Lobo R, et al. - Considering the REPLENISH trial demonstrating significantly improved vasomotor symptoms among women receiving TX-001HR—an oral, softgel capsule, combining 17β-estradiol (E2) and progesterone (E2 mg/P4 mg 1/100, 0.5/100), while having their endometrium protected from hyperplasia, researchers conducted this work defining P4 levels that may be sufficient to counteract the potential endometrial effects of 1 or 0.5 mg oral E2 with TX-001HR. In REPLENISH (phase 3), postmenopausal women treated with TX-001HR (E2 mg/P4 mg: 1/100, 0.5/100, [0.5/50, 0.25/50 and placebo not reported here]) were assessed for serum P4, E2, and estrone (E1) levels, at baseline, week 12, and month 12 for P4, and at baseline, weeks 4 and 12, and months 6, 9, and 12 for E2 and E1. Following 7 daily doses of oral E2 mg/P4 mg (1/100 and 0.5/100), pharmacokinetic parameters were assessed in a phase 1 study. As per findings, the phase 1 and 3 studies were similar regarding P4 levels observed with TX-001HR, and there was no association of the P4 levels with endometrial hyperplasia with either E2 daily dose over 1 year in the REPLENISH phase 3 study, which showed significant improvements in menopausal vasomotor symptoms.