Induction of amenorrhea during hormone replacement therapy: optimal micronized progesterone dose. A multicenter study

The effects of oral micronized progesterone on the endometrium and bleeding pattern have been assessed in a multicenter study of 101 postmenopausal patients. During a minimum of 6 cycles, the participants received either percutaneous 17 beta-estradiol (1.5 mg/day) associated with micronized progesterone (100 mg/day), given at bedtime for 21/28 days or 25 days/calendar month (n = 98) [1], or E2 (3 mg/day) for 25 days associated with progesterone (300 mg/day), from day 16 to day 25 (n = 3) [2], according to their willingness to induce, or not, cyclic withdrawal bleeding. Each endometrial biopsy performed at 6-month minimum was assessed by two independent pathologists: results showed 61% quiescent without mitosis, 23% mildly active with very rare mitoses and 8% partial secretory endometrium. The remaining biopsies showed inadequate tissue (4%) or a sub-atrophy (4%). No hyperplasia was found by any pathologist. In the case of inadequate material, the mean thickness of endometrial mucosa measured by ultrasonography was 3.9 mm. Amenorrhea incidence was 93.3 and 91.6% at the 3rd and 6th month of therapy, respectively. No bleeding occurred in more than 80% of women. The results show that a low dose of oral progesterone (100 mg/day), given during 25 days, efficiently protects the endometrium by fully inhibiting mitoses and induces amenorrhea in the majority of postmenopausal women, allowing better compliance to long-term therapy.