Chlormadinone acetate versus micronized progesterone in the sequential combined hormone replacement therapy of the menopause

Objective: The efficacy and safety of chlormadinone acetate (CA) versus micronized progesterone (P) were assessed in non-hysterectomized postmenopausal women. Materials and methods: This was a multicenter, randomized, parallel group study with a 6-month double-blind period followed by a 12-month open period. Patients were randomized to receive every month during 18 months percutaneous 17 beta -estradiol (E-2) 1.5 mg/day from Day 1 to 24 of treatment cycle, combined from Day I I to 24 to either CA 10 mg/day (n = 167) or P 200 mg/day (n = 169). Endometrial biopsy (EB, main analysis criterion) was performed at baseline, and at Day 18-24 of the 6th and 18th cycles. Results: At Month 6, EB did not evidence any hyperplasia. EB were inadequate for assessment in 24.5% and 47.5% of patients in the CA and MP groups, respectively. CA was found to be as protective as P (96.3% and 92.0% of success). However, the hormonal status of the endometrium differed (P < 0.001): a secretory endometrium was found in 81.5% of the CA patients, compared to 50.7% in the P group. These transformations resulted in predictable, cyclic bleeding in 94.5% of the CA patients, compared to only 62.3% of the P patients (P = 0.0001). Unscheduled bleeding, spotting and/or metrorrhagia, were more frequent under P than under CA (17.9% and 13.7%, respectively). The beneficial effects on hot flushes were more important in the CA group than in the P (P < 0.001). At Month 18, the biopsy and clinical results were similar to those obtained at Month 6. The safety profile, particularly the lipid one, was similar in both groups, except for drowsiness and dizziness, which were significantly more frequent under P than under CA. Conclusion: The progestative effects of CA on the endometrium. and on menopause-related symptoms were at least as good as those of P. Moreover, CA resulted more often than P in secretory effects, and in satisfying bleeding patterns. (C) 2001 Published by Elsevier Science Ireland Ltd.