GnRH agonist + estradiol valerate + progesterone

This is a combination therapy consisting of a gonadotropin-releasing hormone (GnRH) agonist, estradiol valerate (a synthetic estrogen), and progesterone. The regimen is primarily used as "add-back" therapy during or after GnRH agonist treatment for conditions such as endometriosis, uterine fibroids, and in assisted reproductive technology protocols. The GnRH agonist suppresses pituitary gonadotropin secretion, leading to decreased ovarian estrogen production and hypoestrogenic side effects like bone loss and vasomotor symptoms. Estradiol valerate acts as an estrogen receptor agonist to mitigate these hypoestrogenic effects by restoring physiological estrogen levels. Progesterone is added to counteract the risk of endometrial hyperplasia from unopposed estrogen exposure by providing progestogenic activity on the endometrium[1][3][7]. This combination aims to relieve pain symptoms, reduce bone mass loss, alleviate menopausal symptoms, improve quality of life during prolonged GnRH agonist use, and maintain patient compliance[1][3]. Dosing regimens vary but often include daily oral administration of low-dose estradiol valerate (0.5–1 mg) with progesterone (5 mg)[1][3].