CONTINUOUS HORMONE REPLACEMENT THERAPY FOR MENOPAUSE COMBINING NOMEGESTROL ACETATE AND GEL, PATCH, OR ORAL ESTROGEN - A COMPARISON OF AMENORRHEA RATES

This open-label, prospective, randomized, multicenter trial compared t he incidence of amenorrhea in 54 postmenopausal women (mean age, 54.9 +/- 0.6 years) who underwent six 4-week cycles of continuous hormone r eplacement therapy combining a progestin-nomegestrol acetate 2.5 mg/d- plus one of three estrogens: percutaneous 17 beta-estradiol gel(1.5 mg /d, group A), transdermal 17 beta-estradiol patch (50 mu g/d, group B) , or oral estradiol valerate (2 mg/d, group C). Based on an intent-to- treat analysis, the rate of amenorrhea varied significantly according to which estrogen preparation was used. Calculated cycle by cycle, rat es of amenorrhea were 67% to 83% for group A, 25% to 56% for group B, and 53% to 61% for group C. Overall rates of persistent amenorrhea wer e not statistically different between groups for cycles 1 through 3, b ut for cycles 4 through 6, significantly more women in groups A and C (67% and 46%, respectively) experienced amenorrhea than did those in g roup B (12%). Amenorrhea rates for the entire six-cycle period were 78 % for group IA, 48% for group B, and 60% for group C. These difference s were not statistically significant. The differences in rates could n ot be attributed to endometrial atrophy, since when measured by transv aginal sonography, endometrial thickness did not differ significantly between groups. Of the original population, 7% withdrew prematurely be cause of bleeding. The data for all three groups confirmed that in two out of three women, the occurrence of amenorrhea during the first thr ee cycles predicted continuation of amenorrhea during subsequent cycle s and that for 51% of women, less than or equal to 10 days of bleeding during the first three cycles predicted amenorrhea during the last th ree cycles. Calculated as a function of the number of women included i n the trial, the percentage of amenorrheic women (evaluated cycle by c ycle or for the second three-cycle period) was highest when the proges tin was combined with percutaneous 17 beta-estradiol gel, although fin dings were similar with estradiol valerate. The percutaneous 17 beta-e stradiol gel was also associated with a higher percentage of amenorrhe al cycles than was estradiol valerate or transdermal estrogen, althoug h differences were significant only in comparison with the transdermal formulation. This difference may have positive clinical implications.