term management of these patients.

Global psychological assessment with the evaluation of life and sleep quality and sexual and cognitive function in a large number of patients with acromegaly: a cross-sectional study

“…Interestingly, GH levels at diagnosis and IGF-I levels at evaluation and disease control status have been found not to significantly impact sexual function. A strong link between GH and IGF-I excess and sexual dysfunction in men has been extensively elucidated (21,(57)(58)(59)(60)(61)(62). The co-existence of hypogonadotropic hypogonadism due to tumour mass effect or treatments for acromegaly, such as neurosurgery and/or radiotherapy, and high levels of GH and IGF-I has been reported to alter the regular pulsatility of the gonadotropin secretion at the hypothalamic-pituitary level (57), thus contributing to the pathogenesis of erectile dysfunction as the expression of worse sexual health (21,(58)(59)(60).…”

“…A strong link between GH and IGF-I excess and sexual dysfunction in men has been extensively elucidated (21,(57)(58)(59)(60)(61)(62). The co-existence of hypogonadotropic hypogonadism due to tumour mass effect or treatments for acromegaly, such as neurosurgery and/or radiotherapy, and high levels of GH and IGF-I has been reported to alter the regular pulsatility of the gonadotropin secretion at the hypothalamic-pituitary level (57), thus contributing to the pathogenesis of erectile dysfunction as the expression of worse sexual health (21,(58)(59)(60). Concomitant cardiovascular, such as arterial hypertension and endothelial dysfunction, respiratory, mainly OSAS, and metabolic complications, including abnormalities in glucose and lipid profile leading to insulin resistance, diabetes mellitus and dyslipidemia, may further compromise erectile function and induce a decrease of desire and arousability in acromegaly (21,58,60).…”

Approach of Acromegaly during Pregnancy

“…Hypopituitarism (including central hypogonadism), reported in 10–80% of acromegalic cases, and hyperprolactinemia (affecting more than one third of the patients) are associated with a higher rate of subfertility/infertility in acromegalic patients when compared to a non-acromegalic population of the same age, in both females and males [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Pituitary insufficiency and increased prolactin status are related to larger tumors; 90–95% of pituitary GH secreting tumors are macroadenomas; the additional negative role concerning fertility status is caused by secondary DM [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. For instance, one study from 2022 on 529 acromegalic individuals identified a rate of hyperprolactinemia of 39.1% and a prevalence of hypopituitarism of 34.8%, with the gonadal axis being the most affected pituitary axis; there was a hypogonadism frequency of 29.7% [ 45 ].…”

“…In males, the same mechanisms are contributors to erectile dysfunction, while GH growth-promoting effects may be involved in benign prostatic hypertrophy [ 46 , 47 , 48 ].…”

Erectile function and androgen and estrogen beta receptor gene polymorphisms in acromegalic men

“…This intertwined function appears to be characterized by several dynamic redundancies during the transition age, which become evident since puberty, while in adult life, both axes disturbances may impact on reproductive function [ 15 ]. In fact, it is known that, both in peri-pubertal boys and in elderly subjects, exogenous testosterone or GnRH administration is associated with an increase in GH levels [ 16 ]. Likewise, Leydig and Sertoli cells and primary spermatocytes respond to IGF-1, which may also be secreted under gonadotropin control by the Leydig and Sertoli cells themselves [ 16 ].…”