Low-dose add-back therapy during postoperative GnRH agonist treatment

Abstract

Objective: Low-dose add-back therapy during postoperative GnRH agonist treatment could lower the risk of add-back-induced endometriosis recurrence and reduce treatment dropout compared with a regular dose. However, the effect of low-dose add-back therapy is still unknown. The aim of this study was to determine whether low-dose add-back therapy can also effectively relieve the hypoestrogenic side effects and simultaneously maintain a therapeutic response of GnRH agonist treatment.

Materials and methods: This analysis was a prospective cohort study. During postoperative GnRH agonist treatment, a total of 107 women were prescribed add-back therapy [oral combination tablet; estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg)] (Indivina; Orion, Espoo, Finland) for 20 weeks. Patients in the low dose add-back therapy group were prescribed the tablet once a day, and patients in the regular dose group were given the tablet twice a day. Hypoestrogenic side effects, such as hot flashes and insomnia, were recorded. Patients were also questioned regarding their pelvic symptoms and pain to evaluate the possibility of endometriosis recurrence. Lumbar spine (L2-L4) bone mineral density was measured using dual X-ray absorptiometry. The dropout rates in both groups were also evaluated.

Results: The incidence of hypoestrogenic side effects was lower in the low dose group compared with the regular dose group, including hot flashes (19.2% vs. 21.8%, p = 0.741) and insomnia (15.4% vs. 18.2%, p = 0.699), although there were no significant difference between the groups. In addition, a higher number of patients in the regular dose group dropped out of treatment compared to the low dose group (14.5% and 9.6%, respectively, p = 0.435). The patients in both groups had a significant loss of mean bone mineral density during therapy (p < 0.001 and p = 0.018 for the low dose and regular dose groups, respectively).

Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

Keywords: add-back therapy; endometriosis; low-dose.