Long-term adherence to continuous combined HRT: Seven-year update on the Heikkinen study

Abstract

The Heikkinen study is a randomised double-blinded study of the effects of six different continuous combined HRT regimens (Indivina, estradiol valerate and medroxyprogesterone acetate, Orion Pharma Finland). Four-hundred-and-nineteen healthy postmenopausal women received 1 or 2 mg oestradiol valerate (E₂V) with either 2.5 or 5 mg medroxyprogesterone acetate (MPA).

In two groups, the dose of E₂V was increased from 1 to 2 mg after six months of treatment. Women recorded their symptoms and were reviewed by clinic staff at regular intervals. After two years, all treatment arms experienced significant improvements in bleeding patterns and climacteric symptoms. After seven years of therapy, adherence continues to be good, with nearly 78% of the women in the 1 mg E₂ V groups and almost 60% of the women in the 2 mg E₂ V groups remaining in the study. The majority of the women who discontinued therapy were taking the 2 mg E₂ V + 2.5 mg MPA dose combination. Improvements in lipid profile and bone mineral density have been maintained and endometrial protection has been safeguarded. A total of 97 subjects (23.2%) presented with a serious adverse event over the course of the study period. In 60 subjects (14.6%) adverse events were possibly related to treatment. There were fewer treatment-related adverse effects in women in the lowest-dose group compared to the higher-dose E₂ V groups (p<0.001). Quality of life in the study population was rated as better than that of an age- and sex-matched sample of the general population (p<0.05).