The sharp decline of estradiol (E2) production in females following menopause results in accelerated loss of skeletal muscle contractile function, increasing injury risk and declines in quality of life. E2 deficiency can influence contractile function chronically, by impairing response to loading and injury repair and acutely by impairing muscle excitability. Preclinical research introducing E2 following ovariectomy suggests that E2 likely enhances phosphorylation of myosin regulatory light chain (RLCp), which facilitates crossbridge formation and force generation. Post-activation potentiation (PAP), is defined by acute elevations in force generating capacity in response to prior activation and is largely regulated by RLCp. The impact of estrogen deficiency on potentiation in humans is less well understood, especially in the context of age. Therefore the objective of this study is to investigate the relationship between circulating E2 and PAP. We recruited younger adult females with both high and low E2 levels along with older, postmenopausal females with age-related E2 depletion. We hypothesized that younger and older females with E2 depletion will exhibit reductions in PAP compared with females with relatively high E2. METHODS: We recruited three groups of female participants: young eumenorrheic, young using progesterone-only hormonal contraceptives and older, postmenopausal. Blood serum estradiol levels were measured via liquid chromatography-mass spectrometry via standard phlebotomy. Muscle morphology was assessed using ultrasound (Philips Ultrasound Inc., Church Hill, PA) of participants’ dominant quadriceps. Vastus lateralis (VL) and quadriceps cross sectional area (CSA) were approximated from transverse panoramic images. We used a Biodex dynamometer (Evome Medical Technologies Inc., Carlsbad, CA) to measure PAP. Briefly, participants completed 3, 5 second maximum voluntary isometric knee extensions (MVICs) of their dominant limb. Electrode pads were then placed on the anterior thigh, and electrical stimulus (1 pulse, 400µs) intensity was adjusted to obtain a twitch producing 10% peak torque (calculated from the average of the 3 MVICs). Thereafter, a 20min rest period was observed, followed by a 10 second MVIC to stimulate RLCp. Last, another electrically stimulated twitch was delivered to compare with that delivered prior to 10s MVIC. PAP was defined as the percent change in force between two twitches separated by the 10s MVIC. RESULTS: There were no main effects of group on measures of whole muscle size or MVIC. Similarly, there were no significant main effects of group on PAP. However, we found trends of positive correlation between serum E2 and PAP (R = 0.47; p = 0.068), and potentiated twitch torque normalized to quadriceps CSA (0.54; p = 0.047). When considering associations within younger females only, we also found trends of positive correlation between serum E2 and these measures (R = 0.52; p = 0.067 and R = 0.54; p = 0.088, respectively). DISCUSSION: Preliminary results are consistent with our hypothesis that E2 provides a protective effect on contractile function at the whole muscle level, especially related to potentiation. Stronger associations between E2 and PAP were observed when older adults were excluded from analyses suggesting they did not depend on age-related effects. Our current findings prompt the collection of additional data to increase the statistical power with which we can test our hypothesis. FUNDING: Wu Tsai Human Performance Alliance and Achievement Rewards for College Scientists (ARCS), Oregon This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Gulati et al. (Fri,) studied this question.