Hypothalamic–Pituitary Diseases and Erectile Dysfunction

Abstract

Several hormones contribute to ensure penile erection, a neurovascular phenomenon in which nitric oxide plays a major role. Erectile dysfunction (ED), which is defined as the persistent inability to obtain or maintain penile erection sufficient for a satisfactory sexual performance, may be due to arteriogenic, neurogenic, iatrogenic, but also endocrinological causes. The hypothalamus–pituitary axis plays a central role in the endocrine system and represents a fundamental link between the brain and peripheral glands, including gonads. Therefore, the hormonal production of the hypothalamic–pituitary axis can control various aspects of sexual function and its dysregulation can compromise erectile function. In addition, excess and deficiency of pituitary hormones or metabolic alterations that are associated with some pituitary diseases (e.g., Cushing’s disease and acromegaly, hypopituitarism) can determine the development of ED with different mechanisms. Thus, the present review aimed to explore the relationship between hypothalamic and pituitary diseases based on the most recent clinical and experimental evidence.

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).…”

“…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). On the other hand, testosterone decline is known to occur physiologically in ageing men leading to the so-called late-onset (i.e., functional) hypogonadism (63)(64)(65)(66)(67)(68)(69), and to act either as a cause or consequence of some chronic comorbidities, such as metabolic syndrome, diabetes mellitus, hypertension, and cardiovascular disease, commonly seen also in patients with acromegaly (63,68,70).…”

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 ].…”

Lithium and Erectile Dysfunction: An Overview

“…It is well established that the dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis is involved in the pathogenesis of mood disorders [ 80 ] and sexual dysfunction [ 81 ]. Overall, glucocorticoids regulation is exerted on hypothalamic corticotropin-releasing factor (CRF) neurons in the PVN [ 82 ] and on other central regions, including the hippocampus and amygdala [ 83 ].…”