Transdermal hormone replacement therapy, serum lipids and lipoproteins.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J C Stevenson.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
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 17 beta-oestradiol (2 mg/day) continuously with dydrogesterone (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)%; both p < 0.01) and 24 months of treatment (r = -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.
Low peak adult bone mass in a premenopausal woman puts her at increased risk for osteoporosis postmenopausally. Episodes of hypo-estrogenism premenopausally are associated with loss of bone density. This is seen with gonadotropin-releasing hormone agonist therapy for endometriosis, and thus prolonged or repeated courses of such treatment may increase the future risk of osteoporosis. Danazol and related compounds do not result in any bone loss but may have certain metabolic disadvantages.
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 relationships 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 throughout 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 may directly influence lipoprotein metabolism.
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 HDL2 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 HDL2 (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.
OBJECTIVE: To determine whether treatment of endometriosis with a GnRH analogue (GnRH-a; goserelin) combined with continuous estrogen and progestogen hormone replacement therapy (HRT) would prevent the hypoestrogenic effects, including loss of bone density, while maintaining efficacy for treatment of endometriosis. DESIGN: Randomized controlled trial. PATIENTS: Fifty premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Score for endometriosis implants equal to four or greater) and significant symptoms of dysmenorrhoea, dyspareunia, and other pelvic pain. INTERVENTION: Patients were randomized to receive either goserelin alone, 3.6 mg SC depot every 4 weeks for 24 weeks, or goserelin, 3.6 mg SC depot every 4 weeks for 24 weeks, plus HRT (25 micrograms transdermal 17 beta E2 daily and 5 mg medroxyprogesterone acetate orally daily) for 20 weeks commencing with the second goserelin injection. RESULTS: There was a significant reduction in the extent of pelvic endometriosis in both groups, with no difference between the groups. Both groups experienced an improvement in symptoms and signs, again with no difference between groups. Hypoestrogenic side effects of hot flushes and loss of libido were significantly less in the group that received HRT. The amount of bone mineral density loss was significantly less in the HRT group at the lumbar spine, although it was not prevented completely. CONCLUSION: The addition of HRT to GnRH-a for the treatment of endometriosis did not reduce the efficacy of treatment, and adverse hypoestrogenic effects were decreased, although not abolished.
In order to compare the predictive value of the Apache II, the Glasgow Coma Scale and Revised Trauma Scoring systems in relation to outcome in a neurosurgical department high dependency unit (HDU), all 109 patients entering the unit under the care of one consultant were studied. All patients in the HDU were self-ventilating, so that motor responses were not suppressed by muscle relaxants or sedation. Initial Minimum and Maximum Glasgow Coma Scale Scores, Revised Trauma Score, Apache II and the Apache minus neurological weighting (Apache-NW) scores, were compared as predictors of outcome (as assessed by the Glasgow Outcome Score at 6 months). Twenty-eight patients had a bad outcome, i.e. Glasgow Outcome Scores 1-3, and 72 individuals a good outcome, i.e. scores 4 or 5. Statistical analysis was by the Spearman Ranked Correlation Test, and comparison of Receiver Operational Characteristics Curves. Data were complete on 100 patients (91.7%) and show the Maximum Glasgow Coma Score, followed by the Apache II score, as the best predictors of outcome analysed. This was also true if all patients except those with head injury were analysed as a group. All scoring systems were significantly better predictors of outcome in the head injured patient. For this group, Apache II had an outcome predictive value of 97% compared with 93% for initial and 95% for minimum GCS. Removing the neurological weighting from Apache II weakened its predictive ability in all patients, emphasizing that it is the neurological status of the patient which best predicts overall functional outcome. Apache II data are also much more time-consuming to collect than GCS data.(ABSTRACT TRUNCATED AT 250 WORDS)
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.
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.
Preston's two-census method of demographic estimation is applied to three pairs of reconstructed censuses from the records of a migrating Mennonite church congregation covering the period 1780-1890. The three pairs of censuses correspond to three periods (1780-1790, 1850-1860, and 1880-1890) and to stays in three settings (Prussia, Russia, and Kansas, respectively). The Mennonites' stay in Prussia was a period of hardship. In Russia they expanded their economic base and developed new farming methods, dramatically increasing their productivity. The Mennonites took these skills to Kansas, where they continued to be successful. The increase in life expectancy at age 5 corroborates this picture. The Prussian period exhibits the shortest life expectancy for both sexes. After the move to Russia, life expectancy increased for both sexes and continued to increase with the move to Kansas. The model also provides limited evidence for fertility depression following the move to Kansas.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Transdermal hormone replacement therapy (HRT) is now an accepted form of treatment, but the long-term skeletal effects have not been assessed. Sixty-six early postmenopausal women were randomized to receive either transdermal HRT (continuous 17 beta-oestradiol 0.05 mg/day, with 0.25 mg/day of norethisterone acetate added for 14 days of each 28-day cycle) or oral HRT (continuous conjugated equine oestrogens 0.625 mg/day, with 0.15 mg/day dl-norgestrel added for 12 days of each 28-day cycle). Treatment was given for 3 years and 30 matched untreated women were studied concurrently as a control group. Bone density was measured in the lumbar spine and proximal femur by dual-photon absorptiometry at 6-monthly intervals. Bone turnover was assessed by measurement of biochemical markers. At 3 years bone density had declined by 4% in the lumbar spine and by more than 5% in the femoral neck in the untreated group. By comparison bone density increased in both treatment groups at both sites (p < 0.001 vs. untreated) and biochemical measurements indicated a significant reduction in bone turnover. There were no significant differences between the treatment groups. Twelve per cent of women on transdermal or oral treatments lost a significant amount of bone from the femoral neck by 3 years despite adequate compliance. Women taking therapy primarily for hip fracture prevention may require a follow-up bone density measurement to establish the efficacy of treatment.
Routine insulin assays measure not only biologically active insulin but also the relatively inactive propeptides, proinsulin and desdipeptide proinsulin. Such measurements may be misleading if insulin propeptide levels are increased, as has been reported in patients with non-insulin-dependent diabetes mellitus (NIDDM). Inferences regarding insulin resistance, based on hyperinsulinemia, could thus be invalidated where routine insulin assays have been used. We have measured plasma insulin levels using a routine assay, together with measurements of the major circulating insulin propeptides, intact proinsulin and des 31,32proinsulin, in various clinical situations associated with apparently increased insulin levels and insulin resistance. Major increases of insulin propeptide levels relative to insulin levels were not seen in obese subjects or in patients taking oral contraceptives or danazol, or in obese subjects compared with non-obese controls. Although the insulinemic responses observed with routine radioimmunoassay in these situations associated with insulin resistance are not confounded by major changes in the proportion of circulating insulin propeptides, further studies will be necessary to validate investigations in other insulin-resistant states.