PMC

Prevalence and type of hypogonadism before (T0) and during (T1-T3) mitotane therapy; prevalence and type of hypogonadism before (T3) and six months after (T4) T gel therapy; prevalence of erectile dysfunction (ED) before (T3) and six months after (T4) androgen replacement therapy (ART); IIEF total score. (A), Prevalence of eugonadism (Eu), compensated hypogonadism (CH), hypogonadotropic hypogonadism (Hypo H), hypergonadotropic hypogonadism (Hyper H) and overt hypogonadism (Overt H) in the whole cohort at baseline (T0) and 6 (T1), 12 (T2) and 18 (T3) months after the initiation of mitotane therapy. (B), Prevalence of eugonadism (Eu), compensated hypogonadism (CH), hypogonadotropic hypogonadism (Hypo H), hypergonadotropic hypogonadism (Hyper H), and overt hypogonadism (Overt H) in five men before (T3) and after six months (T4) of T gel therapy. (C), Prevalence of erectile dysfunction (ED) in six men before (T3) and after six months (T4) of androgen replacement therapy (ART, including patients under T gel [n=3] and DHT gel [n=3] therapy). (D), Total score of International Index of Erectile Function-15 (IIEF-15) in six men before (T3) and after six months (T4) of ART. *p <0.05, comparing the prevalence of overt hypogonadism at T1, T2 and T3 vs. T0. **p <0.05, comparing the prevalence of hypergonadotropic hypogonadism at T1, T2 and T3 vs. T0.

Causes of hypogonadism. (a) Causes of secondary hypogonadism. (b) Causes of primary hypogonadism. In middle-aged and older men, functional (late-onset, age-related onset, or adult onset) hypogonadism is usually associated with low or normal gonadotropin levels. In contrast to organic secondary hypogonadism due to structural, destructive, or congenital pathology, functional hypogonadism is due to functional HPT axis suppression. Whereas organic hypogonadism typically presents with clinically and biochemically severe androgen deficiency and is not usually reversible, functional hypogonadism often presents with less severe androgen deficiency, is potentially reversible, and is more common than organic hypogonadism. IHH, idiopathic hypogondadotropic hypogonadism; GnRH, gonadotropin-releasing hormone; FSH, follicle-stimulating hormone; T, testosterone; T2DM, type 2 diabetes mellitus. Adapted from Matsumoto ().

Hypogonadism may be caused by a primary testicular pathology (primary hypogonadism, otherwise known as hypergonadotropic hypogonadism, which is defined as low testicular hormones, with high gonadotropins) resulting from malfunction at the level of the testes due to a genetic cause, injury, inflammation or infection (panel a). Conversely, central defects of the hypothalamus or the pituitary gland lead to secondary hypogonadism (also called central hypogonadism or hypogonadotropic hypogonadism, which is defined as low testicular hormones, with low or normal gonadotropins), which is most often caused by genetic defects, neoplasm or infiltrative disorders (panel b). FSH, follicle-stimulating hormone; GnRFI, gonadotropin-releasing hormone; LH, luteinizing hormone. Adapted with permission from REF., Oxford University Press.

Genes associated with congenital secondary hypogonadism. GnRH, gonadotropin-releasing hormone.