One main concern of sequential hormone replacement therapy is the development of endometrial hyperplasia, despite the addition of a progestogen. David Sturdee and his colleagues (pages 1392–1400) investigated the prevalence of endometrial hyperplasia in 1106 women taking sequential hormone replacement therapy which was then replaced by continuous combined hormone replacement therapy, together with 661 women taking the continuous combined preparation as their first form of hormone replacement therapy. The prevalence of endometrial hyperplasia in the women taking sequential hormone replacement therapy was 6%; but there was not a single case of endometrial hyperplasia after nine months of continuous combined treatment. All the women who had complex endometrial hyperplasia on sequential therapy had normal or atrophic endometrium on continuous combined hormone replacement therapy.
In a complementary study W. Perry and R.A. Wiseman (pages 1401–1406) investigated the effects of continuous combined hormone replacement therapy on bone mineral density in 131 post-menopausal women. Bone mineral density was measured three years after starting continuous combined treatment, and the results were compared with the expected decline in bone density in post-menopausal women not treated with hormone replacement therapy. In all the areas studied bone mineral density increased, but especially at the sites which had a preponderance of cancellous bone. There was no association between the concentrations of oestradiol or oestrone in the blood and the increase in bone mineral density, this result being due either to difficulties in the timing of the oestrogen samples, or to there being a threshold of oestrogen beyond which no further increase in bone mineral density can occur.
The results of these studies are important in establishing the benefits of continuous combined hormone replacement therapy. The effects of combined treatment on bone mineral density are expected, but what is important is the protective effect of continuous combined hormone replacement therapy on the endometrium, compared with sequential therapy. What is not clear is whether women on continuous combined hormone replacement therapy who have post-menopausal bleeding require endometrial biopsy.