Prevention of endometrial abnormalities.

Exogenous oestrogens are highly effective in relieving not only the acute symptoms of ovarian failure, such as vasomotor instability and vaginal dryness, but also in conserving postmenopausal bone mass. However, the oestrogen doses needed to achieve these benefits also induce endometrial proliferation. The risk of endometrial hyperplasia and carcinoma are thereby increased and unopposed oestrogen therapy is associated with a high incidence of abnormal vaginal bleeding requiring appropriate, invasive investigations. The cost-effectiveness of therapy and patient compliance are likely to be correspondingly reduced. Various strategies have been proposed to try to overcome the risk of endometrial hyperstimulation and these strategies have been reviewed. Based upon the available evidence, progestogen addition appears the most sensible and has been shown to be effective. It is now clear that progestogens should, in sequential therapies, be administered for 12 days each cycle for maximum protection. Concern has been expressed that the regular withdrawal bleed induced by sequential treatment will reduce patient compliance. Progestogens have, therefore, been added in a continuous fashion to try to prevent endometrial proliferation and thereby induce amenorrhoea. The ideal continuous, oestrogen/progestogen regimen has not yet been developed: all those evaluated to date are associated with a high incidence of breakthrough bleeding which is likely to restrict their use. Progestogens can cause undesirable physical, psychological and metabolic effects. The incidence and severity of side-effects will depend upon the type of progestogen prescribed, the route of administration, and the dose. Minimum effective daily doses of certain types of progestogens have now been established in terms of endometrial protection. Regrettably, few data are available on the physical and psychological effects of these progestogen doses: more information is available on lipid and lipoprotein effects but the data are confused and, at times, contradictory. More research is urgently needed to determine which of these progestogens is most suitable for addition to postmenopausal oestrogen therapy.