Impact of percutaneous oestradiol gels in postmenopausal hormone replacement therapy on clinical symptoms and endometrium.

OBJECTIVE

To compare the effects on endometrium, climacteric symptoms and the menstrual cycle, and the clinical and biological tolerance of two percutaneous oestradiol gels used as hormone replacement therapy.

DESIGN

A large open randomised multicentre study.

SETTING

France and Belgium.

PARTICIPANTS

Two-hundred and fifty-four women with an intact uterus and who had experienced a natural menopause received either Oestrogel (n = 126) or Estreva, a new formulation of oestradiol gel (n = 128), (1.5 mg of oestradiol/day) for the 24 first days of each calendar month during six consecutive months. Nomegestrol acetate (Lutenyl), a norprogesterone derivative, was administered (5 mg/day) from day 11 to day 24 of each oestradiol cycle.

MAIN OUTCOME MEASURES: Examination of endometrial biopsies taken before treatment and between days 18 and 24 of the last treatment cycle, climacteric symptoms assessed using a modified Kupperman index, control of menstrual cycle evaluated by diary cards, and clinical and biological tolerance.

RESULTS

Both treatments lowered the frequency and intensity of hot flushes and the global Kupperman index. 96% of the cycles were followed by withdrawal bleeding. Breakthrough bleeding or spotting resulted in premature discontinuation of treatment in one volunteer. Mastodynia occurred in 20 women and contributed to the premature termination of treatment in three of them. Endometrial biopsies taken at the end of treatment showed identical histologies in both groups, with a secretory pattern in the majority of women, and absence of hyperplasia.

CONCLUSIONS

This trial confirmed that, when the two oestradiol gels tested were administered cyclically with nomegestrol acetate to postmenopausal women, they were well tolerated, effective and suitable for the treatment of oestrogen deficiency syndrome.