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Biomedical subjects

V Wynn

Publications and source records attributed to V Wynn.

At least 55 records · Page 3Linked to original sources
PubMed1991

Coronary heart disease risk markers in users of low-dose oral contraceptives.

Seven combination oral contraceptives (OCs) were studied for their effects on glucose, insulin, triglyceride and lipoprotein concentrations. Subjects included 925 women using fixed-dose (monophasic) or variable-dose (triphasic) formulations and 418 premenopausal women not using OCs. The monophasics contained 150 or 250 micrograms of levonorgestrel, 500 or 1,000 micrograms of norethindrone or 150 micrograms of desogestrel as the progestin. Triphasic progestin doses were 50-125 micrograms of levonorgestrel or 500-1,000 micrograms of norethindrone. All the formulations increased the fasting serum triglycerides. No changes were seen in serum total cholesterol. The effects on serum lipoproteins depended on the progestin type and dose. Monophasics containing 500 micrograms of norethindrone or 150 micrograms of desogestrel lowered low density lipoprotein (LDL) cholesterol and increased high density lipoprotein (HDL) cholesterol. Monophasics containing levonorgestrel reduced HDL cholesterol. The triphasics did not affect LDL or HDL cholesterol but altered the balance of HDL subfractions. All the formulations caused a deterioration in glucose tolerance and insulin resistance and increased pancreatic insulin secretion. The greatest effects were seen with formulations containing levonorgestrel. The study showed that a reduction in the progestin dose and use of novel progestins can reduce the potentially adverse effects of OCs on metabolic risk markers for coronary heart disease.

Adolescent↗
PubMed1990

The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.

BACKGROUND: Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes. METHODS: We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone. RESULTS: As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects. CONCLUSIONS: The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles.

Adolescent↗
PubMed1990

Low-dose oral contraceptives and carbohydrate metabolism.

Combined oral contraceptive use has been associated with increased incidence of impaired and diabetic glucose tolerance. Although increased risk of overt symptoms of diabetes has not been associated with oral contraceptive use, increased risk of coronary heart disease has been consistently demonstrated. Diabetes is associated with increased risk of coronary heart disease, especially in women. Elevated plasma glucose and insulin concentrations are also associated with increased risk of coronary heart disease. Studies of the effects of low-dose oral contraceptives on glucose tolerance test plasma glucose and insulin levels are reviewed. Low-dose combined oral contraceptives induced changes in measures of carbohydrate metabolism in directions consistent with increased risk of coronary heart disease. The magnitude of these changes may depend on the dose and type of progestogen. The clinical implications of these changes are unknown, but it would seem advisable to minimize them where possible.

Blood Glucose↗
PubMed1990

Rising cholesterol levels in children with familial hypercholesterolaemia.

Reference ranges (5th to 95th percentile) for fasting total serum cholesterol concentration were calculated for 571 unrelated children aged 4-19 years, without known predisposition to hypercholesterolaemia. Values were 3.31-5.81 mmol.l-1 for boys and 3.20-5.66 mmol.l-1 for girls, without significant differences between sexes at any age, compared to our laboratory reference ranges for men (3.46-6.87 mmol.l-1) and women (3.00-6.38 mmol.l-1). A further 85 children, each with a first degree relative with Familial Hypercholesterolaemia (FH), were studied. Initially, 39 had high cholesterol concentrations suggestive of FH. Repeated serial measurements were carried out in 18 of the 46 apparently unaffected children. Seven of these showed marked increases in serum cholesterol over 1-7 years, reaching concentrations above the 95th centiles of the appropriate reference ranges. The annual rate of increase was significantly higher than in the 11 who remained normocholesterolaemic. In 3 of these 7 children, diagnosis of FH was confirmed retrospectively, using recombinant DNA technology to show that each had inherited the defective allele of the LDL-receptor gene from an affected parent. Thus, serial cholesterol measurements may be needed to confirm or exclude FH in potential heterozygotes, while DNA studies can be used for definitive diagnosis in some families.

Adolescent↗
PubMed1989

Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives.

1. Azole antifungal agents such as ketoconazole act by inhibiting cytochrome P-450 mediated sterol synthesis in the fungal cell membrane and thus have the potential to interfere with mammalian steroidogenesis. Fluconazole is a novel orally-effective antifungal triazole which has been reported to have more specific effects on the cytochrome P-450 enzymes involved in fungal sterol synthesis. 2. Due to the potential value of systemic antifungal agents in the treatment of infections commonly occurring in women, we assessed the effect of oral fluconazole on the metabolic profile of 18 healthy premenopausal women, 10 of whom were taking combined oral contraceptives (OC). Each woman acted as her own control, being studied both before and 21-28 days after fluconazole therapy (50 mg daily), in the luteal phase of consecutive menstrual cycles. 3. The endocrinological profile included measurement of serum oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) concentrations, short tetracosactrin adrenal stimulation test and thyroid function tests. Carbohydrate metabolism was investigated by means of an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations. Serum lipids, lipoproteins and apolipoproteins were analysed on samples taken after an overnight fast. 4. Minor biochemical changes associated with fluconazole treatment included increases in serum thyroxine and testosterone concentrations (but not in women taking OC as well as fluconazole) and in insulin and apolipoprotein B levels (but only in women taking OC as well as fluconazole). In general, these changes were small and of no clinical significance with the values remaining within the laboratory normal range. There were no adverse side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The treatment of a hyperandrogenic and virilizing state in an elderly female with a synthetic LHRH agonist.

A case of hyperandrogenism and virilization is described in an elderly female. She had elevated testosterone levels, but normal DHEAS and 24-h urinary 17-oxosteroid excretion, suggesting an ovarian tumor. Stimulation and suppression tests, and radioisotopic and radiological scans proved unhelpful in the diagnosis although hyperthecosis of the ovary was later suggested by ultrasound. Testosterone and gonadotropin levels fell during therapy with cyproterone acetate and subsequently ethinyl estradiol. Because of side effects encountered on these drugs, she was treated with a synthetic, slow-release preparation of an LHRH agonist, D-TRP-6-LHRH (Decapeptyl), with symptomatic and biochemical improvement. Long term LHRH agonists might be a valuable treatment for hyperandrogenic states in elderly patients.

Aged↗
PubMed1988

Oral contraceptives and coronary heart disease: modulation of glucose tolerance and plasma lipid risk factors by progestins.

Widespread use of oral contraceptive formulations by women throughout their reproductive life has given rise to concerns about the effects of oral contraceptives on risk factors for coronary heart disease. Oral contraceptive-induced changes in both carbohydrate and lipoprotein risk factors may contribute to an increased risk of coronary heart disease. Carbohydrate and lipoprotein risk factors for coronary heart disease are reviewed, and oral contraceptive-induced changes in carbohydrate and lipoprotein metabolism, which may lead to altered risk status for coronary heart disease, are discussed. The importance of methodology in evaluating the results of studies assessing such oral contraceptive-induced changes is stressed. The role of progestins in influencing coronary heart disease risk factors is surveyed, and differences among progestins commonly used in oral contraceptive formulations are discussed. In addition, the effect of various combination oral contraceptives on risk factor status is outlined. Finally, the implications of available evidence for the selection of progestins for oral contraceptive formulations of the future are discussed. Current data indicate that medium- and low-fixed-dose oral contraceptive formulations containing estrogen/norethindrone acetate have less metabolic impact than do comparable levonorgestrel-containing formulations, including multiphasic formulations. Triphasic formulations may have less effect on coronary heart disease risk factors, although data are not yet conclusive. Novel progestins such as desogestrel may also have lesser effects on metabolic functions, but the reduced androgenicity of such compounds may expose women to an increased risk of estrogen-induced hypertriglyceridemia.

Cholesterol, HDL↗
PubMed1987

Derivation of a quantitative measure of insulin sensitivity from the intravenous tolbutamide test using the minimal model of glucose dynamics.

Using the decay phase of the glucose response during an intravenous tolbutamide test, a minimal model of glucose dynamics was used to calculate a value for an "index of insulin sensitivity". This index describes the efficiency of insulin in accelerating the instantaneous rate of glucose disposal, and provides a measure of insulin resistance. The validity of estimates of the index of insulin sensitivity obtained from the intravenous tolbutamide test have been assessed with reference to estimates of this index derived from the intravenous glucose tolerance test for which the model was originally designed. There were three studies: (A) estimates of the index of insulin sensitivity obtained from the intravenous tolbutamide test in a group of normal, healthy men and women were compared with results obtained in a comparable group of subjects using the intravenous glucose tolerance test. The two methods gave estimates of the index of insulin sensitivity that were identical; (B) A group of patients taking methandienone, an anabolic steroid previously shown to cause marked insulin resistance, were tested whilst taking the steroid and either before, or at least two months after treatment. Each patient was tested by both intravenous tolbutamide test and intravenous glucose tolerance test on both occasions. Estimates of the index of insulin sensitivity from intravenous glucose tolerance or intravenous tolbutamide procedures both on and off treatment were significantly correlated (off treatment: rs = 0.71, n = 9, p less than 0.05; on treatment: rs = 0.69, n = 9, p less than 0.05); (C) A group of patient undergoing investigations for suspected disturbances in carbohydrate metabolism was studied, each patient having had both an intravenous tolbutamide and intravenous glucose tolerance test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

The effects of reverse sequential anti-androgen therapy (cyproterone acetate and ethinyl estradiol) on hematological parameters.

Hematological parameters were studied in female patients receiving reverse-sequential anti-androgen therapy for hirsutism and acne. A significant fall in hemoglobin, total red cell count and packed cell volume occurred after 3-month treatment in 30 patients during the 10-day cyproterone acetate and ethinyl estradiol phase; this change was sustained in 14 patients studied to 12 months. A fall in hemoglobin and packed cell volume alone occurred after 3 months in 31 patients in the ethinyl estradiol phase. Reverse-sequential therapy may influence hemopoiesis by its anti-androgenic action on erythropoiesis, although we found no relationship between changes in hematological parameters and total testosterone levels.

Acne Vulgaris↗
PubMed1987

Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions.

We review the hypothesis that the incidence of coronary heart disease (CHD) is higher in men than in women due to differences in plasma lipoprotein risk factors between the sexes. Men and women appear to be equally susceptible to the effects of lipoprotein risk factors for CHD, and the difference between the sexes in lipoprotein risk factors for CHD appears to be consistent with their being, at least in part, responsible for the sex difference in CHD. This is apparent both when men and women of equal age are compared, and when age-related variations in the sex differences in plasma lipoproteins and CHD are considered. Differences between the sexes in lipoprotein concentrations are still present when sex differences in adiposity, cigarette smoking, physical activity, and diet are taken into account. Evidence relating these sex differences in CHD and lipoproteins to the effects of sex hormones is critically examined. It is commonly accepted that androgens induce changes in lipoprotein concentrations that would predispose towards CHD, whereas estrogens are held to have opposite effects. However, much of the evidence for this comes from studies of changes associated with administration of synthetic gonadal steroids or with changes in gonadal function. Studies of differences in lipoprotein metabolism in normal men and women are extremely limited. In males high-density lipoprotein (HDL) cholesterol levels fall at puberty, correlating with the rise in plasma testosterone concentrations. In females, HDL levels do not change at puberty, despite the rise in estrogen concentrations. Evidence for lipoprotein changes during the menopause, when estrogen levels decline, is equivocal. Similarly, the evidence for an increase in CHD incidence at the menopause is inconclusive. National mortality data indicate that the decreasing sex difference in CHD after 50 years of age is due to a declining rate of increase in men rather than to an acceleration in CHD incidence in women. In men the age-related increase in low-density lipoprotein (LDL) concentrations diminishes beyond 50 years of age, whereas in women the rate of increase remains unchanged. Studies of the effects of gonadectomy are of doubtful relevance in assessing the roles of sex hormones in CHD, and have not been performed with sufficient rigor to provide definitive conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Lipoprotein analyses in varying degrees of glucose tolerance. Comparison between non-insulin-dependent diabetic, impaired glucose tolerant, and control populations.

Atherosclerosis is the major cause of death in diabetic patients. Lipoproteins and lipids are frequently altered in non-insulin-dependent diabetes. These lipoprotein alterations are of interest because of their possible role in the origin of the accelerated atherosclerosis found in diabetes. Because of the link between lipoproteins and diabetes, serum lipids and lipoproteins were measured in 215 middle-aged patients (107 female, 108 male) with varying degrees of glucose tolerance: control subjects, subjects with impaired glucose tolerance (IGT), and patients with non-insulin-dependent diabetes mellitus (NIDDM). In male subjects, levels of fasting total triglycerides were significantly greater in those with NIDDM compared with control subjects. In female subjects, fasting total cholesterol levels were significantly greater in NIDDM compared with IGT. Both high-density lipoprotein (HDL) cholesterol and HDL2 cholesterol values were significantly lower in both sexes with NIDDM compared with control subjects. Low-density lipoprotein (LDL) cholesterol levels were elevated in the male subjects with IGT. No differences in HDL cholesterol or its subfractions were seen in both sexes with IGT compared with control subjects. Bivariate analyses showed that the reduced HDL cholesterol and HDL subfraction levels were most closely associated with both total triglycerides and weight. This study shows that reduced HDL cholesterol and HDL2 cholesterol levels occur in NIDDM, whereas persons with "impaired glucose tolerance" do not have the dramatic alterations in HDL levels.

Arteriosclerosis↗
PubMed1987

Apolipoprotein B gene variants are involved in the determination of serum cholesterol levels: a study in normo- and hyperlipidaemic individuals.

We have investigated the frequencies of 3 restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apo B) gene in normo- and hyperlipidaemic individuals. In individuals with type III hyperlipidaemia, the allele frequency for the RFLP detected with XbaI was significantly different from the allele frequency in normolipidaemic individuals and in those with other types of hyperlipidaemia. No significant difference in allele frequency was found among these groups for the RFLPs detected with MspI or EcoRI. Within a sample of 62 normolipidaemic individuals, homozygotes for the X2 allele (cutting site) of the XbaI RFLP had a significantly higher serum cholesterol level than homozygotes for the XI allele, with individuals of the genotype X1X2 having an intermediate value (X2X2 mean 5.71 mmol/l, X1X1 mean 4.81 mmol/l, X1X2 mean 5.30 mmol/l). There were also significant differences in serum triglyceride levels in individuals with different XbaI genotypes. In these normolipidaemic individuals there was no correlation between the EcoRI and MspI RFLP genotypes and levels of any serum lipid variable. Information from the XbaI and EcoRI RFLPs was used in conjunction to define apo B haplotypes. These haplotypes are a more precise measure of the genotypic variation, and they explain a greater fraction of the serum cholesterol and triglyceride levels than the single-site polymorphisms considered separately. This study suggests that variations in the gene for apo B are associated with the determination of serum cholesterol and triglyceride levels both in patients with type III hyperlipidaemia and in the normal population.

Adult↗
PubMed1987

Reduction in resting energy expenditure in relation to lean tissue loss in obese subjects during prolonged dieting.

Resting energy expenditure (REE) was measured by indirect calorimetry during dieting (2.74-3.30 MJ/day) for up to 200 days in overweight patients undergoing continuous metabolic balance studies. The initial rapid reduction in REE in the first 2 weeks of dieting was related to the extent of the immediate nitrogen deficit that follows caloric restriction and was larger (p less than 0.01) in men dieting de novo than either women (NS) or 4 patients of comparable lean body mass who had dieted prior to admission (NS). Because of their smaller metabolic energy deficit on our diets, the reduction in REE in women was small and not significant. In men, the slower long-term reduction in REE (p less than 0.05) was related to a continuing loss of lean tissue with no changes in the REE/m2, REE/kg body weight and REE/mmol creatinine excreted with time. We have previously shown that total energy expenditure (estimated from the rate of fat loss as measured by the difference between body weight changes and weight changes in fluid and protein) does not change significantly during prolonged dieting. The fall in REE in parallel with lean body mass suggests that some increase in the energy expended in daily activities must have occurred.

Adult↗