Postmenopausal bone loss: does HRT always work?

In a 3-year study comparing oral and transdermal HRT, we measured bone density in the spine and proximal femur by dual-photon absorptiometry. Sixty-six women were randomly allocated to receive either oral conjugated equine oestrogens, 0.625 mg daily, together with cyclical oral dl-norgestrel, 0.15 mg daily, or transdermal 17 beta-oestradiol, 0.05 mg daily, together with cyclical transdermal norethisterone acetate, 0.25 mg daily. We found that only 2% showed significant vertebral bone loss on either treatment, whilst approximately 12% lost from the proximal femur. Compliance was demonstrated by monitoring all used patches and pill packets, recording all side effects and bleeding patterns, and by the demonstration of appropriate changes in levels of gonadal steroids and lipoproteins. Comparing the bone losers with the ten highest gainers, lowers were closer to their menopause but were not different in body mass or life style. Serum oestradiol levels were similar, and both groups showed a similar response in terms of changes in bone biochemical markers and lipoproteins in response to HRT. In thus seems that a small proportion of women do not conserve bone density in the proximal femur with standard doses of HRT. It remains to be determined whether they could be identified by more specific biochemical markers of bone turnover, and whether they would maintain with a higher dose of oestrogen.