Impact of oral contraceptives on cardiovascular and sympathetic responses to isometric handgrip exercise in young women

Nearly 80% of women in the United States will use the oral contraceptive pill (OCP) at some point in their lifetime. OCP use is linked to hypertension, a well-established risk factor for cardiovascular disease, yet the mechanisms that contribute to this association are not well understood. Blood pressure (BP) and sympathetic reactivity, defined as the degree to which BP and sympathetic activity increase in response to a perturbation, are predictive of the future development of hypertension. However, data on the effects of OCP use on BP and sympathetic reactivity remain equivocal. Purpose: The purpose of this analysis was to test the hypothesis that OCP users will have greater BP and sympathetic reactivity to isometric handgrip exercise compared to naturally cycling (NAT) women. Methods: We retrospectively analyzed data in 64 healthy, young premenopausal women (OCP: n=35, 22±3yrs, BMI: 22±3kg/m2; NAT: n=29, 23±4yrs, BMI: 22±3kg/m2). OCP users were tested during the placebo phase and NAT women were tested during the early follicular phase of their menstrual cycle. BP and sympathetic reactivity were assessed during two minutes of isometric handgrip (HG) exercise at 30% of maximal voluntary contraction and post-exercise ischemia (PEI; isolated activation of the skeletal muscle metaboreflex). Beat-by-beat BP and heart rate (HR) were measured using a finometer (Finapres Medical Systems, Amsterdam, The Netherlands). Muscle sympathetic nerve activity (MSNA) was measured in a subset of women (OCP: n=14, NAT: n=14) using peroneal microneurography. Changes in BP, HR, and MSNA were measured continuously throughout the HG exercise and PEI. Results: Resting mean arterial pressure (MAP) (OCP: 80±7mmHg vs. NAT: 78±6mmHg, P=0.31), HR (OCP: 63±9bpm vs. NAT: 62±10bpm, P=0.75), and MSNA (OCP: 10±5 bursts/min vs. NAT: 8±5 bursts/min, P=0.48) were not different between groups. As expected, HG exercise elicited increases in MAP, HR, and MSNA in both groups (P< 0.0001). During the last minute of HG exercise, the increase in MAP (OCP: ∆17±8mmHg vs. NAT: ∆13±7mmHg, P=0.044) and MSNA (OCP: ∆12±7 bursts/min vs. NAT: ∆7±4 bursts/min, P=0.034) were significantly greater in OCP users. The increase in HR (OCP: ∆15±9bpm vs. NAT: ∆14±9bpm, P=0.85) was not different between groups. MAP, HR, and MSNA remained elevated during PEI but did not differ between groups (P >0.1). Conclusion: Consistent with our hypothesis, these data indicate that both BP and sympathetic reactivity to isometric HG exercise are greater in women using OCPs compared to NAT women. This greater reactivity may explain, in part, the greater future risk for hypertension in OCP users. Supported by NIH R01 HL 146558 and P20 GM113125 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.