Altered Blood Pressure Reflexes in Women With Endometriosis

Abstract

Background: Endometriosis is a risk factor for cardiovascular disease. COX (Cyclooxygenase) is upregulated in endometriotic lesions, potentially exaggerating pressor reflexes, a major risk factor for adverse cardiovascular events. The purpose of this study was to determine whether women with endometriosis demonstrate exaggerated pressor responses. We hypothesized that women with endometriosis would show exaggerated blood pressure (BP) compared with healthy women during handgrip exercise and cold pressor testing (CPT).

Methods: In a single-blind, randomized, crossover design, women with (Endo; n=11) and without (healthy control [HC]; n=9) endometriosis underwent a CPT and handgrip with postexercise ischemia (HG+PEI) following aspirin (a nonselective COX inhibitor; 650 mg) or placebo. BP was continuously monitored during baseline (5 minutes) and hand submersion (3 minutes; 4-8 °C) during CPT, and during baseline (5 minutes), 30% maximal voluntary contraction handgrip (2 minutes), and postexercise ischemia (3 minutes) for HG+PEI.

Results: Women with endometriosis demonstrated attenuated pressor responses to CPT (change in mean arterial pressure [∆MAP] Endo 21±16 versus HC 34±20 mm Hg; P<0.01) and HG+PEI (HG+PEI: ΔMAP Endo=12±13/13±10 mm Hg, HC=24±14/20±8 mm Hg; P<0.01). There was no effect of aspirin on blood pressure response to either CPT or HG+PEI.

Conclusions: Compared with age-matched HC, women with endometriosis demonstrate lower increases in blood pressure in response to cold exposure and exercise. Aspirin, a COX inhibitor, had no impact on these responses. Collectively, these results suggest that women with endometriosis demonstrate altered central integration and attenuated sympathetic outflow or end-organ responsiveness.

Keywords: aspirin; blood pressure; endometriosis; immersion; risk factors.

Figure 1.

Pressor and cardioaccelerator responses to CPT. For ΔSBP (A), ΔDBP (B), and ΔMAP (C), the endo group was significantly lower (p < 0.01), but ASA had no effect (p = 0.61, p = 0.65, and p = 0.57, respectively). For ΔHR (D), there was no effect of condition (p = 0.40) or treatment (p = 0.93). Red circles represent responses during ASA, open circles represent responses during placebo. Data were analyzed with linear mixed effects model (SAS v. 9.4).

Figure 2.

Pressor and cardioaccelerator responses to HG+PEI. For ΔSBP (A), ΔDBP (B), and ΔMAP (C), the endo group was significantly lower (p < 0.01), but ASA had no main effect (p = 0.07, p = 0.17, and p = 0.26, respectively). Phase (HG v PEI) had no main effect on ΔSBP, ΔDBP, or ΔMAP (p = 0.67, p = 0.45, and p = 0.88, respectively). ΔHR (D) was not different by group (p = 0.18), and was unaffected by ASA (p = 0.48), but was significantly lower in the PEI phase compared with HG (p < 0.01). Red circles represent responses during ASA, open circles represent responses during placebo. Data were analyzed with linear mixed effects model corrected for a priori multiple comparisons with Bonferroni’s method to directly compare HC v. Endo for each phase (SAS v. 9.4).

Figure 3.

Pain responses to CPT (A) and HG+PEI (B). A) For CPT,there were no differences between groups (p = 0.55) or treatments (p = 0.51). BL, baseline; S1 – S3, submerge minute 1 – 3; R1 – R15, recovery minute 1 – 15. B) There were no differences between groups (p = 0.15) or treatments (p = 0.17). BL, baseline; HG1 – HG2, HG minute 1 – 2; PEI1 – PEI3, PEI minute 1 – 3; R1 – R5, recovery minute 1 – 5. Endo is represented by squares, HC by circles, ASA with red in either group, Placebo with open shapes in either group. Data were analyzed with linear mixed effects model (SAS v. 9.4).

Figure 4.

Onset of ΔHR (A) and ΔMAP (B) response to HG onset. The Endo group (squares) showed significant delays in initiating cardioaccelerator and pressor responses compared with the HC group (circles). ASA (red) attenuated the early cardioaccelerator and pressor responses in both groups (p < 0.01). Data were analyzed with linear mixed effects model (SAS v. 9.4).

Figure 5.

Relation of average force output of hand grip exercise and peak pressor response during that time for HC (A; circles) and endo (B; squares). There were no significant associations of peak pressor responses with maintained force output (p ≥ 0.18 all comparisons). ΔSBP is represented in red, ΔDBP is represented in blue, ΔMAP is represented in purple. Data were analyzed with simple linear regression (GraphPad Software).