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

Objective: To determine serum parameters reflective of androgen status in p ostmenopausal 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, meno pause clinic. Patient(s): 100 postmenopausal women greater than or equal to 45 years. Intervention(s): Daily use of the progestogen tibolone (2.5 mg; n = 50) or continuous combined 17-beta -estradiol (2 mg) and norethindrone acetate (ENA, 1 mg; n = 50). Main Outcome Measure(s): Measurements of total testosterone (total T), dehy droepiandrosterone sulfate (DHEAS), androstenedione (A) FSK, and sex-hormon e-binding globulin (SHBG), and calculations of free testosterone (free T). Assessment of changes from baseline within and between groups after 6 and 1 2 months. Result(s): We found significant differences (% changes) in the tibolone gro up compared to baseline within the groups after both 6 and 12 months, respe ctively. Levels of free T doubled, total T decreased slightly, and SHBG dec reased 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 de creased, and SHBG increased. Pre-trial levels of DHEAS, A, and total T were significantly higher in the E+NA group. Between groups throughout the stud y, the changes from baseline were significant due to the different extent o f FSH reduction, and opposite changes of free T, SHBG, and DHEAS. Conclusion(s): Both regimens modify plasma androgens, DHEAS, and SHBG diffe rently. Tibolone decreased the levels of SHBG, and substantially increased free T and to a lesser extent increased DHEAS; this may reflect a modificat ion of adrenal androgen production. Continuous combined estradiol and noret hindrone acetate HRT. suppressed the peripheral plasma androgens mediated b y increased levels of SHBG. (C) 2001 by American Society for Reproductive M edicine.