Acute effects of a transdermal nitric oxide donor on perifollicular and intrauterine blood flow

Nitric oxide is a potent vasodilator and is involved in several physiological events during the female reproductive cycle.

The aim of this study was to determine the acute effects of a nitric oxide donor on ultrasound-derived indices of blood flow in the intact human uterus and ovaries during the follicular phase of the normal menstrual cycle.

The plan was to perform an observational study of six healthy volunteers, recruited during days 9-12 from day 1 of the last menstruation. Subjects were scanned transvaginally, with B-mode and color Doppler imaging around 12.00, and 2 h after the application of a transdermal glyceryl trinitrate (GTN) patch 10 mg/24 h. The patch was then removed and the subjects were rescanned 2 h later. END-POINTS: The main outcome measures were the peak systolic velocity (PSV), time-averaged maximum velocity (TAMV) and the pulsatility index (PI) derived from flow velocity waveforms, in the left and right main uterine arteries, a radial artery and subendometrial vessels, and from vessels at the rim of the dominant ovarian follicle.

One woman was scanned on day 9, two on day 10 and three on day 12 of the cycle. The median pretreatment values for endometrial thickness and follicular volumes were 7.2 mm (range 6.0-10.0 mm) and 3.1 ml (range 0.3-6.8 ml), respectively. GTN induced a significant (p < 0.05) increase in the PSV and TAMV in the subendometrial vessels in all subjects. There was a corresponding decrease in the PI in four cases. Changes in blood flow were reversible (50% of the changes in PSV, TAMV and PI were essentially reversed 2 h after the patch had been removed). In the uterine arteries, PSV and TAMV were significantly (p < 0.01) and progressively decreased with a concomitant significant (p < 0.01) increase in PI. There was also a tendency for the mean PI to decrease progressively in the vessels at the rim of the dominant follicle with decreased post-treatment values in four out of six subjects.

GTN induces a reversible increase in subendometrial blood flow velocity during days 9-12 of the menstrual cycle. The expected circadian decrease in uterine artery blood flow seemed to be partly interrupted by GTN treatment.

These data justify the implementation of randomized controlled studies to determine the potential beneficial effects of transdermal GTN on ovarian and uterine blood flow and function.