title: Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa.
abstract: Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low BMD in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategies to improve BMD in adolescents with AN have not been identified. Specifically, high estrogen doses given as an oral contraceptive do not improve BMD. The impact of physiologic estrogen doses that mimic puberty on BMD has not been examined. We enrolled 110 girls with AN and 40 normal-weight controls 12 to 18 years of age of similar maturity. Subjects were studied for 18 months. Mature girls with AN (bone age [BA] ≥15 years, n = 96) were randomized to 100 µg of 17β-estradiol (with cyclic progesterone) or placebo transdermally for 18 months. Immature girls with AN (BA < 15 years, n = 14) were randomized to incremental low-dose oral ethinyl-estradiol (3.75 µg daily from 0 to 6 months, 7.5 µg from 6 to 12 months, 11.25 µg from 12 to 18 months) to mimic pubertal estrogen increases or placebo for 18 months. All BMD measures assessed by dual-energy X-ray absorptiometry (DXA) were lower in girls with AN than in control girls. At baseline, girls with AN randomized to estrogen (AN E + ) did not differ from those randomized to placebo (AN E-) for age, maturity, height, BMI, amenorrhea duration, and BMD parameters. Spine and hip BMD Z-scores increased over time in the AN E+ compared with the AN E- group, even after controlling for baseline age and weight. It is concluded that physiologic estradiol replacement increases spine and hip BMD in girls with AN.
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. mmisra@partners.org
authors.forename: Madhusmita
authors.initials: M
authors.lastname: Misra
authors.forename: Debra
authors.initials: D
authors.lastname: Katzman
authors.forename: Karen K
authors.initials: KK
authors.lastname: Miller
authors.forename: Nara
authors.initials: N
authors.lastname: Mendes
authors.forename: Deirdre
authors.initials: D
authors.lastname: Snelgrove
authors.forename: Melissa
authors.initials: M
authors.lastname: Russell
authors.forename: Mark A
authors.initials: MA
authors.lastname: Goldstein
authors.forename: Seda
authors.initials: S
authors.lastname: Ebrahimi
authors.forename: Laura
authors.initials: L
authors.lastname: Clauss
authors.forename: Thomas
authors.initials: T
authors.lastname: Weigel
authors.forename: Diane
authors.initials: D
authors.lastname: Mickley
authors.forename: David A
authors.initials: DA
authors.lastname: Schoenfeld
authors.forename: David B
authors.initials: DB
authors.lastname: Herzog
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000856:Anorexia Nervosa / Q000503:physiopathology*; D015519:Bone Density; D002648:Child; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans