Ayla Harmanci

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.

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 patients unaffected mother and her affected sister. Despite the molecular diagnosis of PHP-Ib, which is characterized by parathyroid hormone resistance in the absence of Albrights 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.

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

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.

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.

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.

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

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.

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.

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

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.

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/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.

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.