Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover

Patricia M Crofton (1) , Nancy Evans (2) , Louise Bath (3) , Pamela Warner (4) , Tessa Whitehead (5) , Hilary O D Critchley (6) , Christopher J H Kelnar (7) , William Hamish Wallace (8)

1 paediatric biochemistry
2 HRSU
3 paediatric endocrinology
4 Centre for population Health Sciences
5 Child Health
6 Centre for Reproductive Biology
7 Reproductive and Developmental Sciences
8 Paediatric oncology

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 randomised controlled crossover trial, 34 women with POF were randomised to 4-week cycles of pSSR (transdermal oestradiol, 100µg daily for week 1, 150µg for weeks 2-4; vaginal progesterone, 200mg twice-daily weeks 3-4) or sHRT (oral ethinyloestradiol 30µg and 1.5mg 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/post washout and after 3, 6 and 12 months of each treatment. Results 18 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. Keywords Ovarian failure, sex hormone replacement, bone mineral density, bone turnover markers.

Mots clés: Medicine

Patricia M Crofton, Nancy Evans, Louise Bath, Pamela Warner, Tessa Whitehead, et al.. Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover. Clinical Endocrinology, 2010, 73 (6), pp.707. ⟨10.1111/j.1365-2265.2010.03868.x⟩. ⟨hal-00593439⟩