Effects Of A Randomized Placebo-Controlled Oral Salsalate Intervention On Flow-Mediated Dilation In Women With Endometriosis

PURPOSE: Endometriosis is an estrogen-dependent gynecological disorder associated with impaired endothelial function and elevated cardiovascular disease risk. The mechanisms underpinning these impairments are unclear; however, systemic inflammation has been postulated as a contributing factor. Thus, the purpose of this study was to investigate whether endothelial function (indexed by shear rates and flow-mediated dilation; FMD) could be preferentially altered in women with endometriosis via inhibition of the universal transcription factor, nuclear factor κB (NF-κB), using oral salsalate supplementation. We hypothesized that women with endometriosis would exhibit improved shear rates and FMD following 5 days of salsalate administration. METHODS: We examined vascular responses in three women with surgically confirmed endometriosis (mean (SD), 32 (7) y, BMI 22.7 (5.1) kg·m-2) following 5 days of randomized salsalate or placebo intervention. Shear rates and brachial artery diameter were measured by blinded assessors using duplex Doppler ultrasound at rest and following 5-min forearm occlusion. Resting and peak values were calculated as the mean of 60 s pre-occlusion and the highest 3 s mean value post-occlusion, respectively. Post-salsalate and placebo FMD (percent increase from rest to peak artery diameter) and shear rates were compared using dependent t-tests. Data collection is ongoing. RESULTS: Endometriosis patients did not exhibit differences in resting shear rate (Salsalate: 66 (34) s-1 vs Placebo: 48 (33) s-1; p = 0.149) or FMD (Salsalate: 5.1 (3.8) % vs Placebo: 3.0 (5.6) %; p = 0.116) following salsalate compared to placebo interventions. However, there was a trend for greater peak shear rates (Salsalate: 443 (222) s-1 vs Placebo: 287 (184) s-1; p = 0.053) during hyperemia following salsalate than placebo. CONCLUSIONS: In this preliminary dataset, a 5-day salsalate intervention did not augment FMD nor resting shear rate but did tend to increase peak shear rate during hyperemia in women with endometriosis, compared to the placebo intervention. These data indicate that inhibiting NF-κB via short-term salsalate administration may alter shear rate responses, but targeting other mechanisms is likely required to more wholistically improve endothelial function in endometriosis patients.