title: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; National Yang-Ming University, School of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Tsai
authors.affiliation: National Yang-Ming University, School of Medicine, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Wang
authors.affiliation: National Yang-Ming University, School of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University Hospital, Ilan, Taiwan.
authors.forename: Ben-Shian
authors.initials: BS
authors.lastname: Huang
authors.affiliation: National Yang-Ming University, School of Medicine, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Nae-Fang
authors.initials: NF
authors.lastname: Twu
authors.affiliation: National Yang-Ming University, School of Medicine, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ming-Shyen
authors.initials: MS
authors.lastname: Yen
authors.affiliation: National Yang-Ming University, School of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: chenyj@vghtpe.gov.tw.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects; D004338:Drug Combinations; D004715:Endometriosis / Q000188:drug therapy* / Q000601:surgery; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D020249:Hormone Replacement Therapy; D019584:Hot Flashes / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D016729:Leuprolide / Q000009:adverse effects*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D010352:Patient Dropouts; D011446:Prospective Studies; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D004338:Drug Combinations; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D016729:Leuprolide
keywords: add-back therapy; endometriosis; low-dose