Oral contraceptive plus antiandrogen therapy and cardiometabolic risk in polycystic ovary syndrome.

OBJECTIVE: Oral contraceptives alone or in combination with antiandrogens are commonly used in the treatment for polycystic ovary syndrome (PCOS). We aimed to determine the effects of ethinyl estradiol/drospirenone (EE-DRSP) plus spironolactone therapy on inflammation and cardiometabolic risk in PCOS. DESIGN: Prospective cohort study. PATIENTS: Twenty-three lean, normal glucose-tolerant patients with PCOS and 23 age- and body mass index (BMI)-matched healthy control women. MEASUREMENTS: Androgens, high-sensitivity C-reactive protein (hsCRP), homocysteine, lipids, fasting insulin, and glucose levels during a standard 75-g, 2-h oral glucose tolerance test were measured. Patients with PCOS were evaluated before and after receiving EE-DRSP (3 mg/30 µg) plus spironolactone (100 mg/day) for 6 months. Healthy controls were evaluated at baseline only. RESULTS: hsCRP, homocysteine, lipids, insulin and glucose levels were similar between patient and control groups at baseline. EE-DRSP plus spironolactone increased hsCRP and homocysteine levels in patients with PCOS (0.50 ± 0.28 vs 1.5 ± 1.3 mg/l, P < 0.05 and 13.1 ± 5.2 vs 17.6 ± 5.3 µm, P < 0.05, respectively). BMI, waist-to-hip ratio, LDL, HDL cholesterol and triglycerides, and glucose tolerance did not change. Modified Ferriman-Gallwey hirsutism scores, testosterone levels and free androgen index improved (9.1 ± 4.2 vs 6.2 ± 3.4, P = 0.001; 80.6 ± 31.1 47.8 ± 20.3 ng/dl, P < 0.05; and 10.5 ± 7.4 vs 1.1 ± 0.8, P < 0.001, respectively). CONCLUSIONS: EE-DRSP plus spironolactone therapy in 6 months improves androgen excess in lean PCOS women without any adverse effects on adiposity, glucose tolerance status or lipid profile. However, this combination increases hsCRP and homocysteine levels.

Ethinyl estradiol-drospirenone vs ethinyl estradiol-drospirenone plus metformin in the treatment of lean women with polycystic ovary syndrome.

OBJECTIVE: Oral contraceptive use might be associated with cardiometabolic risk in PCOS. We aimed to compare the effects of ethinyl estradiol-drospirenone (EE/DRSP) alone vs EE/DRSP plus metformin on clinical and cardiometabolic parameters in PCOS. DESIGN: Prospective observational study. PATIENTS: Forty-five lean patients with PCOS who received EE/DRSP (30 µg/3 mg) (n = 25) or EE/DRSP plus metformin (1700 mg/day) (n = 20) and 45 BMI-matched healthy controls. MEASUREMENT: BMI, waist-to-hip ratio (WHR), hirsutism scores, androgens, lipids, glucose and insulin levels during an OGTT were measured before and after 6 months of treatment in patients and compared to controls. RESULTS: At baseline, patients with PCOS showed similar glucose, insulin and lipids but increased 2 h glucose values compared to controls. Hirsutism scores and free androgen index decreased in both treatment groups. BMI and WHR did not show any change in the EE/DRSP group, while metformin addition resulted in a decrease in BMI. Lipid levels increased in both groups. Glucose and insulin parameters did not change in any group, but metformin addition compared to EE/DRSP alone significantly decreased waist circumference, fasting insulin and HOMA-IR. After-treatment values for both EE/DRSP alone and in combination with metformin compared to the control group showed increased 2 h glucose and increased lipids in patients with PCOS. CONCLUSION: EE/DRSP alone or in combination with metformin improves clinical and biochemical hyperandrogenism in lean PCOS. Both treatments similarly alter lipid profile. EE/DRSP alone does not affect insulin sensitivity, whereas combining EE/DRSP with metformin might improve it.

Serum resistin and high sensitive CRP levels in patients with subclinical hypothyroidism before and after L-thyroxine therapy.

BACKGROUND: Subclinical hypothyroidism (SH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) and free triiodothyronine (fT3) levels. Resistin is secreted from adipose tissue and is reported to be associated with insulin resistance and/or inflammation. High sensitive CRP (hs-CRP) is a reliable marker of inflammation. Data related to levels of resistin and hs-CRP in SH and the effect of L-thyroxine treatment on those is limited. We aimed to determine the levels of resistin and hs-CRP in women with SH, and potential effects of L-thyroxine therapy on those levels. MATERIAL AND METHODS: Thirty-six patients with SH and 27 age- and BMI-matched healthy control women were included. Waist circumference (Wc), waist-to-hip ratio (WHR), resting energy expenditure (REE), fat mass (FM) and lean mass (LM), TSH, free T4 (fT4), free T3 (fT3), total cholesterol (TC), triglycerides (TG), and HDL- and LDL-cholesterol were determined in all participants. Patients received L-thyroxine treatment for 6 months, after which all measurements were repeated. Resistin and hs-CRP levels were studied from frozen samples after the completion of the study. RESULTS: The 2 groups had similar values for Wc, WHR, FM, LM, TC, TG, HDL-C, LDL-C, resistin, and hs-CRP at the beginning. fT4 were higher, whereas TSH was lower in the control group. Resistin and hs-CRP levels did not change after treatment. hs-CRP correlated with BMI and FM before and after treatment. CONCLUSIONS: Our results suggest that achievement of euthyroid status by replacement therapy did not change resistin or hs-CRP levels in women with SH. hs-CRP correlated with parameters of obesity, which emphasizes the role of body weight in inflammation.

Effect of an oral contraceptive on emotional distress, anxiety and depression of women with polycystic ovary syndrome: a prospective study.

STUDY QUESTION: We aimed to determine the impact of an oral contraceptive (OC) treatment on health-related quality of life (HRQOL), depressive and anxiety symptoms in polycystic ovary syndrome (PCOS). SUMMARY ANSWER: OC therapy in PCOS improves hirsutism and menstrual disturbances, along with HRQOL. This improvement is not associated with any change in the prevalence of depressive and anxiety symptoms. WHAT IS KNOWN AND WHAT THIS ARTICLE ADDS: Limited data are available regarding the effects of an OC on HRQOL, and depressive and anxiety symptoms in PCOS. This study reports the effects of the ethinyl estradiol/drospirenone (EE/DRSP) OC on an HRQOL questionnaire for women with PCOS (PCOSQ), depressive and anxiety symptoms after 6 months of treatment. DESIGN: Prospective observational study. All participants completed PCOSQ, Beck Depression Inventory, Hospital Anxiety and Depression Scale and General Health Questionnaire. Serum androgens, fasting insulin, fasting and postload glucose values during an oral glucose tolerance test were measured. Changes in these variables and the scores of questionnaires were evaluated after 6 months of treatment with EE/DRSP (3 mg/30 µg). PARTICIPANTS AND SETTING: Thirty-six patients with PCOS without a previous psychiatric diagnosis were included in the study. MAIN RESULTS AND THE ROLE OF CHANCE: The main complaints of the patients were hirsutism and irregular menses. Accordingly, menstrual and hirsutism problems were the most serious concerns followed by emotional problems on the PCOSQ. Eight patients (22.2%) had clinical depression scores. After treatment, regular menstrual cycles were attained and hirsutism was significantly improved in all patients. Hirsutism and emotion domains of the PCOSQ improved at 6 months (P< 0.05 for both). Depression was improved in five of eight depressive patients and four new patients showed increased depression scores. Overall, depression, anxiety mean scores and depression rates did not show a significant change. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The study is subject to the strengths and limitations of observational study design. A limitation of our study is the small sample size and lack of data related to possible confounding factors. GENERALIZABILITY TO OTHER POPULATIONS: Generalizable to Caucasian PCOS.

Depression, anxiety and cardiometabolic risk in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with psychological and metabolic disturbances. The aim of this study was to determine whether depression, anxiety and reduced health-related quality of life (HRQOL) are more common in women with PCOS and associated with metabolic risk. METHODS: The study included 226 PCOS patients and 85 BMI-matched healthy control women. All participants completed standardized questionnaires assessing depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory) and both depression and anxiety (Hospital Anxiety and Depression Scale and General Health Questionnaire). Patients also completed a PCOS HRQOL questionnaire. Hirsutism scores, serum androgens and lipids were obtained. All subjects underwent a standard oral glucose tolerance test. RESULTS: 28.6% of PCOS women versus 4.7% of control women had clinical depression scores indicating an 8.1-fold increased risk of depression in PCOS (P < 0.001). Depression and anxiety scores were higher in PCOS women than controls (P < 0.01 for all subscales). Obese PCOS subjects had higher depression scores and rates than non-obese PCOS women (P < 0.05). Depression scores were significantly correlated with insulin resistance and lipid parameters and with the number of components comprising the metabolic syndrome. Menstrual and hirsutism problems were the most serious concerns followed by emotional problems on the HRQOL. CONCLUSIONS: Depression and anxiety are more common in patients with PCOS compared with healthy women. Depression in PCOS might be associated with obesity and metabolic abnormalities including insulin resistance and dyslipidemia.

Dynamics of Nampt/visfatin and high molecular weight adiponectin in response to oral glucose load in obese and lean women.

BACKGROUND: High molecular weight adiponectin (HMWA) is the active circulating form of adiponectin. Nampt/visfatin is the enzyme secreted from adipocytes in an active form and is one of the putative regulators of insulin secretion. OBJECTIVE: To investigate the dynamics of total adiponectin (TA), HMWA and Nampt/visfatin in obese and lean women during oral glucose tolerance test (OGTT). METHODS: We studied normal glucose-tolerant (NGT), age-matched, 30 obese and 30 lean women. All subjects underwent a standard 75 g, 2-h OGTT, and area under the curve (AUC) during OGTT for glucose, insulin, Nampt/visfatin, TA and HMWA was calculated. Body fat mass was assessed by bioimpedance analysis. Results Obese women had significantly higher basal and AUC values for insulin and Nampt/visfatin, whereas basal and AUC-HMWA were significantly lower in this group. Alternatively, obese and lean groups had similar basal and AUC values for glucose and TA. Basal insulin levels were negatively correlated with HMWA levels, but not with basal Nampt/visfatin. AUC-insulin was correlated positively with AUC-visfatin, and negatively with AUC-HMWA. Total and truncal body fat mass showed positive correlation with basal and AUC-visfatin, and negative correlation with basal and AUC-HMWA. CONCLUSION: In the NGT state, obese women have higher Nampt/visfatin and lower HMWA levels, both basally and in response to oral glucose challenge. The dynamics of Nampt/visfatin and HMWA during OGTT appear to be linked with insulin and adiposity. Counter-regulatory adaptations in HMWA and Nampt/visfatin might have an impact on suggested adipoinsular axis, contributing to maintenance of normal glucose tolerance.

Visfatin and retinol-binding protein 4 concentrations in lean, glucose-tolerant women with PCOS.

Since insulin resistance is accepted to be a common feature of polycystic ovary syndrome (PCOS), the exact molecular mechanism(s) involved in glucose and lipid metabolism have been under investigation in the syndrome. Recently, two novel adipokines, namely visfatin and retinol-binding protein 4 (RBP4), have been suggested to play a role in insulin resistance and diabetes. This study sought to determine whether plasma concentrations of visfatin and RBP4 are altered in PCOS by comparing a total of 27 lean, normal glucose-tolerant PCOS patients with 19 age- and body mass index-matched healthy controls. The mean plasma visfatin concentrations were higher in PCOS patients than those in healthy subjects (37.9+/-18.2 versus 19.8+/-17.5, P<0.01), while RBP4 concentrations were similar between the two. Both adipokines were correlated with each other in the whole (r=0.50, P<0.01) and in PCOS (r=0.52, P<0.01) groups but not in controls. The results suggest that lean, glucose-tolerant women with PCOS have increased circulating visfatin and unaltered RBP4 concentrations compared with healthy lean women. In order to clarify overlapping effects and their potential contribution to the pathophysiology of PCOS, further studies are needed.

Molecular diagnosis and clinical characterization of pseudohypoparathyroidism type-Ib in a patient with mild Albright's hereditary osteodystrophy-like features, epileptic seizures, and defective renal handling of uric acid.

We describe a patient who presented with epileptic seizures unresponsive to anticonvulsive treatment. Laboratory investigations demonstrated epileptiform seizure activity in the brain but also revealed severe hypocalcemia, hyperphosphatemia, and elevated serum parathyroid hormone. In addition, the patient showed a reduced serum level of 25-[OH]-vitamin D. The diagnosis of pseudohypoparathyroidism type-Ib (PHP-Ib) was made based on these clinical findings and upon identification of a 3-kb deletion within the STX16 locus, a genetic defect frequently associated with autosomal dominant PHP-Ib. This mutation was also present in the patient's unaffected mother and her affected sister. Despite the molecular diagnosis of PHP-Ib, which is characterized by parathyroid hormone resistance in the absence of Albright's hereditary osteodystrophy (AHO), the patient had a round face, slightly short stature, and short fourth metacarpals, which were consistent with mild AHO. The patient and her affected sister, who lacked AHO-like features, showed reduced serum levels of uric acid and increased fractional excretion of uric acid, a finding that was reported only once previously for PHP-Ib. Unlike the previous report, the fractional uric acid excretion and serum uric acid levels returned to normal in our patient and her sister after 3 months of treatment period. These findings underscore several important points with respect to the pathogenesis and clinical presentation of PHP-Ib. Furthermore, the findings in the index case present interesting novel aspects, including a previously undescribed coexistence of the 3-kb STX16 deletion and AHO-like features and a clinical course complicated by concomitant 25-[OH]-vitamin D deficiency, which may have resulted, at least partly, from long-term use of antiepileptic drugs.

Predictive ability of fasting plasma glucose for a diabetic 2-h postload glucose value in oral glucose tolerance test: spectrum effect.

The performance of diagnostic tests may vary according to patient characteristics. The aim of this study is to find out the factors, if any, that may affect the performance of fasting plasma glucose (FPG) to predict a diabetic 2-h postload glucose level (> or =200 mg/dl) in oral glucose tolerance test (OGTT). One hundred ninety-six patients with known risk factors for diabetes mellitus to whom OGTT was applied were included. Factors that may have an effect on the performance of FPG in prediction of a diabetic value in OGTT were determined by using logistic regression and likelihood ratios (LRs). The cutoff of FPG predicting a 2-h postload glucose of > or =200 mg/dl was calculated by receiver operating characteristic curve as 110 mg/dl (sensitivity, 76.7%; specificity, 75.9%). Waist-to-hip ratio (WHR) and body mass index (BMI) influenced sensitivity, whereas age, family history, and presence of hyperlipidemia affected specificity of FPG. Significant factors for positive LR were age and hyperlipidemia, whereas sex, smoking, hyperlipidemia, physical inactivity, WHR, and BMI influenced negative LR. Fasting plasma glucose performance as a diagnostic test can be affected by many factors that are clearly stated as risk factors for diabetes mellitus. These data emphasize how the interpretation of a diagnostic test varies as the patient characteristics vary; the criteria that we confidently rely on may not be that reliable, changing between just two different patients.

Thrombin-activatable fibrinolysis inhibitor activity and global fibrinolytic capacity in Type 1 diabetes: evidence for normal fibrinolytic state.

Hypofibrinolysis is a state that is commonly observed in type 2 diabetic patients, a finding also possibly related to obesity and insulin resistance. There is little information, however, regarding the status of fibrinolytic system in Type 1 diabetes, in particular as reflected by thrombin-activatable fibrinolysis inhibitor (TAFI) activity and global fibrinolytic capacity (GFC). To provide information in this respect, 30 Type 1 diabetic patients (median age=16) and 28 healthy controls (median age=14) were enrolled in this study. The median duration of diabetes was 7 years, and median HbA(1c) was 8.85% (range: 5.5-11.9%) in the diabetic group. None of the patients had macrovascular complications. Microvascular complications were present in a total of eight patients (nephropathy: n=5; retinopathy: n=3). A comparison of the TAFI activity between the patient (median 84.9, range: 71.5-103.3%) and the control groups (median=83.3, range: 63.7-97.4%) yielded no statistically significant difference (P=.950). Similarly, GFC was comparable between the two groups (median=8.22, range: 0.72-22.38 microg/ml, and median=13.32, range: 3.0-23.22 microg/ml, respectively, in the diabetic and control groups, P=.086). TAFI activity did not significantly correlate with age, albumin excretion, fasting plasma glucose, HbA(1c), D-dimer, and fibrinogen by Spearman rank correlation test. There was as a significant inverse correlation between GFC and TAFI activity (r=-.414, P=.006). Contrary to the previous observations in Type 2 diabetes, our data suggest that fibrinolytic activity is not adversely affected by Type 1 diabetes, and it has no relationship with the degree of metabolic control.

Vitamin D status and seasonal changes in plasma concentrations of 25-hydroxyvitamin D in office workers in Ankara, Turkey.

BACKGROUND: Lack of sun exposure is one of the primary causes of epidemic vitamin D deficiency worldwide. The aim of this study was to investigate vitamin D status and seasonal changes in summer and winter in office workers. METHODS: This study was conducted in Ankara located at 39° 52' 30" N, 32° 52' E. The study consisted of 118 premenopausal women and men aged between 21 and 52 years-old. Seasonal changes were evaluated in August and February. Fasting serum was obtained for intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D (25OHD). Additional data were collected by a questionnaire that enquired about age, weight, height, wearing style, dietary calcium intake and sunlight exposure. Serum 25OHD concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a 25OHD concentration less than 30 ng/mL. RESULTS: Mean serum 25OHD concentration in summer was 28.4±10.4 ng/mL and 13.8±6.6 ng/mL in winter (p<0.001). 35.6% of the subjects were vitamin D insufficient in summer and 12.7% in winter (p<0.001) while 31.5% were vitamin D deficient in summer and 83.9% in winter (p<0.001). A significant increase in iPTH levels (33.1±15.9 pg/mL vs 49.6±24.3 pg/mL, p<0.001) was observed throughout the seasonal change. No significant association was found between 25OHD levels and iPTH, body mass index, age and sun exposure index (p>0.05 for all) in both seasons. CONCLUSION: Vitamin D deficiency is very prevalent in office workers even in summer time and this should be accepted as a public health problem.

Effects of L-thyroxine therapy on circulating leptin and adiponectin levels in subclinical hypothyroidism: a prospective study.

Subclinical hypothyroidism (SCH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) levels. Controversial data are available regarding the effects of SCH on adipose tissue. Adiponectin and leptin are two major adipokines secreted from adipose tissue. We aimed to determine the levels of adiponectin and leptin in women with SCH and potential effects of L-thyroxine therapy on those levels. Forty three women with SCH and 53 age- and BMI-matched healthy euthyroid control women were included. Adiponectin and leptin levels, total cholesterol (TC), triglycerides (TG), HDL-, and LDL cholesterol, fat mass (FM) and fat-free mass (FFM) were determined in all participants. Patients received L-thyroxine treatment for 6 months after which all measurements were repeated. Patients with SCH and controls had similar baseline values for adiponectin, leptin, lipids, FM and FFM. All patients reached euthyroid status after 6 months of replacement therapy. Treatment resulted in an increase in adiponectin (p <0.01) and a decrease in leptin levels (p <0.05). Lipid levels, FM and FFM did not show a significant change. Achievement of euthyroid status by replacement therapy increases adiponectin and decreases leptin levels in women with SCH in this prospective study independent of a change in body fat mass.

Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome.

BACKGROUND: Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women. METHODS: The study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured. RESULTS: T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p < 0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p < 0.05). All subphenotypes had similar basal and AUC values for cortisol. CONCLUSION: PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype.

Increased circulating soluble P-selectin in polycystic ovary syndrome.

OBJECTIVE: To determine whether the P-selectin-von Willebrand factor (vWF) pathway is altered in patients with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING(S): Tertiary care academic medical center. PATIENT(S): Thirty-two normal glucose-tolerant patients with PCOS and 21 age- and body mass index-matched healthy women were prospectively enrolled. All the patients with PCOS had clinical and/or biochemical hyperandrogenism and chronic oligoanovulation, and 89% had polycystic ovaries on ultrasound. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Soluble P-selectin (sP-selectin), vWF, total T, sex hormone-binding globulin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, fasting glucose and insulin, 2-hour glucose, and homeostatic model assessment-insulin resistance. RESULT(S): Soluble P-selectin levels were significantly higher in patients with PCOS compared with controls (58.7 +/- 19.0 vs. 45.3 +/- 15.0 ng/mL), whereas PCOS and control groups had similar vWF levels (46.7 +/- 24.2 vs. 39.5 +/- 22.3, respectively). There was no correlation between sP-selectin and anthropometric measurements or any of the androgen, lipid, or insulin resistance parameters. CONCLUSION(S): Our results suggest increments in the circulating sP-selectin concentrations associated with unaltered vWF levels in PCOS. Increased sP-selectin might potentially contribute to the future risk of cardiovascular disease in patients with PCOS.

Evaluation of subclinical coronary atherosclerosis in mild asymptomatic primary hyperparathyroidism patients.

OBJECTIVE: Although there is sufficient data supporting the increased cardiovascular risk in patients with advanced stage of primary hyperparathyroidism (pHPT), it is not clear whether same is valid for patients with subclinical forms of this disease. In this study we aimed to evaluate coronary atherosclerosis burden of asymptomatic pHPT patients by using tomographic coronary calcification scoring. PATIENTS AND METHODS: Thirty-one mild asymptomatic pHPT patients (28 female, 3 male; mean age: 54.4 +/- 12.1 years) and 19 gender- and age-matched normotensive healthy controls (17 female, 2 male; mean age: 50.6 +/- 5.8) constituted our study population. Asymptomatic pHPT patients were subdivided according to presence of hypertension (19 hypertensive and 12 non-hypertensive patients). All subjects in study population underwent tomographic coronary calcification scoring by using 16-multidetector computed tomography (16-MDCT). RESULTS: Median tomographic coronary calcification score was comparable between the whole group of pHPT patients [0.0 (Interquartile Range, IQR:18.70] and the controls [0.0 (IQR: 0.90). Median tomographic coronary calcification scores of pHPT patients with hypertension was 0.90 (IQR: 75.0) HU, whereas no calcification was noted in coronary arteries of normotensive pHPT patients. Calcification scores of hypertensive pHPT patients were significantly higher than both normotensive pHPT patients (P = 0.014) and controls (P = 0.046). There was no significant difference regarding calcification scores of normotensive pHPT patients versus controls. In the binary logistic regression model, only the presence of hyperlipidemia was found to be independently associated with presence of calcification on coronary arteries (relative risk 6.56, 95% CI 1.18-36.56, P = 0.032). CONCLUSION: These results suggest that mild asymptomatic pHPT with serum calcium levels in the high-normal range does not constitute an independent risk factor for coronary atherosclerosis. The combined presence of classic cardiovascular risk factors determines the severity of coronary atherosclerosis in these patients.

The Genetic Basis of the Polycystic Ovary Syndrome: A Literature Review Including Discussion of PPAR-gamma.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the women of reproductive age. Familial clustering of PCOS has been consistently reported suggesting that genetic factors play a role in the development of the syndrome although PCOS cases do not exhibit a clear pattern of Mendelian inheritance. It is now well established that PCOS represents a complex trait similar to type-2 diabetes and obesity, and that both inherited and environmental factors contribute to the PCOS pathogenesis. A large number of functional candidate genes have been tested for association or linkage with PCOS phenotypes with more negative than positive findings. Lack of universally accepted diagnostic criteria, difficulties in the assignment of male phenotype, obscurity in the mode of inheritance, and particularly small sample size of the study populations appear to be major limitations for the genetic studies of PCOS. In the near future, utilizing the genome-wide scan approach and the HapMap project will provide a stronger potential for the genetic analysis of the syndrome.