Comparative endometrial histology in postmenopausal women with sequential hormone replacement therapy of estradiol and, either chlormadinone acetate or micronized progesterone.

Objectives: To determine the endometrial response in postmenopausal women treated with a sequential hormone replacement therapy (HRT) of estradiol and, either chlormadinone acetate (CA) or micronized progesterone (MP).

Methods: Three hundred and thirty-six postmenopausal women with a normal endometrium were randomized in the double-blind study. All patients received percutaneous estradiol 1.5 mg/day from day 1 to day 24 and either CA 10 mg/day or oral MP 200 mg/day from day 10 to day 24. The total duration of treatment was 18 months. Endometrial biopsies were performed before treatment and between day 18 and day 24 of the 18th month of HRT.

Results: Of the 336 patients selected, 317 had a biopsy at inclusion. Of them, 244 patients (124 in the CA group and 120 in the P group) were suitable for evaluation for analysis at the 18th month. Insufficient sampling occurred in 33.9% in the CA group and 60% in the MP group (probably atrophic). No case of hyperplasia could be reported in both groups. The endometrium was atrophic in 19.5 versus 27.1%, proliferative in 3.7 versus 8.3% and secretory in 76.8 versus 62.5% in CA and MP groups, respectively. It was possible to see histological differences induced by the two progestins. The CA endometria showed fewer glands lined by a cubo-cylindrical epithelium, with an edematous stroma, compared to the MP endometria which had more glands lined by a cylindrical epithelium, stroma being poorly edematous. These figures varied in intensity due to the length of progestative impregnation, predecidualization occurring later in the CA group, with distended capillaries.

Conclusions: These results show that CA 10 mg/day is a powerful progestin compared to MP 200 mg/day, on weakly estradiol-primed endometria, giving a molecule-specific histological aspect with a good endometrial safety.