Exposure to phenols, parabens and UV filters: Associations with loss-of-function mutations in the filaggrin gene in men from the general population.

BACKGROUND: Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals. OBJECTIVES: We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations. METHODS: Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine. RESULTS: FLG mutation carriers had 80% (13-180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13-219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03). CONCLUSION: FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication.

Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men.

OBJECTIVE: Study associations between three measures of alcohol consumption (recent, typical/habitual, binging), semen quality and serum reproductive hormones. DESIGN: Cross-sectional population based study. SETTING AND PARTICIPANTS: 1221 young Danish men, aged 18-28 years were recruited when they attended a compulsory medical examination to determine their fitness for military service from 2008 to 2012. Total alcohol consumption: (1) in the week preceding (habitual/typical) the visit (recent alcohol intake), (2) in a typical week and (3) frequency of 'binge drinking' (consuming more than 5 units/day)) in the past 30 days was estimated. MAIN OUTCOME MEASURES: Semen quality (volume, sperm concentration, total sperm count, and percentages of motile and morphologically normal spermatozoa) and serum concentration of reproductive hormones (follicle-stimulating hormone, luteinising hormone, testosterone, sex hormone binding globulin, oestradiol, free testosterone and inhibin B). RESULTS: Sperm concentration, total sperm count and percentage of spermatozoa with normal morphology were negatively associated with increasing habitual alcohol intake. This association was observed in men reporting at least 5 units in a typical week but was most pronounced for men with a typical intake of more than 25 units/week. Men with a typical weekly intake above 40 units had a 33% (95% CI 11% to 59%) reduction in sperm concentration compared to men with an intake of 1-5 units/week. A significant increase in serum free testosterone with increasing alcohol consumption the week preceding the visit was found. Binging was not independently associated with semen quality. CONCLUSIONS: Our study suggests that even modest habitual alcohol consumption of more than 5 units per week had adverse effects on semen quality although most pronounced associations were seen in men who consumed more than 25 units per week. Alcohol consumption was also linked to changes in testosterone and SHBG levels. Young men should be advised to avoid habitual alcohol intake.

Association between perfluorinated compounds and time to pregnancy in a prospective cohort of Danish couples attempting to conceive.

BACKGROUND: Perfluorinated chemicals (PFCs) have been widely used and have emerged as important food contaminants. A recent study on pregnant women suggested that PFC exposure was associated with a longer time to pregnancy (TTP). We examined the association between serum concentrations of PFCs in females and TTP in 222 Danish first-time pregnancy planners during the years 1992-1995. METHODS: The couples were enrolled in the study when discontinuing birth control and followed for six menstrual cycles or until a clinically recognized pregnancy occurred. Fecundability ratio (FR) was calculated using discrete-time survival models. In addition, odds ratio (OR) for TTP >6 cycles was calculated. RESULTS: OR for TTP >6 cycles for those with PFC concentrations above the median were 0.96 [95% confidence interval (CI): 0.54-1.64] for perfluorooctane sulfonic acid (PFOS), the major PFC, compared with those below the median. FRs for those with PFOS concentrations above the median were 1.05 (95% CI: 0.74-1.48) compared with those below the median. Other PFCs showed the same lack of association with TTP. The results were not affected by adjustment for covariates. PFOS and perfluorooctanoic acid concentrations were similar to those observed in a previous Danish study. CONCLUSIONS: These findings suggest that exposure to PFCs affects TTP only to a small extent, if at all.

Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men.

OBJECTIVE: To examine the relationship between body mass index (BMI) and semen quality among young men from the general population. DESIGN: Cross-sectional study. SETTING: Danish young men were approached when they attended a compulsory physical examination to determine their fitness for military service. PATIENT(S): From 1996-1998, 1,558 (19%) young men (mean age 19 years) volunteered. MAIN OUTCOME MEASURE(S): Semen volume (in milliliters), sperm concentration (in million per milliliter), percentage of motile spermatozoa, percentage of spermatozoa with normal morphology, total sperm count (in million), and testis size (in milliliters). In addition, serum reproductive hormones were measured. RESULT(S): Serum T, sex hormone-binding globulin (SHBG), and inhibin B all decreased with increasing BMI, whereas free androgen index and E(2) increased with increasing BMI. Serum FSH was higher among slim men. After control for confounders, men with a BMI <20 kg/m(2) had a reduction in sperm concentration and total sperm count of 28.1% (95% confidence interval [CI] 8.3%-47.9%) and 36.4% (95% CI 14.6%-58.3%), respectively, and men with a BMI >25 kg/m(2) had a reduction in sperm concentration and total sperm count of 21.6% (95% CI 4.0%-39.4%) and 23.9% (95% CI 4.7%-43.2%), respectively, compared to men with BMI between 20-25 kg/m(2). Percentages of normal spermatozoa were reduced, although not significantly, among men with high or low BMI. Semen volume and percentage of motile spermatozoa were not affected by BMI. CONCLUSION(S): High or low BMI was associated with reduced semen quality. It remains to be seen whether the increasing occurrence of obesity in the Western world may contribute to an epidemic of poor semen quality registered in some of the same countries. If so, some cases of subfertility may be preventable.