Intrauterine 10μg and 20μg levonorgestrel systems in postmenopausal women receiving oral oestrogen replacement therapy:: clinical, endometrial and metabolic response

Objective The clinical and endometrial efficacy and lipid response of two different doses of intrauterine levonorgestrel were assessed in comparison with sequential oral medroxyprogesterone acetate in postmenopausal women receiving continuous oral E-2-valerate. Design One-year prospective multicentre randomised control trial. Setting Four outpatient clinics in Oulu, Helsinki and Jyvaskyla, Finland. Population A total of 163 healthy volunteer postmenopausal women with climacteric complaints or already using hormone replacement therapy (HRT). Interventions Subjects were randomly allocated to receive a new intrauterine system releasing 10mug of levonorgestrel daily or an established intrauterine system (Mirena) releasing 20mug of levonorgestrel daily or sequential oral medroxyprogesterone acetate (5mg/day, 14/30 days). All three regimens were combined with an oral daily dose of 2mg of E-2-valerate. Main outcome measures Bleeding patterns were assessed by diaries kept by the subjects. Endometrial effects were evaluated by histologic biopsies taken at the baseline and after six and 12 months of therapy. Serum concentrations of total, HDL and LDL cholesterol, triglycerides and lipoprotein(a) were determined at the baseline and after six and 12 months of therapy. Results Insertion of the smaller 10mug levonorgestrel system was easy in 70% and difficult in 4% and that of Mirena was easy in 46% and difficult in 21% of the subjects. After six months of therapy, 43 (95.6%) of the 47 subjects receiving 10mug levonorgestrel and 54 (98.2%) of the 55 subjects receiving 20mug levonorgestrel had no bleeding, while the sequential medroxyprogesterone acetate regimen produced typical cyclic withdrawal bleedings. Endometrial hyperplasia was not observed in any of the treatment groups during the 12-month study. After 12 months of therapy, strong endometrial suppression was found in 46/47 and 55/55 of the subjects receiving 10mug and 20mug of levonorgestrel, respectively, while the endometrium was proliferative in 18/47 of the subjects in the medroxyprogesterone acetate group. Serum total cholesterol decreased in all treatment groups. HDL cholesterol increased in women receiving medroxyprogesterone acetate or the smaller intrauterine dose of levonorgestrel. Conclusions Both intrauterine doses of levonorgestrel provided good endometrial protection in postmenopausal women on oestrogen replacement therapy. The advantage of the 10mug system with a smaller size is the easier insertion of the system and a minimal attenuation of the favourable effects of oral oestrogen on the serum lipid profile.