Miriam de Kleijn | RAND Corp. (original) (raw)

Papers by Miriam de Kleijn

Research paper thumbnail of Does the beneficial effect of HRT on endothelial function depend on lipid changes

Maturitas, Jan 1, 2003

To determine whether improvement in endothelial function of the brachial artery observed in women... more To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. Hundred-and-five healthy postmenopausal women, aged 50-65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: -0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: -18%; -7%), LDL-cholesterol with 23% (95% CI: -30%; -15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: -26%; -2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids.

Research paper thumbnail of Indicators for the total duration of premenopausal endogenous estrogen exposure in relation to BMD

Human …, Jan 1, 2004

BACKGROUND: Previous studies have shown that age at menopause is an important indicator of durati... more BACKGROUND: Previous studies have shown that age at menopause is an important indicator of duration of endogenous estrogen exposure. The present study investigates whether combining more information on reproductive factors is useful in estimating individual total duration of exposure to endogenous estrogens. METHODS: Bone mineral density (BMD) was used as operational outcome. The study population consisted of 3476 white women living in Eindhoven, The Netherlands, aged 46-57 years, either pre-(n 5 2420) or postmenopausal (n 5 1056). BMD of the lumbar spine was measured by dual X-ray absorptiometry. Information on reproductive factors was obtained with questionnaires. RESULTS: The number of reproductive years explained 4.8% of the variance in BMD, while age at menopause alone accounted for 3.6%. Duration of lactation or oral contraceptive use did not add to the proportion of variance explained. The effect of reproductive years on BMD was stronger in older women. No significant associations with BMD were found for other reproductive variables. The number of miscarriages in premenopausal women (b 5 0.00760, SE 5 0.00357, P 5 0.03) explained only 0.16% of the variance in BMD. CONCLUSIONS: We conclude that it is not necessary to use more reproductive factors besides age at menopause and menarche in determining total duration of endogenous estrogen exposure.

Research paper thumbnail of Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women

Atherosclerosis, Jan 1, 2000

Background. Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascu... more Background. Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objecti6es. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. Methods. One hundred and five healthy postmenopausal women aged 52 -67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. Results. Flow mediated dilatation was inversely related to the plasma log Lp(a) level. Mean change per unit log Lp(a) increase: −2.83% (95% CI: −5.22-− 0.43). Elevated Lp(a) (\239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4% 9 1.2) compared to Lp(a) 5 239 mg/l (5.2% 9 0.7). Adjustment for other cardiovascular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) (5 239 mg/l) (8.09 1.2 vs 11.4%9 0.8). Conclusion. Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women.

Research paper thumbnail of Hormone replacement therapy in perimenopausal women and 2-year change of carotid intima-media thickness

Maturitas, Jan 1, 1999

In a 2-year longitudinal, calcium-controlled study we evaluated bone density and metabolism in pe... more In a 2-year longitudinal, calcium-controlled study we evaluated bone density and metabolism in perimenopausal women with initial ovarian failure, and the effects of hormone replacement with a low dose oral contraceptive preparation (OC). In perimenopausal oligomenorrhoic women (n = 16) a significant (P < 0.01) increase in cycle length and plasma FSH levels as well as a parallel decrease in plasma estradiol levels (P < 0.01) were evident. In this group, despite the calcium supplementation (500 mg/day), a significant (P < 0.001) increase in the biochemical markers of bone remodelling paralleled a significant (P < 0.001) decrease (-3.4% after 24 months) in bone density. Conversely, in premenopausal oligomenorrhoic women treated with a low dose oral contraceptive (CC) formulation (30 mcg ethinyl estradiol plus 75 mcg gestodene, n = 16), bone markers showed a significant (P < 0.01) decrease, that paralleled a slight but significant (P < 0.01) increase (+ 1.71%) in bone density. These data suggest that premenopausal administration of OC can prevent the acceleration of bone turnover and reverse the decrease in bone density that follows the premenopausal impairment of ovarian function.

Research paper thumbnail of Reproductive history and cardiovascular disease risk in postmenopausal women: a review of the literature

Maturitas, Jan 1, 1999

Objecti6es: it is widely believed that oestrogen protects postmenopausal women from cardiovascula... more Objecti6es: it is widely believed that oestrogen protects postmenopausal women from cardiovascular disease. It is unknown, however, whether reproductive history, which affects endogenous oestrogen levels during a woman's life, also influences cardiovascular disease risk in postmenopausal women. We present an overview of the studies which investigate the relationship between reproductive history and risk for cardiovascular disease in women. Methods: we conducted a Medline search of literature pertaining to age at menarche, age at menopause, parity and gravidity, breast-feeding, and length and regularity of the menstrual cycle in relation to cardiovascular diseases. Data extraction and synthesis were performed by comparing odds ratios and relative risks presented or calculated. Results: age at menarche was not found to influence cardiovascular disease risk, while menstrual cycle irregularity was associated with this risk. The studies pertaining to parity presented conflicting results: protection against as well as an increase in the risk of cardiovascular disease were found in parous women. Pregnancy loss appeared to be related to cardiovascular disease risk. Age at menopause proved to be the reproductive factor most clearly related to cardiovascular disease risk. Conclusions: only menstrual cycle irregularity, pregnancy losses, and age at menopause are possibly related to cardiovascular disease risk in postmenopausal women. All reproductive factors need to be studied together in order to assess reproductive history in a proper manner. Research of this kind will be essential if we are to further increase our knowledge regarding the nature of the effects of endogenous oestrogen on cardiovascular disease.

Research paper thumbnail of Hormone replacement therapy and endothelial function:: Results of a randomized controlled trial in healthy postmenopausal women

Atherosclerosis, Jan 1, 2001

Objecti6e: To compare the effects of 3 months treatment with tibolone (a single entity synthetic ... more Objecti6e: To compare the effects of 3 months treatment with tibolone (a single entity synthetic steroid hormone with estrogenic, progestanic and androgenic activities), or continuous combined conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA), with placebo, on endothelial function. Design: A single center, randomized, double-blind, placebo-controlled study. Setting: Research center as part of the University Medical Center Utrecht. Subjects: One hundred and five healthy postmenopausal women, sampled from the general population. Inter6entions: Three months treatment with tibolone or CEE + MPA or placebo. Main outcome measure: At baseline and after 3 months, endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. Results: Results are presented as mean differences between treatment groups of endothelium dependent flow mediated dilatation (fmd) and endothelium independent nitroglycerine induced dilatation with 95% confidence intervals (95% CI). After treatment, there was a significant difference in mean fmd between the CEE + MPA group and the placebo group of 2.5% (95% CI: 0.3-4.6) while the tibolone group and the placebo group did not differ significantly (0.6%; 95% CI: 1.6-2.8). Nitroglycerine induced dilatation did not differ significantly between the groups. Conclusions: Hormone replacement therapy with CEE + MPA for 3 months increases endothelium dependent fmd of the brachial artery in healthy postmenopausal women. Tibolone did not alter fmd. The clinical significance of this improvement in fmd for cardiovascular disease risk needs to be established.

Research paper thumbnail of Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women

American journal of …, Jan 1, 2002

In this study, the authors investigated whether combined information on reproductive factors has ... more In this study, the authors investigated whether combined information on reproductive factors has additive value to the single reproductive factor age at menopause for assessing endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. They conducted a population-based cohort study that included 9,450 postmenopausal women from Nijmegen, the Netherlands, who were aged 35-65 years at enrollment in 1975, with a median follow-up of 20.5 years. A Cox proportional hazards model and Receiver Operating Curves were used to analyze the data. Women aged 52 years or more at menopause had an 18% reduction in cardiovascular mortality (hazard ratio = 0.82, 95% confidence interval (CI): 0.69, 0.98) compared with those aged 44 years or less. Women with more than 18 years of exposure to endogenous estrogen had a statistically significant 20% reduction in cardiovascular mortality (hazard ratio = 0.80, 95 percent CI: 0.67, 0.96) compared with those who had 13 years of exposure or less. The area under the curve of the Receiver Operating Curves for the two models was identical (area under the curve = 0.67, 95 percent CI: 0.66, 0.68). This study shows that age at menopause is related to cardiovascular disease mortality and that a newly developed composite measure of endogenous estrogen exposure does not add to the predictive value of age at menopause for cardiovascular mortality. Am J Epidemiol 2002;155:339-45.

Research paper thumbnail of Intake of dietary phytoestrogens by Dutch women

The Journal of …, Jan 1, 2002

... Lital Keinan Boker * 2 , Yvonne T. Van der Schouw * , Miriam JJ De Kleijn * , Paul F. Jacques... more ... Lital Keinan Boker * 2 , Yvonne T. Van der Schouw * , Miriam JJ De Kleijn * , Paul F. Jacques † , Diederick E. Grobbee * and Petra HM Peeters *. ... Horn-Ross, PL, Barnes, S., Lee, M., Coward, L., Mandel, JE, Koo, J., John, EM &amp;amp;amp;amp;amp;amp;amp;amp; Smith, M. (2000) Assessing phytoestrogen exposure ...

Research paper thumbnail of Dietary intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile in postmenopausal US women: the Framingham study

The Journal of …, Jan 1, 2002

Hypertension, central obesity and dyslipidemia are associated with high cardiovascular risk. Estr... more Hypertension, central obesity and dyslipidemia are associated with high cardiovascular risk. Estrogen therapy in women has beneficial effects on some of these metabolic cardiovascular risk factors. It is not known whether dietary estrogens have similar effects, especially in Western populations. We studied the association between dietary phytoestrogen intake and metabolic cardiovascular risk factors in postmenopausal women. For this purpose, 939 postmenopausal women participating in the Framingham Offspring Study were included in this cross-sectional study. Mean blood pressure, waist-hip ratio (WHR) and lipoprotein levels were determined in quartile categories of dietary phytoestrogen (isoflavones and lignans) intake, determined by a food-frequency questionnaire. In addition, a metabolic syndrome score was defined according to WHO criteria (range 0 -6). The WHR was lower in women in the highest quartile of intake of lignans compared with the lowest [Ϫ0.017; 95% confidence interval (CI) Ϫ0.030 to Ϫ0.0016]. In the highest quartile of intake of isoflavones, plasma triglyceride levels were 0.16 mmol/L lower (95% CI, Ϫ0.30 to Ϫ0.02) compared with the lowest quartile of isoflavones; for lignan intake, this difference was 0.23 mmol/L (95% CI, Ϫ0.37 to Ϫ0.09). In the highest quartile of isoflavone intake, the mean cardiovascular risk factor metabolic score was 0.43 points lower (95% CI, Ϫ0.70 to Ϫ0.16) than the lowest quartile. The difference in this score between the extreme quartiles of intake of lignans was Ϫ0.55 points (95% CI, Ϫ0.82 to Ϫ0.28). In conclusion, high intake of phytoestrogens in postmenopausal women appears to be associated with a favorable metabolic cardiovascular risk profile. J. Nutr. 132: 276 -282, 2002.

Research paper thumbnail of Intake of Dietary Phytoestrogens Is Low in Postmenopausal Women in the United States: The Framingham Study1–4

The Journal of …, Jan 1, 2001

Many plants that are consumed contain phytoestrogens. Only a few published studies have examined ... more Many plants that are consumed contain phytoestrogens. Only a few published studies have examined the dietary intake of phytoestrogens in the general Western population. The potentially positive health effects of phytoestrogens might be of relevance to postmenopausal women. The aim of the present study was to estimate the intake of dietary isoflavones, coumestans and lignans by healthy Western postmenopausal women. For this purpose, we studied 964 postmenopausal, Caucasian women who participated in the Framingham Offspring Study and completed the Willett food-frequency questionnaire (FFQ). By searching the medical and agricultural literature and contacting experts, we identified food sources of phytoestrogens. The concentrations of the different isoflavones, coumestrol and lignans in each food in the FFQ were scored in seven categories and multiplied by the serving size of the food and the frequency of its consumption. The estimated daily median intake of the isoflavone daidzein was 39 microg (24-57 microg); of genistein, 70 microg (28-120 microg); of formononetin, 31 microg (13-44 microg); and of biochanin A, 6 microg (2-11 microg). Median total intake of isoflavones was 154 microg (99-235 microg). The main sources of isoflavones were beans and peas. The estimated daily intake of coumestans was 0.6 microg (0.2-1.7 microg), with broccoli as the main source. The estimated daily median intake of matairesinol was 19 microg (12-28 microg) and of secoisolariciresinol 560 microg (399-778 microg). The median total intake of lignans was 578 microg (416-796 microg). The main source of the lignans was fruits. The daily dietary intake of phytoestrogens in healthy postmenopausal Caucasian women in the United States is &amp;amp;lt;1 mg.

Research paper thumbnail of Does the beneficial effect of HRT on endothelial function depend on lipid changes

Maturitas, Jan 1, 2003

To determine whether improvement in endothelial function of the brachial artery observed in women... more To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. Hundred-and-five healthy postmenopausal women, aged 50-65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: -0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: -18%; -7%), LDL-cholesterol with 23% (95% CI: -30%; -15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: -26%; -2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids.

Research paper thumbnail of Indicators for the total duration of premenopausal endogenous estrogen exposure in relation to BMD

Human …, Jan 1, 2004

BACKGROUND: Previous studies have shown that age at menopause is an important indicator of durati... more BACKGROUND: Previous studies have shown that age at menopause is an important indicator of duration of endogenous estrogen exposure. The present study investigates whether combining more information on reproductive factors is useful in estimating individual total duration of exposure to endogenous estrogens. METHODS: Bone mineral density (BMD) was used as operational outcome. The study population consisted of 3476 white women living in Eindhoven, The Netherlands, aged 46-57 years, either pre-(n 5 2420) or postmenopausal (n 5 1056). BMD of the lumbar spine was measured by dual X-ray absorptiometry. Information on reproductive factors was obtained with questionnaires. RESULTS: The number of reproductive years explained 4.8% of the variance in BMD, while age at menopause alone accounted for 3.6%. Duration of lactation or oral contraceptive use did not add to the proportion of variance explained. The effect of reproductive years on BMD was stronger in older women. No significant associations with BMD were found for other reproductive variables. The number of miscarriages in premenopausal women (b 5 0.00760, SE 5 0.00357, P 5 0.03) explained only 0.16% of the variance in BMD. CONCLUSIONS: We conclude that it is not necessary to use more reproductive factors besides age at menopause and menarche in determining total duration of endogenous estrogen exposure.

Research paper thumbnail of Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women

Atherosclerosis, Jan 1, 2000

Background. Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascu... more Background. Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objecti6es. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. Methods. One hundred and five healthy postmenopausal women aged 52 -67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. Results. Flow mediated dilatation was inversely related to the plasma log Lp(a) level. Mean change per unit log Lp(a) increase: −2.83% (95% CI: −5.22-− 0.43). Elevated Lp(a) (\239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4% 9 1.2) compared to Lp(a) 5 239 mg/l (5.2% 9 0.7). Adjustment for other cardiovascular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) (5 239 mg/l) (8.09 1.2 vs 11.4%9 0.8). Conclusion. Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women.

Research paper thumbnail of Hormone replacement therapy in perimenopausal women and 2-year change of carotid intima-media thickness

Maturitas, Jan 1, 1999

In a 2-year longitudinal, calcium-controlled study we evaluated bone density and metabolism in pe... more In a 2-year longitudinal, calcium-controlled study we evaluated bone density and metabolism in perimenopausal women with initial ovarian failure, and the effects of hormone replacement with a low dose oral contraceptive preparation (OC). In perimenopausal oligomenorrhoic women (n = 16) a significant (P < 0.01) increase in cycle length and plasma FSH levels as well as a parallel decrease in plasma estradiol levels (P < 0.01) were evident. In this group, despite the calcium supplementation (500 mg/day), a significant (P < 0.001) increase in the biochemical markers of bone remodelling paralleled a significant (P < 0.001) decrease (-3.4% after 24 months) in bone density. Conversely, in premenopausal oligomenorrhoic women treated with a low dose oral contraceptive (CC) formulation (30 mcg ethinyl estradiol plus 75 mcg gestodene, n = 16), bone markers showed a significant (P < 0.01) decrease, that paralleled a slight but significant (P < 0.01) increase (+ 1.71%) in bone density. These data suggest that premenopausal administration of OC can prevent the acceleration of bone turnover and reverse the decrease in bone density that follows the premenopausal impairment of ovarian function.

Research paper thumbnail of Reproductive history and cardiovascular disease risk in postmenopausal women: a review of the literature

Maturitas, Jan 1, 1999

Objecti6es: it is widely believed that oestrogen protects postmenopausal women from cardiovascula... more Objecti6es: it is widely believed that oestrogen protects postmenopausal women from cardiovascular disease. It is unknown, however, whether reproductive history, which affects endogenous oestrogen levels during a woman's life, also influences cardiovascular disease risk in postmenopausal women. We present an overview of the studies which investigate the relationship between reproductive history and risk for cardiovascular disease in women. Methods: we conducted a Medline search of literature pertaining to age at menarche, age at menopause, parity and gravidity, breast-feeding, and length and regularity of the menstrual cycle in relation to cardiovascular diseases. Data extraction and synthesis were performed by comparing odds ratios and relative risks presented or calculated. Results: age at menarche was not found to influence cardiovascular disease risk, while menstrual cycle irregularity was associated with this risk. The studies pertaining to parity presented conflicting results: protection against as well as an increase in the risk of cardiovascular disease were found in parous women. Pregnancy loss appeared to be related to cardiovascular disease risk. Age at menopause proved to be the reproductive factor most clearly related to cardiovascular disease risk. Conclusions: only menstrual cycle irregularity, pregnancy losses, and age at menopause are possibly related to cardiovascular disease risk in postmenopausal women. All reproductive factors need to be studied together in order to assess reproductive history in a proper manner. Research of this kind will be essential if we are to further increase our knowledge regarding the nature of the effects of endogenous oestrogen on cardiovascular disease.

Research paper thumbnail of Hormone replacement therapy and endothelial function:: Results of a randomized controlled trial in healthy postmenopausal women

Atherosclerosis, Jan 1, 2001

Objecti6e: To compare the effects of 3 months treatment with tibolone (a single entity synthetic ... more Objecti6e: To compare the effects of 3 months treatment with tibolone (a single entity synthetic steroid hormone with estrogenic, progestanic and androgenic activities), or continuous combined conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA), with placebo, on endothelial function. Design: A single center, randomized, double-blind, placebo-controlled study. Setting: Research center as part of the University Medical Center Utrecht. Subjects: One hundred and five healthy postmenopausal women, sampled from the general population. Inter6entions: Three months treatment with tibolone or CEE + MPA or placebo. Main outcome measure: At baseline and after 3 months, endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. Results: Results are presented as mean differences between treatment groups of endothelium dependent flow mediated dilatation (fmd) and endothelium independent nitroglycerine induced dilatation with 95% confidence intervals (95% CI). After treatment, there was a significant difference in mean fmd between the CEE + MPA group and the placebo group of 2.5% (95% CI: 0.3-4.6) while the tibolone group and the placebo group did not differ significantly (0.6%; 95% CI: 1.6-2.8). Nitroglycerine induced dilatation did not differ significantly between the groups. Conclusions: Hormone replacement therapy with CEE + MPA for 3 months increases endothelium dependent fmd of the brachial artery in healthy postmenopausal women. Tibolone did not alter fmd. The clinical significance of this improvement in fmd for cardiovascular disease risk needs to be established.

Research paper thumbnail of Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women

American journal of …, Jan 1, 2002

In this study, the authors investigated whether combined information on reproductive factors has ... more In this study, the authors investigated whether combined information on reproductive factors has additive value to the single reproductive factor age at menopause for assessing endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. They conducted a population-based cohort study that included 9,450 postmenopausal women from Nijmegen, the Netherlands, who were aged 35-65 years at enrollment in 1975, with a median follow-up of 20.5 years. A Cox proportional hazards model and Receiver Operating Curves were used to analyze the data. Women aged 52 years or more at menopause had an 18% reduction in cardiovascular mortality (hazard ratio = 0.82, 95% confidence interval (CI): 0.69, 0.98) compared with those aged 44 years or less. Women with more than 18 years of exposure to endogenous estrogen had a statistically significant 20% reduction in cardiovascular mortality (hazard ratio = 0.80, 95 percent CI: 0.67, 0.96) compared with those who had 13 years of exposure or less. The area under the curve of the Receiver Operating Curves for the two models was identical (area under the curve = 0.67, 95 percent CI: 0.66, 0.68). This study shows that age at menopause is related to cardiovascular disease mortality and that a newly developed composite measure of endogenous estrogen exposure does not add to the predictive value of age at menopause for cardiovascular mortality. Am J Epidemiol 2002;155:339-45.

Research paper thumbnail of Intake of dietary phytoestrogens by Dutch women

The Journal of …, Jan 1, 2002

... Lital Keinan Boker * 2 , Yvonne T. Van der Schouw * , Miriam JJ De Kleijn * , Paul F. Jacques... more ... Lital Keinan Boker * 2 , Yvonne T. Van der Schouw * , Miriam JJ De Kleijn * , Paul F. Jacques † , Diederick E. Grobbee * and Petra HM Peeters *. ... Horn-Ross, PL, Barnes, S., Lee, M., Coward, L., Mandel, JE, Koo, J., John, EM &amp;amp;amp;amp;amp;amp;amp;amp; Smith, M. (2000) Assessing phytoestrogen exposure ...

Research paper thumbnail of Dietary intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile in postmenopausal US women: the Framingham study

The Journal of …, Jan 1, 2002

Hypertension, central obesity and dyslipidemia are associated with high cardiovascular risk. Estr... more Hypertension, central obesity and dyslipidemia are associated with high cardiovascular risk. Estrogen therapy in women has beneficial effects on some of these metabolic cardiovascular risk factors. It is not known whether dietary estrogens have similar effects, especially in Western populations. We studied the association between dietary phytoestrogen intake and metabolic cardiovascular risk factors in postmenopausal women. For this purpose, 939 postmenopausal women participating in the Framingham Offspring Study were included in this cross-sectional study. Mean blood pressure, waist-hip ratio (WHR) and lipoprotein levels were determined in quartile categories of dietary phytoestrogen (isoflavones and lignans) intake, determined by a food-frequency questionnaire. In addition, a metabolic syndrome score was defined according to WHO criteria (range 0 -6). The WHR was lower in women in the highest quartile of intake of lignans compared with the lowest [Ϫ0.017; 95% confidence interval (CI) Ϫ0.030 to Ϫ0.0016]. In the highest quartile of intake of isoflavones, plasma triglyceride levels were 0.16 mmol/L lower (95% CI, Ϫ0.30 to Ϫ0.02) compared with the lowest quartile of isoflavones; for lignan intake, this difference was 0.23 mmol/L (95% CI, Ϫ0.37 to Ϫ0.09). In the highest quartile of isoflavone intake, the mean cardiovascular risk factor metabolic score was 0.43 points lower (95% CI, Ϫ0.70 to Ϫ0.16) than the lowest quartile. The difference in this score between the extreme quartiles of intake of lignans was Ϫ0.55 points (95% CI, Ϫ0.82 to Ϫ0.28). In conclusion, high intake of phytoestrogens in postmenopausal women appears to be associated with a favorable metabolic cardiovascular risk profile. J. Nutr. 132: 276 -282, 2002.

Research paper thumbnail of Intake of Dietary Phytoestrogens Is Low in Postmenopausal Women in the United States: The Framingham Study1–4

The Journal of …, Jan 1, 2001

Many plants that are consumed contain phytoestrogens. Only a few published studies have examined ... more Many plants that are consumed contain phytoestrogens. Only a few published studies have examined the dietary intake of phytoestrogens in the general Western population. The potentially positive health effects of phytoestrogens might be of relevance to postmenopausal women. The aim of the present study was to estimate the intake of dietary isoflavones, coumestans and lignans by healthy Western postmenopausal women. For this purpose, we studied 964 postmenopausal, Caucasian women who participated in the Framingham Offspring Study and completed the Willett food-frequency questionnaire (FFQ). By searching the medical and agricultural literature and contacting experts, we identified food sources of phytoestrogens. The concentrations of the different isoflavones, coumestrol and lignans in each food in the FFQ were scored in seven categories and multiplied by the serving size of the food and the frequency of its consumption. The estimated daily median intake of the isoflavone daidzein was 39 microg (24-57 microg); of genistein, 70 microg (28-120 microg); of formononetin, 31 microg (13-44 microg); and of biochanin A, 6 microg (2-11 microg). Median total intake of isoflavones was 154 microg (99-235 microg). The main sources of isoflavones were beans and peas. The estimated daily intake of coumestans was 0.6 microg (0.2-1.7 microg), with broccoli as the main source. The estimated daily median intake of matairesinol was 19 microg (12-28 microg) and of secoisolariciresinol 560 microg (399-778 microg). The median total intake of lignans was 578 microg (416-796 microg). The main source of the lignans was fruits. The daily dietary intake of phytoestrogens in healthy postmenopausal Caucasian women in the United States is &amp;amp;lt;1 mg.