title: Hormonal Add-Back Therapy for Females Treated With Gonadotropin-Releasing Hormone Agonist for Endometriosis: A Randomized Controlled Trial.
abstract: OBJECTIVE
  To assess whether add-back therapy with norethindrone acetate or norethindrone acetate plus conjugated equine estrogens is superior to maintain bone health in adolescents and young women using gonadotropin-releasing hormone agonists for endometriosis. Gonadotropin-releasing hormone agonists are associated with deleterious effects on bone. Hormonal add-back may mitigate these effects.
  
  
  METHODS
  Adolescents and young women (n=51) received a random, double-blind assignment to add-back with norethindrone acetate (5 mg/day) plus conjugated equine estrogens (0.625 mg/day) or norethindrone acetate plus placebo for 12 months. Body composition, bone mineral content, and bone mineral density (BMD) were obtained by dual-energy X-ray absorptiometry every 6 months. Quality-of-life measures were collected every 3 months. Intention-to-treat comparison of outcomes was conducted by repeated-measures analysis of variance.
  
  
  RESULTS
  Thirty-four adolescents and young women completed the trial; dropouts did not differ from those who completed the trial. Bone mineral density was normal at baseline. At 12 months, total body bone mineral content and BMD had increased in the norethindrone acetate plus conjugated equine estrogens group (bone mineral content +37 g, P<.001 and BMD +0.012 g/cm, P=.05), but not in those receiving norethindrone acetate plus placebo (bone mineral content P=.19 and BMD P=.95). Lean mass increased only in those receiving conjugated equine estrogens (+1.4 kg, P=.001). Improvements in physical functioning domains of quality-of-life assessments were greater with norethindrone acetate plus conjugated equine estrogens (P=.005). No differences were seen at the hip or lumbar spine by dual-energy X-ray absorptiometry. No significant adverse events occurred.
  
  
  CONCLUSIONS
  Hormonal add-back successfully preserved bone health and improved quality of life for adolescents and young women with endometriosis during 12 months of gonadotropin-releasing hormone agonist therapy. Combination norethindrone acetate plus conjugated equine estrogens add-back appears to be more effective for increasing total body bone mineral content, areal BMD, and lean mass than norethindrone acetate monotherapy.
  
  
  BACKGROUND
  ClinicalTrials.gov; www.clinicaltrials.gov, NCT00474851.
  
  
  METHODS
  I.
authors.affiliation: Division of Adolescent Medicine, the Division of Gynecology, and the Clinical Research Program, Children's Hospital Boston, the Boston Center for Endometriosis, and the Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts; the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and the Divisions of Adolescent Medicine and Endocrinology, Hasbro Children's Hospital, Providence, Rhode Island.
authors.forename: Amy D
authors.initials: AD
authors.lastname: DiVasta
authors.forename: Henry A
authors.initials: HA
authors.lastname: Feldman
authors.forename: Jenny
authors.initials: J
authors.lastname: Sadler Gallagher
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Stokes
authors.forename: Marc R
authors.initials: MR
authors.lastname: Laufer
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hornstein
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Gordon
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000293:Adolescent; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000139:chemically induced / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004715:Endometriosis / Q000175:diagnosis / Q000188:drug therapy*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D006801:Humans; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D011446:Prospective Studies; D011788:Quality of Life; D018570:Risk Assessment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004966:Estrogens, Conjugated (USP); D007987:Gonadotropin-Releasing Hormone; D000077563:Norethindrone Acetate; D009640:Norethindrone