Hypogonadism in men with prolactinoma: Diagnosis, treatment, and management of persistent hypogonadism.

Prolactin-secreting adenomas comprise approximately 50 % of all clinically relevant pituitary adenomas. Most men with prolactinomas present with large and invasive tumors. Despite effective medical therapy with dopamine agonists and prolactin normalization, over 20 % of men with prolactinomas will remain with hypogonadism. There are two suggested mechanisms for hypogonadism: central suppression of the hypothalamic-pituitary-gonadal axis caused by elevated prolactin levels leading to inhibition of the kisspeptin neurons in the hypothalamus and loss of pulsatile luteinizing hormone secretion, and tumor mass effect with compression of the normal pituitary tissue and destruction of gonadotroph cells. Hypogonadism in men results in sexual dysfunction, low libido, anemia, fatigue, and infertility. Identification of patients who are likely to recover the damaged gonadal axis upon prolactin suppression is important. These are men that harbor smaller tumors, with higher testosterone levels at diagnosis, no visual field defects, and without impairment in the secretion of other pituitary hormones. Testosterone replacement should be offered to patients with lower chance of restoring normal function of the gonadal axis. However, most men will achieve spontaneous recovery of the hypothalamic-pituitary-gonadal axis within 12 months after prolactin normalization. For men with prolactinoma and hypogonadism persistence who wish to restore fertility, treatment with gonadotropins or with clomiphene citrate has been found to be safe and effective. In the present review, we propose an algorithm for the management of hypogonadism persistence in men with macroprolactinomas.