No specific markers of the severity or prognosis of hypothalamic-pituitary-gonadal axis disturbances associated with weight loss amenorrhea (WLA) are currently available. Circulating nitric oxide (NO), which is involved in the control of the reproductive function in women and is correlated with body mass index (BMI), at least in over-weight and obese subjects, might be a marker of the severity and/or progression of WLA. To test this hypothesis, we studied circulatingNO levels in 11 women (age 27.1±1.59 yr) affected by WLA for 5.1±1.0 yr; in all patients hormonal therapy had been discontinued 10.0±3.15 months earlier. NO, determined by measuring its stable catabolite nitrite/nitrates (NOx), was compared with some clinical parameters and sex hormone levels. Subsequently, changes in NOx during pulsatile GnRH therapy (120 ng/kg bw sc every 120 min) were compared with the clinical and hormonal data. Fifteen normal women (27.3±1.6 yr) served as a control group. NOx was significantly lower (p<0.01) in WLA (8.8±2.0 μmol/l) than in control (18.7±2.5 μmol/l) subjects. No correlation between NOx and clinical parameters was noted in either WLA or control subjects. As a result of GnRH therapy, ovulatory cycles reappeared in 91% of WLA women. During the 1st cycle, periovulatory 17β-estradiol levels were 110% higher than those noted in controls. During the 2nd cycle, NOx showed a slight increase in the follicular phase (+12% vs 1st cycle) followed by a drop during the luteal phase (−40% from the follicular phase); indeed, at that time, NOx correlated negatively with progesterone in both WLA (rS −0.32, p<0.05) and control (rS −0.48, p<0.05) subjects. NOx correlated with BMI at the time of the 2nd cycle (rS 0.71, p<0.05) In conclusion, this study shows that in WLA patients: 1) NO is low, as in other conditions of chronic anovulation; 2) it does not correlate with clinical data; 3) it takes longer than sex steroids to increase and show normal-like fluctuations; 4) its fluctuations are restored earlier in patients with greater BMI.