Hypogonadism and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD), recently proposed to be renamed to metabolic dysfunction-associated steatotic liver disease (MASLD), is a major global public health concern, affecting approximately 25-30% of the adult population and possibly leading to cirrhosis, hepatocellular carcinoma, and liver transplantation. The liver is involved in the actions of sex steroids via their hepatic metabolism and production of the sex hormone-binding globulin (SHBG). Liver disease, including NAFLD, is associated with reproductive dysfunction in men and women, and the prevalence of NAFLD in patients with hypogonadism is considerable. A wide spectrum of possible pathophysiological mechanisms linking NAFLD and male/female hypogonadism has been investigated. As therapies targeting NAFLD may impact hypogonadism in men and women, and vice versa, treatments of the latter may affect NAFLD, and an insight into their pathophysiological pathways is imperative. This paper aims to elucidate the complex association between NAFLD and hypogonadism in men and women and discuss the therapeutic options and their impact on both conditions.

Nonalcoholic fatty liver disease in males with low testosterone concentrations.

AIMS: There are limited clinical data on the association between serum testosterone concentrations and nonalcoholic fatty liver disease (NAFLD) in men. The main aim of this study was to evaluate the association between testosterone concentrations and NAFLD in adult men, in terms of noninvasive indices of NAFLD and hepatic fibrosis. METHODS: In this cross-sectional study, 98 men were recruited on an outpatient basis and were divided into low-testosterone (<12 nmol/l or <346 ng/dl, n = 37) or high-testosterone groups (≥12 nmol/l or ≥346 ng/dl, n = 61). Serum testosterone concentrations were measured by immuno-chemiluminescence. Hepatic steatosis index (HSI) and Triglyceride-to-HDL-C ratio (THR), as non-invasive indices of NAFLD, as well as AST-to-Platelet Ratio Index (APRI), fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), as non-invasive indices of hepatic fibrosis, were calculated based on standard formulas. RESULTS: Both the non-invasive indices of NAFLD (HSI and THR) were higher in low-testosterone compared with high-testosterone group (HSI: 47.5 ± 2.9 vs. 38.4 ± 1.0, p = 0.005; THR: 1.70 ± 0.16 vs. 0.98 ± 0.07, p < 0.001). On the contrary, none of the non-invasive indices of hepatic fibrosis was different between groups. HSI (p = 0.038), but not THR, remained inversely independently associated with serum testosterone, after adjustment for potential confounders, including sex hormone-binding globulin. CONCLUSIONS: Men with low testosterone concentrations have higher non-invasive indices of NAFLD (HSI and THR), but not of hepatic fibrosis (APRI, FIB-4, NFS), compared with counterparts of high testosterone concentrations. HSI was inversely and independently associated with testosterone concentrations.

The effect of excess body fat on female and male reproduction.

The dramatic increase in the prevalence of obesity coincides with a decline in reproductive health indices in both sexes. Energy excess mediates changes to the regulatory mechanisms of the reproductive system. Obese individuals exhibit increased estrogen concentrations, due to the overexpression of aromatase in the adipose tissue; via a negative feedback loop, men present with symptoms of hypogonadotropic hypogonadism. These hormonal changes, along with increased oxidative stress, lipotoxicity and disturbances in the concentrations of adipokines, directly affect the gonads, peripheral reproductive organs and the embryo. Clinical evidence is somewhat contradicting, with only some studies advocating worse semen parameters, increased incidence of erectile dysfunction, increased doses of ovulation induction medications, and worse live birth rates in assisted reproductive technology (ART) cycles in obese individuals compared with those of normal weight. Similar conclusions are drawn about patients with insulin resistance syndromes, namely polycystic ovary syndrome (PCOS). As far as treatment options are concerned, lifestyle changes, medical therapy and bariatric surgery may improve the reproductive outcome, although the evidence remains inconclusive. In this review, we summarize the evidence on the association of obesity and reproductive health on both the molecular and the clinical level, and the effect of weight-loss interventions on reproductive potential.

Evidence for a manifold role of selenium in infertility.

This review aimed to assess the evidence from observational and interventional studies in humans and animals regarding the role of selenium (Se) in male and female infertility. As oxidative stress can seriously impair male, and possibly also female, reproductive functions, it can be speculated that the antioxidant properties of Se could constitute one of the pathways by which this element is involved in fertility. Specifically, there are strong indications that Se influences the growth, maturation, and replication of oocytes, though the precise mechanisms have not as yet been fully elucidated. Given that it is not clear at present which tissue sample (blood, serum, seminal plasma, sperm, or follicular fluid) renders the most accurate picture of Se concentration in terms of its role in reproduction, the data are still insufficient to recommend routine assessment of Se status in men and women seeking fertility. Nevertheless, the existing evidence, despite being of limited quantity and somewhat low quality, suggests that Se supplementation (< 200 µg/d) is possibly beneficial in men through its improvement of sperm motility. Well-designed, randomized control studies are needed to reveal the seemingly diverse protective/positive role of Se supplementation in men and women seeking fertility treatment.

Insulin Secretion and Resistance in Normoglycemic Patients with Sickle Cell Disease.

Diabetes mellitus has been described in chronic hemolytic anemias, but data are scarce regarding glucose metabolism in normoglycemic patients. To address this issue, we evaluated insulin sensitivity and secretion in patients with sickle cell disease (SCD) and normal oral glucose tolerance test (OGTT). Forty-five adult patients with homozygous sickle cell disease and Hb S/ß-thalassemia (ß-thal) (mean age 42.5 ± 9.5 years) and 45 healthy individuals matched for age and body mass index (BMI) were included in the study. All participants underwent an oral glucose tolerance test (OGTT) after an overnight fast. All patients had normal OGTT. Fasting glucose values did not differ significantly between groups, however, fasting insulin levels were significantly lower in the patient group compared to the control group (5.1 ± 2.7 µUI/mL vs. 11.3 ± 6.6 µUI/mL, p <0.005, respectively). Pancreatic ß-cell insulin secretion index in the fasting state was significantly lower in patients with sickle cell disease compared with controls as assessed by calculations of the homeostatic model assessment for ß-cell function (HOMA ß%) (77.0 vs. 106.0%, respectively, p <0.001), while HOMA insulin resistance (HOMA IR), was lower in the sickle cell disease patients, albeit not statistically significant (0.8 vs. 1.1, respectively, p = 0.054). The HOMA ß% was significantly correlated with ferritin levels (r = -526, p <0.001) (negative correlation) and with 25-hydroxy (OH)-vitamin D levels (r = 0.479, p <0.001) (positive correlation), even when adjusted for serum ferritin levels. Normoglycemic patients with sickle cell disease demonstrated impaired ß-cell function with reduced insulin secretion even before OGTT was impaired.

Laparoscopic Cystectomy In-a-Bag of an Intact Cyst: Is It Feasible and Spillage-Free After All?

This prospective study was conducted to assess the feasibility of laparoscopic cystectomy of an intact adnexal cyst performed inside a water proof endoscopic bag, aiming to avoid intraperitoneal spillage in case of cyst rupture. 102 patients were recruited. Two of them were pregnant. In 8 of the patients the lesions were bilateral, adding up to a total of 110 cysts involved in our study. The endoscopic sac did not rupture in any case. Mean diameter of the cysts was 5.7 cm (range: 2.3-10.5 cm). In 75/110 (68.2%) cases, cystectomy was completed without rupture, whereas in the remaining 35/110 (31.8%) cases the cyst ruptured. Minimal small spillage occurred despite every effort only in 8/110 (7.2%) cases with large (>8 cm) cystic teratomas. There were no intraoperative or postoperative complications. We concluded that laparoscopic cystectomy in-a-bag of an intact cyst is feasible and oncologically safe for cystic tumors with a diameter < 8 cm. Manipulation of larger tumors with the adnexa into the sac may be more difficult, and in such cases previous puncture and evacuation of the cyst contents should be considered.

Patient With Severe Hyponatremia Caused by Adrenal Insufficiency Due to Ectopic Posterior Pituitary Lobe and Miscommunication Between Hypothalamus and Pituitary: A Case Report.

Hyponatremia may be one of the clinical manifestations of adrenal insufficiency (AI) and during the diagnostic workup of hyponatremic patients investigation of AI should be included.We report the case of an 82-year-old patient who was admitted to our hospital with clinical symptoms and laboratory findings of hyponatremia. Following the diagnostic algorithm of hyponatremia we reached the diagnosis of AI. Clinician's attention must focus on the underlying cause of AI which in this case was hidden in a miscommunication between hypothalamus and pituitary due to an ectopic posterior pituitary lobe and became apparent by a pituitary magnetic resonance imaging (MRI) scan. Treatment with oral hydrocortisone resulted in full clinical recovery and electrolyte balance, which was maintained after 7 months of follow-up.Secondary AI is related with hyponatremia through increased ADH secretion. Although a hyponatremic episode may be the first presentation of AI, clinical suspicion is of high importance in order to place the right diagnosis. Disruption of communication between hypothalamus and pituitary is a rare but considerable cause of AI.

Somatostatin Analogue Treatment of a TSH-Secreting Adenoma Presenting With Accelerated Bone Metabolism and a Pericardial Effusion: A Case Report.

Increased bone turnover and other less frequent comorbidities of hyperthyroidism, such as heart failure, have only rarely been reported in association with central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma (TSHoma). Treatment is highly empirical and relies on eliminating the tumor and the hyperthyroid state.We report here an unusual case of a 39-year-old man who was initially admitted for management of pleuritic chest pain and fever of unknown origin. Diagnostic work up confirmed pericarditis and pleural effusion both refractory to treatment. The patient had a previous history of persistently elevated levels of alkaline phosphatase (ALP), indicative of increased bone turnover. He had also initially been treated with thyroxine supplementation due to elevated TSH levels. During the diagnostic process a TSHoma was revealed. Thyroxine was discontinued, and resection of the pituitary tumor followed by treatment with a somatostatin analog led to complete recession of the effusions, normalization of ALP, and shrinkage of pituitary tumor.Accelerated bone metabolism and pericardial and pleural effusions attributed to a TSHoma may resolve after successful treatment of the tumor. The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with these rare pituitary adenomas.

Maternal age demographic trends in Greece from 1980 to 2008.

OBJECTIVE: To identify maternal age trends in Greece over a 29-year period from 1980 to 2008. STUDY DESIGN: Data concerning live births after 24 gestational weeks was collected from the Hellenic Vital Statistics records and analyzed. Mothers were categorized into age groups. Data was further sorted according to birth in urban or non-urban areas, and the relative contribution of each group was estimated. RESULTS: In contrast to 1980, when the most prevalent maternal age group was 20-24 years, in 1990 the prevalent maternal age group was 25-29 years. In 2008 the prevalent maternal age group shifted to 30-34 years of age. Adolescent births do not pose a major problem in Greece and present a steadily declining trend throughout the years studied. Urban population exhibited an earlier and more intense shift towards older maternal ages. Demand for assisted reproductive technology methods showed an increase among women > or = 40 years of age. CONCLUSION: Maternal age patterns in Greece over the past 3 decades are described. The differences in birth patterns in women giving birth in urban areas are identified and compared to birth patterns in the rest of the country. The adolescent pregnancy rate in Greece was found to be very low.

Preterm birth trends in Greece, 1980-2008: a rising concern.

OBJECTIVE: To identify preterm birth trends in Greece. DESIGN: Retrospective epidemiological study. SETTING: Women giving birth in Greece from 1980 to 2008. POPULATION: Live births beyond the 24th gestational week. METHODS: Data acquisition from the Hellenic Vital Statistics records. Statistical analysis of preterm birth rate among neonates estimated for each year. MAIN OUTCOME MEASURES: Total number of births and preterm births, as well as rate of preterm birth by gestational week. Stillbirth rates by gestational age. RESULTS: 3 218 463 births occurred during the period under study, 151 594 (4.7%) of which were preterm. A steep rise in preterm births was noted during the final years of the study, reaching 9.6% in 2008. This was mainly due to the "late preterm" sub-group (34(+0) -36(+6) gestational weeks). The rates of stillbirth fell in a constant way regardless of the maturity index. CONCLUSIONS: Although preterm birth etiology is multifactorial, the selective rise in the "late preterm" group possibly was due to an increase in medical reasons necessitating a preterm delivery, changes in obstetric practice, or both. Further studies are needed to estimate the precise effect of each contributing factor.

Can isosorbide mononitrate be useful in second trimester termination of pregnancies?

BACKGROUND: Isosorbide mononitrate (IMN) administration is thought to enhance in the cervical ripening process. We sought to identify the clinical usefulness and safety of IMN administration for shortening the time to termination of the second trimester pregnancy procedures when used in addition to misoprostol. STUDY DESIGN: Women were randomly selected to receive either the standard misoprostol treatment (control group) or, additionally, receive vaginally IMN as well as the misoprostol treatment. RESULTS: The mean induction to complete abortion interval was 20.4 h [95% confidence interval (CI)=16.63-24.17] in the misoprostol group compared with 12.4 h (95% CI=10.33-14.47) in the misoprostol plus IMN group. This difference was statistically significant (p<.05). In the subgroups of nulliparas and multiparas, the shortening effect of the IMN was also statistically significant. CONCLUSIONS: A net benefit after the combined use of IMN and misoprostol was noted. Therefore, we believe that IMN has a clinical role in the ripening process.

Polycystic ovary syndrome: double click and right check. What do patients learn from the Internet about PCOS?

OBJECTIVE: To identify the websites most visited by patients regarding polycystic ovary syndrome (PCOS), and to evaluate the quality of information provided by these websites. STUDY DESIGN: We sought data regarding the popularity of sites providing information about PCOS regardless of the way the visitors reached the site. We then scrutinized the top sites for predefined quality check points to evaluate the quality of information provided, including Health on Net Foundation (HON) accreditation. Finally, we searched for the expansion of these sites in social networks (Facebook and Twitter). RESULTS: Of the top 15 sites, 8 were HONcode certified. The mean performance of content presence for all sites was 7.33 (min=4, max=10, SD=1.633). There was a moderate correlation of higher performance score with HON accreditation (R: 0.535, p<0.05). Several sites have expanded in social media. None of the high-score sites has a page dedicated to PCOS. CONCLUSIONS: There exists a lack of HON accreditation in many sites and a wide variability in the quality of the information provided. In some cases, key elements of content, necessary for complete appreciation of PCOS, are missing. Official and high authority healthcare organisms should introduce themselves in the social media world.

Optimum mode of delivery in gestations complicated by preterm premature rupture of the membranes.

OBJECTIVES: To provide evidence about the preferable mode of delivery, vaginal (VD) or caesarean section (CS), in PPROM. METHODS: A retrospective study of 190 cases. Survival analysis was used to identify statistically significant differences in mortality rates. RESULTS: A total of 126 pregnancies were included in our study. Mean gestational age of rupture was 28(+0) weeks (min = 15, max = 36(+4), sd = 5.796). Mean birth age was 30(+0) weeks (min = 15, max = 37(+2), sd = 5.353). CS was performed in 55 cases (43.7%), VD in 71 cases (56.3%). Data analysis showed that, regardless of presentation, there was a statistically significant benefit on survival in favor of the CS in births below 30 gestational weeks (n = 39, nCS = 18, nND = 21, χ(2) = 7.946, p = 0.005). Hazard ratio estimation set the critical gestational age at 28 weeks. For vaginal deliveries, breech presentation was associated with inferior survival outcome compared to vertex (nTotal = 71; nVertex = 63, nBreech = 8, χ(2) = 13.012, p < 0.001.Also in breech presentation, VD survival outcome was inferior to CS (nTotal = 9; nVD = 6, nCS = 3, χ(2) = 5.145, p < 0.05). CONCLUSIONS: According to our results, in cases of PPROM, CS was beneficial below 28 weeks and in breech presentation below 30 weeks.

Preterm birth seasonality in Greece: an epidemiological study.

OBJECTIVE: Seasonality of preterm birth has been noted, although not conclusively studied. Weather is also thought to play a role. We sought preterm birth seasonality and additionally studied the effect of weather parameters in the preterm birth pattern. METHODS: Vital statistics from the Hellenic Statistical Authority were retrieved, covering the years from 1980 to 2008. Additionally, weather data were retrieved for the years of the study. Time series analysis was used to create various statistical models that would be compared to each other for their accuracy to predict preterm birth. Factors used in the modeling included month of birth, gender and weather factors. RESULTS: Preterm birth seasonality was exhibited. Two peaks of higher risk of preterm birth were noted: One during summer and one during winter. Males were more influenced by seasonality and exhibited slightly different seasonal patterns than females, although no higher risk for preterm birth was noted. The best model that described seasonal pattern of preterm birth was the one that included meteorological factors. Notably, extreme (hotter or colder) weather was accompanied by an increase in preterm birth. CONCLUSIONS: Evidence for seasonality of preterm birth was shown and extreme weather was associated with a higher incidence of it.

Effects of leptin on the expression of fatty acid-binding proteins in human placental cell cultures.

The present study aimed to evaluate the protein expression of the transmembrane translocase FAT/CD36 and cytoplasmic H-FABP and L-FABP in human trophoblast tissue and evaluate the effects of exogenous leptin upon differential expression of each biomolecule; consequently, it aimed to derive information regarding the effects of leptin upon the expression of proteins implicated in fatty acid metabolism. Protein and total RNA were isolated from 72 samples of trophoblast tissue obtained from chorionic villous sampling. Of these, 36 samples were evaluated for protein (supernatant and pellet fraction separated) and the other 36 for total RNA expression. For each subgroup of samples, 12 were treated immediately and 24 were cultured. Half of the cultured samples were treated with 10 ng/-ml exogenously added leptin and the other half were untreated. Western blotting and PCR techniques were used for the evaluation of biomolecule expression. Our results were obtained from samples at a mean gestational week of 12+5 (n=72; min, 11+0; max, 14+1 gw; SD,0.89). In promptly treated samples we observed the presence of FAT/|CD36 protein and absence of cytoplasmic FABPs. In the latter, only mRNA transcription of H-FABP was noted. A cytoplasmic pool of FAT/CD36 was also noted in the supernatant fraction of proteins. For cultured samples, when leptin was added, a statistically significant increase in FAT/CD36 protein expression was observed (n=24, p<0.001; mean difference, 0.219; SD, 0.0315; CI, -0.284 to -0.154). In our study we demonstrated the protein and mRNA expression of biomolecules implicated in fatty acid metabolism in human placenta. A cytoplasmic pool of the transmembrane protein FAT/CD36 was noted. Leptin caused the increase in FAT/CD36 protein expression in the cultured samples. Therefore, we conclude that leptin has an immediate effect and plays a role in lipid metabolism in human placenta.

Gitelman syndrome-associated severe hypokalemia and hypomagnesemia: case report and review of the literature.

We report a case of a woman with Gitelman syndrome who presented to our hospital mainly due to hyperemesis. Following her admission, intravenous potassium and magnesium supplementation was commenced to counter the observed hypokalemia and hypomagnesemia. Hyperemesis receded and although serum potassium remained low, she became asymptomatic. Oral potassium and magnesium supplementation was administered throughout pregnancy and biweekly ion level measurements were scheduled. Despite the intensive replacement, ion levels remained constantly low. She delivered at 38 weeks with an elective caesarean section because of a breech presentation, a healthy female baby weighing 3350 g. Neonatal electrolyte profile was normal.