Endometrial morphology and bleeding patterns as a function of progestogen supplementation

Progestogens are added to estrogen replacement therapy for postmenopausal women to prevent endometrial hyperplasia and adenocarcinoma, and in sequential therapy to promote a regular and predictable bleed. This protective effect of progestogens is well recognized, but it is not due to endometrial shedding at a withdrawal bleed and cannot be predicted from the pattern or timing of the bleed. While irregular bleeding may be a reflection of endometrial abnormality and possibly insufficient progestogen, a regular controlled bleed may also occur in the presence of endometrial abnormality. A large multicenter study of postmenopausal women who were taking standard 28-day sequential regimens of estrogen and progestogen found a 2.7% prevalence of complex hyperplasia, and most of these women had a normal and regular bleeding pattern. Regular bleeding may also occur from an atrophic endometrium. Therapy employing a longer cycle with a course of progestogen given every 4 or 4 months may improve patient continuance for long-term therapy. During the estrogen-only phase, the endometrium becomes increasingly proliferative, and simple or cystic hyperplasia may develop only after about 12 weeks, and then can be corrected by progestogen. Women seem to prefer a less frequent withdrawal bleed despite the higher incidence of breakthrough bleeding compared to a monthly loss. Continuous combined therapy with estrogen and progestogen taken every day causes no withdrawal bleed, though some will have light breakthrough bleeding for the initial 2 or 3 months. The continuous progestogen keeps the endometrium atrophic and also converts preexisting complex endometrial hyperplasia occurring during sequential therapy to a normal state. As yet, there are no clinical guidelines that can give reassurance about the state of the endometrium in postmenopausal women who are taking hormone replacement therapy.