Estrogens and phytoestrogens in male infertility.

PURPOSE OF REVIEW: A time-related negative trend in male reproductive function has been suggested. It has been hypothesized that this is due to exposure to chemicals interfering with the action of sex hormones. Also a negative effect of phytoestrogens on male fertility has been postulated. This review aimed to review the epidemiological evidence of deteriorating male reproductive function and summarize the most recent literature on exposure to endocrine disrupters and phytoestrogens in relation to male fertility and/or semen quality. RECENT FINDINGS: There is no doubt that the incidence of testicular cancer has increased through the past 50 years, a decline in sperm counts, if any, may have leveled off during the past decade. There are some reports indicating negative association between exposure to certain chemicals and sperm parameters such evidence has not been found for phytoestrogens. The majority of these studies have been limited to assessing postnatal exposure. SUMMARY: Although possible negative impact of industrial chemicals and male fertility is an important issue on the research agenda, so far, it has no clinical implications. The future research should focus on looking at the impact of low dose exposure to a mixture of chemicals, two generation studies and gene-environment interaction

Estrogen receptor alpha single nucleotide polymorphism as predictor of diabetes type 2 risk in hypogonadal men.

Abstract Estradiol (E2) is, apart from its role as a reproductive hormone, also important for cardiac function and bone maturation in both genders. It has also been shown to play a role in insulin production, energy expenditure and in inducing lipolysis. The aim of the study was to investigate if low circulating testosterone or E2 levels in combination with variants in the estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2) genes were of importance for the risk of type-2 diabetes. The single nucleotide polymorphisms rs2207396 and rs1256049, in ESR1 and ESR2, respectively, were analysed by allele specific PCR in 172 elderly men from the population-based Tromsø study. The results were adjusted for age. In individuals with low total (≤11 nmol/L) or free testosterone (≤0.18 nmol/L) being carriers of the variant A-allele in ESR1 was associated with 7.3 and 15.9 times, respectively, increased odds ratio of being diagnosed with diabetes mellitus type 2 (p = 0.025 and p = 0.018, respectively). Lower concentrations of E2 did not seem to increase the risk of being diagnosed with diabetes. In conclusion, in hypogonadal men, the rs2207396 variant in ESR1 predicts the risk of type 2 diabetes

Negative Association between Testosterone Concentration and Inflammatory Markers in Young Men: A Nested Cross-Sectional Study.

Low grade systemic inflammation (LGSI) as well as androgen deficiency has in older men been associated with several pathologies, including cardiovascular disease (CVD). We wanted to investigate whether low testosterone levels are linked to biomarkers of LGSI already in young age, before any concurrent manifestations of CVD or other systemic diseases

Determination of serum amyloid P component in seminal plasma and correlations with serum hormone levels in young, healthy men.

Abstract Serum amyloid P component (SAP) belongs to the pentraxin family of proteins. SAP is evolutionary conserved, and involved in amyloidosis, innate immunity, inflammation, and apoptosis. We have previously described SAP in the male reproductive tract, where it occurs in seminal fluid, on spermatozoa, and in epididymal, seminal vesicle, and prostate tissue. In the present investigation, our aim was to characterize SAP in male reproduction. In short, we developed and evaluated an immunoassay, analysed the concentration of SAP in seminal plasma and serum in samples from healthy men (N = 203), and studied hormonal regulation. SAP in seminal plasma showed a positively skewed distribution and a median concentration of 1.01 mg/L (inter quartile range [IQR] 0.56-1.65 mg/L). SAP in serum had a Gaussian distribution and a median concentration of 40.5 mg/L (IQR 34.2-49.2 mg/L). Furthermore, SAP concentrations in seminal plasma were not correlated with serum concentrations of SAP, testosterone, sex hormone-binding globulin (SHBG), the testosterone/SHBG ratio, inhibin B, or estradiol. Only a weak negative correlation was found between seminal plasma SAP and serum levels of follicle-stimulating hormone (FSH) (Spearman's rho -0.159; p = 0.023) and luteinizing hormone (LH) (Spearman's rho -0.162; p = 0.021). In conclusion, all men investigated had measurable SAP levels in seminal plasma and in serum. SAP concentrations were 40 times lower in seminal fluid than in serum, and there was no correlation between those two variables. It seems that hormonal regulation is not the major pathway regulating seminal plasma SAP, and seminal plasma SAP and serum SAP are not co-regulated

Dioxin-like activities in serum across European and Inuit populations

BACKGROUND: Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay. RESULTS: The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group. CONCLUSION: No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors

Male reproductive health statement:(XIIIth international symposium on Spermatology, May 9th--12th 2018, Stockholm, Sweden

International audienc

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

<p>Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.</p> <p>Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.</p> <p>Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.</p> <p>Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.</p> <p>Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.</p> <p>Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.</p&gt

Fertility in four regions spanning large contrasts in serum levels of widespread persistent organochlorines: a cross-sectional study

BACKGROUND: Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited. METHODS: Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample. RESULTS: Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundability was reduced among couples from Kharkiv [adjusted fecundability ratio (FR) 0.64 (95% CI 0.5-0.8)] and elevated in Swedish fishermen families [FR 1.26 (95% CI 1.0-1.6)]. Adjusted geometric means of sperm counts and morphology did not differ between regions while sperm motility was higher in men living in Warsaw. CONCLUSION: We observed regional differences in time to pregnancy and sperm motility that may be related to regional differences in POP blood levels, but other interpretations are also plausible. In particular, differences in access to safe contraception and in the prevalence of contraceptive failures are most likely to bias comparisons of time to pregnancy

FSH receptor N680S genotype-guided gonadotropin choice increases cumulative pregnancy and live birth rates after in vitro fertilization

ObjectiveThis study aimed to compare cumulative [fresh and frozen embryo transfers from one ovarian stimulation (OS) cycle] pregnancy and live birth rates in women for whom the choice between recombinant FSH (rFSH) and urinary FSH (uFSH) for OS was linked to FSH receptor (FSHR) N680S genotype and compared these to non-genotyped controls.MethodsTo define the optimal combination of FSH type and FSHR genotype, 475 women were allocated to either the rFSH group or to the uFSH group for OS. The number of aspirated oocytes, cumulative pregnancy rates, and live birth rates in the first OS cycle were determined. Subsequently, their FSHR N680S (rs6166) variant was analyzed. Clinical data were backed up by in vitro experiments, in which COS-1 cells were transfected with homozygous FSHR variants and stimulated with either uFSH or rFSH. cAMP was measured to evaluate receptor activity. Thereafter, a sub-cohort of 221 who received optimal FSH treatment in relation to their FSHR genotype was selected from the total cohort of 475 women. Cumulative pregnancy and live birth rates were compared between 991 non-genotyped controls and these 221 women. Binary logistic regression was used to explore the odds ratios (ORs) and 95% confidence intervals (CIs) for cumulative pregnancy and live birth rates in the first OS cycle among genotyped and optimally treated women, with the non-genotyped cohort set as the reference. Adjustment was made for age, body mass index, and method of fertilization.ResultsThe combined clinical and in vitro data indicated that uFSH was the optimal choice for FSHR N680S S-allele carriers, whereas rFSH was the hormone of choice for asparagine (NN) subjects. The sub-cohort consisting of uFSH-treated S-carriers together with rFSH-treated NN-carriers had a significantly higher chance of pregnancy (51% vs. 40%; OR: 1.40, 95% CI 1.12-1.75, p=0.003) and live birth (40% vs. 29%; OR: 1.55, 95% CI 1.23-1.96, p<0.001) compared to non-genotyped women, in whom the choice of hormone was based on a standard clinical evaluation.ConclusionA significantly increased chance of pregnancy and live birth can be achieved by a genotype-guided approach. While the administration of uFSH should be the choice for S-carriers, rFSH is beneficial for NN-carrying women