Superior compliance and efficacy of continuous combined oral estrogen-progestogen replacement therapy in postmenopausal women

We assessed compliance, relief of climacteric symptoms, and impact on lumbar bone mineral density in two groups of 140 patients treated with a sequential estrogen-progestogen or a continuous combined replacement therapy in comparison with controls.

Patients were randomized to 2 mg of estradiol valerate daily and 5 mg of medroxyprogesterone acetate daily for 12 days per month sequentially to induce withdrawal bleeding (group A) or 2 mg of estradiol, 1 mg of estriol, and 1 mg of norethisterone acetate daily continuously to maintain amenorrhea (group B) or a control group (group C).

Compliance was 93% after 1 year and 73% after 2 years in group B and 66% and 49% in group A after 1 and 2 years, respectively. Improvement of climacteric symptoms was similar in groups A and B. Uterine bleeding in 24% of patients in group A and 3% in group B was the most frequent reason for discontinuation of drug intake. Only continuous combined therapy (group B) increased bone mineral density after 1 and 2 years compared with baseline: +13% and 17% (p = 0.01). In groups A and C no significant changes in bone mineral density were recorded. Compliance was unrelated to the age of menopause.

Continuous combined therapy is superior to sequential estrogen progestogen replacement in compliance and prevention of bone loss but not with regard to relief of climacteric symptoms.