Association of Testosterone-Related Dietary Pattern with Testicular Function among Adult Men: A Cross-Sectional Health Screening Study in Taiwan

Diets could play an important role in testicular function, but studies on how adherence to the dietary patterns influences human testicular function in Asian countries are scarce. Herein, we examined the association between testosterone-related dietary patterns and testicular function among adult men in Taiwan. This cross-sectional study recruited 3283 men who attended a private medical screening program from 2009 to 2015. Testosterone-related dietary pattern was generated by the reduced rank regression (RRR) method. The association between adherence to quartile of dietary pattern scores with sex hormones (testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2)) and sperm quality (sperm concentration (SC), total sperm motility (TSM), progressive motility (PRM), and normal sperm morphology (NSM)) were examined by multivariable linear regression. Hemoglobin (β = 0.57, p < 0.001), hematocrit (β = 0.17, p = 0.002), triglyceride (β = −0.84, p < 0.001), HDL-cholesterol (β = 3.58, p < 0.001), total cholesterol to HDL-cholesterol ratio (β = −0.78, p < 0.001), and uric acid (β = −10.77, p < 0.001) were highly correlated with testosterone levels. Therefore, these biomarkers were used to construct a testosterone-related dietary pattern. Highest adherence (Q4) to dietary pattern scores were negatively associated with lower testosterone in the pooled analysis (β = −0.89, p = 0.037) and normal-weight men (β = −1.48, p = 0.019). Likewise, men in the Q4 of the dietary pattern had lower SC (β = −5.55, p = 0.001) and NSM (β = −2.22, p = 0.007) regardless of their nutritional status. Our study suggesting that testosterone-related dietary pattern (rich in preserved vegetables or processed meat or fish, deep-fried foods, innards organs, rice or flour products cooked in oil, and dipping sauce, but low in milk, dairy products, legumes, or beans, and dark or leafy vegetables) was associated with a poor testicular function.     

Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men

Background: Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10% of Europeans and 5% of Asians carry at least one null allele in the filaggrin gene (FLG). Reduced expression of filaggrin in carriers of the null allele is associated with facilitated transfer of allergens across the epidermis. We hypothesized that these individuals may have increased transdermal uptake of endocrine disruptors, including phthalates.Objectives: We investigated urinary excretion of phthalate metabolites and testicular function in young men with and without FLG loss-of-function variants in a cross-sectional study of 861 young men from the general Danish population.Methods: All men were genotyped for FLG R501X, 2282del4, and R2447X loss-of-function variants. We measured urinary concentrations of 14 phthalate metabolites and serum levels of reproductive hormones. We also evaluated semen quality.Results: Sixty-five men (7.5%) carried at least one FLG-null allele. FLG-null carriers had significantly higher urinary concentrations of several phthalate metabolites, including a 33% higher concentration of MnBP (mono-n-butyl phthalate; 95% CI: 16, 51%). FLG-null variants were not significantly associated with reproductive hormones or semen quality parameters.Conclusion: This study provides evidence that carriers of FLG loss-of-function alleles may have higher internal exposure to phthalates, possibly due to increased transepidermal absorption. FLG loss-of-function variants may indicate susceptible populations for which special attention to transepidermal absorption of chemicals and medication may be warranted.Citation: Joensen UN, Jørgensen N, Meldgaard M, Frederiksen H, Andersson AM, Menné T, Johansen JD, Carlsen BC, Stender S, Szecsi PB, Skakkebæk NE, Rajpert-De Meyts E, Thyssen JP. 2014. Associations of filaggrin gene loss-of-function variants with urinary phthalate metabolites and testicular function in young Danish men. Environ Health Perspect 122:345–350; http://dx.doi.org/10.1289/ehp.1306720     

Variability over 1 Week in the Urinary Concentrations of Metabolites of Diethyl Phthalate and Di(2-Ethylhexyl) Phthalate among Eight Adults: An Observational Study

Background

Phthalates are metabolized and eliminated in urine within hours after exposure. Several reports suggest that concentrations of phthalate metabolites in a spot urine sample can provide a reliable estimation of exposure to phthalates for up to several months.

Objectives

We examined inter- and intraperson and inter- and intraday variability in the concentrations of monoethyl phthalate (MEP), the major metabolite of diethyl phthalate, commonly used in personal care products, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), a polyvinyl chloride plasticizer of which diet is the principal exposure source, among eight adults who collected all urine voids (average, 7.6 samples/person/day) for 1 week.

Methods

We analyzed the urine samples using online solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry.

Results

Regardless of the type of void (spot, first morning, 24-hr collection), for MEP, interperson variability in concentrations accounted for > 75% of the total variance. By contrast, for MEHHP, within-person variability was the main contributor (69–83%) of the total variance. Furthermore, we observed considerable intraday variability in the concentrations of spot samples for MEHHP (51%) and MEP (21%).

Conclusions

MEP and MEHHP urinary concentrations varied considerably during 1 week, but the main contributors to the total variance differed (interday variability, MEHHP; interperson variability, MEP) regardless of the sampling strategy (spot, first morning, 24-hr collection). The nature of the exposure (diet vs. other lifestyle factors) and timing of urine sampling to evaluate exposure to phthalates should be considered. For DEHP and phthalates to which people are mostly exposed through diet, collecting 24-hr voids for only 1 day may not be advantageous compared with multiple spot collections. When collecting multiple spot urine samples, changing the time of collection may provide the most complete approach to assess exposure to diverse phthalates.     

The Effect of Alcohol,Tobacco, and Aspirin Consumption on Seminal Quality among Healthy Young Men

In this study, the authors examined the effects of alcohol, tobacco, and drug use on plasma testosterone and seminal parameters (in accordance with the World Health Organization's standards) in healthy Argentine medical students (n = 34). Some alterations in seminal parameters were detected in 19 (56%) subjects. Alcohol and tobacco use were correlated significantly, p = 0.005; subjects who used these substances exhibited a nonsignificant reduction in sperm concentration, motility, viability, and normal morphology. There was a significant decrease in sperm motility among students who used moderate amounts of aspirin (i.e., ≥ 500 mg/wk). The authors concluded that alcohol, tobacco, and aspirin use could have had detrimental effects on seminal parameters and that men who wish to procreate should be warned of such effects. Doses, exposure time, and interactions with other variables deserve additional study.     

精液质量评估与男性生育力关系

目的不育夫妇中,50%与男性因素相关,随着不育症的发病率增高,对男性生育力的正确评估显得尤为重要。《世界卫生组织人类精液检查与处理实验室手册》的更新不断推动着男科实验室的发展,也提出了问题与挑战。正确认识精液质量评估的各种参数与男性生育力之间的关系对临床诊断以及治疗方案的选择至关重要。     

Healthy Lifestyle Pattern is Protective Against 30-Yr Cancer Incidence in Men and Women: A Cohort Study

Objectives: Investigate associations of healthier behaviors with 30-yr cancer incidence.

Subjects/Methods: In 1982, 632 healthy men and women (ages 40–70) were interviewed for nutritional habits using a Food Frequency Questionnaire and a 24-h physical activity questionnaire. Blood pressure, weight, and height were measured, and blood was drawn for biochemical profiles. Thirteen and four subjects were excluded due to cancer diagnosis ≤1 yr from recruitment and extreme values of reported total daily calorie intake, respectively.

Results: During a mean follow-up of 24.2 yr, 146 cancer incident patients (23.7%) were documented. Total cancer risk was 38% lower in the medium vegetable intake tertile [adjusted hazards ratio (HR) = 0.62, 95%confidence interval (CI): 0.40–0.95], and 66% higher in the medium fruit intake tertile (adjusted HR = 1.66, 95%CI: 1.08–2.55) compared to the lowest tertile. The risk of gastrointestinal cancers was 3 times greater for the highest, compared to the lowest, dairy consumption tertile (HR = 3.06, 95%CI: 1.01–9.23). “Healthy lifestyle” (normal BMI, never smoked, consuming high levels of dietary fiber and vegetables, and more physically active) reduced overall cancer risk (adjusted HR = 0.63, 95%CI: 0.44–0.91) as compared to the rest of the cohort.

Conclusions: Our findings reinforce the importance of lifestyle-related factors, which are relatively low-cost and may contribute to reduction in the burden of malignant diseases.     

Adherence to the Western Pattern Is Potentially an Unfavorable Indicator of Asthenozoospermia Risk: A Case-Control Study

Objective: The aim of this case-control study was to examine the relationship between dietary patterns and asthenozoospermia risk.

Methods: In total, 107 incident asthenozoospermic men and 235 age-matched controls were interviewed through the infertility clinics in Tehran, Iran, from January 2012 to November 2013. Usual dietary intakes were collected using a semiquantitative food frequency questionnaire and semen quality data were analyzed according to the fifth edition of the World Health Organization (WHO) guidelines. Dietary patterns were derived using factor analysis. The first tertile served as the reference category for regression analyses.

Results: In principal component analysis, 2 dietary patterns emerged: a “prudent pattern” (leafy green vegetables, yellow vegetables, other vegetables, tomatoes, fish and other seafood, fruits and natural fruit juices, legumes, whole grains, poultry, tea and coffee, low-fat dairy products, and vegetable oils) and a “Western pattern” (organ meats, red and processed meats, sugar, soft drinks and confectionary, pasta, rice and refined grains, potatoes, french fries and fast foods, high-fat dairy products, hydrogenated fats, mayonnaise and fatty sauces, and snacks). After adjustment for potential confounders, participants in the highest tertile of the prudent pattern scores had 54% lower risk of asthenozoospermia compared to those in the lowest (p for trend: 0.003). Being in the highest tertile of the Western pattern was positively associated with asthenozoospermia risk (odds ratio [OR] = 2.86; 95% confidence interval [CI], 1.83–2.97).

Conclusions: Our findings suggest that adherence to the Western pattern is potentially an unfavorable indicator of asthenozoospermia risk and a diet composed mainly of plant-based foods may be associated with a reduced risk.     

Relationships Between Levels of Estradiol and Testosterone in Seminal Plasma and GSTM1 Polymorphism in Infertile Men

Glutathione S-transferase M1 (GSTM1) enzyme serves as a steroid-binding protein by its ability to bind to testosterone and estradiol. The levels of total estradiol and testosterone were measured by using an electrochemiluminescence immunoassay in serum and seminal plasma from 103 subjects including 62 subfertile patients. GSTM1 polymorphism was examined using polymerase chain reaction. The estradiol and testosterone levels in seminal plasma were not different in control and subfertile subjects. No role for GSTM1 enzyme as a steroid-binding protein seemed likely as there was also no significant difference in seminal plasma estradiol and testosterone levels according to GSTM1 genoytpe.

Significant positive correlations were found between seminal estradiol and serum estradiol in infertile males, and between seminal testosterone and serum testosterone in fertile males, independent of GSTM1 genotype. GSTM1 polymorphism is not a genetic risk factor of seminal estradiol and testosterone levels in infertile males although further studies are warranted.     

Gender Nonconformity, Childhood Rejection, and Adult Attachment: A Study of Gay Men

Several childhood factors are reported to be associated with a homosexual orientation in men, including gender nonconformity and rejection by parents and peers. The purpose of this study was to explore the associations between these childhood factors and attachment anxiety (the tendency to experience anxiety regarding potential loss and rejection in close relationships) and attachment avoidance (the tendency to avoid versus seek out closeness in relationships) in gay and bisexual men. A community sample of 191 gay and bisexual men completed questionnaires and an attachment interview. Gender nonconformity was significantly associated with paternal, maternal, and peer rejection in childhood. In addition, paternal and peer rejection, but not maternal rejection, independently predicted attachment anxiety. Peer rejection and, to a lesser extent, paternal rejection mediated the association between gender nonconformity and attachment anxiety. Finally, peer rejection mediated the association between paternal rejection and attachment avoidance. Findings highlight the role of gender nonconformity in contributing to childhood rejection and the importance of peer relationships in the socialization of gay men.     

A Longitudinal Study of Urinary Phthalate Excretion in 58 Full-Term and 67 Preterm Infants from Birth through 14 Months

Background: Some phthalates have shown antiandrogenic effects in rat offspring. Premature infants may be exposed to high amounts of specific phthalates during hospitalization, and thus are potentially at risk.Objective: We evaluated longitudinal phthalate exposure and metabolism in full-term (FT) and preterm (PT) infants.Methods: Fifty-eight FT and 67 PT (gestational age, 24.7–36.6 weeks) infants were recruited at birth and followed until 14 months (nine times). Urinary concentrations of metabolites of diethyl phthalate (DEP), dibutyl phthalate isomers (DiBP and DnBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and diisononyl phthalate (DiNP) were measured in 894 samples. Daily intake and a hazard index for antiandrogenic effects were estimated, and excretion patterns of DEHP and DiNP metabolites were analyzed.Results: Metabolites of BBzP, DiNP, and DEHP were 5–50 times higher at day 7 (D7) and month 1 (M1) in PT than in FT infants. Thereafter, metabolite concentrations were similar between the two groups. The estimated hazard index for combined DiBP, DnBP, BBzP, and DEHP exposures 7 days after birth exceeded the antiandrogenic threshold in > 80% of PT and > 30% of FT infants, and after M2, in 30% of all infants. The excretion pattern of DEHP and DiNP metabolites changed with age.Conclusion: Most PT infants and approximately one-third of healthy FT newborns were exposed to phthalates during early life at a potentially harmful level according to the European Food Safety Authority’s recommended limits of daily exposure. Changes in the relative proportions of secondary phthalate metabolites over time were consistent with maturation of infant metabolic pathways during the first year of life. Further research is needed on the health effects of phthalate exposures and the influence of changes in metabolic capacity in neonates and infants.Citation: Frederiksen H, Kuiri-Hänninen T, Main KM, Dunkel L, Sankilampi U. 2014. A longitudinal study of urinary phthalate excretion in 58 full-term and 67 preterm infants from birth through 14 months. Environ Health Perspect 122:998–1005; http://dx.doi.org/10.1289/ehp.1307569     

Associations of in Utero Exposure to Perfluorinated Alkyl Acids with Human Semen Quality and Reproductive Hormones in Adult Men

Background: Perfluorinated alkyl acids (PFAAs), persistent chemicals with unique water-, dirt-, and oil-repellent properties, are suspected of having endocrine-disrupting activity. The PFAA compounds perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are found globally in humans; because they readily cross the placental barrier, in utero exposure may be a cause for concern.Objectives: We investigated whether in utero exposure to PFOA and PFOS affects semen quality, testicular volume, and reproductive hormone levels.Methods: We recruited 169 male offspring (19–21 years of age) from a pregnancy cohort established in Aarhus, Denmark, in 1988–1989, corresponding to 37.6% of the eligible sons. Each man provided a semen sample and a blood sample. Semen samples were analyzed for sperm concentration, total sperm count, motility, and morphology, and blood samples were used to measure reproductive hormones. As a proxy for in utero exposure, PFOA and PFOS were measured in maternal blood samples from pregnancy week 30.Results: Multivariable linear regression analysis suggested that in utero exposure to PFOA was associated with lower adjusted sperm concentration (p_trend = 0.01) and total sperm count (p_trend = 0.001) and with higher adjusted levels of luteinizing hormone (p_trend = 0.03) and follicle-stimulating hormone (p_trend = 0.01). PFOS did not appear to be associated with any of the outcomes assessed, before or after adjustment.Conclusions: The results suggest that in utero exposure to PFOA may affect adult human male semen quality and reproductive hormone levels.     

Association between urinary polycyclic aromatic hydrocarbon metabolites and sperm DNA damage: a population study in Chongqing, China

Background

Polycyclic aromatic hydrocarbons (PAHs), a class of the most ubiquitous environmental contaminants, may reduce male reproductive functions, but the data from human population studies are very limited.

Objectives

We designed this study to determine whether environmental exposure to PAHs contributes to the alteration in semen quality, sperm DNA damage, and apoptosis in the general male human population.

Methods

We measured urinary levels of four PAH metabolites and assessed semen quality, sperm apoptotic markers with Annexin V assay, and sperm DNA damage with comet assay in 232 men from Chongqing, China.

Results

We found that increased urinary 2-hydroxynaphthalene (2-OHNa) levels were associated with increased comet parameters, including the percentage of DNA in the tail (tail%) [β coefficient = 13.26% per log unit 2-OHNa (micrograms per gram creatinine); 95% confidence interval (CI), 7.97–18.55]; tail length (12.25; 95% CI, 0.01–24.52), and tail distribution (7.55; 95% CI, 1.28–18.83). The urinary level of 1-hydroxypyrene was associated only with increased tail% (5.32; 95% CI, 0.47–10.17). Additionally, the increased levels of four urinary PAH metabolites were significantly associated with decreased vital Annexin V negative sperm counts. However, there was no significant association between urinary PAH metabolite levels and human semen parameters or morphology of the sperm samples.

Conclusions

Our data indicate that the environmental level of PAH exposure is associated with increased sperm DNA damage but not with semen quality. These findings suggest that exposure to PAHs may disrupt sperm DNA and thereby interfere with human male fertility.     

应用精子质量和彗星试验评价铅对男性生殖功能的影响

[目的]探讨铅对精液质量产生的影响,提出加强男性生殖保健的预防措施。[方法]采用单细胞凝胶电泳(彗星试验)和精子全自动分析仪相结合的方法,对铅接触组和未接触铅的对照组男性的精液标本进行检测。[结果]接触组与对照组精液全自动分析各项指标均无异常,但单细胞凝胶电泳中接触组Ⅰ级彗星率即DNA链断裂数量(4.28±2.73)%明显高于对照组(2.73±1.89)%(P<0.05)。[结论]彗星试验可用于评价职业性铅接触对男性精液质量的影响, 为临床和卫生防护部门能够早期发现精子亚临床损伤提出科学依据。     

Time- and Dose-Related Effects of Di-(2-ethylhexyl) Phthalate and Its Main Metabolites on the Function of the Rat Fetal Testis in Vitro

Background

Endocrine-disrupting effects of phthalates are understood primarily from in utero exposures within the fetal rat testis. Nevertheless, their path of action, dose–response character, and cellular target(s) within the fetal testis are not known.

Objectives

In this study we investigated the effects of di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP), and several of their metabolites on the development of organo-cultured testes from rat fetus.

Methods

We removed testes from 14.5-day-old rat fetuses and cultured them for 1–3 days with or without DEHP, MEHP, and the metabolites.

Results

DEHP (10⁻⁵ M) produced a proandrogenic effect after 3 days of culture, whereas MEHP disrupted testis morphology and function. Leydig cells were the first affected by MEHP, with a number of them being inappropriately located within some seminiferous tubules. Additionally, we found a time- and dose-dependent reduction of testosterone. By 48 hr, gonocyte proliferation had decreased, whereas apoptosis increased. Sertoli cell number was unaffected, although some cells appeared vacuolated, and production of anti-Müllerian hormone decreased in a time- and dose-dependent manner. The derived metabolite mono-(2-ethyl-5-hydroxyhexyl) phthalate was the only one to cause deleterious effects to the rat fetal testis in vitro.

Conclusion

We hope that this in vitro method will facilitate the study of different phthalate esters and other endocrine disruptors for direct testicular effects.     

Potato Fibers Have Positive Effects on Subjective Appetite Sensations in Healthy Men,but Not on Fecal Fat Excretion: A Randomized Controlled Single-Blind Crossover Trial

Dietary fibers can affect appetite and gut metabolism, but the effect of the novel potato fibers FiberBind and rhamnogalacturonan I (RG-I) is unknown. We, therefore, aimed to investigate the effect of daily intake of FiberBind and RG-I on appetite sensations and fecal fat excretion. In a single-blinded, randomized, three-way crossover trial, wheat buns with FiberBind, RG-I, or low fiber (control) were consumed by 18 healthy men during a 21-day period. Appetite sensation and blood samples during a 3 h meal test, fecal fat content, and ad libitum energy intake were assessed after each period. Compared to RG-I and control, FiberBind caused a higher composite satiety score (6% ± 2% and 5% ± 2%), lower prospective food consumption (5% ± 2% and 6% ± 2%), and lower desire to eat (7% ± 3% and 6% ± 3%) (all p < 0.05). FiberBind also caused higher satiety (6% ± 2%) and fullness (9% ± 3%) compared to RG-I (all p < 0.01). No effects on fecal fat excretion or energy intake were found. The RG-I fiber caused higher postprandial glucose concentration compared to FiberBind (p < 0.05) and higher insulin concentration at 180 min compared to control (p < 0.05). Compared to the control, RG-I and FiberBind lowered peak insulin concentration (both p < 0.05) and delayed time to peak for glucose (both p < 0.05). In conclusion, FiberBind intake could be beneficial for appetite regulation, but neither FiberBind nor RG-I affected fecal fat excretion or energy intake.     

Effects of Rape on Men: A Descriptive Analysis

Previous studies of the effects of rape on men have focused mainly on clinical populations. This study extended current research by investigating the effects of rape on a non-clinical sample of men recruited from the general population by media advertising. A total of 40 male rape victims were asked to provide details of their assaults, levels of psychological disturbance, long-term effects, and reporting issues. Results revealed that most assaults had been carried out using physical or violent force, in a variety of different circumstances. All of the victims reported some form of psychological disturbance as a result of being raped. Long-term effects included anxiety, depression, increased feelings of anger and vulnerability, loss of self-image, emotional distancing, self-blame, and self-harming behaviors. Findings are discussed in relation to previous research in the area and perceptions of rape.