Allopregnanolone serum concentrations and neurosteroid sensitivity during withdrawal from postmenopausal hormone...

We have previously compared the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during sequential treatment with estradiol-only (E2-only) and estradiol together with progesterone (E2 + P) in postmenopausal women. The aim of the present study was to evaluate the pharmacodynamic response to pregnanolone during withdrawal from E2-only treatment and during withdrawal from treatment with E2 + P.

Twenty-six postmenopausal women were administered hormone therapy (HT) in a randomized, double blinded, placebo-controlled, crossover study. The women received 2 mg oral estradiol continuously during two 28-day cycles and 800 mg vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle. The pharmacodynamic response to pregnanolone was assessed during the last week of the last treatment cycle and 48 h after termination of the last treatment cycle (withdrawal) by comparing the effects of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye movements.

During E2-only withdrawal the pregnanolone sensitivity was reduced compared with E2-only treatment. Pregnanolone sensitivity remained unaltered between the combined E2 + P treatment regimen and the withdrawal from these steroids.

The study indicates that withdrawal from E2-only treatment might change neurosteroid sensitivity, whereas the immediate withdrawal from E2 + P results in unchanged neurosteroid sensitivity.