Clinical EndocrinologyVolume 36, Issue 1 p. 15-20 Current therapy Hormone replacement therapy: risks and benefits S. I. J. Whitcroft, S. I. J. Whitcroft The Wynn Institute, London, UKSearch for more papers by this authorJ. C. Stevenson, Corresponding Author J. C. Stevenson The Wynn Institute, London, UKDr J. C. Stevenson, The Wynn Institute for Metabolic Research, 21 Wellington Road, London NWS 9SQ, UKSearch for more papers by this author S. I. J. Whitcroft, S. I. J. Whitcroft The Wynn Institute, London, UKSearch for more papers by this authorJ. C. Stevenson, Corresponding Author J. C. Stevenson The Wynn Institute, London, UKDr J. C. Stevenson, The Wynn Institute for Metabolic Research, 21 Wellington Road, London NWS 9SQ, UKSearch for more papers by this author First published: January 1992 https://doi.org/10.1111/j.1365-2265.1992.tb02896.xCitations: 24AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume36, Issue1January 1992Pages 15-20 RelatedInformation

Afro-Caribbean men in the United Kingdom have a favorable lipoprotein profile and are at low risk of coronary heart disease (CHD) compared with Europeans and South Asians, but are at high risk of non-insulin-dependent diabetes mellitus (NIDDM) compared with Europeans. To investigate these differences, a cross-sectional comparison was undertaken for measures of lipoprotein metabolism, body composition, and insulin's glucoregulatory and antilipolytic actions in 92 healthy men (42 to 61 years) of Afro-Caribbean, South Asian, or European origin. Afro-Caribbean men were more insulin-resistant than Europeans (insulin sensitivity [Si], 1.96 v3.01 min(-1) x microU(-1) x mL, P < .01). They nevertheless had a more favorable lipoprotein profile, with lower levels of very-low-density lipoprotein (VLDL) cholesterol (0.21 v 0.40 mmol/L, P < .01) and triglycerides (0.34 v 0.74 mmol/L, P < .01), lower serum total triglycerides, higher high-density lipoprotein 2 (HDL2) cholesterol, and larger low-density lipoprotein (LDL) particle size. These differences were not accounted for by differences in nonesterified fatty acid (NEFA) levels, the sensitivity of suppression of NEFA levels to insulin, or body composition. South Asians were also more insulin-resistant than Europeans but had a less favorable lipoprotein profile. Afro-Caribbean men in the United Kingdom are as insulin-resistant as South Asian men but less susceptible to the lipid disturbances that characteristically accompany insulin resistance. This favorable lipid pattern may relate to more effective VLDL metabolism rather than a reduced supply of NEFA as substrate for triglyceride synthesis.

Objectives. To investigate the associations between risk factors for cardiovascular disease and cigarette smoking, alcohol intake, and physical activity in a group of predominantly healthy men.Design. Cohort study with baseline characterisation, clinical follow-up, and identification of predictors of coronary artery disease and diabetes.Setting. University hospital metabolic day ward.Subjects, Participants in a company health programme (n = 742).Main outcome measures. Routine haematology and biochemistry, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol (on a subset of 522 subjects), and glucose and insulin levels during a 3 h oral glucose tolerance test (OGTT).Results. Independent associations with previous cigarette smoking included high uric acid and low HDL cholesterol, and with current cigarette smoking, high haemoglobin and white cell count and low OGTT insulin. Increasing alcohol intake was associated with increasing blood pressure, uric acid, HDL cholesterol and fasting glucose. The moderate range of exercise intensity in this cohort was associated with decreasing systolic blood pressure, fasting insulin and OGTT glucose and insulin. Factor analysis distinguished principal factors comprising features of the metabolic syndrome with low physical activity, and high white cell count, high haemoglobin concentration and low HDL cholesterol with increasing previous and current cigarette smoking and alcohol intake.Conclusions. Some characteristics of the metabolic syndrome were seen with previous but not current smoking habit. Regular alcohol-consumption was. associated with mainly unfavourable metabolic characteristics, although there was an independent beneficial association with HDL cholesterol. The improved metabolic syndrome profile seen with increasing exercise is consistent with even moderate degrees of physical activity having beneficial effects on metabolism.

The European Spine Phantom (ESP) has recently been developed as a universal standard for instruments measuring bone density. The ESP is composed of three semi-anthropomorphic hydroxyapatite vertebrae of varying densities surrounded by soft tissue equivalent plastic designed to resemble human bone and soft tissue when scanned on bone densitometers. In multi-centre studies it is particularly important to verify that each participating bone densitometer is performing in a stable and linear fashion. The aim of this study was to evaluate the ESP within the context of a multi-centre clinical trial. Eighteen centres in the UK and Canada with dual-energy X-ray absorptiometry (DXA) instruments (Lunar DPX, DPX-alpha and DPX-L) participated in the study. The ESP was scanned 10 times on each instrument without repositioning using standardized protocols. The precision of the bone mineral density (BMD) measurements (L1–3) expressed as a coefficient of variation ranged from 0.4% to 1.1% (mean 0.7%). The mean BMD of each instrument was expressed as a percentage difference from the overall mean and ranged from −1.33% to 1.33%. Linear regression analysis showed that all instruments behaved in a linear fashion across the range of densities with correlation coefficients all ≥0.999 and standard errors of the estimate <1.5% of the mean BMD ESP value. The data from this study demonstrate that the ESP is a useful phantom for assessing the linearity, stability and differences between DXA instruments from one manufacturer.

Polymorphism of the angiotensin-I-converting enzyme (ACE) gene is associated with variations in serum ACE activity and the incidence of cardiovascular disease. Whether a similar association exists with cardiological syndrome X (chest pain, positive ECG exercise test, and normal angiography) is unclear. As ACE activity affects vascular tone, it could be involved in the pathogenesis of this syndrome. We measured serum ACE activity in 18 postmenopausal women with syndrome X and in 18 healthy controls matched for age, adiposity, and menopausal status. The relationship of ACE activity to coronary heart disease risk factors was also examined within these groups. Serum ACE activity did not differ significantly between women with syndrome X and controls. Neither blood pressure, serum total cholesterol, triglyceride, nor high density Lipoprotein subfraction 2 cholesterol was associated with ACE activity in either patient group. However, serum high density Lipoprotein cholesterol, high density Lipoprotein subfraction 3 cholesterol, and apolipoprotein-A-I and -A-II were inversely associated with ACE activity in women with syndrome X, but not in controls. Insulin sensitivity, fasting plasma glucose, insulin, and C-peptide as well as their postglucose challenge concentration profiles were not significantly associated with ACE activity in either group.We conclude that serum ACE activity and, consequently, ACE polymorphism are not associated with syndrome X and are largely independent of metabolic risk factors in these women.

The effect of spinal degenerative changes and aortic calcification on bone mineral density measurements was studied in 115 healthy early postmenopausal women. Lateral lumbar spine radiographs and quantitative computer tomography images were used to determine the presence and severity of aortic calcification and degenerative changes in the lumbar spine. Women with spinal degenerative calcification had higher spine bone density when measured by dual photon absorptiometry compared to those without calcification (P < 0.01), but this was not reflected by the quantitative computer tomography or the proximal femur bone densities, suggesting that spinal calcification artefactually increases spinal bone density when measured by dual photon techniques. Women with aortic calcification had significantly lower quantitative computer tomography and proximal femur bone density compared to those without calcification (both P < 0.05). These women may be at increased risk for both osteoporosis and cardiovascular disease, suggesting a common aetiological factor such as oestrogen deficiency.

PURPOSE: We investigated the relationships between the amount and distribution of body fat and fasting serum lipids and lipoproteins to explore whether coronary artery disease (CAD) risk may be mediated through effects on the serum lipid profile.PATIENTS AND METHODS: We determined serum total cholesterol and triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and HDL subfractions 2 and 3 in 103 healthy men, aged 21 to 77 years (mean 48.7). The amount and distribution of fat were determined directly by dual energy X-ray absorptiometry. Adiposity was determined as the ratio between total body fat tissue and total body lean tissue, while fat distribution was taken as the ratio between the mass of fat tissue in the android (central) and gynoid (hip and thigh) regions.RESULTS: Univariate analysis showed both adiposity and fat distribution to be correlated with total serum cholesterol and triglyceride concentrations (adiposity r = .20, .21; both P <0.05: fat distribution r= .25, .38; P <0.05, P <0.001, respectively). Fat distribution was also negatively correlated with HDL, cholesterol (r = -.20, P <0.05). In multiple linear regression analysis, neither age nor adiposity was significantly correlated with any serum lipid or lipoprotein concentration, while increasing android-to-gynoid ratio was independently associated with elevated total serum triglyceride (r = .40, P <0.01) and decreased HDL, (r = -.25, P <0.05) concentrations.CONCLUSIONS: The association of both age and overall adiposity with the fasting serum lipid profile are mediated via their correlations with body fat distribution. In men, the distribution, rather than the amount, of body fat is related to adverse changes in serum lipids and lipoproteins, and hence potentially to increased CAD risk.

It is well established that hormone replacement therapy (HRT) will prevent postmenopausal loss of bone. However, it is not known to what extent HRT will continue to affect bone mineral density (BMD) in women established on HRT compared with those commencing treatment. We recruited 48 healthy early postmenopausal women into a prospective, comparative study. Twenty-nine women had never taken HRT (group A) whilst 19 women were already taking HRT (group B) (conjugated equine oestrogens, 0.625 mg daily; mean (±SD) years of use 2.2 (1.5) years). All of the women were started on, or switched to, micronized 17β-oestradiol (2 mg/day) continuously with dydroges-terone (10 mg/day) for the first 14 days of each cycle. BMD measurements were performed at the lumbar spine and proximal femur using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 and 24 months of treatment. Group A showed a significantly greater increase in lumbar spine BMD after 12 months (mean (±SD)=5.3 (4.6)%) compared with group B (mean(±SD)=2.1 (2.1)%) and 24 months of treatment (group A, mean(±SD)=6.4 (5.2)%; group B, mean (±SD)=2.3 (2.6)%; bothp<0.01). Femoral neck and Ward's triangle BMD increased significantly in both groups but there were no significant differences between the groups. Baseline BMD correlated with change in lumbar spine BMD for women in group A after 12 months (r=−0.67,p<0.01) and 24 months of treatment (r=−0.59,p<0.05). These data demonstrate that HRT has the greatest effect on BMD when it is first administered, especially in those women with low BMD, but improvements may still be observed in women continuing HRT in the longer term.

The mechanisms by which hormone replacement therapy (HRT) reduces the risk of coronary heart disease (CHD) are incompletely understood, but may include direct arterial effects. We examined the effect of oestrogen/progestagen HRT on serum angiotensin-converting-enzyme (ACE) activity in postmenopausal women. After 6 months, ACE activity was reduced by 20% (p < 0.001) on average in 28 treated women but remained unchanged in 16 controls. Serum ACE activity is modifiable by gonadal steroids and changes in serum ACE may represent a novel mechanism by which HRT reduces CHD risk in women.

OBJECTIVE--To determine whether postmenopausal women with cardiological syndrome X (chest pain and abnormal exercise electrocardiogram despite normal coronary angiography) exhibit disturbances in the full range of proposed components of the putative "insulin resistance syndrome". PATIENTS AND METHODS--20 postmenopausal women with syndrome X and 20 healthy controls each underwent measurement of insulin resistance (by minimal model analysis of the intravenous glucose tolerance test), lipid, lipoprotein, and apolipoprotein concentrations, a range of haemostatic variables, serum uric acid concentration, and centrality of body fat distribution (by dual energy x ray absorptiometry). RESULTS--Women with syndrome X had higher fasting triglyceride concentrations than controls (median: 1.60 v 1.02 mmol/l, P < 0.05). Concentrations of high density lipoprotein cholesterol were lower (1.33 v 1.61 mmol/l, P < 0.05) as were those of the high density lipoprotein apolipoproteins AI and AII. Insulin and C peptide responses to the intravenous glucose tolerance test were higher (27.6 v 19.8 microU/ml/min, P < 0.01; 101 v 72 pmol/ml/min, P < 0.05, respectively), and insulin sensitivity was lower (1.89 v 3.09 min/microU/ml, P < 0.05). There were, however, no significant differences between other proposed components of the insulin resistance syndrome (blood pressure, glucose tolerance, proportion of central body fat, serum uric acid concentration, and plasminogen activator inhibitor-1 activity). Antithrombin III activity was higher in women with syndrome X (121 v 113%, P < 0.01). CONCLUSIONS--Women with syndrome X tend to be insulin resistant and have lipid and lipoprotein abnormalities, but do not exhibit all characteristics of the insulin resistance syndrome. Such variation in correlated risk factors is consistent with underlying heterogeneity in the insulin resistance syndrome and cardiological syndrome X.

Insulin resistance and hyperinsulinaemia may be important in a cluster of coronary heart disease-related metabolic disturbances known as the insulin resistance syndrome. Whether the relationships between insulin and other features of the syndrome are independent of the amount and distribution of body fat is uncertain. We have investigated these interrelationships in 103 healthy males, using dual-energy X-ray absorptiometry to measure body fat directly. Volunteers underwent an intravenous glucose tolerance test (IVGTT), from which insulin sensitivity, secretion and elimination were determined by mathematical modelling analysis. Independently of adiposity and body fat distribution, serum triglyceride concentration was correlated with fasting C-peptide concentration and second-phase intravenous glucose tolerance test insulin concentration (r = 0.42, P < 0.001; r = 0.28, P < 0.05). High density lipoprotein subfraction 2 (HDL2) cholesterol was correlated with fasting C-peptide, first-phase IVGTT insulin concentration, and the hepatic insulin throughput index (r = −0.15, −0.20, −0.20 respectively, all P < 0.05). The association of HDL2 cholesterol with the hepatic throughput index was additionally independent of serum triglyceride concentration (r= −0.18, P < 0.05). Our results suggest that relative hyperinsulinaemia leads to elevated triglyceride concentration, independently of body fat mass and distribution. Furthermore, the independent association of HDL2 cholesterol with hepatic insulin throughput confirms that hepatic insulin processing may directly influence lipoprotein metabolism.

Elevated insulin concentrations are frequently found in both men and women with coronary heart disease (CHD), and are likely to be due to insulin resistance. Hyperinsulinaemia may increase CHD risk by directly promoting atherogenesis, and insulin propeptides may also be important in this respect. However, increased insulin concentrations may adversely affect several other CHD risk factors, and it has been postulated that insulin resistance is a pivotal metabolic disturbance in a constellation of CHD risk factors. There is an association between hyperinsulinaemia and hypertension, although it is not known if this association is direct. Increased insulin concentrations are also associated with high triglycerides, low HDL or HDL2 concentrations, and increased small dense LDL. Obesity is also associated with insulin resistance, and it is the central or android body fat distribution which correlates with these metabolic disturbances. All these associated factors constitute a distinct syndrome--the insulin resistance syndrome--which is a frequent finding in patients with CHD, including microvascular angina. It is possible that the adverse associations of insulin resistance and dyslipidaemia are mediated through increased nonesterified fatty acid flux. Increased insulin levels are also associated with increases in the anti-fibrinolytic factor, plasminogen activator inhibitor-I (PAI-I). Whilst increased insulin levels are typically associated with insulin resistance, reduced hepatic insulin uptake may also be important. We now have techniques which can quantitate insulin secretion, hepatic uptake and release, elimination, and resistance. The menopause has appreciable effect on insulin and glucose metabolism. Estrogen and progesterone augment pancreatic insulin secretion, but the former reduces insulin resistance whilst the latter increases it.(ABSTRACT TRUNCATED AT 250 WORDS)