BACKGROUND: The aim of this exploratory study was to establish whether we could improve skeletal health with a physiological regimen of SSR in young women with premature ovarian failure (POF). PATIENTS AND METHODS: In an open-label randomized controlled crossover trial, 34 women with POF were randomized to 4-week cycles of pSSR (transdermal oestradiol, 100 μg daily for week 1, 150 μg for weeks 2-4; vaginal progesterone, 200 mg twice daily for weeks 3-4) or standard hormone replacement treatment (sHRT) (oral ethinyloestradiol 30 μg and 1·5 mg norethisterone daily for weeks 1-3, week 4 'pill-free') for 12 months. Bone mineral density (BMD) was measured by DEXA at study entry and after each 12-month treatment period. Blood samples for hormones and markers of bone formation (bone alkaline phosphatase, BALP and type I collagen N-terminal propeptide, PINP) and bone resorption (CrossLaps) were collected pre-/postwashout and after 3, 6 and 12 months of each treatment. RESULTS:Eighteen women, mean 27 (range 19-39) years, completed the study. Both regimens caused similar suppression of LH and FSH. Mean baseline lumbar spineBMD z-score was -0·89 (95% CI -1·27 to -0·51) and increased by +0·17 (CI +0·07 to +0·27) in response to pSSR (P = 0·003), compared with +0·07 (CI -0·03 to +0·18) during standard HRT (P = 0·2). During pSSR, the increment in lumbar spine BMD z-score was related positively to oestradiol (r = +0·49, P = 0·04) and inversely to FSH (r = -0·65, P = 0·004). Bone formation markers, BALP and P1NP increased in the pSSR arm (anova P < 0·001) but decreased in the sHRT arm (P < 0·01). Both treatments suppressed the bone resorption marker, CrossLaps (P < 0·001). CONCLUSION: We conclude that pSSR over 12 months has a beneficial affect on bone mass acquisition on the lumbar spine in women with POF, mediated by increased bone formation and decreased bone resorption.
RCT Entities:
BACKGROUND: The aim of this exploratory study was to establish whether we could improve skeletal health with a physiological regimen of SSR in young women with premature ovarian failure (POF). PATIENTS AND METHODS: In an open-label randomized controlled crossover trial, 34 women with POF were randomized to 4-week cycles of pSSR (transdermal oestradiol, 100 μg daily for week 1, 150 μg for weeks 2-4; vaginal progesterone, 200 mg twice daily for weeks 3-4) or standard hormone replacement treatment (sHRT) (oral ethinyloestradiol 30 μg and 1·5 mg norethisterone daily for weeks 1-3, week 4 'pill-free') for 12 months. Bone mineral density (BMD) was measured by DEXA at study entry and after each 12-month treatment period. Blood samples for hormones and markers of bone formation (bone alkaline phosphatase, BALP and type I collagen N-terminal propeptide, PINP) and bone resorption (CrossLaps) were collected pre-/postwashout and after 3, 6 and 12 months of each treatment. RESULTS: Eighteen women, mean 27 (range 19-39) years, completed the study. Both regimens caused similar suppression of LH and FSH. Mean baseline lumbar spine BMD z-score was -0·89 (95% CI -1·27 to -0·51) and increased by +0·17 (CI +0·07 to +0·27) in response to pSSR (P = 0·003), compared with +0·07 (CI -0·03 to +0·18) during standard HRT (P = 0·2). During pSSR, the increment in lumbar spine BMD z-score was related positively to oestradiol (r = +0·49, P = 0·04) and inversely to FSH (r = -0·65, P = 0·004). Bone formation markers, BALP and P1NP increased in the pSSR arm (anova P < 0·001) but decreased in the sHRT arm (P < 0·01). Both treatments suppressed the bone resorption marker, CrossLaps (P < 0·001). CONCLUSION: We conclude that pSSR over 12 months has a beneficial affect on bone mass acquisition on the lumbar spine in women with POF, mediated by increased bone formation and decreased bone resorption.
Authors: Vaishali B Popat; Karim A Calis; Sophia N Kalantaridou; Vien H Vanderhoof; Deloris Koziol; James F Troendle; James C Reynolds; Lawrence M Nelson Journal: J Clin Endocrinol Metab Date: 2014-06-06 Impact factor: 5.958
Authors: Jasna Aleksova; Alexander J Rodriguez; Robert McLachlan; Peter Kerr; Frances Milat; Peter R Ebeling Journal: Curr Osteoporos Rep Date: 2018-12 Impact factor: 5.096
Authors: Malinda Wu; Erika L Bettermann; Neha Arora; William R Hunt; Courtney McCracken; Vin Tangpricha Journal: Am J Med Sci Date: 2020-06-06 Impact factor: 2.378
Authors: Hanneke M van Santen; Marry M van den Heuvel-Eibrink; Marianne D van de Wetering; W Hamish Wallace Journal: Horm Res Paediatr Date: 2019-01-31 Impact factor: 2.852
Authors: Wendy van Dorp; Renée L Mulder; Leontien C M Kremer; Melissa M Hudson; Marry M van den Heuvel-Eibrink; Marleen H van den Berg; Jennifer M Levine; Eline van Dulmen-den Broeder; Natascia di Iorgi; Assunta Albanese; Saro H Armenian; Smita Bhatia; Louis S Constine; Andreas Corrias; Rebecca Deans; Uta Dirksen; Clarisa R Gracia; Lars Hjorth; Leah Kroon; Cornelis B Lambalk; Wendy Landier; Gill Levitt; Alison Leiper; Lillian Meacham; Alesandro Mussa; Sebastian J Neggers; Kevin C Oeffinger; Alberto Revelli; Hanneke M van Santen; Roderick Skinner; Andrew Toogood; William H Wallace; Riccardo Haupt Journal: J Clin Oncol Date: 2016-07-25 Impact factor: 44.544