[A "no-bleeding" substitute hormone treatment with an oral microdose progesterone. A prospective multicenter study]

Study of influence of different sequences of oral micronized progesterone (Pg) on endometrial morphology and the incidence of bleeding.

Prospective comparative multicentric study conducted in 101 post-menopausal patients.

98 patients who did not wish any regular withdrawal bleeding were given percutaneous oestradiol 17-beta (E2) (1.5 mg/d) associated with micronized Pg (100 mg/d) at bedtime during either 21 out of 28 days (group I), or 25 days per calendar month (group III), during a minimum of 6 months. For those wishing withdrawal bleeding (n = 3), E2 (3 mg/d) during 25 days was associated with Pg (300 mg/d) from the 16th to the 25th day of the month (group III). Endometrial biopsies were performed after 6 months of the same treatment and blindly analysed; transvaginal ultrasonography (measurement of endometrial mucosa thickness) was done in case of insufficient amount of tissue.

Groups I and II: 61% of the endometrium were quiescent without mitosis, 23% were slightly active with rare mitoses, 8% partly secretory and 4% subatrophic. Sampling was inadequate in the remaining 4%. Mitotic activity of glands was low on the overall samplings (average < 0.53/1,000 cells). The average mucosa thickness was at 3.9 mm. No bleeding (spotting or withdrawal bleeding) occurred in 73.3% and 82.1% of cycles at the 3rd and 6th months of administration, respectively. Group III: endometrium were quiescent or slightly active and combined with frequent withdrawal bleeding.

A relatively low dose of oral progesterone (100 mg/d) combined with E2 during 21d/28d or 25 d/month efficiently controls proliferation, induces a very low endometrial cyclic activity--while reducing spottings--and maintains an amenorrhea in the majority of women. This simple treatment is likely to improve compliance.