Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy

Abstract

Objective: To determine serum parameters reflective of androgen status in postmenopausal women using two types of hormone replacement therapy (HRT). Design: Randomized, double-blind, prospective 1-year trial of two oral HRT regimens. Setting: University hospital, department of obstetrics and gynecology, menopause clinic. Patient(s): 100 postmenopausal women ≥ 45 years. Intervention(s): Daily use of the progestogen tibolone (2.5 mg; n = 50) or continuous combined 17-β-estradiol (2 mg) and norethindrone acetate (E+NA, 1 mg; n = 50). Main Outcome Measure(s): Measurements of total testosterone (total T), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), FSH, and sex-hormone-binding globulin (SHBG), and calculations of free testosterone (free T). Assessment of changes from baseline within and between groups after 6 and 12 months. Result(s): We found significant differences (% changes) in the tibolone group compared to baseline within the groups after both 6 and 12 months, respectively. Levels of free T doubled, total T decreased slightly, and SHBG decreased by half; DHEAS increased by approximately 20%; and FSH decreased. In the E+NA group, levels of free T, total T, androstenedione, and FSH all decreased, and SHBG increased. Pre-trial levels of DHEAS, A, and total T were significantly higher in the E+NA group. Between groups throughout the study, the changes from baseline were significant due to the different extent of FSH reduction, and opposite changes of free T, SHBG, and DHEAS. Conclusion(s): Both regimens modify plasma androgens, DHEAS, and SHBG differently. Tibolone decreased the levels of SHBG, and substantially increased free T and to a lesser extent increased DHEAS; this may reflect a modification of adrenal androgen production. Continuous combined estradiol and norethindrone acetate HRT suppressed the peripheral plasma androgens mediated by increased levels of SHBG.