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P141 The influence of age and serum oestradiol levels on resistance to blood flow in the internal carotid artery in postmenopausal women
P139
P140
INFLUENCE OF ORAL GESTAGEN ON THE EFFECT OF T~SD~~AL ESTROGEN ~FLAC~MENT TH~~PY (ERT) ON ENDOTHELIAL DYSFUNCTION IN POSTMENOPAUSAL WOMEN
AN OPEN STUDY OF THE EFFECTS OF ORAL 17B OEST~DIOL AND ORAL DYDROGEST~RONE ON THE INTERNAL CAROTID ARTERY PULSATILITY INDEX IN HYSTERECTOMISED WOMEN
H. raiser*, C. ~a~ha~er*, K. Wagner*, J. Pa~fa~~~, C. IVauert+ , F. C. Luff *, *Franz Voihard Clinic, Hum boldt University, 13122 Berlin, +~one-Poulenc Rorer GmbH, 50792 Cologne, Germany
A Cmuer~ II Ross, C Spencer, M ~a~h, J ~fevensan~ M Whiteheaa! Wynn Division of Metabolic Medicine, London, UK
ERT seems to have a beneficial effect on endothelial cell dysfunction, however, gestagen replacement may have adverse effect. We therefore investigated whether oral gestagen alters the effect of transdermal ERT on endothelial cell dysfunction in postmenopausal women. We investigated in 37 healthy, postmenopausal women (mean age 57.1, BMI 24.2) the effects of transdermal ERT (50 ug Et/d) with or without oral gestagen (1 mg NETA/d) on endothelial cell dysfunction. Endothelial cell dys~n~tion was assessed using an echotra~king device (Nius 02) and we measured the ischemia-induced versus the nitrate-induced v~odilation of the radial artery to the response after four and eight weeks of treatment ~double-blind, placebo controlled). Transdermal ERT resulted in an increase in ischemia-induced (= endothelial-dependent) vasorelaxation in 9 women out of 14 after four weeks. Transdermal ERT in combination with oral gestagen only improved 4 out of 11. This was not different from the placebo group. After eight weeks there was no further increase of the estrogen effect while the negative effect of gestagen seemed to be lessened. Transdermal ERT has a beneficial effect on the diminished endothelia cell function in postmenopausal women. This is reduced by a concomit~t oral gestagen substitution.
P140 (cant)
Doppler ultrasound with colour flow imaging may be used to record flow velocity waveforms from human arteries. The pulsatility index (PI), computed from these waveforms, represents resistance to blood flow distal to the point of sampling. We compared oral oestradiol with a C21 progestogen, dydrogesterone, in their effect on internal carotid artery PI. 2 1 healthy postmenopau~, hyste~ctomised women were given continuous 178 oestradiol 2mgld (Zumenon, Solvay Healthcare Ltd, Southampton) for 9 cycles of 28 days. In the last 3 cycles, women also received oral dydrogesterone, lOmg/d (Duphaston, Solvay Health~~e Ltd, Sou~~pton), from days 15 to 28 PI was measured before commencement of treatment and after 12, 24, 34 (oestrogen only phase) and 36 weeks (combined phase) of therapy. Three me~urements of PI were made on each carotid artery and the mean of these taken for each patient. On treatment PI values were compared with baseline using Wilcoxon paired signed ranks test. At 12, 24 and 34 weeks the median (range) change in internal carotid artery PI was -7.5% (-41.1 to +7.7%), -7.0% (-23.9 to +12.70/n)and -9.0% (-28.8 to +19.1%), respectively. At 12 and 34 weeks PI was signi~c~tly lower than baseline fp<0.05). Continued
P141
During dydrogesterone administration at 36 weeks the PI was almost unch~ged compared to baseline (+0.6%(-3 1.8 to + 37.7%) p=O.8), and was not significantly different from the oestradiol-only value at 34 weeks. This study shows that oral oestradiol reduces internal carotid artery PI. There is a suggestion that addition of a progestogen may partially oppose the potentially beneficial effect of oral oestradiol, although the PI value during the combined phase of therapy was not si~i~~~tiy different from the nearest oestradiol only value.
THE INFLUENCE OF AGE AND SERUM OESTRADIOL LEVELS ON RESISTANCE TO BLOOD FLOW IN THE INTERNAL CAROTID ARTERY IN POSTMENOPAUSAL WOMEN MS Marsh *+, l.3Rass *+, JC Stevcinsoni-, MI Whitehead*. *Menopause clinic, King’s College Hospital, London. +Wynn Department of Metabolic Medicine, National Heart and Lung Institute, London Cardiovascular disease risk is less in users of oestrogen hormone replacement therapy (ERT) than non-users, but the mech~isms for this effect are unclear. We have previously shown that ERT reduces internal carotid artery resistance to blood flow, measured as pulsatility index (PI). In the present study we aimed to determine whether carotid artery PI was related to serum oestradiol (E2) concentrations in untreated postmenopausal women. Forty-five hysterectomised postmenopausal women (mean age 52.6 yr) were recruited. Internal carotid artery PI was measured on two occasions two weeks apart using Doppler ultrasound with colour flow mapping (Philips@ P 700). Serum E2 concentrations were measured at the first visit. PI correlated with age (~0.31, P
160
P140
INFLUENCE OF ORAL GESTAGEN ON THE EFFECT OF T~SD~~AL ESTROGEN ~FLAC~MENT TH~~PY (ERT) ON ENDOTHELIAL DYSFUNCTION IN POSTMENOPAUSAL WOMEN
AN OPEN STUDY OF THE EFFECTS OF ORAL 17B OEST~DIOL AND ORAL DYDROGEST~RONE ON THE INTERNAL CAROTID ARTERY PULSATILITY INDEX IN HYSTERECTOMISED WOMEN
H. raiser*, C. ~a~ha~er*, K. Wagner*, J. Pa~fa~~~, C. IVauert+ , F. C. Luff *, *Franz Voihard Clinic, Hum boldt University, 13122 Berlin, +~one-Poulenc Rorer GmbH, 50792 Cologne, Germany
A Cmuer~ II Ross, C Spencer, M ~a~h, J ~fevensan~ M Whiteheaa! Wynn Division of Metabolic Medicine, London, UK
ERT seems to have a beneficial effect on endothelial cell dysfunction, however, gestagen replacement may have adverse effect. We therefore investigated whether oral gestagen alters the effect of transdermal ERT on endothelial cell dysfunction in postmenopausal women. We investigated in 37 healthy, postmenopausal women (mean age 57.1, BMI 24.2) the effects of transdermal ERT (50 ug Et/d) with or without oral gestagen (1 mg NETA/d) on endothelial cell dysfunction. Endothelial cell dys~n~tion was assessed using an echotra~king device (Nius 02) and we measured the ischemia-induced versus the nitrate-induced v~odilation of the radial artery to the response after four and eight weeks of treatment ~double-blind, placebo controlled). Transdermal ERT resulted in an increase in ischemia-induced (= endothelial-dependent) vasorelaxation in 9 women out of 14 after four weeks. Transdermal ERT in combination with oral gestagen only improved 4 out of 11. This was not different from the placebo group. After eight weeks there was no further increase of the estrogen effect while the negative effect of gestagen seemed to be lessened. Transdermal ERT has a beneficial effect on the diminished endothelia cell function in postmenopausal women. This is reduced by a concomit~t oral gestagen substitution.
P140 (cant)
Doppler ultrasound with colour flow imaging may be used to record flow velocity waveforms from human arteries. The pulsatility index (PI), computed from these waveforms, represents resistance to blood flow distal to the point of sampling. We compared oral oestradiol with a C21 progestogen, dydrogesterone, in their effect on internal carotid artery PI. 2 1 healthy postmenopau~, hyste~ctomised women were given continuous 178 oestradiol 2mgld (Zumenon, Solvay Healthcare Ltd, Southampton) for 9 cycles of 28 days. In the last 3 cycles, women also received oral dydrogesterone, lOmg/d (Duphaston, Solvay Health~~e Ltd, Sou~~pton), from days 15 to 28 PI was measured before commencement of treatment and after 12, 24, 34 (oestrogen only phase) and 36 weeks (combined phase) of therapy. Three me~urements of PI were made on each carotid artery and the mean of these taken for each patient. On treatment PI values were compared with baseline using Wilcoxon paired signed ranks test. At 12, 24 and 34 weeks the median (range) change in internal carotid artery PI was -7.5% (-41.1 to +7.7%), -7.0% (-23.9 to +12.70/n)and -9.0% (-28.8 to +19.1%), respectively. At 12 and 34 weeks PI was signi~c~tly lower than baseline fp<0.05). Continued
P141
During dydrogesterone administration at 36 weeks the PI was almost unch~ged compared to baseline (+0.6%(-3 1.8 to + 37.7%) p=O.8), and was not significantly different from the oestradiol-only value at 34 weeks. This study shows that oral oestradiol reduces internal carotid artery PI. There is a suggestion that addition of a progestogen may partially oppose the potentially beneficial effect of oral oestradiol, although the PI value during the combined phase of therapy was not si~i~~~tiy different from the nearest oestradiol only value.
THE INFLUENCE OF AGE AND SERUM OESTRADIOL LEVELS ON RESISTANCE TO BLOOD FLOW IN THE INTERNAL CAROTID ARTERY IN POSTMENOPAUSAL WOMEN MS Marsh *+, l.3Rass *+, JC Stevcinsoni-, MI Whitehead*. *Menopause clinic, King’s College Hospital, London. +Wynn Department of Metabolic Medicine, National Heart and Lung Institute, London Cardiovascular disease risk is less in users of oestrogen hormone replacement therapy (ERT) than non-users, but the mech~isms for this effect are unclear. We have previously shown that ERT reduces internal carotid artery resistance to blood flow, measured as pulsatility index (PI). In the present study we aimed to determine whether carotid artery PI was related to serum oestradiol (E2) concentrations in untreated postmenopausal women. Forty-five hysterectomised postmenopausal women (mean age 52.6 yr) were recruited. Internal carotid artery PI was measured on two occasions two weeks apart using Doppler ultrasound with colour flow mapping (Philips@ P 700). Serum E2 concentrations were measured at the first visit. PI correlated with age (~0.31, P
160