Progesterone does not modulate myofibrillar protein synthesis at rest or following acute resistance exercise in premenopausal females

Progesterone has been proposed to modulate skeletal muscle protein turnover, although direct support for this hypothesis is lacking. We examined whether acute elevation of progesterone alters myofibrillar protein synthesis (MyoPS) at rest and following resistance exercise (RE) in naturally menstruating females. Twenty premenopausal females (21 ± 3 years of age) were randomised in a double‐blind, placebo‐controlled trial to receive oral micronized progesterone (400 mg) or matching placebo at −34 and −10 h before a stable isotope infusion on days 1–5 of their menstrual cycle. One leg performed RE while the contralateral leg remained rested, followed by ingestion of 30 g whey protein. MyoPS was quantified using the l ‐[ring‐ 1 3 C 6 ]‐phenylalanine precursor–product method across fasted–rested, fed–rested and fed–exercised conditions. Progesterone elevated serum concentrations well above the luteal‐phase range (185 ± 105 vs . 1.0 ± 0.2 ng mL −1 ). Despite this, we detected no difference in MyoPS groups in any conditions, including the exercise‐induced increment (treatment × leg interaction, P = 0.945). Both protein feeding ( P = 0.00459) and RE ( P < 0.001) independently stimulated MyoPS above resting fasted levels. Progesterone was associated with modestly lower total amino acid concentrations, but not essential amino acid or leucine specifically; postprandial kinetics did not differ between groups. Acute elevation of circulating progesterone above the luteal‐phase range does not detectably modify the skeletal muscle anabolic response to RE or protein feeding in premenopausal females. These findings challenge the characterisation of progesterone as catabolic (or anabolic) to skeletal muscle and indicate that menstrual cycle phase‐based training recommendations predicated on a progesterone‐driven effect warrant critical re‐evaluation. image Key points Progesterone has been proposed to exert catabolic effects on skeletal muscle, yet direct evidence in premenopausal adult females is absent. We examined whether pharmacological elevation of progesterone augments myofibrillar protein synthesis (MyoPS) at rest and following resistance exercise. Oral micronized progesterone administered at 34 and 10 h before testing successfully elevated serum progesterone to well above the luteal‐phase range (185 ± 105 vs . 1.0 ± 0.2 ng mL −1 ) during the early follicular phase. Despite this, MyoPS did not differ between progesterone and placebo in fasted–rested, fed–rested or fed–exercised conditions. Resistance exercise robustly elevated MyoPS above the fed–rested conditions, confirming model sensitivity. Neither postprandial amino acid availability nor individual progesterone exposure was associated with MyoPS. These findings challenge the characterisation of progesterone as pro‐catabolic/anti‐anabolic to skeletal muscle and indicate that menstrual cycle phase‐based training and nutrition recommendations predicated on progesterone‐driven effects on skeletal muscle are not supported by direct mechanistic evidence.