Hormonal Add-Back Therapy for Females Treated With Gonadotropin-Releasing Hormone
Agonist for Endometriosis: A Randomized Controlled Trial.
Author(s): DiVasta AD(1), Feldman HA, Sadler Gallagher J, Stokes NA, Laufer MR, Hornstein
MD, Gordon CM.
Affiliation(s): Author information:
(1)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.
Publication date & source: 2015, Obstet Gynecol. ,
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.
CONCLUSION: 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.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; www.clinicaltrials.gov,
NCT00474851.
LEVEL OF EVIDENCE: I.
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