Menstrual cycle phase differences in myofiber damage and macrophage infiltration following electrical stimulation-induced muscle injury

The purpose of this study was to examine the effects of menstrual cycle phase on myofiber injury, regenerative events and inflammation after electrical-stimulation (ES) induced myofiber damage. 28 premenopausal women (21.3 ± 2 yrs) were randomized into an early follicular (EF; N=14) or late follicular (LF; N = 14) group. After menstrual cycle tracking and phase confirmation, subjects underwent 200 electrically stimulated eccentric muscle contractions one week after providing a muscle biopsy. 7 days post-ES, subjects provided a final biopsy. Primary outcomes included: serum estradiol, indirect markers of muscle damage, direct indicators of myofiber necrosis and regeneration, satellite cell number, and macrophage infiltration. Women in the LF group had higher serum estradiol (122.1 ± 23.4 vs. 81.7 ± 30.8 pg/ml; P<0.001) compared to the EF group on the day of ES. Whereas the EF group recovered baseline maximal isometric strength by 4 days post-ES, the LF group did not. Only women in the LF group showed significant and consistent evidence of myofiber necrosis and regeneration pre- to post-ES. Despite showing more evidence of myofiber damage, women in the LF group also experienced reduced total and CD206 + macrophage infiltration relative to the EF group. Satellite cell quantity increased significantly post-ES in both groups, with no differences between groups. Collectively, the data suggest that the high estrogen LF phase may be associated with increased susceptibility to myofiber injury while also limiting the subsequent intramuscular inflammatory response.