GnRH agonists are effective at treating endometriosis symptoms, but they have numerous limitations, including a delayed therapeutic impact because of the flare-up effect, excessive suppression of E2 to less than 20 pg/mL (with related unfavorable side effects), inability to titrate E2 levels, and unpredictable reversibility of treatment when injectable depot forms of GnRH agonists are used [95,96,97,98]. The gene discussed is GNRH1; the disease is endometriosis.