Estrogen replacement therapy with sequential progestin at greater than monthly intervals has been frequently used in practice to reduce progestational side-effects and bleeding episodes, but clinical trials are still lacking. Two new regimens were tested. The main objective was to evaluate efficacy, predominantly in urogenital complaints, tolerability, and patient acceptance. Transdermal estradiol (0.05 mg/day) and norethisterone acetate orally (2.5 mg/day) were administered for 12 days every 2 or 3 months (group A, n = 83, group B, n = 89) to patients whose menopause had begun at least 4 years earlier. Study duration was three long cycles in each group within 7-10 months. Efficacy was good [group A/B = 94/92%], as was systemic tolerability [95/97%]; major skin reactions occurred in 7 and 4%, respectively. Patients' acceptance for continuation of spaced-out treatment was 88 and 87%, respectively. Progestin-associated withdrawal bleedings occurred in 66 (61%) of patients; mean duration 4.3 +/- 1.9/4.8 +/- 1.6 days, with no significant changes during therapy; intensity decreased during therapy. Breakthrough bleeding which required sonographic or histological work-up occurred in 8 and 13%, respectively. Despite the low dosage, transdermal estradiol proved to be efficacious in urogenital complaints. The high acceptance and the reduction of the overall progestin dose to avoid side-effects are of particular prognostic importance with regard to the prevention of cardiovascular diseases. Transdermal estradiol combined with 2- or 3-monthly progestin may be a valid regimen in the late post-menopause, but further studies using spacing-out regimens are urgently needed.

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The objective of the study was to investigate histological changes in the endometrium in 20 volunteers treated with a low-dose, gestodene-containing triphasic oral contraceptive. Endometrial biopsy specimens were taken before, during a 6-month period of oral contraceptive use and in a post-treatment period. These specimens were evaluated using light microscopy, scanning and transmission electron microscopy. In addition, ultrasound examinations of the uterus, endometrial thickness and ovaries were performed. The low-dose, gestodene-containing triphasic oral contraceptive had no adverse effects on the endometrium (e.g. no proliferation, no polyps, no inflammatory processes), was well tolerated and showed a low side-effect profile. The inhibition of endometrial transformation was demonstrated both by endometrial morphology as well as by endometrial thickness, as measured by transvaginal ultrasound examination.

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