Glucocorticoid Induced Hypothalamic-Pituitary Axis Alterations Associated with Hypogonadotropic Hypogonadism

Abstract

Since the existence of cortisol in 1930 to current multiple formulations of glucocorticoids, it has been one of the most widespread medications to use for the treatment of simple to serious maladies. Glucocorticoids have gained unprecedented importance in treating autoimmune and inflammatory diseases, with one study conducted between 1998-2008 signifying that 1.2% of Americans over the age of 20 were at one point on glucocorticoid therapy, accounting for approximately 2.5 million Americans over the course of a decade. In this brief review, we focused on consequences of glucocorticoid therapy on alteration of sex steroids mainly in men with subsequent low libido, fatigue, erectile dysfunction, loss of muscle mass, increasing adipose tissue and osteoporosis. Effects of glucocorticoids appraised, based on current and available evidence at the level of the hypothalamus and pituitary, could cause alteration on the adipocyte-kisspeptin-gonadotropin-releasing hormone (GnRH)-luteinizing hormone (LH)-follicle-stimulating hormone (FSH) axis, especially with long-term use. The resultant hypogonadism occurs by suppression of GnRH-receptors, GnRH, LH, and FSH. Hypogonadism in patients with rheumatological diseases has multiple reasons, one of which is functional due to current illness and alteration in cytokines and inflammatory markers, and the other is a consequence of glucocorticoid therapy, which in either situation treatment of hypogonadism may improve quality of life and prevent complications of hypogonadism.