[Amenorrhea during menopausal hormone replacement therapy with a percutaneous estradiol and oral micronized...

The effects of oral micronized progesterone-administered at a low dose-on the endometrium and on bleeding pattern have been evaluated during a multicenter study in which 101 patients were involved. For a minimum of 6 months, patients who did not wish to have withdrawal bleeding (98) received the association of 17 beta-percutaneous estradiol (1.5 mg/d) and oral micronized progesterone (100 mg/d, at bedtime) during 25 days per month (or 21 d/28). The few women (3) who wished regular bleeding were given progesterone (300 mg/d) with estradiol (3 mg/d), from the 16th to the 25th of the month. No hyperplasia was observed among the endometrial biopsies performed after 6 months minimum of treatment. 8% of the endometria were partially secretory, 4% were sub-atrophic, 23% were mildly active with rare mitoses and 61% were quiescent without mitoses. The remaining 4% were considered inadequate. Mitotic activity of the glands was minimal in all samplings (mean < 0.53/1,000 cells). The average thickness of the mucosa was measured by ultrasonography at 3.9 mm, in the cases of insufficient samplings. No bleeding (or spotting, or cyclic bleeding) occurred in 73.3% and 80.9% of the cycles, in the 3rd and 6th month of therapy. Therefore a low dose of oral Pg (100 mg/d) combined with E2 during 25 days/month efficiently controls endometrial proliferation, while allowing a very weak cyclic activity. This situation makes it possible to minimize spottings and to maintain an amenorrhea in the majority of patients, thus letting us hoping for an improvement in the observance of this simplified therapy.