A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women.
OBJECTIVE
To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen.


METHODS
This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28.


RESULTS
Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium.


CONCLUSIONS
The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile.
Koninckx
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PR
Department of Gynaecology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Kuleuven, Belgium. philippe.koninckx@uz.kuleuven.ac.be
Spielmann
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D000284:Administration, Oral; D000328:Adult; D001835:Body Weight / Q000187:drug effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004714:Endometrial Hyperplasia / Q000517:prevention & control; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D017698:Postmenopause / Q000187:drug effects; D011397:Promegestone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D014592:Uterine Hemorrhage / Q000139:chemically induced*
D004338:Drug Combinations; C050319:trimegestone; D004958:Estradiol; D000077563:Norethindrone Acetate; D011397:Promegestone; D009640:Norethindrone