Efficacy and tolerability of a new estradiol delivering matrix patch (Estraderm MX) in postmenopausal women.

OBJECTIVE: To examine the efficacy and tolerability of a new matrix patch delivering estradiol (E2 Matrix) at doses of 0.05 and 0.10 mg per day (Estraderm MX 50, 100) in the treatment of moderate to severe postmenopausal symptoms. METHODS: A total of 254 postmenopausal women were randomized to receive treatment with E2 Matrix 0.10 mg (N = 86), E2 Matrix 0.05 mg (N = 82), or placebo (N = 86) in a double-blind, double-dummy fashion for a period of 12 weeks continuously. Patches were applied twice weekly to the buttocks with each patient wearing two patches at all times. The primary efficacy criterion was the difference from baseline of the mean number of moderate to severe hot flushes per 24 h during the last 2 weeks of treatment. Other efficacy variables included reduction in hot flushes at 4 and 8 weeks, reduction in daytime flushing and night sweats, and Kupperman Index at 4, 8, and 12 weeks. RESULTS: E2 Matrix 0.10 and 0.05 mg were both significantly superior to placebo in reducing hot flushes per 24 h after 4, 8, and 12 weeks of treatment (P < 0.001). Also, for all other efficacy parameters studied, both dosage strengths of E2 Matrix were statistically significantly superior to placebo at all time points (P < 0.001). Local tolerability was good in both groups. A slight increase in estrogen related adverse effects (breast tenderness, leukorrhoea) was seen with the 0.10 mg patch. Adhesion of patches and compliance were good. Overall systemic tolerability was good in both treated groups. However, a 4.8% overall incidence of endometrial hyperplasia was observed in patients with an intact uterus. CONCLUSIONS: This new matrix patch offers an effective and well tolerated dosage form for delivery of 0.05 and 0.1 mg estradiol per day. It may be particularly suitable for those women who experience local sensitivity to alcohol-containing systems. In light of the observed hyperplasia after treatment in five patients, estrogen therapy should as yet be supplemented monthly with a progestogen in women with an intact uterus.

The effects of continuous combined transdermal oestrogen-progestogen treatment on bleeding patterns and the endometrium in postmenopausal women.

Fifty postmenopausal women requiring hormone replacement therapy for the treatment of climacteric symptoms were recruited in six centers. All patients received a new combined norethisterone acetate (NETA)/oestradiol (E2)-TTS, (Estragest TTS, Ciba-Geigy Ltd), delivering 0.25 mg NETA and 50 micrograms E2 per day, continuously for 12 calendar months. Bleeding occurred in 38 (76%) of the 50 patients at any time during the 1 year treatment. The percentage of patients without bleeding increased gradually each month, from 24% in the second month to a relatively stable level of approximately 80% in month 7 and thereafter. Twenty-seven patients (54%) did not complete the whole trial period; 15 of which discontinued the treatment within the first few months due to irregular bleeding. In patients who remained in the trial, a clear decrease in the frequency and intensity of the bleeding was observed with time. Bleeding was mostly light or consisted of spotting only. None of the post-trial biopsies showed proliferation or hyperplasia of the endometrium. The treatment resulted in a substantial decrease of climacteric symptoms (Kupperman index) within 4 months and was well tolerated. It was concluded that the continuous NETA/E2-TTS treatment is an effective and safe alternative for the treatment of climacteric symptoms in selected patients.