Anxiety and mood disorders associated with gonadotropin-releasing hormone agonist therapy

Gonadotropin-releasing hormone (GnRH) agonists are synthetic derivatives of the native decapeptide produced by the hypothalamus. These agents cause a reversible suppression of the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary gland. With GnRH agonist therapy, there is a resulting loss of endogenous ovarian gonadotropin stimulation and a severe hypo-estrogen state consistent with castrate levels of estrogen. Recently, GnRH agonists such as leuprolide and goserelin have been noted to be effective in treating mild to severe endometriosis. Side effects of these agents are consistent with the physiological effects of ovarian suppression, such as vasomotor instability, vaginal dryness, and headaches. However, despite some reports of emotional lability as an adverse effect of GnRH agonists, it appears that the occasional, rather severe psychiatric consequences of these agents are underappreciated. In this article, we present the case reports of 4 women of reproductive age with no prior psychiatric history who were treated with a GnRH agonist for endometriosis. These women developed symptoms consistent with various psychiatric disorders, including panic disorder and major depression with and without psychotic features. Three of these patients were given sertraline while on GnRH agonist therapy, which improved their mood and anxiety symptoms. Women undergoing GnRH agonist therapy may provide a model with which to investigate mood disorders during the perimenopausal stage of life.