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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functional ovarian hyperandrogenism, a variant of polycystic ovary syndrome, is often associated with hyperinsulinism and dyslipidemia. The mechanisms interlinking this triad are poorly understood; both hyperandrogenism and hyperinsulinism have been proposed as factors involved in the pathogenesis of the dyslipidemia. Precocious pubarche (PP) in girls is a risk factor for subsequent anovulation, ovarian and adrenal hyperandrogenism, hyperinsulinism and dyslipidemia. Flutamide, a nonsteroidal antiandrogen, is known to be effective in reducing hirsutism in patients with ovarian hyperandrogenism. However, the effects of flutamide on the endocrine-metabolic correlates of hyperandrogenism are uncertain. We assessed the effects of low dose flutamide treatment (250 mg daily for 18 months) on hormonal and metabolic variables in 18 nonobese adolescent girls (age, 16.8 +/- 0.3 yr) with functional ovarian hyperandrogenism (diagnosis by GnRH agonist test) after PP. Flutamide treatment was accompanied by a marked decrease in the hirsutism score, free androgen index, and testosterone, androstenedione, and dehydroepiandrosterone levels and by an increase in sex hormone-binding globulin concentrations. However, there were no substantial changes in the pattern of menstrual cycles, gonadotropin, estradiol, or dehydroepiandrosterone sulfate concentrations, and there was no detectable effect on the 17-hydroxyprogesterone response to GnRH agonist. Serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels decreased markedly during flutamide therapy, whereas high-density lipoprotein cholesterol, fasting glycemia/insulinemia, and the insulin response to a glucose load remained unchanged. Flutamide was well tolerated. In conclusion, low dose flutamide treatment was found to be an effective and safe approach to reduce hirsutism and circulating androgen, low-density lipoprotein cholesterol, and triglyceride levels in girls with functional ovarian hyperandrogenism after PP. However, flutamide failed to increase high-density lipoprotein cholesterol levels or decrease hyperinsulinemia, i.e. to affect two major risk factors for subsequent cardiovascular disease.
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PMID:Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide. 1099 17

The prevalence of ovarian hyperandrogenism, hyperinsulinism and dyslipidemia is increased among adolescent girls with a history of premature pubarche (defined as the appearance of pubic hair before the age of 8 yr). The ovarian hyperandrogenism is characterized by clinical signs of androgen excess and by an exaggerated ovarian 17-hydroxyprogesterone response to GnRH agonist stimulation. The hyperinsulinism and dyslipidemia are detectable before and during pubertal development, and are commonly accompanied by low serum levels of insulin-like growth factor binding-protein 1 (IGFBP-1) and sex hormone-binding globulin (SHBG), and by an increased prevalence of anovulation from late adolescence onwards, even in the absence of clinical signs of androgen excess. In girls, premature pubarche, hyperinsulinism, low IGFBP-1, dyslipidemia, anovulation and hyperandrogenism--and some combinations of these--have been related to reduced fetal growth, indicating that these constellations or sequences may have a prenatal origin. Together, these findings suggest that premature pubarche in girls should no longer be merely regarded as a normal variant of development, but rather as a childhood marker pointing to an increased risk for a polyendocrine-metabolic disorder of prenatal origin.
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PMID:Precocious pubarche in girls and the development of androgen excess. 1111 66

Compensatory hyperinsulinemia stemming from peripheral insulin resistance is a well-recognized metabolic disturbance that is at the root cause of diseases and maladies of Syndrome X (hypertension, type 2 diabetes, dyslipidemia, coronary artery disease, obesity, abnormal glucose tolerance). Abnormalities of fibrinolysis and hyperuricemia also appear to be members of the cluster of illnesses comprising Syndrome X. Insulin is a well-established growth-promoting hormone, and recent evidence indicates that hyperinsulinemia causes a shift in a number of endocrine pathways that may favor unregulated tissue growth leading to additional illnesses. Specifically, hyperinsulinemia elevates serum concentrations of free insulin-like growth factor-1 (IGF-1) and androgens, while simultaneously reducing insulin-like growth factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin (SHBG). Since IGFBP-3 is a ligand for the nuclear retinoid X receptor alpha, insulin-mediated reductions in IGFBP-3 may also influence transcription of anti-proliferative genes normally activated by the body's endogenous retinoids. These endocrine shifts alter cellular proliferation and growth in a variety of tissues, the clinical course of which may promote acne, early menarche, certain epithelial cell carcinomas, increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding. Consequently, these illnesses and conditions may, in part, have hyperinsulinemia at their root cause and therefore should be classified among the diseases of Syndrome X.
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PMID:Hyperinsulinemic diseases of civilization: more than just Syndrome X. 1452 33

Among girls with precocious pubarche (PP), those with low birth weight (LBW) are, even if nonobese, at risk for progression to polycystic ovary syndrome (PCOS) including hyperinsulinemic hyperandrogenism, dyslipidemia, dysadipocytokinemia, and central fat excess. Recently, we disclosed the efficacy of insulin sensitization with metformin to disrupt progression from PP to PCOS in formerly LBW girls who were postmenarche. In LBW-PP girls, we have now extended the exploration of early insulin sensitization therapy in two directions: 1) metformin therapy was started before puberty; and 2) we assessed the effects of metformin discontinuation in girls who had started metformin treatment after menarche. Prepubertal LBW-PP girls (n = 33; mean age, 8.0 yr; body mass index, 18.5 kg/m(2)) were randomly assigned to remain untreated or to receive metformin (425 mg/d) for 6 months. Postpubertal LBW-PP girls (n = 24; age, 12.4 yr; body mass index, 21.0 kg/m(2)) had been randomized (at -12 months) to remain untreated or to receive metformin (850 mg/d) for 12 months, at which time (0 month) a treatment cross-over was performed for 6 months. Fasting blood glucose and serum insulin, SHBG, dehydroepiandrosterone sulfate, androstenedione, testosterone, lipid profile, IL-6, and adiponectin were assessed at 0 and 6 months, as was body composition (by dual x-ray absorptiometry). In the prepubertal study (group A), comparisons of untreated vs. treated girls disclosed normalizing effects of metformin on SHBG, androstenedione, dehydroepiandrosterone sulfate, low and high density lipoprotein cholesterol, triglycerides, IL-6, adiponectin, total and abdominal fat mass, and lean body mass. In the postpubertal study (group B), treatment cross-over at 0 month was in each subgroup followed by a striking reversal in the course of the endocrine-metabolic state, adipocytokinemia, and body composition; all changes pointed to normalizing effects of metformin treatment. In conclusion, these two studies provide the first evidence that 1) prepubertal metformin therapy has normalizing effects on PCOS features in high risk girls with a combined history of LBW and PP; and 2) in adolescence, metformin's normalizing effects are reversed as soon as metformin therapy is discontinued.
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PMID:Insulin sensitization for girls with precocious pubarche and with risk for polycystic ovary syndrome: effects of prepubertal initiation and postpubertal discontinuation of metformin treatment. 1535 29

Polycystic ovary syndrome (PCOS), a common endocrinopathy of women of reproductive age, is associated with the early appearance of multiple risk factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and diabetes mellitus. However, premature atherosclerosis of the carotid artery has not yet been demonstrated in young women with PCOS. Measurement of carotid intima-media thickness (IMT) is considered an easy and reliable index of subclinical atherosclerosis, which is predictive of subsequent myocardial infarction and stroke. To evaluate the cardiovascular risk of PCOS and the participation of the hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode ultrasound as well as hormonal and several cardiovascular disease-associated parameters in 75 young women with PCOS and 55 healthy, age- and body mass index-matched women. The PCOS women had significantly increased carotid IMT (0.58 vs. 0.47 mm, P < 0.001) and abdominal adiposity; higher levels of androgens, insulin, homeostasis model assessment score of insulin sensitivity, and total and low-density lipoprotein-cholesterol; and significantly lower levels of SHBG and high-density lipoprotein-cholesterol. In the studied population (n = 130), PCOS status, age, body mass index, and parental history of coronary heart disease were strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate was a strong negative predictor. In PCOS patients lower delta4-androstenedione and high-density lipoprotein-cholesterol levels were additionally strong positive predictors of carotid IMT, whereas in control women only total cholesterol was the additional positive predictor of carotid IMT. In conclusion, young women with PCOS have an early increase of cardiovascular risk factors and greater carotid IMT, both of which may be responsible for subclinical atherosclerosis. The hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the dysmetabolic phenotype on the vascular wall.
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PMID:Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome. 1574 Dec 56

Polycystic ovary syndrome (PCOS) is a diagnosis made between late adolescence and the menopause in 5-10% of women. PCOS is a heterogeneous disorder of unknown etiology characterized by hyperandrogenic chronic anovulation. This syndrome consists of a diverse constellation of signs and symptoms, such as hirsutism, acne, acanthosis nigricans, obesity, menstrual irregularities, anovulation, and/or infertility. Features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia, are common in this patient population. Recent insights into the pathophysiology of PCOS have shown insulin resistance and hyperinsulinemia to play a substantial role. Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Recent studies show that serum levels of inflammatory mediators, such as tumor necrosis factor-alpha and interleukin-6, are increased in the insulin-resistant conditions of obesity and PCOS. The optimal modality for long-term treatment should have positive effects on androgen synthesis, sex hormone-binding globulin production, the lipid profile, insulin sensitivity, inflammatory mediators, and clinical symptoms including acne, hirsutism, and irregular menstrual cycles. Treatment with insulin-sensitizing agents is a relatively new therapeutic strategy in women with PCOS. Current research has shown that the use of diabetes mellitus management practices aimed at reducing insulin resistance and hyperinsulinemia (such as weight reduction and the administration of oral antidiabetic drugs) can not only reverse testosterone and luteinizing hormone abnormalities and restore menstrual cycles, but can also improve glucose, insulin, proinflammatory cytokine, and lipid profiles.Clinical treatment with troglitazone, a member of the thiazolidinedione family, for the management of PCOS complications such as insulin resistance, hyperandrogenism, and anovulation was found to have beneficial effects; however, it was taken off the market over concerns of hepatotoxicity. Although troglitazone is no longer available in the US, numerous clinical trials have established the role of thiazolidinediones in the treatment of women with PCOS. Clinical data emerging regarding the utility of two of the newer, safer thiazolidinediones, pioglitazone and rosiglitazone, for this patient population, consistently demonstrate effective improvements of endocrine and ovulatory performance in women with PCOS. The benefit and importance of lifestyle modification and weight reduction, when it can be achieved, is still an important component in the long-term treatment of PCOS. Pharmacologic reduction in insulin levels using thiazolidinediones appears to offer another therapeutic modality for PCOS, which may ameliorate the progress of both hyperinsulinemia and hyperandrogenism. However, additional studies of patients so treated are necessary before these agents can be considered first-line treatment for PCOS. Convincing data from randomized controlled trials with sufficient power to detect both the benefits and risks of long-term treatment with thiazolidinediones in women with PCOS remain to be obtained.
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PMID:Thiazolidinediones for the therapeutic management of polycystic ovary syndrome : impact on metabolic and reproductive abnormalities. 1667 59

The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age- and body mass index-adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: >or=19%) in women with PCOS increased the risk of elevated blood pressure (SBP >or=130 mm Hg and/or DBP >or=85 mm Hg) with an odds ratio of 3.817 (P=0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia.
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PMID:Relationship between androgen levels and blood pressure in young women with polycystic ovary syndrome. 1757 51

Serum sex hormone-binding globulin (SHBG) is related to cardiometabolic disorders; but whether or not this relationship is purely secondary to hyperinsulinemia and/or obesity, which down-regulates SHBG, is unknown. The aim of the study was to investigate the association of SHBG and total testosterone with atherogenic dyslipidemias, metabolic syndrome (MS), and diabetes among predominantly elderly Turkish adults. After appropriate exclusions, 777 randomly selected male and female subjects with available measurements of both variables were eligible and were analyzed cross-sectionally, with diabetic subjects analyzed separately. Free testosterone was calculated. Metabolic syndrome was identified by the modified criteria of the Adult Treatment Panel III. Metabolic syndrome was identified in half the sample, which had a median age of 58 years. The odds of low SHBG concentrations (<45 nmol/L in men, <55 nmol/L in women) for the likelihood of 2 types of dyslipidemias, MS, and diabetes were examined by regression analyses in standard models including age, smoking status, presence of abdominal obesity, and insulin resistance (homeostasis model assessment of insulin resistance). In both sexes, low SHBG was associated independently with high triglyceride/low high-density lipoprotein dyslipidemia and with MS, at significant 2.2- to 4.5-fold odds ratios, independent of waist circumference or homeostasis model assessment of insulin resistance index. Low SHBG among women was additionally associated with the likelihood of hypertriglyceridemia with elevated apolipoprotein B and-at borderline significance-with that of diabetes, again when adjusted for the same confounders. In an elderly population with prevalent MS, low SHBG levels significantly associate with high triglyceride/low high-density lipoprotein dyslipidemia, MS, and, in women alone, diabetes and a dyslipidemia marking small dense low-density lipoprotein particles, all independent of abdominal obesity and insulin resistance. Low SHBG may be an important independent factor for cardiometabolic risk, particularly in women.
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PMID:Serum sex hormone-binding globulin, a determinant of cardiometabolic disorders independent of abdominal obesity and insulin resistance in elderly men and women. 1788 45

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by obesity-related risk factors for cardiovascular disease. The objective of our study was to determine values of key lipid and lipoprotein fractions in PCOS, and their possible relation to insulin resistance. A total of 75 women with PCOS (aged 23.1 +/- 5.1 years, BMI 24.9 +/- 4.7 kg/m(2)), and 56 age- and BMI-matched controls were investigated. In all subjects, basal glucose, cholesterol (total, HDL, and LDL), oxidized LDL (OxLDL), triglycerides, apolipoprotein (apo)A1, apoB, and apoE, nonesterified fatty acids, insulin, testosterone, sex hormone-binding globulin, homeostasis model assessment (HOMA) index, and free androgen index were determined in the follicular phase of the cycle. PCOS patients compared with controls had increased indices of insulin resistance, basal insulin (p < 0.001), and HOMA index (p < 0.001), and worsened insulin resistance-related dyslipidemia with decreased HDL cholesterol (p < 0.01), elevated triglycerides (p = 0.010), and pronounced LDL oxidation (p < 0.001). In conclusion, characteristic dyslipidemia of insulin resistance and unfavorable proatherogenic lipoprotein ratios were present only in women with PCOS and not in controls. Elevated OxLDL and the relation of apoE and nonesterified fatty acids with insulin resistance suggest that women with PCOS are at increased risk for premature atherosclerosis.
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PMID:Lipid and lipoprotein profile in women with polycystic ovary syndrome. 1841 29

Over the last three decades, it has become apparent that testosterone plays a significant role in glucose homeostasis and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a pro-inflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome. There is evidence that hypotestosteronemia should be an element in the definition of the metabolic syndrome since low levels of testosterone are associated with or predict the development of the metabolic syndrome and of diabetes mellitus. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis. So far, studies on the effects of normalization of testosterone in hypogonadal men on glucose homeostasis are limited, but convincing, and if diabetes mellitus is viewed in the context of the metabolic syndrome, the present results of testosterone treatment are very encouraging.
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PMID:The role of testosterone in type 2 diabetes and metabolic syndrome in men. 2012 41


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