Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol and norethisterone acetate. A two-year follow-up study.
Postmenopausal women (PMW) have an increased risk of cardiovascular disease that is attenuated by hormone replacement therapy (HRT). Inasmuch as hypertension and atherosclerosis are associated with diminished endothelium-derived nitric oxide (NO), we investigated whether HRT augments 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 continuous transdermal administration of 17 beta-estradiol (Estraderm-TTS-50) supplemented with oral norethisterone acetate (NETA) on days 1 through 12 of each month, and the other group (control PMW, n = 13) did not receive HRT. Blood samples in the HRT-PMW group were collected without regard to whether subjects were taking NETA at the time of blood sampling. 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 in NO2 + NO3 levels in HRT-PMW was significantly greater compared with the change in control PMW (P = .037). Likewise, when only those samples collected 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Rosselli
M
M
Department of Obstetrics and Gynecology, Clinic of Endocrinology, University Hospital, Zurich, Switzerland.
Imthurn
B
B
Keller
P J
PJ
Jackson
E K
EK
Dubey
R K
RK
D004359:Drug Therapy, Combination; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D017698:Postmenopause / Q000097:blood*
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone