GNRH1 and major depressive disorder: The use of GnRH agonists and antagonists is still based on the mechanism of estrogen suppression; therefore, they are often associated with irreversible osteoporosis, depression, and acne.10–12 Even with add-back therapy to address hypoestrogenism caused by GnRH antagonism, the dosing regimens used to titrate estrogen levels are complex and time-consuming.