BACKGROUND: The effects of long-term estrogen (E2) replacement therapy (ERT) on circulating and bone marrow total plasma nitric oxide (NOx) levels were determined in rhesus monkeys. In addition changes in circulating NOx during the menstrual cycle were measured. MATERIAL/METHODS: We measured NOx levels in 20 ovariectomized animals and 27 cycling animals. In the first group monkeys were ovariectomized (OVX; n=10) and treated with estrogen implants for 21 months. The control group (n=10) was OVX and received vehicle implants only. After 21 months systemic NOx status was measured. In a second group of cycling animals NOx was measured during the follicular and luteal phases, and correlated with body composition parameters determined by dual energy X-ray absorptiometry (DXA) analysis. CONCLUSIONS: Replacement of estrogen in OVX monkeys resulted in reduced circulating but not bone marrow plasma NOx compared to OVX monkeys. Circulating NOx levels in these animals correlated negatively (r(2)= -0.35; P=0.03) with estradiol levels. In cycling monkeys luteal levels of NOx were found to be significantly higher than follicular levels and correlated negatively (r(2) = -0.4; P=0.036) with estradiol but not progesterone levels. Negative correlations between NOx levels and body weight, fat and lean mass were also found. RESULTS: Long-term ERT influences systemic NOx levels in a negative fashion without effects on bone marrow plasma NOx. Circulating NOx was higher during the luteal phase. In both ERT treated and cycling monkeys estradiol correlated negatively with NOx suggesting the existence of a negative feedback of NO on either NOS activity or expression.

Keywords: Menstrual Cycle - blood