Vasoactive biomarkers and oxidative stress in healthy recently postmenopausal women treated with hormone replacement therapy.
BACKGROUND
Despite biologically plausible mechanisms for cardiac protection from estrogen therapy, recent clinical trials have suggested possible cardiovascular risk rather than benefit. However, it has been speculated that cardioprotective benefits from hormone replacement therapy (HRT) may be more evident in the early postmenopausal period. We have previously reported early beneficial effects on biochemical markers of endothelial function in healthy women after short-term estradiol replacement therapy. In this study we aimed to evaluate the effect of long-term HRT on different vasoactive factors and oxidative stress in healthy recently postmenopausal women.


METHODS
Fifteen women (age 50 +/- 1 years, time since menopause 1.6 +/- 0.1 years) were randomized to a sequential oral and transdermal estradiol regimen (2 mg oral micronized 17beta-estradiol/day or 1.5 mg 17beta-estradiol gel/day). Oral dydrogesterone (10 mg/day, 12 days/month) was then cyclically combined with either of the estrogen therapies for 1 year. Blood samples were collected at baseline and after 1, 2, 6 and 12 months of therapy to evaluate levels of follicle stimulating hormone (FSH), estradiol, 6-keto PGF1alpha (prostacyclin metabolite), nitrite/nitrate, epinephrine, norepinephrine, 8-isoprostane (8-epi PGF2alpha) and lipid profile values.


RESULTS
FSH levels decreased (p < 0.001) while estradiol levels increased (p < 0.001) during HRT. Levels of epinephrine (p < 0.001), norepinephrine (p < 0.01), mean blood pressure (p < 0.01) and low density lipoprotein (LDL) cholesterol (p < 0.01) decreased, and nitrite/nitrate levels increased (p < 0.01) during HRT, which did not significantly affect 8-epi PGF2alpha levels.


CONCLUSIONS
One-year HRT significantly reduced the levels of catecholamines, mean blood pressure and LDL cholesterol while it increased levels of nitrite/nitrate, indicating cardiovascular benefit in healthy recent postmenopausal women. Levels of 8-epi PGF2alpha did not change, suggesting no evident relationship between HRT and oxidative stress.
Maffei
S
S
CNR Institute of Clinical Physiology, Pisa, Italy.
Mercuri
A
A
Prontera
C
C
Zucchelli
G C
GC
Vassalle
C
C
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000279:Administration, Cutaneous; D000284:Administration, Oral; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D015237:Dinoprost / Q000097:blood; D004394:Dydrogesterone / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D017698:Postmenopause / Q000097:blood*
D015415:Biomarkers; D008078:Cholesterol, LDL; D009566:Nitrates; D009573:Nitrites; D004958:Estradiol; D015121:6-Ketoprostaglandin F1 alpha; D005640:Follicle Stimulating Hormone; D004394:Dydrogesterone; D015237:Dinoprost; D009638:Norepinephrine; D004837:Epinephrine