Plasma Adenosine Levels in Peri-Menopausal Women Having Frequent Hot Flushes

Abstract

enopause is associated with an increased risk of cardiovascular disease. Several protective actions of estrogen, including peripheral vasodilation, have been described, 1,2 but the mechanisms underlying these effects remain unclear. Increased adrenergic activity and/or higher cardiovascular responsiveness have been reported to occur in peri-and postmenopausal women, 3,4 although not all authors concur with this finding. 5 For example, Komesaroff et al observed that estrogen supplementation attenuates blood pressure, glucocorticoid, and catecholamine responses to psychological stress in perimenopausal women. 6 Hot flushes, one of the most common and earlier symptoms of the climacteric (peri-menopausal) syndrome, are characteristic sudden sensations of intense heat with sweating and flushing, but these episodes typically disappear after 1-5 years in the vast majority of postmenopausal women. 7 Hot flushes have also been reported to be associated with endocrine changes such as increased catecholamine production in the brain. 7 Adenosine is a vasoactive purine metabolite that is a potent vasodilator in many organs and a metabolic regulator in the cardiovascular system. 8 In earlier studies of patients with chronic heart failure, elevation of plasma adenosine levels was observed and thought to attenuate the cardiovascular effect of norepinephrine. 9-13 Although some earlier studies have denied the effect of estrogen on adenosine as a primary endothelium-independent vasodilator in postmenopausal women, 14,15 changes in plasma adenosine levels in peri-menopausal women with hot flushes have not previously been examined. In this study, we measured plasma adenosine levels and observed the effect of hormone (estrogen) replacement therapy (HRT) on the adenosine level in peri-menopausal women experiencing hot flushes. MethodsIn accordance with hospital policies on human research, informed consent was obtained from all subjects prior to the study. Between April 2002 and March 2005, we obtained 8.0 ml samples of blood from 32 outpatients whose chief compliant was hot flushes and 29 healthy female volunteers who came to the hospital for cancer screening. Using these samples, we measured serum estradiol (E2) and folliculestimulating hormone (FSH) levels by radioimmunoassay with commercially available kits according to the manufacturer's instructions. Peri-menopause was defined as the presence of hot flushes with serum E2 <30 pg/ml and FSH ≥40 mIU/ml. In this study, peri-menopausal women with hot flushes were divided into 2 groups: >5 times per day was defined as frequent hot flushes (n=13); <1 or 2 times per day was defined as few hot flushes (n=9). Thirteen perimenopausal patients with frequent hot flushes (average age, 48.1±2.0 (range: 44-52) years old, frequent hot flushes group) received 28-day cycle HRT: oral conjugated equine estrogens 0.625 mg/day (Premarin) from days 5 to 18, a combination of Premarin with 2.5 mg/day continuous medroxyprogesterone acetate (Provera) from days 19 to 25 then a 7-day drug withdrawal. Before ...