Relations between bleeding pattern, endometrial histology, and oestrogen treatment in menopausal women

Abstract

Summary and conclusionsVacuum curettage was performed on 348 women who had received various regimens of oestrogen treatment for an average of 9 7 months for climacteric symptoms. In 62 cases (18%) the specimens were unsatisfactory for histological assessment; among the remainder, however, they showed a normal endometrium in 257 cases (90%), cystic hyperplasia in 21 (7%), adenomatous hyperplasia in 7 (2%), and endometrial adenocarcinoma in one.Cyclical unopposed oral oestrogen treatment (98 cases) was associated with a 12% incidence of endometrial hyperplasia, but among those given an additional fiveday course of progestogen in each cycle (37 cases) the incidence was only 8%. No case of hyperplasia occurred among 102 women taking regimens including 10 or 13 days of progestogen. Among women treated with subcutaneous oestradiol implants and monthly five-day courses of oral progestogen (50 cases) there was a 28% incidence of hyperplasia including the one case of carcinoma, though some of those with hyperplasia may not have taken the full course of progestogen. Regular withdrawal bleeding during treatment was associated with a lower incidence of endometrial hyperplasia (6%) than unscheduled breakthrough bleeding (28%), but the one patient with carcinoma had experienced regular bleeding only.

Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime

“…The incidence of hyperplasia in women on unopposed oestrogen therapy has been estimated to be between 20% and 57% after one year depending on the dose and duration of the oestrogen. 18 -21 Adding a sequential progestogen decreases this risk, 5,22 although there may be a residual additional risk of endometrial hyperplasia despite standard regimes of progestogen. 6 For this reason continuous combined HRT has been suggested to be most favourable for the maintenance of endometrial safety.…”

“…1 In the 1970s, clinical studies began to universally establish this link, 2,3 and since then it has been widespread practice to add in a progestogen of varying duration to counteract the malignant potential of oestrogen on the endometrium. It has been shown that adding a synthetic progestogen may effectively reduce the risk of endometrial disease 4,5 ; however, this therapy is not without its own problems. Firstly, sequential additions of progestogens often initiates a withdrawal bleed which limits its initiation and compliance for some women.…”

Prevention of postmenopausal osteoporosis and associated fractures: Clinical evaluation of the choice between estrogen and bisphosphonates

“…Irregular bleeding in postmenopausal women using hormonal treatment is not acceptable to users, requires endometrial investigation and as such is considered costly. The early writings on the use of progestogens documented the induction of regular withdrawal bleeding with short courses of progestogens [105]. In further attempts to eliminate the possibility of endometrial hyperplasia, the duration of progestogen usage was extended to 12 days [106].…”

An open-label study of subdermal implants of estradiol-onlyversussubdermal implants of estradiol plus nomegestrol acetate: effects on symptom control, lipid profile and tolerability

“…Unopposed estrogen therapy, however, increases the incidence of endometrial hyperplasia [3][4][5][6] and the risk of endometrial carcinoma [7]. Addition of a progestin to estrogen replacement therapy has been shown to reduce this risk to the endometrium [8,9].…”