Serum vascular endothelial growth factor (VEGF) in the normal menstrual cycle: association with changes in ovarian and uterine Doppler blood flow

OBJECTIVE To investigate whether changes in circulating serum vascular endothelial growth factor (VEGF) concentrations during the menstrual cycle are associated with changes in blood flow within the ovaries and uterus. PATIENTS AND MEASUREMENTS Serum VEGF concentrations were measured and pulsed and colour Doppler blood flow waveforms recorded within the ovarian stroma and uterine arteries during the early follicular, the immediate preovulatory and the midluteal phases of the menstrual cycle of 14 healthy women. RESULTS Mean (+/-SD) serum VEGF concentrations rose from 2.44 +/- 0.1 ng/ml in the early follicular phase to 3 +/- 0.8 ng/ml in the pre-ovulatory phase and to 4.4 +/- 0.9 ng/ml in the mid-luteal phase (P < 0.0001) of the menstrual cycle, Mean peak systolic blood flow velocity (PSV) and time-averaged maximum flow velocity (TAMXV) were higher within the ovarian stroma of the ovary bearing the dominant follicle and the uterine arteries in the pre-ovulatory and mid-luteal phase than in the same sites during the early follicular phase of the menstrual cycle. PSV rose significantly from the early follicular phase (11 +/- 6 cm/s) to 14 +/- 4 cm/s in the pre-ovulatory phase and further in the mid-luteal phase (26 +/- 7 cm/s, P = 0.0001). Within the uterine arteries, mean PSV rose significantly from 28 +/- 9 cm/s in the early follicular phase to 31 +/- 8 cm/s in the preovulatory phase and further in the mid-luteal phase (44 +/- 11 cm/s, P < 0.005). Serum VEGF correlated with serum progesterone concentrations in the luteal phase (r = 0.85, P < 0.001), with serum oestradiol concentrations in the early follicular (r = 0.67, P = 0.009), pre-ovulatory (r = 0.57, P = 0.03) and luteal phases (r = 0.68, P < 0.005) and with serum testosterone in the early follicular phase (r = 0.63, P = 0.01). CONCLUSIONS Cyclical changes in serum vascular endothelial growth factor concentrations are associated with coincident changes in ovarian and uterine blood flow.