Highlights
- Women with endometriosis display attenuated, not exaggerated, blood pressure reflexes to cold and exercise stress.
- Cyclooxygenase (COX) inhibition with aspirin does not modify these altered pressor responses.
- Findings suggest disrupted central autonomic integration and sympathetic outflow in endometriosis.
- These results challenge assumptions about heightened cardiovascular reactivity in this population.
Study Background and Disease Burden
Endometriosis is a chronic gynecological disorder affecting up to 10% of reproductive-age women. Characterized by ectopic growth of endometrial tissue, it causes significant pain, infertility, and systemic inflammation. Recent epidemiological studies link endometriosis to elevated long-term risk of cardiovascular disease (CVD), including hypertension and ischemic heart disease. The mechanistic pathways connecting endometriosis and CVD remain unclear, but upregulation of cyclooxygenase (COX) enzymes in endometriotic lesions is hypothesized to influence vascular function and sympathetic nerve activity. An exaggerated pressor response—an abnormal increase in blood pressure (BP) during physical or cold stress—is a recognized risk factor for adverse cardiovascular events. This study aimed to clarify whether women with endometriosis exhibit heightened BP responses to standardized stressors, an issue of both pathophysiological interest and clinical significance.
Study Design
The investigators conducted a single-blind, randomized, crossover trial involving 20 premenopausal women: 11 with laparoscopically confirmed endometriosis (Endo group) and 9 healthy controls (HC group) without the disease. Participants underwent two stress protocols—cold pressor test (CPT) and handgrip exercise with postexercise ischemia—after ingesting either 650 mg aspirin (a nonselective COX inhibitor) or placebo. The primary endpoints were changes in mean arterial pressure (MAP) during these tests, providing a measure of sympathetic vasomotor reactivity. BP was continuously monitored at baseline and during each provocation (CPT: 3 minutes of hand submersion in 4–8°C water; handgrip: 2 minutes at 30% maximal voluntary contraction, followed by 3 minutes of postexercise ischemia).
Key Findings
Contrary to the original hypothesis, women with endometriosis demonstrated significantly attenuated pressor responses compared to healthy controls:
- During CPT, the mean increase in MAP was 21±16 mm Hg for the Endo group versus 34±20 mm Hg for controls (P<0.01).
- During handgrip/postexercise ischemia, MAP increased by 12±13/13±10 mm Hg in the Endo group, compared to 24±14/20±8 mm Hg in controls (P<0.01).
- Aspirin administration had no significant effect on BP responses in either group during CPT or handgrip protocols.
These data suggest that, rather than exaggerated, the acute sympathetic and pressor responses to physical and cold stress are blunted in women with endometriosis. This attenuation was consistent across both types of physiological stress and unaffected by nonselective COX inhibition.
Expert Commentary
This study challenges the prevailing assumption that women with endometriosis are predisposed to heightened pressor and sympathetic responses due to local and systemic inflammation. The observed blunting of BP reflexes indicates possible dysregulation of central autonomic integration or diminished sympathetic outflow and vascular responsiveness. This is clinically relevant, as it suggests that traditional risk markers—such as exaggerated pressor reactivity—may not apply in this population, and that cardiovascular risk in endometriosis may operate through alternative mechanisms, possibly involving chronic inflammation, endothelial dysfunction, or altered neurovascular signaling.
Several limitations warrant mention. The sample size was modest (n=20), limiting power to detect subtler effects or subgroup differences. Subjects were relatively young and free from overt cardiovascular disease, which may restrict generalizability to older or higher-risk populations. The crossover design and rigorous physiological monitoring strengthen internal validity, but replication in larger and more diverse cohorts is advisable.
Current guidelines do not specifically address the management of cardiovascular risk in women with endometriosis. These findings underscore the need for tailored risk assessment and further mechanistic studies in this population.
Conclusion
Women with endometriosis exhibit blunted blood pressure responses to both cold exposure and isometric exercise, independent of COX inhibition. These findings suggest altered autonomic and vascular regulation, challenging assumptions about sympathetic overactivity in endometriosis. Further research is needed to elucidate the clinical implications for cardiovascular risk stratification and management in this population.
References
Williams AC, Alexander LM. Altered Blood Pressure Reflexes in Women With Endometriosis. Hypertension. 2025 Aug 1. doi: 10.1161/HYPERTENSIONAHA.125.25089. Epub ahead of print. PMID: 40747556.
Other literature for context:
– Mu F, Rich-Edwards J, Rimm EB, et al. Endometriosis and risk of coronary heart disease. Circulation. 2016;133(21):2051-2059.
– Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261-275.