Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy.
OBJECTIVE
Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated.


METHODS
Randomised, double-blind placebo controlled study.


METHODS
Twenty-three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days).


METHODS
Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin.


RESULTS
In women not on replacement therapy melatonin was ineffective. In HRT-treated women, melatonin reduced internal carotid artery PI (P = 0.005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0.038) and 4 mmHg (P = 0.045), respectively, while NOx levels were significantly increased (P = 0.024).


CONCLUSIONS
The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.
Cagnacci
A
A
Institute of Obstetrics and Gynaecology of Modena, University of Modena, Italy. cagnacci@unimo.it
Arangino
S
S
Angiolucci
M
M
Melis
G B
GB
Facchinetti
F
F
Malmusi
S
S
Volpe
A
A
D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008550:Melatonin / Q000627:therapeutic use*; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D017698:Postmenopause / Q000378:metabolism* / Q000502:physiology; D011673:Pulsatile Flow / Q000187:drug effects; D018615:Ultrasonography, Doppler, Color; D014664:Vasodilation / Q000187:drug effects*
D009569:Nitric Oxide; D008550:Melatonin