CIRCULATING NITRIC-OXIDE (NITRITE NITRATE) LEVELS IN POSTMENOPAUSAL WOMEN SUBSTITUTED WITH 17-BETA-ESTRADIOL AND NORETHISTERONE ACETATE - A2-YEAR FOLLOW-UP-STUDY/

Postmenopausal women (PMW) have an increased risk of cardiovascular di sease that is attenuated by hormone replacement therapy (HRT). Inasmuc h as hypertension and atherosclerosis are associated with diminished e ndothelium-derived nitric oxide (NO), we investigated whether HRT augm ents NO release in PMW. We determined serum levels of nitrite/nitrate (NO2+NO3) at baseline and during the 6th, 12th, and 24th months of the study in two groups of PMW. One group (HRT-PMW, n=13) received contin uous transdermal administration of 17 beta-estradiol (Estraderm-TTS-50 ) supplemented with oral norethisterone acetate (NETA) on days 1 throu gh 12 of each month, and the other group (control PMW, n=13) did not r eceive HRT. Blood samples in the HRT-PMW group were collected without regard to whether subjects were taking NETA at the time of blood sampl ing. Serum NO2+NO3 levels increased in HRT-PMW for the duration of the study, whereas serum NO2+NO3 levels remained unchanged in control PMW . When all samples regardless of timing of collection with respect to NETA treatment were included in the statistical analysis, the change i n NO2+NO3 levels in HRT-PMW was significantly greater compared with th e change in control PMW (P=.037). Likewise, when only those samples co llected when estradiol-treated subjects were not taking oral NETA were included in the statistical analysis, the change in NO2+NO3 levels in the HRT-PMW group remained significant (P=.047) compared with control PMW. In contrast, when only those samples collected when estradiol-tr eated subjects were taking NETA were included in the analysis, the cha nge in NO2+NO3 levels in the HRT-PMW group was not significant (P=.23) compared with control PMW. These results indicate that HRT increases NO levels in PMW, an effect that may contribute to the cardiovascular protection afforded by HRT in PMW. In addition, our data suggest, but do not prove, that concomitant administration of a progestin may atten uate the beneficial effects of estrogen replacement therapy with regar d to NO release.