Prolactinomas are benign prolactin-secreting pituitary tumors. Prolactinomas are the most common type of hormone-secreting adenomas of the pituitary, comprising approximately 50 % of all clinically relevant pituitary adenomas (Daly & Beckers, 2020). Prolactinomas are found in 3.6–5.9 % of the population in unselected autopsy studies (Ezzat et al., 2004). Prolactinomas are categorized into microprolactinomas, smaller than 10 mm in diameter, mainly seen in premenopausal women, and larger adenomas with diameter ≥10 mm, termed macroprolactinomas, mainly seen in men and postmenopausal women (Colao et al., 2003). Serum prolactin levels are usually 60–200 ng/ml in microprolactinomas, and over 200 ng/ml in most macroprolactinomas. Prolactinomas result in two distinct clinical scenarios: (a) hyperprolactinemia, in all patients, and (b) tumor mass effect, in patients with large and invasive tumors.

Hyperprolactinemia in men causes secondary hypogonadism in 50 % of microprolactinoma and over 70 % of macroprolactinoma patients (Colao et al., 2004). Hyperprolactinemic males may suffer from decreased libido, erectile dysfunction, infertility (with low sperm counts), gynecomastia, and rarely galactorrhea. In females, menstrual disturbances are seen in over 75 % of patients with microprolactinoma and in almost all macroprolactinoma patients.

Tumor mass effect is caused by the pressure exerted by the growing adenoma on adjacent structures, including the optic chiasm (may cause visual field damage), the cranial nerves dwelling within the cavernous sinus (manifested by cranial nerve palsy and diplopia), and the normal anterior pituitary (leading to partial or complete hypopituitarism). Prolactinomas in men are larger and invasive compared with those in women (Duskin-Bitan & Shimon, 2020). This is reflected by the more prominent hyperprolactinemia in males, and in the higher rates of visual damage and hypopituitarism. In our cohort of 150 macroprolactinoma patients, including 121 men and 29 women, 30 % of men vs 10 % of women suffered from visual morbidity, and 19 % of men and 7 % of women presented with hypopituitarism (central hypocortisolism and/or central hypothyroidism). Hypogonadism was evident in 85 % of men and in 91 % of women.

Hypogonadism per se, with or without hyperprolactinemia, has significant implications for men’s health. Low testosterone levels are associated with low libido, sexual dysfunction, hot flashes, fatigue, loss of physical strength, depressive disorders, and changes in cognition and memory (Hackett et al., 2023). In some male prolactinoma patients, infertility is the main medical problem (Colao et al., 2004), a situation that can be both stressful and frustrating.

Additionally, male hypogonadism has metabolic effects, which are more pronounced in prolactinoma patients, mainly due to the profound suppression of testosterone levels; especially low bone mass (Naliato et al., 2005) and anemia (Shimon, Benbassat, Tzvetov, & Grozinsky-Glasberg, 2011). In light of the clinical manifestations, the main goals of treatment in male prolactinoma are serum prolactin normalization, tumor size reduction, and restoration of normal gonadal function (Auriemma et al., 2023). In general, treatment with dopamine agonists which normalizes prolactin levels in over 80 % of cases results in improvement of sexual function and fertility in men with prolactinomas (De Rosa et al., 1998). And yet, despite effective drug treatment with dopamine agonists, a significant proportion of patients suffer from hypogonadism persistence. In this review, we will focus on the diagnosis and treatment of hypogonadism in adult men with prolactinoma, with special emphasis on hypogonadism persistence.