Dose-response and withdrawal effects on climacteric symptoms after hormonal replacement therapy. A placebo-controlled therapeutic trial

Out of a sample of 162 early post-menopausal women, aged 45–54 yr, 131 completed a placebo-controlled study to investigate the effect of sex hormones on mild climacteric symptoms with special reference to the dose-response relationship and withdrawal effects. The women were followed up for 42 mth under four different study programmes. All the women were examined every 3 mth and a blind assessment made of the menopausal index estimated according to Kupperman et al. The data revealed a highly significant reduction in climacteric symptoms in the hormone-treated women as compared with the placebo group (P < 0.001), a highly significant dose relationship between climacteric symptoms and treatment with 4, 2 and 1 mg oestradiol, respectively (P < 0.001), a highly significant and dose-dependent rebound phenomenon after withdrawal of hormone treatment (P < 0.001) - which levelled off after 6 mth following withdrawal — and complete relief of hot flushes with the two highest doses of oestradiol (4 and 2 mg oestradiol). It is concluded that sex hormones have a beneficial effect in post-menopausal women with even mild symptoms.