Continuous versus cyclical transdermal estrogen replacement therapy in postmenopausal women: influence on climacteric symptoms, body weight and bleeding pattern.

OBJECTIVES

To compare continuous and cyclical transdermal estrogen replacement therapy (ERT) with or without an oral progestogen regarding climacteric symptoms, body weight and bleeding pattern.

METHODS

A total of 2459 postmenopausal women were treated for three cycles of 28 days in an open, randomized, parallel group multicenter study. Patients received an estrogen matrix patch (50 micrograms 17/beta-estradiol/day) twice weekly, either continuously (eight patches/cycle) or cyclically (six patches/cycle, i.e. 3 weeks on, 1 week off). A total of 1232 patients were treated continuously and 1227 cyclically. In the study group 1150 patients had an intact uterus (543 in the continuous and 607 in the cyclical treatment arm) and received, in addition to the estrogen patch, an oral progestogen in a transformation dose for 12 days of each cycle. Hysterectomized patients totaling 1309 (689 in the continuous versus 620 in the cyclical group) did not receive progestogen. Of the 2459 patients, 771 (31.4%) participated in a follow-up study with two further treatment cycles, which was offered to the patients at the end of the main study. The main outcome measures were climacteric symptoms, measured at the end of cycles 1-3 by a Visual Analogue Scale at baseline, and body weight measured at baseline at the end of cycles 3 and 5. In addition, the bleeding time per cycle (days) was evaluated in all patients with an intact uterus.

RESULTS

Continuous and cyclical transdermal ERT reduced, over three treatment cycles, the average climacteric symptom score by 1.77 and 1.70, respectively. The percentage remission and improvement rates for the ten climacteric symptoms ranged between 69.3 and 88.0% and did not differ between the two groups. In patients with a higher symptom score at baseline, the continuous treatment was slightly more effective. However, this effect was statistically not significant. After three treatment cycles body weight increased in both treatment groups by between 500 and 700 g. Further treatment during the follow-up study induced an additional average weight gain of 200-400 g. These results were not influenced by the addition of an oral progestogen. In patients with an intact uterus, the average bleeding time at the end of the first cycle (5.4 days in the continuous versus 5.3 days in the cyclical group) increased slightly during cycle 2 and returned to baseline values at the end of cycle 3.

CONCLUSIONS

Continuous and cyclical transdermal ERT were equally effective in reducing climacteric symptoms. The short term use of five cycles transdermal ERT induced a slight increase in body weight which was independent of the treatment regimen. These results were not influenced by the type and mode of administration of a progestogen. Both ERT regimens were very well tolerated and are suitable alternatives for estrogen replacement therapy of postmenopausal women.