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

OBJECTIVE: 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. STUDY DESIGN: 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). RESULTS: 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. CONCLUSION: 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.