Peripheral Microvascular Vasodilatory Response to Estradiol and Genistein in Women with Insulin Resistance

Objective: E2 enhances vasodilation in healthy women, but vascular effects of the phytoestrogen GEN are still under investigation. IR compromises microvascular function. We therefore examined the interaction of E2 , GEN, and IR on microvascular vasodilatory responsiveness.

Methods: We hypothesized that E2 and GEN increase microvascular vasodilation in healthy women (control, n = 8, 23 ± 2 year, BMI: 25.9 ± 2.9 kg/m2) but not in women with IR (n = 7, 20 ± 1 year, BMI: 27.3 ± 3.0 kg/m2). We used the cutaneous circulation as a model of microvascular vasodilatory function. We determined CVC with laser Doppler flowmetry and beat-to-beat blood pressure during local cutaneous heating (42 °C) with E2 or GEN microdialysis perfusions. Because heat-induced vasodilation is primarily an NO-mediated response, we examined microvascular vasodilation with and without L-NMMA.

Results: In C, E2 enhanced CVC (94.4 ± 2.6% vs. saline 81.6 ± 4.2% CVCmax , p < 0.05), which was reversed with L-NMMA (80.9 ± 7.8% CVCmax , p < 0.05), but GEN did not affect vasodilation. Neither E2 nor GEN altered CVC in IR, although L-NMMA attenuated CVC during GEN.

Conclusions: Our study does not support improved microvascular responsiveness during GEN exposure in healthy young women, and demonstrates that neither E2 nor GEN improves microvascular vasodilatory responsiveness in women with IR.