Effects of different add-back regimens on hypoestrogenic problems by postoperative gonadotropin-releasing hormone agonist treatment in endometriosis

OBJECTIVE To compare the efficacy of different add-back regimens on hypoestrogenic symptoms during postoperative gonadotropin-releasing hormone (GnRH) agonist treatment in endometriosis patients. METHODS This prospective cohort study included reproductive-aged women who underwent conservative laparoscopic surgery for ovarian endometriosis and received add-back therapy during a 6-month course of GnRH agonist therapy after surgery. Participants received one of four different add-back regimens: 1 mg of estradiol valerate, 2.5 mg of tibolone, or a combination of 1 mg of estradiol and 2 mg of drospirenone or 0.5 mg of norethisterone acetate. Changes in quality of life, hypoestrogenic symptoms, and bone mineral density were compared according to add-back regimens. RESULTS A total of 57 participants completed a 6-month course of GnRH agonist and add-back therapy. All components of quality of life did not differ across groups. However, within the same treatment group, social relationship factors decreased significantly with estradiol valerate and tibolone alone, and environmental factors decreased significantly with estradiol valerate alone. Menopausal Rating Scale score did not change significantly, but the incidence of hot flushes significantly decreased with a combination of estradiol and norethisterone acetate. Bone mineral densities at the lumbar spine declined significantly after treatment in all groups except with a combination of estradiol and norethisterone acetate. CONCLUSION This preliminary study suggests that an add-back regimen containing estradiol valerate and norethisterone acetate may have better efficacy in terms of quality of life, hypoestrogenism-associated symptoms, and bone mineral density.