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Biomedical subjects

C D Stehouwer

Publications and source records attributed to C D Stehouwer.

At least 109 records · Page 6Linked to original sources
PubMed1998

Abnormalities of vascular function in hyperhomocysteinaemia: relationship to atherothrombotic disease.

Hyperhomocysteinaemia is a risk factor for atherothrombotic disease, but data are limited on the arterial histology in humans with hyperhomocysteinaemia, either with or without other risk factors. Studies in vitro and in animals have shown that hyperhomocysteinaemia, possibly by increasing oxidant stress as well as by other mechanisms, may induce dysfunction of the vascular endothelium and proliferation of vascular smooth muscle cells, both key processes in atherogenesis. In clinically healthy subjects with hyperhomocysteinaemia, endothelium-dependent vasodilation may be impaired, but endothelial antithrombotic and profibrinolytic function appear normal at this stage. In patients with atherosclerosis and hyperhomocysteinaemia, endothelial antithrombotic properties appear more severely impaired than in similar patients with normohomocysteinaemia. Controlled data on the effects of homocysteine-lowering treatment on vascular function in humans are not available. The increased risk of atherothrombotic disease conferred by hyperhomocysteinaemia may be related to homocysteine-associated impairments in endothelial and vascular smooth muscle cell function. The precise mechanisms by which homocysteine affects vascular cell function, however, are unknown.

Animals↗
PubMed1998

Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure.

Microalbuminuria (MA) is associated with microangiopathy (renal and retinal lesions) in insulin-dependent diabetic (IDDM) patients. In contrast MA does not reflect microvascular damage in a substantial number of non-insulin-dependent diabetic (NIDDM) patients. MA predicts cardiovascular disease in NIDDM patients with increased von Willebrand factor (vWF) plasma levels which are hypothesized to reflect endothelial dysfunction. However, it is not known whether MA is consequent to generalised endothelial dysfunction or to renal injury. Thus, this study evaluated vWF plasma levels in relation to renal and retinal structural abnormalities in NIDDM patients with MA. Kidney biopsies, fundoscopy and measures of vWF plasma levels were performed in 32 NIDDM patients with MA. These patients were allocated to two renal structural categories: A) Without renal structural abnormalities (C I, n = 10): normal or near-normal renal structure, and B) With renal structural abnormalities (n = 22), further divided into: C II (n = 12) with typical diabetic nephropathology, predominantly glomerulopathy, and C III (n = 10) with atypical patterns of renal injury (more advanced tubulo-interstitial and arteriolar than glomerular changes). vWF plasma levels were significantly higher in category B (C II: 195+/-49% and C III: 161+/-46%) than in category A (C I: 119+/-42%), (chi-square, p < 0.05). Diabetic retinopathy was also related to vWF plasma levels (ANOVA, p < 0.05). These data suggest that there are two types of MA in NIDDM: one associated with increased vWF levels, established renal injury and frequently retinopathy, and the other characterized by normal vWF levels, normal renal structure and absent or mild diabetic retinopathy. We propose that vWF plasma levels in NIDDM patients with MA may help to identify patients with important renal structural changes, increased retinopathy risk and, perhaps, generalised endothelial dysfunction. Whether vWF plasma levels predict end-stage renal disease and cardiovascular events deserves longitudinal studies.

Adult↗
PubMed1998

Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn Study.

Microalbuminuria is a strong predictor of cardiovascular disease. The aim of this study was to investigate whether microalbuminuria is part of a cluster of risk factors, the insulin resistance syndrome (IRS), or whether it is only associated with, and presumably a complication of, hypertension and non-insulin-dependent diabetes mellitus (NIDDM). An age-, sex- and glucose tolerance-stratified random sample from a 50-75 year old general population (n = 622) was investigated. The urinary albumin-to-creatinine ratio was measured in an early morning spot urine sample. Microalbuminuria was defined as an albumin-to-creatinine ratio greater than 2.0 mg/ mmol. We considered, as IRS-related variables, fasting hyperinsulinaemia, insulin resistance (IR; calculated from the formula of the homeostasis model assessment), dyslipidaemia, glucose intolerance, hypertension and waist-to-hip ratio (WHR). Dyslipidaemia was defined as levels of HDL-cholesterol in the lowest and/or levels of triglyceride in the highest tertile. Fasting insulin levels, IR and WHR were divided into tertiles; the highest tertiles were compared to the lowest tertiles. Age-, sex- and glucose tolerance-adjusted analyses showed microalbuminuria to be significantly associated with hypertension, NIDDM and WHR. In multiple logistic regression analyses, microalbuminuria showed independent associations with hypertension, NIDDM and WHR, with odds ratios (ORs [95% confidence interval]) of 3.33 (1.86-5.96), 2.26 (1.14-4.48) and 2.49 (1.09-5.70), respectively. No associations were found with impaired glucose tolerance, hyperinsulinaemia, IR or dyslipidaemia. Multiple logistic regression analyses in diabetic and non-diabetic subjects separately showed that microalbuminuria was independently associated only with hypertension (ORs 4.31 and 2.69). In this Caucasian population, microalbuminuria was associated with hypertension, NIDDM and WHR and not with other variables of the IRS. It is therefore likely that microalbuminuria is a complication of hypertension and NIDDM, and not an integral part of the IRS.

Age Factors↗
PubMed1998

Short-term variability and sampling distribution of various parameters of urinary albumin excretion in patients with non-insulin-dependent diabetes mellitus.

We determined the degree of variability and sampling distribution of several commonly used parameters of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM) and proposed a sampling strategy for estimating the level of albuminuria. Four patients with NIDDM with previously documented microalbuminuria collected 30 consecutive split (overnight and daytime) 24-hour urine samples (experiment A). These samples were analyzed for total 24-hour albumin excretion; daytime, overnight, and 24-hour albumin concentration; and daytime, overnight, and 24-hour albumin-to-creatinine ratio. In a second experiment (B), 10 patients collected 10 consecutive overnight urine samples. Finally, a total of 300 separate triplicate urine samples were analyzed for the variability of 24-hour albumin excretion (100 samples) and albumin-to-creatinine ratios in 24-hour urine (100 samples) and overnight urine (100 samples). We found that the sampling distribution shape of all parameters of albuminuria is positively skewed, without consistent evidence of log-normality. When two methods were used for quantifying day-to-day variability (the interquartile range/median ratio and the chance of a single measurement being >50% off the actual value of albuminuria), the overnight albumin-to-creatinine ratio is the least-variable parameter of albuminuria, scoring 0.38% and 10% on both methods, respectively, in experiment A. Collecting multiple samples of overnight urine improves accuracy. The largest gain in precision in estimating the actual value of albuminuria is obtained for sample sizes of three and five and does not increase with nonconsecutive sampling of urine. Based on the combined data from experiments A and B, the expected mean deviation of the median of three and five overnight samples from the actual level of the overnight albumin-creatinine ratio is 17.9% and 12.1%, respectively. An analysis of variability in three sets of 100 triplicate 24-hour urine samples shows that the overnight albumin-to-creatinine ratio is a significantly more-constant parameter of microalbuminuria than the amount of albumin excreted in 24 hours or the albumin-to-creatinine ratio in 24-hour urine (p < 0.05). We concluded that the parameters of diabetic albuminuria have positively skewed, non-log-normal sampling distributions. The overnight albumin-to-creatinine ratio is the least-variable parameter of microalbuminuria. We recommend collecting three consecutive early morning urine samples, using the median value of the albumin-to-creatinine ratio in these samples for quantifying albuminuria.

Aged↗
PubMed1998

The effect of renal transplantation on hyperhomocysteinaemia in dialysis patients, and the estimation of renal homocysteine extraction in patients with normal renal function.

BACKGROUND: The pathophysiology of hyperhomocysteinaemia in chronic renal failure (CRF) is unknown. Possible mechanisms are decreased renal homocysteine (Hcy) catabolism or inhibition of extrarenal Hcy metabolism by uraemic toxins. METHODS: We studied the short-term effect on plasma Hcy concentration of improvement of renal function after successful kidney transplantation (n = 8), and determined renal Hcy extraction by measurement of total Hcy in arterial and renal venous blood in 7 cardiac patients with normal renal function. RESULTS: Post-transplantation, plasma Hcy decreased with improving renal function. In the cardiac patients, no significant renal Hcy extraction could be demonstrated, but tubular disposal of the filtered load could not be excluded. CONCLUSIONS: Because loss of such renal metabolism could lead to hyperhomocysteinaemia in CRF, it is necessary to determine the renal extraction of free Hcy in subjects with normal renal function to further investigate renal homocysteine metabolism.

Adult↗
PubMed1998

Ambulatory--not office--blood pressures decline during hormone replacement therapy in healthy postmenopausal women.

Hormone replacement therapy (HRT, estrogen plus progestagen) in postmenopausal women has beneficial effects on the cardiovascular system. However, effects on blood pressure, determined with office measurements, remain controversial. We studied the effects of HRT in 29 healthy normotensive postmenopausal women (mean age 52.3 [3.8] years, median duration of amenorrhea 34.5 months), using ambulatory blood pressure monitoring at baseline and at 3 and 12 months of follow-up. Women were randomized to two groups: an HRT group (N = 14), treated with 1 mg 17beta-estradiol once daily and 5 or 10 mg dydrogesterone once daily during the third and fourth week of every 4 weeks; and a control group (C-group, N = 15), which did not receive therapy. Blood pressures did not differ between the groups at baseline (HRT group 117.1 (9.2)/74.4 (6.6) mm Hg, C-group 113.8 (11.2)/71.3 (7.4) mm Hg). During the follow-up period, changes from baseline of office blood pressures did not differ significantly between the groups. However, changes (95% CI) of mean 24-h blood pressures differed significantly between the two groups after 1 year of follow-up: a decrease of blood pressures was observed in the HRT group (delta systolic/delta diastolic = -5.54 [-8.86 to -2.21]/-4.23 [-6.66 to -1.80] mm Hg), whereas an increase was found in the C-group (+3.33 [-0.69 to +7.35]/+1.67 [-1.75 to +5.09] mm Hg; P [HRT v control group] = .001/.005). We conclude that HRT may have blood pressure lowering properties in healthy, normotensive postmenopausal women.

Analysis of Variance↗
PubMed1998

Serum homocysteine level and protein intake are related to risk of microalbuminuria: the Hoorn Study.

BACKGROUND: Microalbuminuria (MA) is a strong predictor of cardiovascular disease, but its causes are incompletely understood. Hyperhomocysteinemia is a recently recognized risk factor for cardiovascular disease independent of established risk factors. It is not known whether hyperhomocysteinemia is associated with MA, and thus could be a possible cause of microalbuminuria. METHODS: We studied an age-, sex- and glucose-tolerance-stratified random sample of a 50- to 75-year old general Caucasian population (N = 680). The urinary albumin-to-creatinine ratio (ACR) was measured in an early morning spot urine sample. MA was defined as an ACR > 3.0 mg/mmol. RESULTS: The prevalence of MA was 4.3% (13 of 304) in subjects with normal glucose tolerance, 9.2% (17 of 185) in impaired glucose tolerance and 18.3% (30 of 164) in non-insulin-dependent diabetes mellitus (NIDDM); it was 3.7% (15 of 402) in subjects without hypertension and 17.9% (45 of 251) in those with hypertension. After adjusting for age, sex, glucose tolerance category, hypertension, dyslipidemia and smoking, the odds ratio [OR; 95% confidence interval (95%CI)] for MA per 5 mumol/liter total homocysteine increment was 1.33 (1.08 to 1.63). Additional adjustment for HbA1c, waist-hip ratio, protein intake and serum creatinine did not attenuate the association between MA and total homocysteine. A 0.1 g/kg.day increment of protein intake was also associated with an increased risk for MA after adjustment for age, sex, classical risk factors and serum total homocysteine [OR (95% CI); 1.20 (1.08 to 1.32)]. CONCLUSION: Both hyperhomocysteinemia and protein intake are related to microalbuminuria independent of NIDDM and hypertension. Hyperhomocysteinemia may partly explain the link between MA and increased risk of cardiovascular disease.

Aged↗
PubMed1998

No net renal extraction of homocysteine in fasting humans.

BACKGROUND: The pathophysiological mechanism of hyperhomocysteinemia in chronic renal failure in humans is unknown. The loss of a putative renal homocysteine extraction in chronic renal failure has been hypothesized as significant homocysteine uptake has been demonstrated in the normal rat kidney. We studied homocysteine extraction in the normal human kidney. METHODS: We measured plasma total (free and protein-bound) and free homocysteine (tHcy and fHcy, respectively) in arterial and renal venous blood sampled from the aorta and right-side renal vein during cardiac catheterization in 20 fasting patients with normal renal function. Renal homocysteine extraction was calculated as the arteriovenous difference divided by the arterial levels times 100%. RESULTS: No significant renal extraction was demonstrated either for tHcy: 0.9% (SD 5.8; 95% CI -1.8 to +3.6) or for fHcy: -0.2% (11.0; -5.4 to +4.9). CONCLUSIONS: We conclude that no significant net renal uptake of homocysteine occurs in fasting humans with normal renal function. The loss of such uptake, therefore, cannot cause hyperhomocysteinemia in patients with renal failure.

Aged↗
PubMed1998

Hyperhomocysteinemia and atherothrombotic disease.

Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease. The mechanism by which homocysteine induces atherosclerosis and thrombosis is not fully understood. Data on arterial histology in humans with homocystinuria and mild hyperhomocysteinemia are limited. In vitro studies as well as studies in animals and humans indicate that hyperhomocysteinemia induces dysfunction of the vascular endothelium, with loss of endothelium-dependent vasodilation and endothelial antithrombotic properties, and proliferation of vascular smooth muscle cells, which are key processes in current models of atherogenesis and thrombosis. One of the hypotheses is that homocysteine can lead to cellular dysfunction through a mechanism involving oxidative damage but future studies in humans are needed to confirm this. Studies in hyperhomocysteinemic vascular patients have shown that endothelial antithrombotic properties appear to be more severely impaired than in similar patients with normohomocysteinemia. Furthermore, impaired endothelium-dependent vasodilation has been observed in clinically healthy hyperhomocysteinemic subjects in whom no abnormalities were found in endothelial antithrombotic properties. Future studies involving homocysteine-lowering treatment in hyperhomocysteinemic patients with vascular disease and in clinically healthy hyperhomocysteinemic subjects are necessary to investigate the mechanisms by which homocysteine causes atherothrombotic disorders in humans.

Arteriosclerosis↗
PubMed1998

No change in impaired endothelial function after long-term folic acid therapy of hyperhomocysteinaemia in haemodialysis patients.

BACKGROUND: Hyperhomocysteinaemia is frequent in chronic haemodialysis patients. Because of its potential role in athero- and thrombogenesis, the effects of long-term homocysteine-lowering treatment on endothelial function are of interest. METHODS: We conducted a randomized, controlled trial in 35 haemodialysis patients. In phase 1, patients were treated with 5 mg folic acid or 5 mg folic acid and 4 g betaine per day for 12 weeks, and in phase 2 with 1 or 5 mg folic acid daily for 40 weeks. In phase 3, all patients received 15 mg folic acid daily for four weeks. Endothelial function was assessed before and after 52 weeks of treatment by determination of flow-mediated vasodilatation of the brachial artery, and by measuring plasma levels of endothelium-derived proteins. RESULTS: Non-fasting predialysis plasma total homocysteine was markedly elevated at baseline (46.9 +/- 6.3 mumol/l) and decreased rapidly after initiation of therapy. Significant differences in plasma homocysteine between the groups were found neither during phase 1 nor phase 2. Plasma total homocysteine had normalized in only two out of 30 patients at the end of phase 2. Increasing the daily folic acid dose to 15 mg did not further reduce plasma total homocysteine. Endothelial function parameters did not improve. CONCLUSIONS: We concluded that betaine is not effective in conjunction with folic acid in the treatment of hyperhomocysteinaemia in haemodialysis patients. Normalization of plasma total homocysteine is seldom achieved with 1, 5 or 15 mg folic acid daily, which may explain why long-term homocysteine-lowering treatment with 1 or 5 mg folic acid does not ameliorate endothelial function.

Adult↗
PubMed1998

Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) patients have a high risk of cardiovascular mortality, which is not completely explained by conventional risk factors. Other factors related to chronic renal failure and/or dialysis treatment might lead to endothelial dysfunction, which is associated with an adverse cardiovascular outcome. One such factor is hyperhomocysteinaemia, which has a high prevalence in PD patients. METHODS: A vessel wall movement detector system was used to investigate endothelium-dependent, flow-mediated, and endothelium-independent, glyceryl trinitrate-induced, vasodilatation of the brachial artery in 29 PD patients and 29 control subjects. RESULTS: Endothelium-dependent vasodilatation was markedly reduced in the PD group: 5.7 +/- 1.0% vs 10.4 +/- 1.3% in the control group (P = 0.004). Endothelium-independent vasodilatation was not impaired. Plasma total homocysteine was elevated in the PD patients (45.2 +/- 6.2 micromol/l), but was not related to endothelium-dependent vasodilatation. CONCLUSION: Chronic peritoneal dialysis patients have impaired endothelium-dependent vasodilatation, which may reflect an increased susceptibility for the development of atherosclerosis and thrombosis.

Arteriosclerosis↗
PubMed1998

Determinants of the limits of agreement between the sphygmomanometer and the SpaceLabs 90207 device for blood pressure measurement in health volunteers and insulin-dependent diabetic patients.

OBJECTIVE: To compare the limits of agreement between the SpaceLabs 90207 oscillometric blood pressure measurement device and the sphygmomanometer for patients with insulin-dependent diabetes mellitus (IDDM) versus healthy control subjects. DESIGN: A retrospective analysis of six simultaneous blood pressure measurements in 106 IDDM patients aged 32.6+/-12.0 years (mean +/- SD) and 92 healthy control subjects aged 27.1+/-8.9 years with the SpaceLabs device and a sphygmomanometer. RESULTS: For both groups, overestimation of the systolic blood pressure occurred with the SpaceLabs device, being more severe for the IDDM group (1.7 mmHg more overestimation, P= 0.009). Mean arterial blood pressure was underestimated for the control group and overestimated for the IDDM group (2.7 mmHg underestimation and 0.8 mmHg overestimation, respectively). Diastolic blood pressures for both groups were underestimated by use of the SpaceLabs device, but less severely so for the IDDM group (4.2 mmHg, P< 0.0001 less underestimation). Multiple regression analysis revealed that these differences were mainly due to the presence of diabetes. Other determinants of these limits of agreement were age (for control group subjects) and duration of diabetes (for IDDM group patients). CONCLUSION: Limits of agreement between the SpaceLabs 90207 device and the sphygmomanometer differ between IDDM patients and healthy controls. These limits are influenced by the presence of diabetes, age and duration of diabetes. Available protocols for the evaluation of automated blood pressure measurement devices of the British Hypertension Society and the Association for the Advancement of Medical Instrumentation do not consider limits of agreement in subpopulations such as diabetic patients. Therefore, we recommend that tests for the limits of agreement of blood pressure measurement devices for subgroups should be added to these protocols.

Adolescent↗
PubMed1998

Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study.

A high serum total homocysteine (tHcy) level is an independent risk factor for cardiovascular disease. Because it is not known whether the strength of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease, we compared the three separate risk estimates in an age-, sex-, and glucose tolerance-stratified random sample (n=631) from a 50- to 75-year-old general white population. Furthermore, we investigated the combined effect of hyperhomocysteinemia and diabetes mellitus with regard to cardiovascular disease. The prevalence of fasting hyperhomocysteinemia (>14.0 micromol/L) was 25.8%. After adjustment for age, sex, hypertension, hypercholesterolemia, diabetes, and smoking, the odds ratios (ORs; 95% confidence intervals) per 5-micromol/L increment in tHcy were 1.44 (1.10 to 1.87) for peripheral arterial, 1.25 (1.03 to 1.51) for coronary artery, 1.24 (0.97 to 1.58) for cerebrovascular, and 1.39 (1.15 to 1.68) for any cardiovascular disease. After stratification by glucose tolerance category and adjustment for the classic risk factors and serum creatinine, the ORs per 5-micromol/L increment in tHcy for any cardiovascular disease were 1.38 (1.03 to 1.85) in normal glucose tolerance, 1.55 (1.01 to 2.38) in impaired glucose tolerance, and 2.33 (1.11 to 4.90) in non-insulin-dependent diabetes mellitus (P=.07 for interaction). We conclude that the magnitude of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease in a 50- to 75-year-old general population. High serum tHcy may be a stronger (1.6-fold) risk factor for cardiovascular disease in subjects with non-insulin-dependent diabetes mellitus than in nondiabetic subjects.

Aged↗
PubMed1998

Visceral fat accumulation is an important determinant of PAI-1 levels in young, nonobese men and women: modulation by cross-sex hormone administration.

Increased plasminogen activator inhibitor type-1 (PAI-1) levels, leading to impaired fibrinolysis, are associated with increased visceral fat in middle-aged and obese subjects. It is unknown, however, whether this association is independent of other disturbances clustered in the insulin resistance syndrome. We analyzed this association in young, nonobese transsexual men and women before and after administration of cross-sex steroids, which potentially influence many elements of the insulin resistance syndrome, including PAI-1 levels and visceral fat accumulation. We assessed the visceral fat area (by MRI); total body fat; insulin sensitivity (with a glucose clamp technique); and plasma levels of PAI-1, insulin, and triglycerides in young (<37 years old), nonobese (body mass index <28 kg/m2), healthy men (n=18) and women (n=15) before and after 12 months of cross-sex hormone administration. Men were treated with ethinyl estradiol 100 microgram/d plus cyproterone acetate 100 mg/d, and women were treated with testosterone esters 250 mg IM every 2 weeks. At baseline, only visceral fat area was significantly correlated with plasma PAI-1 levels in both men (r=0.57, P=0.03) and women (r=0.59, P=0.03). In multivariate linear regression analysis, this association was independent of total body fat, insulin sensitivity, and plasma levels of triglycerides and insulin. After 12 months of cross-sex hormone administration, the plasma PAI-1 levels were no longer correlated with visceral fat (which had increased). We conclude that in young, nonobese men and women, visceral fat area is an important determinant of plasma PAI-1 levels. After cross-sex hormone administration, this association was no longer demonstrable.

Adipose Tissue↗
PubMed1998

Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10-year follow-up.

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease in the middle-aged. We investigated whether a high serum homocysteine level is a risk factor for vascular disease in 878 elderly men (mean age at baseline, 71.5 years; range, 64 to 84 years) in a population-based, representative cohort followed up for 10 years in Zutphen, the Netherlands. Thirty-one percent had nonfasting homocysteine levels >/=17 micromol/L. After adjustment for other major risk factors, high homocysteine levels at baseline (the third compared with the first tertile) were associated with an increased baseline prevalence of myocardial infarction (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.07 to 3.08; P for trend, 0.03) and with a marginally significant increase in the risk of dying of coronary heart disease (relative risk [RR], 1.58; 95% CI, 0.93 to 2.69; P for trend, 0.09) but not with an increased risk of first-ever myocardial infarction. In addition, high homocysteine levels at baseline were associated with an increased baseline prevalence of stroke (OR, 4.61; 95% CI, 1.79 to 11.89; P for trend, 0.002) and with an increased risk of dying of cerebrovascular disease in subjects without hypertension (RR, 6.18; 95% CI, 2.28 to 16.76) but not in those with hypertension. High homocysteine levels were associated with an increased risk of first-ever stroke among normotensive subjects that was not statistically significant (RR, 1. 77 [95% CI, 0.83 to 3.75; P for trend, 0.14]). In a general population of elderly men, a high homocysteine level is common and is strongly associated with the prevalence of coronary heart disease and cerebrovascular disease. It is a strong predictive factor for fatal cerebrovascular disease in men without hypertension but less so for coronary heart disease.

Adult↗
PubMed1998

Effects of sex steroids on plasma total homocysteine levels: a study in transsexual males and females.

Plasma total homocysteine (tHcy) levels are higher in men vs. premenopausal women, but it is not known whether this difference is related to sex steroids. The effects of cross-sex hormone administration on plasma tHcy levels were therefore investigated. Plasma tHcy levels were measured at baseline and after 4 months of treatment in 17 male-to-female (M-->F) transsexuals treated with ethinyl estradiol (100 micrograms/day), in combination with the antiandrogen, cyproterone acetate (100 mg/day), and in 17 female-to-male (F-->M) transsexuals treated with testosterone esters (250 mg/2 weeks, im). In M-->F transsexuals, the plasma tHcy level decreased from geometric mean 8.2 mumol/L to 5.7 mumol/L (P < 0.001); and in F-->M transsexuals, it increased from 7.7 mumol/L to 9.0 mumol/L (P = 0.005). In M-->F transsexuals, changes in serum sex hormone-binding globulin levels correlated negatively, and changes in plasma creatinine and albumin levels correlated positively, with changes in plasma tHcy levels. In F-->M transsexuals, changes in serum 17 beta-estradiol levels correlated negatively, and changes in plasma creatinine levels correlated positively, with changes in plasma tHcy levels. We conclude that tHcy levels decrease after estrogen + antiandrogen administration to male (transsexual) subjects, and levels increase after androgen administration to female (transsexual) subjects. These changes may be both primary and secondary to the anabolic/catabolic effects, as reflected by changes of creatinine and albumin levels after cross-sex hormone administration.

Androgen Antagonists↗