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This study aims to compare the pharmacokinetics and oral bioavailability of a capsule combining 17β-estradiol and progesterone in a non–peanut oil–containing formulation with those of widely used and approved separate formulations of estradiol and progesterone coadministered to healthy postmenopausal women.This was an open-label, balanced, randomized, single-dose, two-treatment, three-period, three-sequence, cross-over, partial-replicate, reference-scaled study. Postmenopausal women (aged 40-65 y) were randomly assigned to one of three dosing sequences of test and reference products (TRR, RTR, or RRT, where T is the test drug and R is the coadministered reference product), with each of the three periods separated by a 14-day washout. The primary pharmacokinetic endpoints were Cmax, AUC(0-t), and AUC(0-inf) for the test and reference products, assessed for bioequivalence using the scaled average bioequivalence or unscaled average bioequivalence method. Safety was assessed by clinical observation, participant-reported adverse events, and laboratory data, including blood levels of hormones.Sixty-six women were randomly assigned, and 62 women (94.0%) completed all three study periods. All AUC and Cmax parameters met bioequivalence criteria for all analytes (estradiol, progesterone, and estrone), except Cmax for total estrone. The extent of estradiol and progesterone absorption was similar between the test product and the reference products. Four adverse events—all considered mild and unrelated to the study drugs—were reported.The combination 17β-estradiol/progesterone product demonstrates bioavailability similar to those of the respective reference products of estradiol and progesterone. If regulatory approval is obtained, this new hormone therapy would be the first treatment of menopause symptoms to combine progesterone with 17β-estradiol in an oral formulation.