Vibha Singhal1, Nazanin Hazhir Karzar2, Amita Bose3, Colleen Buckless4, Kathryn E Ackerman5, Miriam A Bredella6, Anne Klibanski7, Madhusmita Misra8. 1. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Division of Pediatric Endocrinology, Mass General Hospital for Children and Harvard Medical School, Boston, MA, United States; MGH Weight Center, Massachusetts General Hospital, Boston, MA, United States. Electronic address: Vsinghal1@partners.org. 2. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: nhazhirkarzar@mgh.harvard.edu. 3. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: Abose1@mgh.harvard.edu. 4. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: Cbuckless@mgh.harvard.edu. 5. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: Kathryn.ackerman@childrens.harvard.edu. 6. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: mbredella@mgh.harvard.edu. 7. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. Electronic address: aklibanski@partners.org. 8. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Division of Pediatric Endocrinology, Mass General Hospital for Children and Harvard Medical School, Boston, MA, United States. Electronic address: mmisra@mgh.harvard.edu.
Abstract
CONTEXT: Low energy availability causes disruption of hypothalamic gonadotropin-releasing hormone secretion leading to functional hypothalamic amenorrhea (FHA) and hypoestrogenism, which in turn contributes to decreased bone mineral density (BMD) and increased bone marrow adipose tissue (MAT). Transdermal estradiol administration in physiologic doses increases BMD in adolescents and adults with FHA. However, the impact of estrogen replacement on MAT in relation to changes in BMD has not been studied in adolescents and young adults. We hypothesized that physiologic estrogen replacement would lead to decreases in MAT, associated with increases in BMD. METHODS AND MATERIALS: We studied 15 adolescent and young adult females with FHA (14-25 years). All participants received a17β- estradiol transdermal patch at a dose of 0.1 mg/day (applied twice weekly) for 12 months. Participants also received cyclic progestin for 10-12 days each month. We quantified MAT (lipid/water ratio) of the fourth lumbar (L4) vertebral body and femoral diaphysis by single proton (1H)-magnetic resonance spectroscopy, and compartmental volumetric BMD of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. RESULTS: Transdermal estradiol therapy over 12 months resulted in a decrease in MAT at the lumbar (L4) vertebra from 0.92 ± 0.55 at baseline to 0.63 ± 0.29 at 12-months (p = 0.008), and an increase in radial and tibial cortical vBMD (p = 0.006, p = 0.0003). Changes in L4 MAT trended to be inversely associated with changes in radial cortical vBMD (rho = -0.47, p = 0.08). CONCLUSION: We show that in adolescent and young adult girls with FHA, MAT decreases following transdermal estrogen therapy and these changes are associated with increased cortical vBMD.
CONTEXT: Low energy availability causes disruption of hypothalamic gonadotropin-releasing hormone secretion leading to functional hypothalamic amenorrhea (FHA) and hypoestrogenism, which in turn contributes to decreased bone mineral density (BMD) and increased bone marrow adipose tissue (MAT). Transdermal estradiol administration in physiologic doses increases BMD in adolescents and adults with FHA. However, the impact of estrogen replacement on MAT in relation to changes in BMD has not been studied in adolescents and young adults. We hypothesized that physiologic estrogen replacement would lead to decreases in MAT, associated with increases in BMD. METHODS AND MATERIALS: We studied 15 adolescent and young adult females with FHA (14-25 years). All participants received a17β- estradiol transdermal patch at a dose of 0.1 mg/day (applied twice weekly) for 12 months. Participants also received cyclic progestin for 10-12 days each month. We quantified MAT (lipid/water ratio) of the fourth lumbar (L4) vertebral body and femoral diaphysis by single proton (1H)-magnetic resonance spectroscopy, and compartmental volumetric BMD of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. RESULTS: Transdermal estradiol therapy over 12 months resulted in a decrease in MAT at the lumbar (L4) vertebra from 0.92 ± 0.55 at baseline to 0.63 ± 0.29 at 12-months (p = 0.008), and an increase in radial and tibial cortical vBMD (p = 0.006, p = 0.0003). Changes in L4 MAT trended to be inversely associated with changes in radial cortical vBMD (rho = -0.47, p = 0.08). CONCLUSION: We show that in adolescent and young adult girls with FHA, MAT decreases following transdermal estrogen therapy and these changes are associated with increased cortical vBMD.
Authors: Pouneh K Fazeli; Mark C Horowitz; Ormond A MacDougald; Erica L Scheller; Matthew S Rodeheffer; Clifford J Rosen; Anne Klibanski Journal: J Clin Endocrinol Metab Date: 2013-02-07 Impact factor: 5.958
Authors: Catherine M Gordon; Kathryn E Ackerman; Sarah L Berga; Jay R Kaplan; George Mastorakos; Madhusmita Misra; M Hassan Murad; Nanette F Santoro; Michelle P Warren Journal: J Clin Endocrinol Metab Date: 2017-05-01 Impact factor: 5.958
Authors: Kirsten Ecklund; Sridhar Vajapeyam; Robert V Mulkern; Henry A Feldman; Jennifer M O'Donnell; Amy D DiVasta; Catherine M Gordon Journal: Pediatr Radiol Date: 2017-04-22
Authors: S Tolonen; M Juonala; M Fogelholm; K Pahkala; M Laaksonen; M Kähönen; H Sievänen; J Viikari; O Raitakari Journal: Calcif Tissue Int Date: 2022-07-27 Impact factor: 4.000