Acquired forms of isolated hypogonadotropic hypogonadism (HH) are often divided into organic (due to structural or genetic damage) and “functional” (related to comorbidities and aging). Even if a proper diagnosis and therapy of functional HH could improve lipid profile, body composition, insulin sensitivity, and glycaemic control in dysmetabolic patients, there is still no consensus if these “functional” forms should be treated. In fact, the potential reversibility of the condition and the lack of trials limited the use of pharmacological therapy. The pathogenetic mechanism of functional HH is also a matter of debate, and there are different hypotheses. In dysmetabolic forms it has been hypothesized that an estrogen excess due to adipose aromatization causes the hypogonadism through negative feedback; another hypothesis attributes the secretion of the reduced gonadotropins to systemic inflammation, or to a reduced neuronal sensitivity to insulin and/or leptin. Finally, it has been shown that in the adult-onset HH there is an enrichment of rare variants in the genes related to congenital HH, independently of the presence of obesity. Moreover, opioid-induced androgen deficiency and relative energy deficit male hypogonadism represent, together with dysmetabolic HH, an interesting field to better understand the consequences and treatments of functional forms of HH.

This research topic aims to collect an up-to-date resume of the current knowledge regarding functional forms of male hypogonadism, highlighting the differences and similarities of the different conditions leading to acquired isolated hypogonadotropic hypogonadism, the pathophysiological mechanisms underlying them, and possibly information about when and how to treat them.

Subtopics of interest include, but are not limited to:
- Genetics and hypothalamic-pituitary-gonadal axis, in acquired hypogonadotropic hypogonadism;
- Environment, lifestyle, metabolism, and hypothalamic-pituitary-gonadal axis, in acquired hypogonadotropic hypogonadism;
- Mechanisms of regulation of the hypothalamic-pituitary-gonadal axis and epigenetics;
- Diabetes and acquired hypogonadotropic hypogonadism;
- Obesity and hypogonadotropic hypogonadism;
- Opioid-induced androgen deficiency;
- Relative energy deficit male hypogonadism;
- HIV and hypogonadotropic hypogonadism;
- Health effects of acquired hypogonadotropic hypogonadism;
- Treatments of acquired hypogonadotropic hypogonadism.

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Frontiers in Endocrinology

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