Hypogonadism in Systemic Diseases

Abstract

Serum testosterone is often lower than normal in patients with acute or chronic systemic diseases. The underlying mechanisms involved in the reduced testosterone secretion depend on the type of systemic disease; thus, many pathogenetic mechanisms might be involved. These mechanisms involve the hypothalamus and the pituitary (secondary hypogonadism), the testis (primary hypogonadism), or both. The resulting low-serum testosterone could be reversible or not depending on the pathogenetic mechanism. Furthermore, the relationships between hypogonadism and the systemic disease are complex since these two clinical conditions may interact with each other in a bidirectional interplay. How to interpret low-serum testosterone in systemic diseases is not easy and univocal. Biochemical hypogonadism should be differentiated into overt clinical hypogonadism and functional hypogonadism, and testosterone treatment should be offered taking into account the primary systemic disease and the possible beneficial or harmful effect on it, as well as the presence of signs and symptoms of hypogonadism. In this chapter the main systemic illnesses associated with hypogonadism will be discussed together with their underlying pathogenetic mechanisms, clinical significance, relevance, and clinical and practical implications

Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV

“…These findings resemble those coming from HIV-uninfected older men where lower TS associated to comorbidities (16,47) to body fat (43) and the prevalence of hypogonadism was considerable in frail men (13,14,42,48,49). These comorbidities, in fact, are highly prevalent in HIV-uninfected men with hypogonadism (15,16,17,20,26) and may concur to the so called functional hypogonadism as in older men (21,22,41,43). Altogether these results confirm that a poor health status is almost constantly linked to low TS.…”

“…It seems that increased body fat, increased E1 and E2/TS, low circulating TS and poor health status in terms of both frailty and MM all take part to a sort of complex and multifactorial vicious circle resulting in HIVrelated hypogonadism whose cause-effect relationships remain uncertain due to the bidirectional action exerted by these elements (39). As an example, low TS levels can be at the same time the cause and the consequence of both changes in body fat and the onset of NICMs (11,13,17,20,21,26,45). This study does not help establishing a cause-effect relationship among all these factors due to its cross-sectional design, but allows starting to move from the interpretation of low TS in men with HIV as a condition of true hypogonadism (10,46) to that of biochemical functional hypogonadism (21,22).…”

“…This study has strengths and limitations. This is a properly designed study to investigate the gonadal function in HIV-infected men by measuring total TS, E2, and E1 with the recommended analytical procedure (ID-LC-MS/MS) alongside SHBG in order to calculate free TS that is recognized to be the most reliable biomarker to detect the gonadal status in these patients (20,22,27). The definition of general health status was performed by prospective data collection about NICMs and frailty, the latter assessed by ad hoc questionnaire validated for HIV-population (36).…”

“…A poor health status seems to be associated to low TS in men (13,14,15,16). In particular, low TS levels are associated to several chronic diseases such as obesity (17), diabetes mellitus (18), dyslipidemia , metabolic syndrome (19) and several other systemic diseases (20). These forms of male hypogonadism are considered as strictly related to poor health, secondary to other morbidities and partially reversible, and endocrinologists tend to classify them as a sort of functional hypogonadism (20,21,22).…”

“…In particular, low TS levels are associated to several chronic diseases such as obesity (17), diabetes mellitus (18), dyslipidemia , metabolic syndrome (19) and several other systemic diseases (20). These forms of male hypogonadism are considered as strictly related to poor health, secondary to other morbidities and partially reversible, and endocrinologists tend to classify them as a sort of functional hypogonadism (20,21,22). Besides, increased body fat is associated to low TS in men, this association being bidirectional (17) and body fat, especially visceral fat, is associated with frailty both in HIV-uninfected (23) and HIV-infected men (24).…”