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. 2002 Dec 13;547(Pt 1):309–316. doi: 10.1113/jphysiol.2002.032524

Basal leg blood flow in healthy women is related to age and hormone replacement therapy status

Kerrie L Moreau *, Anthony J Donato *, Hirofumi Tanaka *, Pamela Parker Jones *, Phillip E Gates *, Douglas R Seals *,†
PMCID: PMC2342605  PMID: 12562958

Abstract

Basal leg blood flow declines with age in healthy men, an effect that is mediated by augmented sympathetic vasoconstriction. However, in women the presence or absence of oestrogen and selective use of hormone replacement therapy (HRT) may alter these relationships with ageing. We studied 103 healthy women: 73 postmenopausal (41 HRT, mean ± s.e.m. 61 ± 1 years; 32 no-HRT, 63 ± 2 years) and 30 premenopausal (29 ± 1 years). Compared with the premenopausal controls, absolute femoral artery blood flow (duplex ultrasound) was 23 % lower (P < 0.001) in the postmenopausal no-HRT group, but only 13 % lower in the HRT group (P < 0.01). The age and HRT group differences in leg blood flow were consistently associated with differences in leg vascular conductance, but not with femoral artery lumen diameter, leg muscle sympathetic nerve activity or cardiac output (systemic arterial blood flow). Leg fat-free mass was smaller in the postmenopausal groups (P < 0.05). Femoral blood flow normalized for leg fat-free mass was 17 % lower (P < 0.01) in the postmenopausal no-HRT compared with the premenopausal women, but was not different in the postmenopausal HRT and premenopausal groups. Femoral artery shear stress was similar in the postmenopausal HRT and premenopausal women, but was lower in the postmenopausal no-HRT group (P < 0.01). Basal whole-leg blood flow declines with age in healthy, oestrogen-deficient women, a phenomenon that is mediated primarily by reductions in leg vascular conductance. Among postmenopausal women, chronic HRT use is associated with augmented basal leg blood flow and vascular conductance. Leg blood flow normalized for leg fat-free mass is preserved with age in women taking chronic HRT. In contrast to men, differences in leg sympathetic vasoconstrictor nerve activity do not explain group differences in leg blood flow and vascular conductance with ageing in women.

Reduced basal limb blood flow and vascular conductance have important implications for both disease risk and physical function in humans. Recently we demonstrated that basal whole-leg blood flow is 25–30 % lower in healthy older men compared with young men (Dinenno et al. 1999, 2001a). Age-related changes in lower-leg blood flow are mediated by a reduction in leg vascular conductance (increase in leg vascular resistance) (Dinenno et al. 1999, 2001a), which is, in turn, associated with elevated leg muscle sympathetic nerve activity (MSNA; Dinenno et al. 1999) and augmented α-adrenergic vasoconstrictor tone (Dinenno et al. 2001c).

Female ageing is unique because of the menopause, the resulting loss of circulating oestrogen and the use of oestrogen-based hormone replacement therapy (HRT) by some postmenopausal women to relieve the symptoms of menopause. These factors may affect basal limb perfusion, given the potent acute vasodilatory (Gilligan et al. 1994; Volterrani et al. 1995; Dubey & Jackson, 2001) and possible sympathoinhibitory (Sudhir et al. 1997; Vongpatanasin et al. 2001; Weitz et al. 2001) actions of oestrogen. Despite these potential effects of changes in circulating oestrogen status on basal limb perfusion with female ageing, no information is available on these issues.

Accordingly, in the present study our primary experimental aims were to determine whether: (1) basal whole-leg blood flow is reduced in healthy oestrogen-deficient postmenopausal women compared with premenopausal women, (2) basal limb blood flow is augmented in oestrogen-supplemented postmenopausal women compared with their oestrogen-deficient peers and (3) these age- and oestrogen status-related differences in basal leg blood flow are associated with corresponding differences in leg vascular conductance, MSNA and/or systemic arterial blood flow.

METHODS

Subjects

One-hundred and three healthy women were studied: 73 postmenopausal who were either oestrogen deficient (n = 32) or taking HRT (n = 41) and 30 premenopausal controls. All postmenopausal women had been without menses for at least 1 year. HRT users had been following their regimen for an average of 11 ± 1 years. Among the HRT users, 22 women were taking an oral preparation of conjugated oestrogens, 13 were taking oral oestradiol and six were taking transdermal oestrogen. Twenty of the HRT users were taking unopposed oestrogen and 21 were taking a combination of oestrogen and progestin. The no-HRT group had not taken any oestrogen preparations for at least the past 2 years. All subjects were normotensive, non-smokers, non-medicated (other than HRT) and were free of overt chronic diseases, as assessed by medical history, physical examination, standard blood chemistries and haematological evaluation. Women over the age of 50 years were further evaluated by ECG and blood pressure during incremental treadmill exercise to exhaustion. Subjects who demonstrated Doppler flow characteristics and/or ankle-brachial pressure index consistent with peripheral vascular disease were excluded (Nomura et al. 1996). All subjects gave their written informed consent to participate. This study was performed according to the Declaration of Helsinki, and all procedures were reviewed and approved by the Human Research Committee.

Measurements

All measurements were performed following a 4 h fast and abstinence from caffeine. Premenopausal women were tested 1–6 days after onset of menstruation (i.e. during the early follicular phase). During the experimental sessions, subjects were examined after 20 min of supine rest in a quiet, temperature-controlled room.

Femoral artery haemodynamics

A duplex ultrasound machine (Toshiba SSH-140, Tochigi, Japan) equipped with a high-resolution (7.5 MHz), linear-array transducer was used to measure blood velocity parameters and vessel diameter on the common femoral artery, as described recently (Dinenno et al. 1999, 2001a,c). Blood flow was calculated as: (mean blood velocity) × (circular area) × 6 × 104, with the constant 6 × 104 being the conversion factor from m s−1 to l min−1. The data were analysed by the same investigator (KLM), who was blinded to the group to which the subject had been assigned. Arterial blood pressure was measured over the brachial artery using the oscillometric technique (Dinamap, Critikon, FL, USA; Dinenno et al. 1999). Femoral vascular conductance was calculated as femoral blood flow/mean arterial blood pressure, and femoral vascular resistance was calculated as mean arterial blood pressure/femoral blood flow. Whole-blood viscosity measured using a cone and plate viscometer (DV-I+, Brookefield) at shear rates of 60 rev min−1 at 37 °C was used to calculate femoral artery wall shear stress based on the following formula, as described previously: (4ηVm)/D, where η is blood viscosity (mPa s), Vm is mean blood velocity (cm s−1) and D is arterial diameter (cm) (Carallo et al. 1999; Dinenno et al. 2001b).

Cardiac output

Cardiac output was measured in 14 postmenopausal oestrogen-deficient women, 16 HRT users and 21 premenopausal women by echocardiography using a Toshiba SSH-140 ultrasound machine equipped with a 2.5 MHz phased-array transducer, as described previously (Spina et al. 1993b, 1996; Seals et al. 1994). Stroke volume was calculated from the cross-sectional area of the aortic annulus and the time-velocity integral of aortic annular flow, and was obtained by pulsed Doppler recording (Dinenno et al. 1999). Cardiac output was calculated by multiplying stroke volume by heart rate (ECG tracing).

MSNA

In 15 postmenopausal oestrogen-deficient, 22 HRT-using and 11 premenopausal women, multiunit recordings of efferent post-ganglionic MSNA were obtained from the peroneal nerve in the right leg using the microneurographic procedure, as described previously (Ng et al. 1993; Jones et al. 1997; Dinenno et al. 1999). MSNA is expressed as burst frequency (bursts min−1).

Body composition and leg tissue mass

Total fat mass and fat-free mass were determined using dual-energy X-ray absorptiometry. Regional analysis of the tissue mass of the right leg was determined from whole-body scans using dual-energy X-ray absorptiometry (DPX-IQ, Lunar, Lunar software version 3.1), as described previously (Dinenno et al. 1999, 2001a).

Metabolic risk factors

Fasting plasma concentrations of cholesterol, glucose and insulin were measured at the Core Laboratory of the University of Colorado General Clinical Research Center, as described previously (Stevenson et al. 1995). Briefly, a blood sample was drawn from an antecubital vein after abstinence from caffeine and a 12 h overnight fast. Plasma total cholesterol levels were analysed with conventional enzymatic methods. Plasma high-density lipoprotein (HDL) cholesterol concentrations were determined by the dextran precipitation technique. Low-density lipoprotein (LDL) cholesterol was determined subsequently from the Friedewald equation (Friedewald et al. 1972). Plasma glucose was determined using a hexokinase/ glucose-6-phospate dehydrogenase method and plasma insulin was determined using solid-phase radioimmunoassay.

Statistical analysis

The main effects of age and HRT status were determined by ANOVA. In the case of a significant F value, a Newman-Keuls post hoc test identified differences among group means. Univariate correlation analyses were used to determine the relationships between variables of interest. All data are reported as the mean ± s.e.m. Statistical significance was set at P < 0.05.

RESULTS

Subjects

These data are given in Table 1. There were no group differences in height, body mass, HDL cholesterol or years of education among the groups. Postmenopausal women had higher body fat percentage and total and LDL cholesterol than the premenopausal controls (P < 0.05). Systolic and diastolic blood pressures were within the normal range for all groups. Systolic blood pressure was higher in the postmenopausal groups compared with the premenopausal women, and diastolic blood pressure was higher in the no-HRT postmenopausal group than in the other two groups (P < 0.05).

Table 1.

Subject characteristics

Variable Premenopausal Postmenopausal no-HRT Postmenopausal HRT
n 30 32 41
Age (years) 29 ± 1 63 ± 1* 61 ± 1*
Height (cm) 165 ± 1 164 ± 1 162 ± 1
Body mass (kg) 59.0 ± 1.3 62.3 ± 1.9 61.2 ± 1.4
Body fat (%) 24 ± 2 32 ± 2* 33 ± 2*
Heart rate (beats min−1) 58 ± 2 59 ± 2 62 ± 2
Systolic BP (mmHg) 105 ± 1 120 ± 3* 117 ± 2*
Diastolic BP (mmHg) 63 ± 1 69 ± 1* 66 ± 1†
Total cholesterol (mmol l−1) 4.0 ± 0.2 5.0 ± 0.2* 5.1 ± 0.2*
LDL cholesterol (mmol l−1) 2.0 ± 0.2 2.9 ± 0.2* 2.8 ± 0.1*
HDL cholesterol (mmol l−1) 1.6 ± 0.1 1.6 ± 0.1 1.9 ± 0.1
Education (years) 16 ± 1 16 ± 1 17 ± 1
Postmenopausal duration (years) — 14 ± 2 14 ± 2
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Data are means ± S.E.M. HRT, hormone replacement therapy; BP, blood pressure; LDL, low-density lipoprotein; HDL, high-density lipoprotein.

*

P < 0.05vs. Premenopausal

†

P < 0.05vs. Postmenopausal no-HRT.

Basal leg blood flow

Absolute basal femoral artery blood flow was 23 % lower (229 ± 10 vs. 298 ± 11 ml min−1, P < 0.001) in the postmenopausal no-HRT women compared with the premenopausal controls (Fig. 1A). Leg fat-free mass was positively related to absolute femoral artery blood flow in the pooled study sample (r = 0.37, P < 0.05), and was smaller in the postmenopausal no-HRT women compared with the premenopausal controls (P < 0.05, Table 2). Thus, femoral blood flow normalized for leg fat-free mass was 17 % lower in the no-HRT group (42 ± 2 vs. 35 ± 2 ml min−1 kg−1, P < 0.01, Fig. 2). Among the postmenopausal women, absolute femoral artery blood flow was ≈13 % higher (P < 0.05) in the HRT than in the no-HRT group (Fig. 1A). Since leg fat-free mass was 6 % lower in the HRT (6.2 ± 0.1 kg) than in the no-HRT group (not significant), femoral blood flow normalized for leg fat-free mass was 17 % higher in the HRT women (35 ± 2 vs. 42 ± 2 ml min−1 kg−1, P < 0.01), and was not different in the HRT group and premenopausal controls (Fig. 2).

Figure 1. Differences in femoral artery haemodynamics in premenopausal and treated and untreated postmenopausal women.

Figure 1

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Resting femoral artery blood flow (A), femoral vascular conductance (B) and femoral vascular resistance (C) in premenopausal women (Pre; n = 30) and in postmenopausal women using hormone replacement therapy (Post HRT; n = 41) and not using HRT (Post No-HRT; n = 32). Data are presented as means ±s. e. m.*P < 0.001vs. Pre; †P < 0.05vs. Post No-HRT.

Table 2.

Physiological determinants of femoral haemodynamics

Variable Premenopausal Postmenopausal no-HRT Postmenopausal HRT
n 30 32 43
Femoral artery velocity (m s−1) 0.094 ± 0.005 0.068 ± 0.003* 0.080 ± 0.003*†
Femoral artery diameter (mm) 8.33 ± 0.14 8.44 ± 0.15 8.29 ± 0.14
Femoral artery shear stress (dyn cm−2) 1.8 ± 0.1† 1.3 ± 0.1 1.7 ± 0.1†
Cardiac output (l min−1) 4.0 ± 0.2 3.5 ± 0.3 3.8 ± 0.3
(n =21) (n =14) (n =16)
Leg fat-free mass (kg) 7.1 ± 0.2 6.6 ± 0.1* 6.2 ± 0.1*
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Data are means ± S.E.M.

*

P < 0.05vs. Premenopausal

†

P < 0.05vs. Postmenopausal no-HRT.

Figure 2. Femoral artery blood flow adjusted for leg fat-free mass.

Figure 2

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Femoral artery blood flow adjusted for leg fat-free mass in premenopausal women (n = 30) and in postmenopausal women using (n = 41) and not using HRT (n = 32). Data are presented as means ± s.e.m.*P < 0.01vs. Pre; †P < 0.01vs. Post No-HRT.

Among the postmenopausal women taking HRT, absolute femoral artery blood flow was not different between those using unopposed oestrogen vs. combined oestrogen and progestin (255 ± 13 vs. 260 ± 15 ml min−1, respectively, P > 0.05), or among the oestrogen subgroups: oral conjugated oestrogens, oral oestradiol and transdermal oestrogen (263 ± 12 vs. 255 ± 22 vs. 268 ± 23 ml min−1, respectively, P > 0.05). There were no differences in leg fat-free mass among any of these HRT subgroups. Femoral artery diameter was not different in the premenopausal women and the postmenopausal HRT and no-HRT groups (Table 2, P > 0.05), or among the HRT subgroups (data not shown). Femoral artery shear stress was similar between the postmenopausal HRT users and premenopausal controls, but was lower in the postmenopausal oestrogen-deficient women (Table 2, P < 0.001)

Femoral vascular conductance and resistance

The lower absolute femoral artery blood flow in the postmenopausal no-HRT group compared with the premenopausal women was associated with a 33 % lower femoral artery vascular conductance and a 42 % higher vascular resistance (P < 0.001, Fig. 1B and C). In the postmenopausal women, the greater absolute femoral blood flow in the HRT group was associated with a 25 % greater femoral vascular conductance and a 25 % lower vascular resistance compared with the no-HRT group (P < 0.05, Fig. 1B and C). There were no differences in femoral vascular conductance or vascular resistance among the HRT subgroups.

Cardiac output

Cardiac output at rest was not significantly different among the premenopausal controls and the postmenopausal no-HRT and HRT groups (Table 2, P > 0.05), and was not related to absolute basal femoral blood flow in the pooled study sample (r = 0.18, P > 0.05).

Muscle sympathetic nerve activity

Leg MSNA during supine rest was 95–100 % higher in the postmenopausal than in the premenopausal women, but was not different between the two postmenopausal groups (P < 0.05; Fig. 3). Moreover, basal MSNA was not related to femoral artery blood flow (absolute or normalized for leg fat-free mass), vascular conductance or vascular resistance within the pooled study sample or any specific group (r = −0.06–0.21, P > 0.05).

Figure 3. Muscle sympathetic nerve activity (MSNA).

Figure 3

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Resting MNSA in premenopausal women (n = 11) and in postmenopausal women using (n = 22) and not using HRT (n = 15). Data are presented as means ± s.e.m.*P < 0.001vs. Pre.

DISCUSSION

The novel findings of the present study are as follows. First, basal leg blood flow is lower in healthy oestrogen-deficient postmenopausal women compared with premenopausal women. Second, basal leg blood flow is augmented in postmenopausal women taking chronic HRT compared with their oestrogen-deficient peers and, when normalized for leg fat-free mass, is not different from premenopausal women. Third, the augmented basal leg blood flow in women on chronic HRT appears to be independent of the type or mode of delivery of oestrogen, or whether the HRT includes progestin. Finally, the group differences in basal leg blood flow are consistently associated with differences in leg vascular conductance (vascular resistance), but not with femoral artery lumen diameter, MSNA or systemic arterial blood flow. These findings suggest that the primary mechanisms responsible for reductions in basal leg blood flow with age in healthy women include decreases in leg fat-free mass, oestrogen deficiency and reductions in leg vascular conductance.

To examine the effect of natural physiological ageing on basal leg blood flow in women we compared healthy postmenopausal oestrogen-deficient women with premenopausal controls. Our results are consistent with our recent observations in healthy men (Dinenno et al. 1999, 2001a,c) that absolute basal leg blood flow decreases by ≈25 % between the ages of 25 and 65 years. Moreover, as we found in men (Dinenno et al. 2001a), normalizing femoral blood flow to leg fat-free mass reduces (e.g. from 23 to 17 % in the present study), but does not eliminate the age-associated differences. Thus, leg blood flow per kilogram of leg fat-free mass and, presumably, skeletal muscle mass, is lower in oestrogen-deficient postmenopausal women compared with young adult females.

Although the acute vasodilatory effect of oestrogen on limb blood flow is well documented (Gilligan et al. 1994; Volterrani et al. 1995), the chronic influence of oestrogen supplementation in postmenopausal women has not been established. In the present study, we demonstrated that leg blood flow normalized to leg fat-free mass is similar in oestrogen-supplemented postmenopausal and in premenopausal women, whereas it is lower in oestrogen-deficient postmenopausal women. One interpretation of these combined observations is that basal leg blood flow is reduced with physiological ageing in healthy women, and the addition of oestrogen simply produces an independent sustained vasodilatory effect. That is, the femoral artery is dilated above the age-associated reduced baseline blood flow, as would occur with the chronic administration of any vasodilatory agent. Alternatively, the fact that basal femoral blood flow (normalized to leg fat-free mass) is reduced only in the absence of circulating oestrogen could be viewed as indicating that the age-associated decrease in leg blood flow is mediated by the lack of oestrogen rather than age per se. However, the latter explanation would appear to be inconsistent with our previous observations of reduced femoral artery blood flow with age in healthy men (Dinenno et al. 1999, 2001a). Whichever view one takes, the key factor appears to involve the fundamental vasodilatory properties of oestrogen, because for the postmenopausal women taking HRT, leg blood flow appeared to be augmented regardless of the type of oestrogen used, its mode of delivery (oral or transdermal patch) or whether or not the HRT regimen included progestin.

The age-related decrease in leg blood flow and the higher leg blood flow associated with HRT were not consistently associated with mean group differences in cardiac output, nor was there a significant correlation among the individual subjects. Rather, group differences in leg blood flow were mediated by differences in leg vascular conductance (vascular resistance). The group differences in leg blood flow and vascular conductance were not associated with differences in femoral artery lumen diameter. The absence of a relationship between leg blood flow and femoral artery lumen diameter is consistent with our recent observations in healthy men, as was the lack of a strong, consistent association with cardiac output (Dinenno et al. 1999, 2001a).

In contrast to our observations in men, we did not find a significant inverse relationship between age-associated decreases in leg blood flow and increases in MSNA. The absence of a consistent association between leg blood flow (vascular conductance) and MSNA in women may be explained by the independent vasodilatory effects of circulating oestrogen. We speculate that these effects are mediated through the modulatory influence of oestrogen on locally produced vasoactive factors such as nitric oxide, reactive oxygen species and/or endothelin-1. For example, tonic reductions in nitric oxide and elevations in endothelin-1 release can occur with ageing and oestrogen deficiency (Amrani et al. 1996; Virdis et al. 2000; Taddei et al. 2001), whereas HRT is associated with augmented nitric oxide bioactivity and reduced endothelin-1 action (Lieberman et al. 1994; Majmudar et al. 2000; Vehkavaara et al. 2000; Virdis et al. 2000). Consistent with this concept, in the present study the group differences in leg blood flow were associated with differences in femoral artery shear stress, an important physiological stimulus for nitric oxide synthesis and release (Davies, 1995). The lack of association between leg blood flow and MSNA among our female subjects may be explained by the direct vascular actions of these local vasoactive factors, by their modulatory effects on noradrenaline release and/or coupling with postjunctional α-adrenergic receptors, or via their modulation of vascular endothelial α2-adrenergic receptor stimulation of nitric oxide release (Zanzinger et al. 1994; Meyer et al. 1997; Binko et al. 1998; Zanzinger, 1999).

Consistent with our earlier observations (Ng et al. 1993), in the present study basal MSNA was elevated in postmenopausal compared with premenopausal women, but did not differ among oestrogen-deficient and oestrogen-supplemented postmenopausal women. HRT is associated with lower basal sympathetic activity in some peri- and postmenopausal women (Sudhir et al. 1997; Vongpatanasin et al. 2001; Weitz et al. 2001); however, an absence of any association has also been observed (Ng et al. 1993; Del Rio et al. 1998; Hunt et al. 2001; Vongpatanasin et al. 2001). Some of the inconsistencies could be explained by differences in the type of oestrogen used or the mode of delivery. For example, transdermal administration of oestradiol appears to be more consistently associated with reductions in sympathetic nerve activity than does oral administration (Hunt et al. 2001; Vongpatanasin et al. 2001; Weitz et al. 2001). In the present study, however, we found no differences among the HRT subgroups. Thus, the influence of oestrogen on sympathetic activity remains unclear.

Since all of our subjects were from the Denver and Boulder areas, it is possible that altitude acclimatization could have modulated MSNA in the present study. However, we do not think that this is the case because the altitude (≈1500 m) is not usually sufficient to significantly alter sympathetic nerve activity. This may be due to the fact that the average arterial O2 tension in Boulder/Denver is in the 70–75 mmHg range, which is still on the flat portion of the O2 dissociation curve. As a result, O2 saturation is close to sea level values. Furthermore, after chronic exposure (2–4 months), any potential sympathoexcitation is likely to have resolved and sympathetic nerve activity would have returned to normal. Thus, because the women in the present study were residents of this area, the modest altitude would not be expected to influence MSNA in the present study. Most importantly, because all of the women were from this area, no systematic bias in group comparisons would be expected.

The primary limitation of the present study is its cross-sectional design. Moreover, our study is limited to healthy postmenopausal women and, as such, the relationships among basal leg blood flow, age and HRT status may be different in women with clinical cardiovascular or metabolic diseases. However, these limitations to the present study may also be considered as strengths for the following reasons. First, excluding women who have various cardiovascular and metabolic diseases such as hypertension and dyslipidaemia allowed us to study postmenopausal women who were matched for arterial blood pressure and blood lipids, thus identifying associations with oestrogen independent of these factors (Dubey & Jackson, 2001). Second, because we studied healthy women who had been chronically taking HRT for ≈11 years, our results support the notion that initiating hormone therapy in the early stages of atherosclerosis (during the perimenopausal years and early years of postmenopause) may preserve the health of the vascular endothelium (Mikkola & Clarkson, 2002). However, to determine more definitively the influence of HRT on leg blood flow, an intervention trial will be required. Nonetheless, our results provide the necessary experimental basis to hypothesize that an HRT intervention might improve leg blood flow in postmenopausal women.

Reduced basal limb blood flow and vascular conductance have important implications for both disease risk and physical function in postmenopausal women. Reduced limb blood flow may exacerbate postprandial hyperlipidaemia (Lind & Lithell, 1993), and could limit peripheral glucose uptake, thus contributing to glucose intolerance and hyperinsulinaemia in middle-aged and older adults (Baron et al. 1990). Indeed, reduced basal limb blood flow has been implicated in the ‘metabolic (insulin resistance) syndrome’ (Lind & Lithell, 1993), which includes hyperinsulinaemia, dyslipidaemia and hypertension (Hjermann, 1992). Moreover, a tonically augmented leg vasoconstrictor state could oppose vasodilatation in response to the acute increases in functional demand imposed by large-muscle dynamic exercise (Wahren et al. 1974; Proctor et al. 1998), feeding-induced hyperinsulinaemia (Meneilly et al. 1995) and ambient heat stress (Kenney, 1997; Kenney et al. 1997). Among postmenopausal women, oestrogen deficiency has been linked to the impaired circulatory adjustments observed in response to both exercise and heat stress (Tankersley et al. 1992; Spina et al. 1993a; Brooks et al. 1997; Dunbar & Kenney, 2000) that may be resolved with HRT (Tankersley et al. 1992; Brooks et al. 1997; Dunbar & Kenney, 2000).

In conclusion, our results support the idea that in women, physiological ageing accompanied by oestrogen deficiency is associated with a reduction in basal whole-leg blood flow and vascular conductance. In marked contrast, basal leg blood flow and vascular conductance are preserved in postmenopausal women taking HRT. Moreover, in contrast to observations in healthy age-matched men, these group differences in healthy women are not obviously related to differences in leg sympathetic vasoconstrictor nerve activity, presumably because of the independent vasodilatory effects of circulating oestrogen.

Acknowledgments

This study was supported by National Institutes of Health awards AG05910, AG00847, AG06537, AG13038, AG00828 and HL03840; the General Clinical Research Center (RR-00051); and American Heart Association grant 9960234Z. We thank Dr Frank Dinenno and Margaret Whitford for their technical assistance.

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