The safety of oestrogen therapy

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Abstract
The initial suspicion that oestrogen therapy predisposed to the development of carcinoma has not so far been confirmed. However, the thromboembolic complications of oestrogen therapy are well documented. Not only is the dose of oestrogen important, but there has been recent speculation that the type of oestrogen preparation is also important. Low doses of oestrogen both natural and synthetic alleviate menopausal symptoms, but the dose of oestrogen that has been studied in relation to the prevention of long-term degenerative effects of the menopause, in particular osteoporosis and cardiovascular disease, has usually been high and the oestrogen has been the synthetic preparation mestranol or its metabolite, ethinyl oestradiol. If low doses of oestrogen are to be recommended for long-term use there must be some indication that, as well as alleviating symptoms, they (a) prevent the degenerative process of the post-menopause and (b) are not associated with adverse changes in the coagulation system. The preliminary results from a study of 40 patients on a 4-month course of either 1.25 mg./day ‘Premarin’ (conjugated equine oestrogens) or 2 mg./day ‘Progynova’ (oestradiol valerate) 3 out of 4 weeks were presented. The results suggest that alleviation of symptoms by these natural oestrogens is excellent. There was a small, but significant fall in plasma cholesterol, and coagulation factors II, V, VII, VII + X, VIII, anti Ha and FDP's were not affected. However, fasting plasma calcium, phosphate and alkaline phosphatase were not altered, and gonadotrophins were not markedly suppressed. In contrast, a preparation containing 30 jjug. mestranol was effective in alleviating symptoms and did suppress gonadotrophins, but caused a significant rise in coagulation factors. Further work is needed to establish the dose and type of oestrogen for use in long-term therapy to prevent degenerative post-menopausal changes, but it would seem that the low doses of both ‘Premarin’ and ‘Progynova’ at present recommended for the treatment of menopausal symptoms are particularly effective and without serious side-effects, while the implant of oestradiol is the most effective way of treating the surgical menopause.