Decline In Serum Research Articles

Association between serum 25-hydroxyvitamin D and glycated hemoglobin levels in type 2 diabetes patients with chronic kidney disease.

Aims/IntroductionVitamin D is suggested to influence glucose homeostasis. An inverse relationship between serum 25‐hydroxyvitamin D (25[OH]D) and glycemic control in non‐chronic kidney disease (CKD) patients with type 2 diabetes was reported. We aimed to examine this association among type 2 diabetes patients with CKD.Materials and MethodsA total of 100 type 2 diabetes participants with stage 3–4 CKD were recruited. Blood for glycated hemoglobin (HbA1c), serum 25(OH)D, renal and lipid profiles were drawn at enrollment. Correlation and regression analyses were carried out to assess the relationship of serum 25(OH)D, HbA1c and other metabolic traits.ResultsA total of 30, 42, and 28% of participants were in CKD stage 3a, 3b and 4, respectively. The proportions of participants based on ethnicity were 51% Malay, 24% Chinese and 25% Indian. The mean (±SD) age and body mass index were 60.5 ± 9.0 years and 28.3 ± 5.9 kg/m2, whereas mean HbA1c and serum 25(OH)D were 7.9 ± 1.6% and 37.1 ± 22.2 nmol/L. HbA1c was negatively correlated with serum 25(OH)D (r s = −0.314, P = 0.002), but positively correlated with body mass index (r s = 0.272, P = 0.006) and serum low‐density lipoprotein cholesterol (P = 0.006). There was a significant negative correlation between serum 25(OH)D and total daily dose of insulin prescribed (r s = −0.257, P = 0.042). Regression analyses showed that every 10‐nmol/L decline in serum 25(OH)D was associated with a 0.2% increase in HbA1c.ConclusionsLower serum 25(OH)D was associated with poorer glycemic control and higher insulin use among multi‐ethnic Asians with type 2 diabetes and stage 3–4 CKD.

Longitudinal changes in serum 25-hydroxyvitamin D in the Dallas Heart Study.

While the prevalence of vitamin D deficiency is well described in various populations, limited data are available regarding longitudinal variation in serum 25-hydroxyvitamin D concentrations. To evaluate the temporal trends in serum 25(OH)D, prevalence of vitamin D deficiency and factors influencing these trends. Adults enrolled in the Dallas Heart Study, a longitudinal, probability-based, multiethnic, population study in Dallas, Texas, USA. Prevalence of vitamin D deficiency and predictors of change in serum 25(OH)D. A total of 2045 participants had serum 25(OH)D measured on two occasions (2000-2002 and 2007-2009) at a median interval of 7years. Serum 25(OH)D decreased (42.7-39.4nmol/L, P<.001) and the prevalence of vitamin D deficiency [25(OH)D <50nmol/L] increased significantly (60.6%-66.4%, P<.0001) despite vitamin D supplementation increasing over the interval (7.2%-23.0%; P<.0001). In a multivariable model adjusting for sex, race, BMI, age, season of blood draw, smoking and exercise, a greater decline in serum 25(OH)D was noted in men compared with women (-8.0 vs -3.5nmol/L, P<.0001), in participants of Hispanic ethnicity vs White and Black ethnicity (P<.0001), in nonobese vs obese participants (-7.2 vs -4.0nmol/L, P=.005) and in nonusers vs users of vitamin D supplements (-5.7 vs -1.7nmol/L, P=.032). Despite increased vitamin D supplementation, serum 25(OH)D decreased in an ethnically diverse cohort of Dallas County residents between 2000-2002 and 2007-2009. Features most predictive of a decline in serum 25(OH)D include male sex, Hispanic ethnicity and weight gain.

Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy.

Legalon SIL (SIL) is a chemically hydrophilized version of silibinin, an extract of milk thistle (Silybum marianum) seeds that has exhibited hepatoprotective and antiviral effectiveness against hepatitis C virus (HCV) in patients leading to viral clearance in combination with ribavirin. To elucidate the incompletely understood mode of action of SIL against HCV, mathematical modelling of HCV kinetics and human hepatocyte gene expression studies were performed in uPA-SCID-chimeric mice with humanized livers. Chronically HCV-infected mice (n = 15) were treated for 14 days with daily intravenous SIL at 469, 265 or 61.5 mg/kg. Serum HCV and human albumin (hAlb) were measured frequently, and liver HCV RNA was analysed at days 3 and 14. Microarray analysis of human hepatocyte gene expression was performed at days 0, 3 and 14 of treatment. While hAlb remained constant, a biphasic viral decline in serum was observed consisting of a rapid 1st phase followed by a second slower phase (or plateau with the two lower SIL dosings). SIL effectiveness in blocking viral production was similar among dosing groups (median ε = 77%). However, the rate of HCV-infected hepatocyte decline, δ, was dose-dependent. Intracellular HCV RNA levels correlated (r = 0.66, P = 0.01) with serum HCV RNA. Pathway analysis revealed increased anti-inflammatory and antiproliferative gene expression in human hepatocytes in SIL-treated mice. The results suggest that SIL could lead to a continuous second-phase viral decline, that is potentially viral clearance, in the absence of adaptive immune response along with increased anti-inflammatory and antiproliferative gene expression in human hepatocytes.

Maintenance of Serum Ionized Calcium during Exercise Attenuates the Exercise-Related Increase in Bone Resorption

Exercise is recommended to build or maintain bone mass, but there is evidence that vigorous or prolonged exercise is associated with bone loss under certain conditions. It is our contention that disruptions in calcium homeostasis during exercise lead to increases in parathyroid hormone (PTH) and bone resorption. PURPOSE: To determine if preventing the decline in serum ionized calcium (iCa) during exercise attenuates the increases in PTH and a marker of bone resorption (carboxy-terminal collagen crosslinks (CTX)). METHODS: Healthy, cycling-trained men (n=11, aged 18-45y) underwent two identical one-hour cycling bouts at ~75% VO2peak under conditions of calcium gluconate versus half-normal saline infusion. Blood was sampled every 5 minutes to adjust the calcium infusion rate, with a goal to maintain serum iCa at ~0.2 mg/dL above baseline. The same infusion protocol was replicated under the saline condition. Blood samples to assess PTH, CTX, bone formation (procollagen type 1 amino procollagen (P1NP)), and total calcium (tCa) were taken every 15 minutes during exercise and hourly for 4 hours post-exercise. RESULTS: Serum iCa was successfully maintained above baseline during Ca infusion and was significantly different from the saline condition during exercise (all time points p<0.01). Compared to saline, the Ca infusion markedly reduced the increase in serum PTH during exercise (p=0.004) and the suppression of PTH persisted throughout the 4-hour recovery period (all p<0.01). Similarly, the increase in CTX during exercise was suppressed with Ca infusion (p=0.003) and remained below the saline condition through recovery (all p<0.001). tCa was also a significantly higher during exercise (p<0.001) with Ca infusion, but values were similar during recovery (all p>0.10). There were no differences between conditions for P1NP at any time points (all p>0.10). CONCLUSIONS: The increase in bone resorption was attenuated when the exercise-related decline in serum iCa was prevented, suggesting a calcium-dependent relationship. There was no effect of Ca infusion on P1NP, but the duration of post-exercise sampling may have been too short to capture any changes. The results are limited to young, trained, men during cycling exercise. Future research should investigate sex- and age-differences and other exercise modalities.

Temporal Changes in Androgens and Estrogens Are Associated With All-Cause and Cause-Specific Mortality in Older Men.

The dynamic temporal relationship between changes in serum reproductive hormones and mortality in men has not been reported. The objective of the study was to examine the relationship between progressive changes in circulating reproductive hormones over time with all-cause and cause-specific mortality in older men. Community-dwelling men aged 70 years and older from the Concord Health and Ageing in Men Project study were assessed at baseline (2005-2007, n = 1705) and at 2-year (n = 1367) and 5-year follow-up (n = 958). At all three time-points, T, DHT, estradiol (E2), and estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, and SHBG, LH, and FSH were determined by immunoassay and calculated free T (cFT) was calculated. Mortality was ascertained through the state death registry. Statistical modeling was by general estimating equations with the Poisson regression. Serum T over time (relative risk [RR] per 1 SD decrease in concentration: 1.18, 95% confidence interval [CI] 1.05-1.32), DHT (RR 1.17, 95% CI 1.05-1.32), and E2 (RR 1.46, 95% CI 1.30-1.63) as well as cFT (RR 1.27, 95% CI 1.13-1.41) was associated with all-cause mortality. After adjusting for multiple covariables, the decline in serum T (RR 1.17, 95% CI 1.03-1.32), DHT (RR 1.17, 95% CI 1.03-1.32), and cFT (RR 1.13, 95% CI 1.08-1.19) remained significantly associated with all-cause mortality. Similar relationships were observed for cancer but not cardiovascular mortality. Progressive decline in serum E2 levels remained significantly associated with all-cause (RR 1.49, 95% CI 1.31-1.69), cancer (RR 1.82, 95% CI 1.45-2.28), and cardiovascular (RR 1.37, 95% CI 1.13-1.66) mortality, even after adjustment for covariables. Serum E1, LH, FSH, and SHBG were not associated with all-cause, cancer, or cardiovascular mortality. Dynamic temporal changes in serum T, cFT, DHT, and E2 (but not E1, LH, FSH, and SHBG) in older men are associated with all-cause and cause-specific mortality in distinct patterns.

Circulating Growth Differentiation Factor 11/8 Levels Decline With Age

Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart. We validated our previous finding that circulating levels of GDF11/8 decline with age in mice, rats, horses, and sheep. Furthermore, we showed by Western analysis that the apparent age-dependent increase in GDF11 levels, as reported by Egerman et al, is attributable to cross-reactivity of the anti-GDF11 antibody with immunoglobulin, which is known to increase with age. GDF11 administration in mice rapidly activated SMAD2 and SMAD3 signaling in myocardium in vivo and decreased cardiac mass in both young (2-month-old) and old (22-month-old) mice in a dose-dependent manner after only 9 days. Our study confirms an age-dependent decline in serum GDF11/8 levels in multiple mammalian species and that exogenous GDF11 rapidly activates SMAD signaling and reduces cardiomyocyte size. Unraveling the molecular basis for the age-dependent decline in GDF11/8 could yield insight into age-dependent cardiac pathologies.

Impact of endometriomas and their removal on ovarian reserve.

The effect of endometrioma on ovulatory function and ovarian reserve was unclear. Conflicting opinions exist regarding effect of endometrioma excision on ovarian reserve. Endometriomas do not seem to affect ovulatory function. Women with endometrioma have lower antral follicle count and serum anti-Müllerian hormone levels than age-matched healthy controls. There is high-quality evidence suggesting a significant decline in serum anti-Müllerian hormone levels following endometrioma excision. However, a similarly significant decline in antral follicle count is not demonstrated. Cauterization seems to be a contributing factor to ovarian damage and suturing the cyst bed could perhaps be a better alternative. It seems prudent to warn patients regarding loss of ovarian reserve following endometrioma excision. Surgeons should cautiously limit the use of cauterization following stripping of endometrioma. Well designed studies comparing effect of various haemostatic measures on ovarian reserve are needed.

Longitudinal Relationships between Reproductive Hormones and Cognitive Decline in Older Men: The Concord Health and Ageing in Men Project.

The longitudinal relationship between declining levels of reproductive hormones and cognitive function remains unclear in older men. The objective of this study was to examine the temporal relationship between changes in major reproductive hormone levels and cognitive decline over time. Men age 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) were assessed at baseline (2005-2007; n = 1705), 2-year followup (2007-2009; n = 1367), and 5-year followup (2010-2013; n = 958). At all assessments, T, dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, and SHBG, LH, and FSH by immunoassay. Dementia was diagnosed at baseline by clinical assessment and review by a specialist panel. Cognitive function was measured at all three assessments by the Mini Mental State Examination. None of the baseline reproductive hormones predicted cognitive decline in men without dementia over 5 years. However, the change in serum hormones over time was associated with cognitive decline. In univariate analysis, change in all the studied hormones, except for E2, was significantly associated with cognitive decline. However, in multivariate-adjusted models accounting for potential confounders, only change in serum T (β = 0.067), DHT (β = 0.394), calculated free T (β = 0.005), and E1 (β = 0.009) remained significantly associated (P < .05) with cognitive decline. Men who had dementia at baseline had significantly greater decline in serum T levels, but not in other studied hormones, over the 5 years. Our findings show that decline in androgen status is associated with cognitive decline in older men, but the causality of this association requires further elucidation.

The clinical observation of methotrexate under hysteroscopy by tubal cavity injection with Huayu shapei prescription in the treatment of tubal pregnancy

Objective To explore the clinical effects of injecting methotrexate with hysteroscopic tubal cannulation combined with Huayu shapei prescription in the treatment of salpingocyesis. Methods 82 unruptured salpingocyesis patients were randomly divided into the two groups.41 patients in the observation group were treated by hysteroscopic tubal cannulation injection of methotrexate combined with Huayu shapei prescription,41 patients in the control group were treated by methotrexate intramuscular injection with oral mifepristone.The clinical efficacy of the two groups were observed, the level of serum β HCG required for tubal pregnancy, the mass absorption and after treatment of tubal patency. Results Compared with the control group, the difference was significant of the decline of serum β HCG in the treatment group(t= 2.67,P< 0.05). Compared with the control group, the treatment effectiveness and the absorption of the mass in fallopian tube in the treatment group, the difference was significant(t= 3.57,P< 0.05). Tubal patency detected treated group was superior compared with the control group, the difference was significant(χ2= 100.23,P<0.05). Conclusion Compared with traditional treatments, injecting methotrexate with hysteroscopic tubal cannulation combined with Huayu shapei prescription in the treatment of salpingocyesis can effectively reduce the HCG levels, promote the absorption and softening of the ectopic pregnancy mass, to achieve the purpose of killing embryos eliminate micro, it will help to improve patients with clinical symptoms and signs, to maximize the recovery of the patient's reproductive function and physical health. Key words: Uteroscop; Prescription salpingocyesis; Methotrexate; Huayu shapei

The longitudinal relationship of sexual function and androgen status in older men: the Concord Health and Ageing in Men Project.

It is unclear whether declining sexual function in older men is a cause or consequence of reduced androgen status. Longitudinal associations were examined between reproductive hormones and sexual function in older men. Men aged 70 years and older from the Concord Health and Ageing in Men Project study were assessed at baseline (n = 1705) and 2-year follow-up (n = 1367), with a total of 1226 men included in the final analyses. At both visits, serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, and SHBG, LH, and FSH were measured by immunoassay. Sexual functions (erectile function, sexual activity, and sexual desire) were self-reported via standardized questions. In longitudinal analyses, although baseline hormones (T, DHT, E2, and E1) did not predict decline in sexual function, the decline in serum T (but not DHT, E2, or E1) over 2 years was strongly related to the change in sexual activity and desire (but not erectile function). For each 1-SD decrease in T from baseline to 2-year follow-up, there was a multivariate-adjusted odds ratio of 1.23 (95% confidence interval, 1.12-1.36) for an additional risk of further decline in sexual activity. However, the magnitude of the decrease in serum T was strikingly small (<10%). Similar associations were found for changes over 2 years in serum T and decline in sexual desire, but not for erectile function. We found a consistent association among older men followed over 2 years between the decline in sexual activity and desire, but not in erectile function, with a decrease in serum T. Although these observational findings cannot determine causality, the small magnitude of the decrease in serum T raises the hypothesis that reduced sexual function may reduce serum T rather than the reverse.

Metformin induces a prompt decrease in LH-stimulated testosterone response in women with PCOS independent of its insulin-sensitizing effects.

BackgroundThe use of insulin-sensitizing drugs has been shown to improve both the reproductive and the metabolic aspects of PCOS. However, the mechanisms by which metformin exerts its effects in PCOS are still not completely understood. There is growing evidence of a direct effect of metformin on ovarian steroidogenesis, independent of its effects on insulin sensitivity.MethodsWe evaluated the short-term effects of metformin compared to placebo on basal and LH- stimulated androgen secretion as well as on hormonal and metabolic parameters in 19 women with PCOS during a four-day randomized, double-blinded placebo-controlled clinical trial. In a three month follow-up evaluation, we investigated the longer-term therapeutic effects of metformin on ovulation, metabolic and endocrine parameters.ResultsCompared to placebo, 2 days of metformin was associated with a borderline significant reduction in the free androgen index (FAI) (p = 0.05) and with a reduction in the serum concentration of LH-stimulated testosterone (T) (p = 0.03). Following three months of use, a decline in serum T was observed, independent of changes in weight, metabolic parameters, or insulin sensitivity.ConclusionsIn women with PCOS, Metformin induces a prompt decrease in LH-stimulated T secretion after only several days of use. This action precedes the medication’s effects on insulin sensitivity or weight loss.

Low serum 25-hydroxyvitamin D levels and bronchiolitis severity in Spanish infants.

This cross-sectional study was performed to examine the prevalence of hypovitaminosis D in infants with acute bronchiolitis compared with control subjects and to evaluate the relationship between serum 25-hydroxyvitamin D (25(OH) D) and the severity of bronchiolitis. Serum 25(OH) D levels were measured by radioimmunoassay in 48 infants with acute bronchiolitis (2.5 ± 2.0 months) and in 30 healthy infants (3.2 ± 2.3 months). 25(OH) D levels (ng/ml) in children with acute bronchiolitis were significantly lower than in the control group (median 29.9 ng/ml (interquartile range (IQR) 21.4-37.5) versus median 38.2 ng/ml ((IQR 26.1-48.1), p = 0.022), mainly in infants with moderate-severe bronchiolitis (median 29.8 ng/ml, IQR 19.2-35.9). The prevalence of hypovitaminosis D was remarkably greater among infants with bronchiolitis than in control subjects (52.1 versus 26.6%). A significant inverse correlation was found between serum 25-hydroxyvitamin D levels and disease severity (rho = -0.457, p < 0.001). The prevalence of hypovitaminosis D is high in Spanish infants with bronchiolitis. The severity of acute bronchiolitis increases with a decline in serum 25 (OH) D level.

Decline in Serum 25 Hydroxyvitamin D Levels in HIV–Hbv-Coinfected Patients after Long-Term Antiretroviral Therapy

Vitamin D insufficiency plays an important role in the development of fibrosis in chronic liver disease. This was a cross-sectional study from Thailand. Liver fibrosis was assessed by transient elastography. Serum 25 hydroxyvitamin D (25[OH]D)<30 ng/ml was defined as hypovitaminosis D. 25(OH)D was assessed prior to and following tenofovir disoproxil fumarate (TDF). Factors related to 25(OH)D levels were determined by logistic regression analysis. A total of 158 HIV-HBV-coinfected patients (32% female, median age 43 years) were included. Overall, liver disease was mild with 13.4% having a fibrosis score (FS) of 7.1-14 kPa and 2% with a FS>14 kPa. Median (IQR) duration on TDF was 5 years (4-7). The median estimated glomerular filtration rate was 96.9 ml/min/1.73 m(2). The median (IQR) serum 25(OH)D levels prior to and following TDF were 24.8 ng/ml (21.3-30.6) and 22.8 ng/ml (18.0-27.7), respectively; P≤0.001). The proportion of patients with hypovitaminosis D significantly increased from 72.2% (95% CI 64.7, 78.6) prior to TDF to 84.2% (95% CI 77.7, 89.0) after taking TDF (P=0.01). Factors associated with hypovitaminosis D by multivariate analysis were female sex (adjusted OR 3.8, 95% CI 1.1, 13.7; P=0.038) and duration of antiretroviral therapy (ART)>5 years (OR 3.3, 95% CI 1.2, 8.8; P=0.017). Vitamin D levels were not associated with significant liver fibrosis. Although our HIV-HBV-coinfected patients live in the tropics, there was a high prevalence of hypovitaminosis D, especially in female patients and those receiving prolonged ART. Since HIV-HBV-coinfection requires long-term use of the HBV-active drug, TDF, which can also contribute to bone loss, routine vitamin D assessment and supplementation as necessary should be considered.

Serum vitamin D is low and inversely associated with LDL cholesterol in the Kazak ethnic population: a cross-sectional study.

BackgroundAccumulating evidence suggests that low concentrations of serum 25(OH)D is coupled with increased risks of hypertension, obesity, and cardiovascular disease. However, this relationship has not been established in populations with very low levels of 25(OH)D. Therefore, the aim of our study was to clarify the associations between 25(OH)D and blood pressure, obesity, sex, and lipid profiles in the Kazak ethnic population, who have an extremely low level of 25(OH)D.Material/MethodsA multistage-cluster sampling survey was carried out for residents with Kazak ethnicity in Xinjiang, China. Anthropometric measurements of each participant were taken and the concentrations of 25(OH)D, calcium, alkaline phosphatase, and lipid profiles were measured. Individuals were classified into different groups in terms of vitamin D status, degree of adiposity, presence of hypertension, and other comorbidities.ResultsThe madian concentration of 25(OH)D was 16.2 (11.8–20.5) ng/mL and the prevalence of vitamin D deficiency was 72.4% in this Kazak population (n=928, 59.0% women). Females had a lower 25(OH)D concentration than males – 14.6 (10.5–19.4) ng/mL vs. 17.7 (14.8–22.5) ng/mL, P<0.001. The subjects were classified into 3 groups according to their vitamin D status. There were significant differences in BMI (P=0.046), waist circumference (P=0.037), hip circumference (P=0.003), systolic BP (P=0.035), and LDL cholesterol (P=0.008) among the groups after adjustment for sex and age. On the other hand, there was no significant difference in vitamin D levels between groups with or without hypertension (P=0.586), and groups with or without obesity (P=0.639). A multifactor-regression analysis revealed that every increment of 1mg/dL in LDL cholesterol was associated with a 1.0 ng/mL decline in serum 25(OH)D.ConclusionsThe insufficiency of vitamin D is highly prevalent in Kazaks. Sex, LDL cholesterol, and hip circumference are 3 variables strongly associated with serum 25(OH)D concentration. In a population with low levels of 25(OH)D, the negative relationship between obesity and serum 25(OH)D, a common finding from most previous studies, could not be established.

Selenoprotein P is the essential selenium transporter for bones

Selenium (Se) plays an important role in bone physiology as best reflected by Kashin-Beck disease, an endemic Se-dependent osteoarthritis. Bone development is delayed in children with mutations in SECIS binding protein 2 (SBP2), a central factor for selenoprotein biosynthesis. Circulating selenoprotein P (SePP) is positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known selenoprotein genes and factors needed for selenoprotein biosynthesis are expressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of Sepp-expression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-specific expression of a SePP transgene in hepatocytes efficiently restores bone Se levels in Sepp-knockout mice. Of the two known SePP receptors, Lrp8 was detected in bones while Lrp2 was absent. Interestingly, Lrp8 mRNA concentrations were strongly increased in bones of Sepp-knockout mice likely in order to counteract the developing Se deficiency. Our data highlight SePP as the essential Se transporter to bones, and suggest a novel feedback mechanism for preferential uptake of Se in Se-deprived bones, thereby contributing to our understanding of hepatic osteodystrophy and the consistent bone phenotype observed in subjects with inherited selenoprotein biosynthesis mutations.

Obesity-Induced Hypogonadism in the Male: Premature Reproductive Neuroendocrine Senescence and Contribution of Kiss1-Mediated Mechanisms

Reproduction is sensitive to insufficient body energy reserves, especially in females. Metabolic regulation of the male reproductive axis is less obvious, and the impact of conditions of persistent energy excess has received moderate attention. Yet, the escalating prevalence of obesity and the clinical evidence of its deleterious effects on male fertility have raised considerable concerns. We report here phenotypic and mechanistic studies of the reproductive impact of postnatal nutritional manipulations (mainly overnutrition) coupled to a high-fat diet (HFD) after weaning. Metabolic and hormonal analyses in young (4 months old) and middle-aged (10 months old) animals revealed that HFD caused profound metabolic perturbations, including glucose intolerance, which were worsened by precedent postnatal overfeeding; these were detectable already in young males but aggravated in 10-month-old rats. Impairment of reproductive parameters took place progressively, and HFD alone was sufficient to explain most of these alterations, regardless of postnatal under- or overnutrition. In young males, testosterone (T) levels and steroidogenic enzyme expression were suppressed by HFD, without compensatory increases of LH levels, which were in fact partially inhibited in heavier males. In addition, obese males displayed suppressed hypothalamic Kiss1 expression despite low T, and HFD inhibited LH responses to kisspeptin. Overweight anticipated some of the neuroendocrine effects of aging, such as the suppression of hypothalamic Kiss1 expression and the decline in serum T and LH levels. Nonetheless, HFD per se caused a detectable worsening of key reproductive indices in middle-aged males, such as basal LH and FSH levels as well as LH responses to kisspeptin. Our study demonstrates that nutritional stress, especially HFD, has a profound deleterious impact on metabolic and gonadotropic function as well as on the Kiss1 system and precipitates neuroendocrine reproductive senescence in the male.

Decline of serum antimüllerian hormone levels after laparoscopic ovarian cystectomy in endometrioma and other benign cysts: a prospective cohort study

To identify the most important factor in predicting ovarian reserve after laparoscopic ovarian cystectomy and to evaluate whether there is any difference in the postoperative decline of ovarian reserve between women with endometrioma and those with other benign ovarian cysts. Prospective cohort study. University hospital. A total of 100 women who had undergone laparoscopic ovarian cystectomy for endometrioma (n = 68) or other benign ovarian cysts (n = 32). Serum antimüllerian hormone (AMH) levels measured by enzyme immunoassay preoperatively and at 3 months after surgery. Rate of AMH decline after surgery and follicle numbers retained in cystectomy specimens. Serum AMH levels were obviously decreased at 3 months after the surgery (4.97 ± 2.83 vs. 3.33 ± 2.08 ng/mL, mean ± standard deviation). Adjusting for several parameters, we could see that bilaterality of the ovarian cyst was the only significant factor in predicting the rate of postoperative decline of AMH levels. The rate of AMH decline did not differ between the endometrioma group and the other benign ovarian cyst group. Bilaterality of the ovarian cyst is the only significant factor in predicting the rate of decline of AMH level after laparoscopic ovarian cystectomy. The rate of decline of AMH levels after surgery was similar between the endometrioma group and the other benign ovarian cyst group.

Aging and Declining Testosterone: Past, Present, and Hopes for the Future

As men age, serum testosterone (T) levels decline, whereas serum luteinizing hormone (LH) levels increase somewhat or remain unchanged. Age-related reductions in T levels may be associated with alterations in body composition; energy level; muscle strength; physical, sexual, and cognitive functions; and mood. The predominant contributor to the decline in serum T levels is the decreased ability of the aging testes to make T. As in humans, the Brown Norway rat demonstrates age-related reductions in serum T levels in the setting of unchanged or modestly increased serum LH levels. In this rat model, the ability of aged Leydig cells, the terminally differentiated T-producing cells of the testis, to produce T in response to LH stimulation is significantly diminished. This review begins with a discussion of what is known of the molecular mechanisms by which T synthesis declines with Leydig cell aging. It concludes with a brief history of T replacement therapy, current guidelines, controversies related to T replacement therapy in older men, and proposed future clinical directions.

Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations

BackgroundCongenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features.Methods and FindingsThirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18–61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHβ were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21–39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q), which was accompanied by another GNRHR mutation (R139H or del309F). In addition, both of the KS patients had a mutation in CHD7 (p.Q51X) or FGFR1 (c.91+2T>A).ConclusionsConsiderable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal.

Immunomodulatory effects and improved prognosis of experimental autoimmune encephalomyelitis after O-tetradecanoyl-genistein treatment

Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis (MS), a human inflammatory demyelinating disease of the central nervous system. Genistein, an isoflavonoid phytoestrogenic compound found in soy, is known to reverse clinical signs of EAE. Although genistein has some potential in clinical application, it has some disadvantages related to its chemical structure, such as rapid in vivo metabolism and a fast decline in serum after oral administration. The present work investigates the treatment of EAE by using 7-O-tetradecanoyl-genistein (TDG), a more lipophilic analog of genistein obtained by esterification. The clinical course of EAE was investigated in C57Bl/6 mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG)35–55 in complete Freund's adjuvant supplemented with Mycobacterium tuberculosis H37RA. After 14days of MOG immunization, mice were treated with TDG for seven days. Numbers of IL-17-producing cells and Foxp3 by CD4+ T cells and CTLA-4 expression by CD3+ T cells from brain were determined by flow cytometry. Levels of IL-6, IFN-γ and IL-10 were evaluated by ELISA. Brain sections were stained by hematoxylin and eosin method. The data obtained indicate that TDG treatment ameliorates the clinical signs of EAE, which correlates with a decrease of IL-17-producing cells and an increase in Foxp3+CD4+ cells in the brain. TDG is also shown to enhance IL-10 production and CTLA-4 expression and to reduce IFN-γ and IL-6. Altogether, these findings suggest an immunomodulatory therapeutic role for TDG in EAE and multiple sclerosis.