A comparison of the central effects of different progestins used in hormone replacement therapy

Objective: To evaluate the central effect exerted by different progestins used for hormone replacement therapy. Methods:Randomised, placebo-controlled study. One hundred-twenty postmenopausal women on continuous hormonal replacement therapy with transdermal estradiol (50g per day) associated, for 10 days every 28 days, with four different progestins: dydrogesterone (DYD; 10 mg per day; n = 20), medroxyprogesterone acetete (MPA; 10 mg per day; n = 20), nomegestrol acetate (NMG; 5 mg per day; n = 20) or norethisterone acetate (NETA; 10 mg per day; n = 20). Other 40 women, 10 for each treatment group, were used as controls and were monitored for a single cycle of 28 days during the administration of transdermal estradiol plus placebo. Morning basal body temperature (BBT) was monitored for 28 days. Anxiety, by the state-trait anxiety inventory, and depression, by the self-evaluation depression scale of Zung, were evaluated just prior to and in the last 2 days of the 10-day progestins adjunct. Results: All progestins except DYD increased ( P< 0.0001) BBT by 0.3–0.5 ◦ C. Anxiety was decreased by DYD (−2.3 + 1.1; P< 0.01) and MPA (−1.5 + 0.5; P< 0.01), but not by NMG or NETA. Depression did not significantly increase during progestins and actually decreased during MPA (−3.0 + 0.7; P< 0.01). Only the effect of DYD on anxiety and that of MPA on depression were significant versus the control group ( P< 0.05). Conclusions: Different progestins exert different central effects. DYD has the peculiarity of not increasing BBT and of decreasing anxiety, which is also decreased by MPA. Depression is not negatively affected by the tested progestins and it may be ameliorated by MPA. The present data may help to individualise the progestin choice of hormone replacement therapy. © 2003 Elsevier Ireland Ltd. All rights reserved.