[Note: hormone therapy (HT) may also be referred to as hormone replacement therapy (HRT).]

This study has evaluated the effects of very low dose oral oestradiol therapy (0.25 mg/day) on bone mineral density and bone metabolism in older postmenopausal women (average age 74 years) in a small randomised placebo-controlled trial . Women who had not had a hysterectomy also received oral micronised progesterone for 2 weeks, every 6 months. All participants were treated with supplementary calcium and Vitamin D.

The primary outcome for the study was change in bone mineral density (BMD) of the hip. Other outcomes were changes in BMD of the spine, wrist and total body as well as blood and urine markers of bone turnover (bone break down and rebuilding). The study did not have sufficient statistical power to examine whether treatment reduced fracture rates.

The trial was small with only 84 women randomised to the placebo group and 83 to the active treatment group. The trial participants were not a very high risk group with respect to BMD, with only 12-13% having osteoporosis as assessed at the femoral neck and the exclusion of women with very low BMD (t-score <-4).

The study showed that the treatment group had an increase in BMD at all sites compared with women in the placebo group as well as a reduction in bone turnover. The mean difference in BMD (total hip) between the active treatment and placebo groups after 3 years was 3.6% (p< 0.001).

There was no difference between the treatment and control groups in the number of adverse events reported, particularly endometrial (uterine) pathology, abnormal mammograms or breast cancer, however the study was small and would have had very limited statistical capacity to detect such differences.

Overall this small study adds to the growing number of studies that show that low dose HT has a beneficial effect on BMD. Whether such an effect translates into significantly reduced fracture risk needs to be determined. The study was also too small to demonstrate safety in relation to cardiovascular disease and breast cancer. What is required in this area is a study large enough to report on the primary end-point of fracture risk and powerful enough to demonstrate that a low dose HT regimen is associated with reduced risk of cardiovascular disease and breast cancer.

Content updated August 27, 2003