Immediate Circulating Cortisol Responses Differ Between Two Functionally Divergent Localized Resistance-Type Plantar Flexion and Elbow Flexions: An Exploratory Within-Participant Crossover Study

Background: Practical localized resistance tasks involving functionally divergent muscle groups may produce different systemic biochemical responses, although neither task isolates a single muscle. Methods: In this exploratory, nonrandomized, order-balanced within-participant crossover study, 102 young adults completed bilateral seated plantar flexion and unilateral elbow flexion, with 51 participants assigned by alternation to each condition sequence. The analysis-ready biochemical dataset contained complete observations for 102 participants. Blood was collected before and 2–3 min after each condition. We analyzed plasma glucose and lactate and serum total cholesterol, HDL-C, LDL-C, triglycerides, creatine kinase, lactate dehydrogenase, GGT, and cortisol. Linear mixed-effects models included exercise condition, sampling time, study period, assigned sequence, and their respective interactions with sampling time as fixed effects. Participant and participant-specific study visit were included as random intercepts where supported by the model. The exercise condition × time interaction remained the primary contrast, and Holm correction was applied across the ten predefined biochemical outcomes. Linear mixed-effects models included exercise condition, sampling time, study period, assigned sequence, and their respective interactions with sampling time as fixed effects. Participant and participant-specific study visit were included as random intercepts where supported by the model. The exercise condition × time interaction remained the primary contrast, and Holm correction was applied across the ten predefined biochemical outcomes. Results: After adjustment for period and sequence and Holm correction across the ten primary interaction tests, cortisol remained the only statistically significant exercise condition × time interaction (149.219 nmol·L−1, 95% CI 62.338 to 236.099; unadjusted p = 0.000821; Holm-adjusted p = 0.008). Glucose showed a negative interaction estimate (−7.013 mg·dL−1, 95% CI −12.238 to −1.788; unadjusted p = 0.009), but did not remain significant after Holm correction (adjusted p = 0.078). No period × time or sequence × time effect remained statistically significant after correction. Sensitivity analyses were not fully concordant with the primary model, supporting cautious interpretation of the cortisol finding. Conclusions: These findings describe immediate responses to two non-equivalent multi-muscle tasks and cannot be attributed to selective soleus or biceps-brachii activation, fiber-type composition, or muscle-specific substrate use.