Investigation and management of abnormal uterine bleeding in reproductive-aged women: a descriptive review of national and international recommendations.

PURPOSE: To review and compare the most recently published recommendations on the investigation and management of abnormal uterine bleeding (AUB). MATERIALS AND METHODS: A descriptive review of recommendations from the American College of Obstetricians and Gynaecologists (ACOG), the National Institute for Health and Care Excellence (NICE), the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC) and the International Federation of Gynaecology and Obstetrics (FIGO) on AUB in reproductive-aged women was carried out. RESULTS: There is a consensus that detailed personal and family history along with physical examination are essential in the investigation of menstrual, intermenstrual or postcoital AUB. All the medical societies recommend transvaginal ultrasound as the first-line imaging modality to determine the AUB cause. Moreover, they agree (except for RANZCOG) that, in women with AUB, endometrial biopsy should only be performed if additional risk factors for endometrial cancer are present. Laboratory tests may be helpful in the AUB investigation; however, there are several discrepancies among the recommendations. Regarding AUB management, NICE, ACOG and SOGC agree that the administration of hormonal or non-hormonal medications should be the first-line treatment modality in bleeding disorders and absent or minor structural pelvic pathology. Surgical management should be preferred in cases of identified polyps, large fibroids or unsuccessful pharmacological treatment. CONCLUSIONS: Since AUB affects a significant proportion of reproductive-aged women, the main objective is to improve the quality of life of these patients without missing cases of malignancy.

Common features and differences of the hypothalamic-pituitary-gonadal axis in male and female.

Male and female reproductive axis, comprised of hypothalamus, pituitary and gonads, present common features and differences, discussed in this review. These include the way hypothalamus regulates pituitary function, and the way pituitary, in turn, affects gonadal function. Finally, age plays an important role in axis regulation, in both genders.

Serum vaspin levels in women with and without gestational diabetes mellitus during pregnancy and postpartum.

Although vaspin is regarded an insulin-sensitizing adipokine, its role in gestational diabetes mellitus (GDM) is currently unknown. We aimed to evaluate serum vaspin levels and their correlation with insulin resistance in women with and without GDM. Forty-four women with GDM [GDM Group - 20 managed with diet only (GDM-diet) and 24 with diet plus insulin (GDM-insulin)] and 44 age-matched pregnant women with normal glucose tolerance (Control Group) were studied. Serum glucose, lipids, uric acid, insulin and vaspin were measured at the 2nd and 3rd trimester of pregnancy and postpartum. The quantitative insulin sensitivity check index (QUICKI) and homeostasis model of assessment-insulin resistance (HOMA-IR) were calculated. Circulating vaspin levels decreased significantly postpartum in all groups (p<0.001), but did not differ between GDM or GDM Subgroups and Control Group in any time point. At the 3rd trimester of pregnancy vaspin was positively correlated to insulin (p=0.022), HOMA-IR (p=0.016) and triglycerides (p=0.033) and negatively correlated to QUICKI (p=0.016) in the GDM women, but not in the Controls. These correlations were not observed at the 2nd trimester or postpartum. Vaspin, in contrast to HOMA-IR, could not independently predict GDM in binary logistic regression. In patients with GDM, insulin treatment did not affect vaspin levels. In conclusion, our data suggest that vaspin levels gradually decrease from the 2nd trimester to postpartum; however, decreases are similar between women with or without GDM. Serum vaspin cannot independently predict GDM and it is not affected by the degree of glucose metabolism deregulation or the exogenous administration of insulin.

Diagnosis and Management of Osteoporosis: A Comprehensive Review of Guidelines.

Importance: Osteoporosis causes increased morbidity and mortality, and thus poses a significant economic burden to the health systems worldwide. Objective: The aim of this study was to review and compare the most recently published major guidelines on diagnosis and management of this common medical entity. Evidence Acquisition: A thorough comparative review of the most influential guidelines from the RACGP (Royal Australian College of General Practitioners), the ESCEO-IOF (European Society for Clinical and Economic Aspects of Osteoporosis-International Osteoporosis Foundation), the NOGG (National Osteoporosis Guideline Group), the NAMS (North American Menopause Society), the ES (Endocrine Society), and the ACOG (American College of Obstetricians and Gynecologists) was conducted. Results: The reviewed guidelines generally agree on the definition, the criteria, and investigations used to diagnose osteoporosis. They also concur regarding the risk factors for osteoporosis and the suggested lifestyle modifications (calcium and vitamin D intake, normal body weight, reduction of alcohol consumption, and smoking cessation). However, there is lack of consensus on indications for fracture risk assessment in the general population and the exact indications for bone mineral density assessment. Referral to a bone specialist is reserved for complex cases of osteoporosis (NOGG, NAMS, and ACOG) or in case of inadequate access to care (RACGP). The use of hip protectors to reduce the risk of fractures is supported by RACGP, NOGG, and NAMS, solely for high-risk elderly patients in residential care settings. All guidelines reviewed recognize the efficacy of the pharmacologic agents (ie, bisphosphonates, denosumab, hormone therapy, and parathyroid hormone analogs). Nonetheless, recommendations regarding monitoring of pharmacotherapy differ, primarily in the case of bisphosphonates. The proposed intervals of repeat bone mineral density testing after initiation of drug therapy are set at 2 years (RACGP), 1-3 years (NAMS, ES, and ACOG), or 3-5 years (ESCEO-IOF and NOGG). All guidelines agree upon the restricted use of bone turnover markers only in bone specialist centers for treatment monitoring purposes. Finally, the definition of treatment failure varies among the reviewed guidelines. Conclusions: Osteoporosis is a distressing condition for women, mainly those of postmenopausal age. Thus, it seems of paramount importance to develop consistent international practice protocols for more cost-effective diagnostic and management techniques, in order to improve women's quality of life.

Management of pregestational diabetes mellitus: a comparison of guidelines.

BACKGROUND: Pregestational diabetes is associated with adverse maternal and neonatal outcomes. The aim of this study was to summarize and compare evidence-based recommendations on pregestational diabetes and to focus especially on issues related to the management of this entity. MATERIALS AND METHODS: A descriptive review of three recently published national guidelines on pregestational diabetes was conducted: the American Diabetes Association on "Diabetes in Pregnancy: Standards of Medical Care in Diabetes - 2019," the National Institute for Health and Care Excellence on "Diabetes in pregnancy: management from preconception to the postnatal period" and the American College of Obstetricians and Gynecologists on "Pregestational Diabetes Mellitus." These guidelines were compared according to recommendations on management, during the preconception, antenatal, intrapartum and postpartum period. RESULTS: There were many similar recommendations regarding the preconception counseling, the antepartum assessment by specialists, the glycemic control target levels, the pharmacologic treatment and the postpartum period among the three guidelines. On the other hand, the American Diabetes Association makes no recommendations regarding fetal monitoring and obstetric management during pregnancy and the intrapartum period, while there are several similarities between the other two guidelines. CONCLUSIONS: The adoption of an international consensus based on evidence - based guidelines will increase the awareness of the healthcare professionals on the management of pregestational diabetes, leading that way to more favorable perinatal outcomes.

Thyroid Disease in Pregnancy: A Descriptive Review of Guidelines.

IMPORTANCE: Thyroid disorders represent one of the most frequent complications of pregnancy associated with adverse obstetric, fetal, and neonatal outcomes, especially in case of delayed diagnosis and suboptimal management. OBJECTIVE: The aim of this study was to review and compare the recommendations of the most recently published guidelines on the diagnosis and management of these common conditions. EVIDENCE ACQUISITION: A descriptive review of guidelines from the Endocrine Society, the European Thyroid Association, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, the American Thyroid Association, and the American College of Obstetricians and Gynecologists on thyroid disease in pregnancy was carried out. RESULTS: There is an overall consensus regarding the diagnosis of overt and subclinical hypothyroidism and hyperthyroidism in pregnancy using the pregnancy-specific reference ranges and the definition of postpartum thyroiditis. The reviewed guidelines unanimously discourage universal screening for thyroid function abnormalities before and during pregnancy and support targeted screening of high-risk patients by measuring serum thyroid-stimulating hormone levels. Moreover, they all highlight the need of treating overt hypothyroidism and hyperthyroidism, not only during pregnancy, but also before conception, suggesting similar management policies and treatment targets. There is also agreement regarding the management of gestational transient hyperthyroidism with hyperemesis gravidarum, suspected fetal thyrotoxicosis, postpartum thyroiditis, and thyroid malignancy. Scanning or treating with radioactive iodine is contraindicated during pregnancy and breastfeeding. On the other hand, there is controversy on the management of subclinical thyroid disease, thyroid function surveillance protocols, and iodine nutrition recommendations. Of note, the American College of Obstetricians and Gynecologists makes some specific recommendations on the treatment of thyroid storm and thyrotoxic heart failure in pregnant women, whereas the American Thyroid Association makes a special reference to the management of women with thyroid cancer. CONCLUSIONS: As the disorders of the thyroid gland affect a significant proportion of pregnant women, it is of paramount importance to develop uniform international evidence-based protocols for their accurate diagnosis and optimal management, in order to safely guide clinical practice and eventually improve perinatal outcomes.

Apelin levels in normal pregnancy.

OBJECTIVE: Apelin is an adipokine secreted from adipose and other tissues with increased expression in obesity, role in glucose metabolism and atherosclerosis, as well as in oxidative stress. Pregnancy is considered a state of hyperlipidemia, oxidative stress and decreased insulin sensitivity. The aim of the present study is to investigate the levels of apelin in human pregnancy and its relation to insulin sensitivity. PATIENTS AND MEASUREMENTS: One hundred and six pregnant women (24th-28th week of gestation), aged 27·9 ± 0·4 years, were compared to 106 age-matched healthy, nonpregnant women (controls). Measured parameters included serum levels of glucose, insulin, apelin, adiponectin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), triglycerides and oxidized LDL (ox-LDL). The body mass index (BMI) and the quantitative insulin sensitivity check index (QUICKI) were calculated as well. RESULTS: BMI, serum lipids and insulin levels were significantly higher, whereas serum apelin and glucose levels were lower in the pregnancy group compared to the control group. There was a significant negative correlation between apelin and adiponectin, in both groups. Additionally, apelin was negatively correlated with ox-LDL and HDL-cholesterol in the pregnancy group. CONCLUSIONS: Although strongly correlated with adiponectin, apelin cannot be used as a marker of insulin sensitivity, but it could serve as a marker of oxidative stress in pregnancy.

A case report of subacute thyroiditis during pregnancy: difficulties in differential diagnosis and changes in cytokine levels.

INTRODUCTION: Thyroid dysfunction during pregnancy may result in both maternal and neonatal complications. Subacute thyroiditis (SAT) is an extremely rare cause of both hyper- and hypothyroidism in pregnant women. CASE DESCRIPTION: A case of first trimester SAT is presented. Diagnosis of SAT was based on fine-needle aspiration biopsy. The disease resolved spontaneously without need for prednisone administration but a hypothyroid phase treated with T4 throughout pregnancy occurred. The pregnancy resulted in a healthy full term infant. We measured various cytokine levels in an attempt to follow their course during SAT as well as throughout the remaining period of pregnancy. Serum thyreoglobulin (Tg) levels correlated best with thyroid function tests (TFTs) and the course of SAT. CONCLUSIONS: The diagnosis of SAT at a pregnancy setting may be intriguing. The measurement of circulating cytokines is not helpful in the differential diagnosis or monitoring of the disease.

Oxidized low-density lipoprotein and adiponectin levels in pregnancy.

INTRODUCTION: The aim of the present study was to investigate whether normal pregnancy represents a complex state of oxidative stress, inflammation and insulin resistance. SUBJECTS AND METHODS: One hundred and six pregnant women, between 24th and 28th week of pregnancy (age 27.9 ± 0.4 years) (study group) and one hundred and six age-matched, healthy, non-pregnant women (control group) participated in the study. Serum levels of glucose, insulin, adiponectin, oxidized LDL (oxLDL) and lipid parameters, i.e. total cholesterol (TC), triglycerides (TG), HDL and LDL, were determined. Body mass index (BMI) and QUantitative Insulin sensitivity ChecK Index (QUICKI) were also calculated. RESULTS: Pregnant women presented higher BMI values, insulin and oxLDL serum levels and lower glucose serum levels than controls. Serum levels of lipids (TC, TG, LDL and HDL) were higher in pregnant women. There was a significant positive correlation of oxLDL to adiponectin (p < 0.01) in the study group, but not in the controls, and no other significant correlation with any of the other parameters, in either of groups. CONCLUSIONS: Pregnancy is a state of insulin resistance, oxidative stress and pro-atherogenic hyperlipidemia. Adiponectin may, though, have cardioprotective role in pregnant women.

Diagnosis and Management of Gestational Diabetes Mellitus: An Overview of National and International Guidelines.

IMPORTANCE: Gestational diabetes mellitus (GDM) represents one of the most frequent complications of pregnancy and is associated with increased maternal and neonatal morbidity. Its incidence is rising, mostly due to an increase in maternal age and maternal obesity rate. OBJECTIVE: The aim of this study was to review and compare the recommendations of the most recently published guidelines on the diagnosis and management of this condition. EVIDENCE ACQUISITION: A descriptive review of guidelines from the National Institute for Health and Care Excellence (NICE), the International Federation of Gynecology and Obstetrics, the Australasian Diabetes in Pregnancy Society (ADIPS), the Society of Obstetricians and Gynecologists of Canada (SOGC), the American College of Obstetricians and Gynecologists (ACOG), the American Diabetes Association, and the Endocrine Society on gestational diabetes mellitus was carried out. RESULTS: The NICE guideline recommends targeted screening only for women with risk factors, whereas the International Federation of Gynecology and Obstetrics, ADIPS, SOGC, and the ACOG recommend screening for all pregnant women at 24 to 28 weeks of gestation in order to diagnose and effectively manage GDM; they also state that women with additional risk factors should be screened earlier (ie, in the first trimester) and retested at 24 to 28 weeks, if the initial test is negative. These guidelines describe similar risk factors for GDM and suggest the same thresholds for the diagnosis of GDM when using a 75-g 2-hour oral glucose tolerance test. Of note, the NICE only assesses the fasting and the 2-hour postprandial glucose levels for the diagnosis of GDM. Moreover, the SOGC and the ACOG do not recommend this test as the optimal screening method. The Endocrine Society alone, on the other hand, recommends the universal testing of all pregnant women for diabetes before 13 weeks of gestation or as soon as they attend the antenatal service and retesting at 24 to 28 weeks if the initial results are normal. In addition, there is a general consensus on the appropriate ultrasound surveillance of pregnancies complicated with GDM, and all the medical societies, except the ADIPS, recommend self-monitoring of capillary glucose to assess the glycemic control and set the same targets for fasting and postprandial glucose levels. There is also agreement that lifestyle modifications should be the first-line treatment; however, the reviewed guidelines disagree on the medical management of GDM. In addition, there are controversies regarding the timing of delivery, the utility of hemoglobin A1c measurement, and the postpartum and lifelong screening for persistent hyperglycemia and type 2 diabetes. However, all the guidelines state that all women in pregnancies complicated by GDM should undergo a glycemic test at around 6 to 12 weeks after delivery. Finally, there is a universal consensus on the importance of breastfeeding and preconception screening before future pregnancies. CONCLUSIONS: As GDM is an increasingly common complication of pregnancy, it is of paramount importance that inconsistencies between national and international guidelines should encourage research to resolve the issues of controversy and allow uniform international protocols for the diagnosis and management of GDM, in order to safely guide clinical practice and subsequently improve perinatal and maternal outcomes.

Clinical practice guidelines on diabetes mellitus and pregnancy: ΙI. Gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disease of pregnancy and is associated with several perinatal complications. GDM is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation. In Europe, in 2016, the prevalence of GDM was estimated to be 5.4% (3.8-7.8). It varied depending on maternal age, year of data collection, country, area of Europe, week of gestation at testing, and diagnostic criteria. The Hellenic Endocrine Society and the Hellenic Society of Maternal-Fetal Medicine commissioned an expert group to construct national guidelines on "Diabetes mellitus and pregnancy: Gestational diabetes mellitus." Following a search for the best available evidence and critical appraisal of the results, the writing group generated a series of consensus recommendations regarding screening tests for the general population, monitoring and management, fetal monitoring, management of preterm labor, planning of labor and delivery, puerperium and breastfeeding, and long-term follow-up of GDM.

Clinical practice guidelines on diabetes mellitus and pregnancy: Ι. Pre-existing type 1 and type 2 diabetes mellitus.

Women with type 1 (T1DM) or type 2 diabetes (T2DM) diagnosed prior to pregnancy are classified as having pre-existing diabetes mellitus (DM). The prevalence of hyperglycemia in pregnancy has been estimated at 17% globally and 5.4% in Europe, differences existing among racial and ethnic groups, following the prevalence of type 2 diabetes. Only a minority (approximately 15%) of the cases of diabetes during pregnancy represent women with pre-existing diabetes. Because of the rising prevalence of obesity and limited screening for diabetes in young women, there has been, globally, an increase in the diagnosis of previously unknown overt diabetes early in pregnancy; these women should be treated as women with pre-existing diabetes, as they may already have unrecognized complications (e.g., nephropathy and retinopathy). The Hellenic Endocrine Society and the Hellenic Society of Maternal-Fetal Medicine commissioned an expert group to construct national guidelines on "Diabetes mellitus and pregnancy: Pre-existing type 1 and 2 diabetes mellitus". Following a search for the best available evidence and critical appraisal of the search results, the writing group generated a series of consensus recommendations regarding preconception counseling and care, care during pregnancy, and care after the pregnancy in cases of pre-existing T1DM and T2DM.

Serum thyrotropin concentration as a biochemical predictor of thyroid malignancy in patients presenting with thyroid nodules.

PURPOSE: Serum thyrotropin (TSH) is a well-established growth factor for thyroid nodules and suppression of TSH concentrations by administering exogenous thyroxine may interfere with the growth of established nodules as well as the formation of new thyroid nodules. The aim of this study was to investigate whether serum TSH at presentation is a predictor of thyroid malignancy in patients with thyroid nodules. METHODS: A total of 565 patients without overt thyroid dysfunction, who presented with palpable thyroid nodule(s) between 1988 and 2004 and underwent at least one fine-needle aspiration biopsy, were retrospectively evaluated. RESULTS: The final diagnostic outcome was established after surgery (n = 122) or after a minimum of 1-year clinical follow-up period. Higher rates of malignancy were observed in patients with serum TSH in the upper tertile of the normal range (P = 0.026). Binary logistic regression analysis revealed significantly increased adjusted odds ratios for the diagnosis of malignancy in patients with serum TSH 1.5-4.0 mIU/l when compared to those with either TSH 0.4-0.8 mIU/l (P = 0.005) or TSH 0.9-1.4 mIU/l (P = 0.007). CONCLUSIONS: The risk of malignancy in thyroid nodules increases in parallel with TSH concentrations within the normal range. TSH concentration at presentation is an independent predictor of thyroid malignancy.

Oxidised low-density lipoprotein concentration - early marker of an altered lipid metabolism in young women with PCOS.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk for cardiovascular diseases. This study examined the variations in oxidised low-density lipoprotein (OxLDL) concentration in relation to insulin levels in young women with PCOS. DESIGN: Cross-sectional clinical study in tertiary cares research hospitals. A total of 179 women with PCOS (79 overweight) and 56 age- and body mass index-matched controls were examined. METHODS: Blood samples were collected in follicular phase of the cycle for the basal glucose, total-, high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol, OxLDL, triglycerides, apolipoprotein-A1 (Apo-A1) and B (Apo-B), lipoprotein (a), insulin, testosterone and sex hormone-binding globulin (SHBG). Homeostatic model index (HOMA) and free androgen index (FAI) were determined. RESULTS: Overweight and normal weight women with PCOS had higher concentrations of OxLDL than their control counterparts (P = 0.007 and 0.003 respectively). Both the basal insulin (P = 0.003) and HOMA values (P < 0.001) were significantly higher in overweight than normal weight patients. Testosterone and FAI were higher in patients than in the respective controls (P < 0.001). The only independent predictor of increased OxLDL concentration in normal weight patients was Apo-B-to-Apo-A1 ratio (P < 0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 2.3-16.4), while in obese PCOS, it was total cholesterol-to-high-density lipoprotein cholesterol ratio (P < 0.001, OR 2.8; 95% CI 1.6-4.9). CONCLUSION: Young normal weight and overweight PCOS women have similarly increased OxLDL levels. Our results may indicate the presence of primary alteration in lipid metabolism in patients with PCOS. To answer the question whether the alteration in LDL particle size can by itself pose a higher cardiovascular risk, a careful follow-up of these women is needed.

Creatine phosphokinase in ectopic pregnancy revisited: significant diagnostic value of its MB and MM isoenzyme fractions.

OBJECTIVE: Although evidence on elevated creatine phosphokinase (CPK) as a tool for the diagnosis of ectopic pregnancy (EP) is rather conflictive, no previous study on CPK isoenzyme levels and their relative ratio was found in the literature. STUDY DESIGN: Forty women with EP, 20 with intrauterine (IU) abortive gestation, and 20 regular pregnant women (controls) were studied. Serum total CPK, CPK-MB, and CPK-MM levels were measured at the time of presentation and 24 hours after surgery. Relative operating characteristic (ROC) curves were plotted. RESULTS: Women with EP had significantly higher CPK concentrations and a significantly decreased CPK-MB relative ratio (CPK-MB%), compared with both women with IU abortive pregnancy and controls. The ROC curves demonstrated a significant discriminatory ability of both increased total CPK and decreased CPK-MB% ratio for the diagnosis of EP. CONCLUSION: Determination of CPK isoenzyme fractions can significantly enhance the diagnostic value of total maternal CPK in the prediction of ectopic pregnancy.

Receiver operator characteristics and diagnostic value of progesterone and CA-125 in the prediction of ectopic and abortive intrauterine gestations.

OBJECTIVE: The study was designed to investigate the predictive value of progesterone and CA-125 in the diagnosis of ectopic pregnancy (EP) and inevitable miscarriage. METHODS: Forty women with EP, 20 with intrauterine (IU) abortive gestation and 20 regular pregnant women (controls) were studied. IU abortive and EP were confirmed and treated by surgery. Serum progesterone and CA-125 levels were measured at the time of presentation and 24h after surgery. RESULTS: Women with EP had significantly lower progesterone concentrations, compared to both women with IU abortive pregnancy and controls. Women with IU abortion had significantly higher CA-125 levels, compared to the other two groups. When using a progesterone concentration of less than 10.75 ng/ml as a cut-point for the diagnosis of EP, sensitivity, specificity, positive and negative predictive values were 85%. When using CA-125 concentration of more than 41.9 U/ml as a threshold for the diagnosis of IU abortive pregnancy, sensitivity was 80%, specificity 87%, the positive predictive value was 66% and the negative predictive value 93%. CONCLUSION: The measurement of progesterone and CA-125 levels is useful in discriminating ectopic and intrauterine abortive from normal gestations.

Indices of insulin sensitivity, beta cell function and serum proinsulin levels in the polycystic ovary syndrome.

BACKGROUND: The study aim was to investigate the relationship between insulin resistance (IR), beta-cell function (betaF), hyperandrogenism and proinsulin levels during an oral glucose tolerance test (OGTT) in women with polycystic ovary syndrome (PCOS). METHODS: One hundred and twenty-six selected women were classified as follows: PCOS, BMI > 25 kg/m2 (n = 39); PCOS, BMI < 25 kg/m2 (n = 54); controls, BMI > 25 kg/m2 (n = 14); controls, BMI < 25 kg/m2 (n = 19). Blood samples were collected between the third and sixth day of a spontaneous menstrual cycle, at 9:00 a.m., after an overnight fast. Serum levels of FSH, LH, PRL, 17alpha-OH-progesterone, SHBG, testosterone, delta4-androstenedione, insulin, proinsulin and glucose were measured. A 75 g OGTT was performed, and concentrations of glucose, insulin and proinsulin were also measured at t = 30, 60, 90, and 120 min. RESULTS: The markers of insulin secretion and the AUC for proinsulin were higher in obese and overweight women and in women with PCOS, respectively. The AUC for proinsulin was positively correlated with markers of IR, betaF and androgen levels. An inverse relationship between PI/I values and indices of IR and betaF was observed. CONCLUSIONS: Increased proinsulin levels reflect, most probably, insulin resistance, which is the key disorder in PCOS-associated metabolic abnormalities. Beta-cell function, pre-proinsulin mRNA processing and proinsulin conversion to insulin could be initially increased as a result of IR. An interaction between circulating proinsulin and androgen biosynthesis or action might also exist.

The involvement of uric acid in the pathogenesis of preeclampsia.

Preeclampsia is a common disorder of human pregnancy and a major cause of worldwide pregnancy-related maternal and neonatal morbidity and mortality. Oxidative stress, angiogenic imbalance, placental ischemia and an inflammatory response have been proposed to play role in the pathogenesis of the disease. Hyperuricemia is a key biochemical feature in preeclampsia with elevated levels of uric acid being diagnosed as early as the 10(th) week of gestation. Traditionally, elevated uric acid levels were considered a result of renal dysfunction known to exist in preeclampsia. The contribution of uric acid in the pathogenesis of preeclampsia is being recently further investigated. We, hereby, review the possible mechanisms by which uric acid contributes to the development of the disease and its complications both on mother and fetus.

Differential effects of unopposed versus opposed hormone therapy, tibolone, and raloxifene on substance p levels.

OBJECTIVE: To evaluate the effects of unopposed therapy (conjugated equine estrogens [CEE]) vs. opposed therapy (CEE and medroxyprogesterone acetate), tibolone, and raloxifene on serum substance p levels. DESIGN: Clinical study. SETTING: University hospital. PATIENT(S): One hundred eight postmenopausal women were assigned to four treatment groups: unopposed hormone therapy (HT) (n = 30), opposed HT (n = 48), tibolone (n = 18), and raloxifene (n = 12). INTERVENTION(S): Conjugated equine estrogens, CEE and medroxyprogesterone acetate, tibolone, and raloxifene were administered orally; blood samples were collected before therapy and 3 months after. MAIN OUTCOME MEASURE(S): Serum substance p levels were measured before and at the end of the third month of the treatment.The serum substance p levels were increased in the unopposed HT group after treatment. On the contrary, substance p levels were decreased in the opposed HT group, in the tibolone group, and in the raloxifene group. CONCLUSION(S): Addition of progesterone (P) to estrogen (E) treatment significantly decreases serum substance p levels. Tibolone and raloxifene exert the same effect.

A polymorphism in the resistin gene promoter is associated with body mass index in women with polycystic ovary syndrome.

Resistin does not appear to be a major gene predisposing to polycystic ovary syndrome (PCOS). However, an association of a resistin variant with body mass index was found in women with PCOS, suggesting that resistin may be related to adiposity in PCOS.