Influence of current and past hormone replacement therapy on bone mineral density: A study of discordant postmenopausal twins

There is controversy about the ideal timing of hormone replacement therapy (HRT) and duration of treatment. In this study we have examined intrapair d ifferences in bone mineral density (BMD) in twins who were discordant for H RT use. Twin pairs in which only one co-twin had been exposed to HRT for mo re than 12 months continuously were selected from 365 postmenopausal monozy gotic (MZ) and dizygotic (DZ) pairs recruited as part of the St Thomas' Adu lt UK Twin Registry of normal volunteers. BMD was measured by dual-energy X -ray absorptiometry at the lumbar spine and femoral neck. Intrapair differe nces in BMD between HRT users and non-users were compared. A total of 65 HR T-discordant pairs were identified, of which 36 were discordant for current HRT use (mean age: 55.3 years, median duration of HRT use: 36 months) and 29 were discordant for past HRT use (mean age: 60.3 years, median HRT durat ion: 30 months). Among current users BMD was consistently and significantly higher than in non-users at both sites (lumbar spine mean intrapair differ ence (IPD%): 12.3%, 95% confidence interval (CI): 7.1%, 17.5%: femoral neck IPD%: 8.6%, 95% CI: 3.4%, 13.7%). The intrapair differences were substanti ally smaller when past users and non-users were compared (lumbar spine IPD% : 2.4%, 95% CI: -3.7%, 8.6%; femoral neck IPD%: 0.4%, 95% CI: -5.3%, 6.0%). These differences remained little changed after adjusting for the potentia l confounding effects of the duration of HRT use, and intrapair differences in alcohol and tobacco consumption and physical exercise. The results conf irm, in a closely matched design, the findings Of other observational resea rch that current use of HRT has a major effect on BMD at the lumbar spine a nd femoral neck. Past users of HRT do not, however, show the same benefits. The clinical implications of these findings are that HRT needs to be used continuously to influence BMD and that alternative treatments need to be co nsidered in those who discontinue HRT.