The Role and Use of Progestogens

Certain epidemiologic, histologic, and biochemical data on the effects of estrogens and progestogens on the endometrial, physical, psychological, and lipid status of postmenopausal women are reviewed. Unopposed estrogen replacement increases the risk of endometrial cancer not only while treatment is being taken but also for many years after it is discontinued. Strategies must be developed for posttreatment surveillance. The addition of a cyclic progestogen reduces this risk, but it is not clear whether the reduction is to, or below, that observed in an untreated population. Protective doses of C-19 (norethindrone) and C-21 (medroxy-progesterone acetate) progestogens are suggested. All progestogens may cause physical, psychological, and metabolic side effects. In addition, most women taking cyclic progestogens experience regular withdrawal bleeding. Continuous/combined therapy has been introduced to minimize these side effects and induce amenorrhea. Published data on the efficacy and safety of continuous combined therapy are few. Although the regimen is effective in relieving menopausal symptoms and inducing endometrial atrophy in most patients, side effects of progestogen are common and there is a high incidence of bleeding in the first few months, which is unacceptable to many patients. In our view, the effect of continuous combined therapy on lipids and lipoproteins has not been properly addressed. Based upon the available literature, we believe that the enthusiasm for continuous combined therapy is premature and we urge caution in its use until further, more conclusive, data become available.