Jaime Mendiola

Shorter Anogenital Distance Predicts Poorer Semen Quality in Young Men in Rochester, New York

Background: In male rodents, anogenital distance (AGD) provides a sensitive and continuous correlate of androgen exposure in the intrauterine environment and predicts later reproductive success. Some endocrine-disrupting chemicals can alter male reproductive tract development, including shortening AGD, in both rodents and humans. Whether AGD is related to semen quality in human is unknown. Objective: We examined associations between AGD and semen parameters in adult males. Methods: We used multiple regression analyses to model the relationships between sperm parameters and two alternative measures of AGD [from the anus to the posterior base of the scrotum (AGDAS) and to the cephalad insertion of the penis (AGDAP)] in 126 volunteers in Rochester, New York. Results: AGDAS, but not AGDAP, was associated with sperm concentration, motility, morphology, total sperm count, and total motile count (p-values, 0.002–0.048). Men with AGDAS below (vs. above) the median were 7.3 times more likely (95% confidence interval, 2.5–21.6) to have a low sperm concentration (< 20 × 106/mL). For a typical study participant, sperm concentrations were 34.7 × 106/mL and 51.6 × 106/mL at the 25th and 75th percentiles of (adjusted) AGDAS. Conclusions: In our population, AGDAS was a strong correlate of all semen parameters and a predictor of low sperm concentration. In animals, male AGD at birth reflects androgen levels during the masculinization programming window and predicts adult AGD and reproductive function. Our results suggest, therefore, that the androgenic environment during early fetal life exerts a fundamental influence on both AGD and adult sperm counts in humans, as demonstrated in rodents.

Are Environmental Levels of Bisphenol A Associated with Reproductive Function in Fertile Men

Background Rodent and in vitro studies have demonstrated the estrogenicity of bisphenol A (BPA). However, few studies have examined the relationship between human exposure to BPA and male reproductive function. Objectives We investigated the relationships between environmental BPA exposure and reproductive parameters, including semen quality and male reproductive hormones, in prospectively recruited fertile men. Methods Participants (n = 375) were partners of pregnant women who participated in the Study for Future Families in four U.S. cities, and all of the men provided blood, semen, and urine samples. BPA was measured in urine. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone (LH), testosterone, inhibin B, estradiol, and sex hormone–binding globulin (SHBG), as well as the free androgen index (FAI). Semen analyses were performed according to World Health Organization criteria. Pearson correlations were used for unadjusted analyses, and multiple linear regression analyses were used to examine associations controlling for age, body mass index, smoking, ethnicity, urinary creatinine concentration, time of sample collection, and duration of abstinence. Results After multivariate adjustment, we observed no significant associations between any semen parameter and urinary BPA concentration. However, a significant inverse association was found between urinary BPA concentration and FAI levels and the FAI/LH ratio, as well as a significant positive association between BPA and SHBG. Conclusions Our results suggest that, in fertile men, exposure to low environmental levels of BPA may be associated with a modest reduction in markers of free testosterone, but any effects on reproductive function are likely to be small, and of uncertain clinical significance.

Food intake and its relationship with semen quality: a case-control study

OBJECTIVE To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive assisted clinic. DESIGN An observational, analytical case-control study. SETTING Private fertility clinics. PATIENT(S) Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our fertility clinics. INTERVENTION(S) We recorded dietary habits and food consumption using a food frequency questionnaire adapted to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes were also carried out. MAIN OUTCOME MEASURE(S) Frequency of intake food items were registered in a scale with nine categories ranging from no consumption to repeated daily consumption. RESULT(S) Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products. CONCLUSION(S) Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality.

A low intake of antioxidant nutrients is associated with poor semen quality in patients attending fertility clinics

OBJECTIVE To compare specific nutrient intake between normospermic and oligoasthenoteratospermic patients attending infertility clinics in two Mediterranean provinces of Spain. DESIGN Case-control study. SETTING Private fertility clinics in southeastern Spain. PATIENT(S) Thirty men with poor semen quality (case subjects) and 31 normospermic control subjects of couples attending our fertility clinics. INTERVENTION(S) We recorded dietary habits and nutrient consumption using a food frequency questionnaire adapted to meet specific study objectives. MAIN OUTCOME MEASURE(S) We calculated nutrient intakes by multiplying the frequency of use for each food by the nutrient composition of the portion size specified on the food frequency questionnaire and by addition across all foods to obtain a total nutrient intake for each individual. Semen quality was assessed by measuring volume, concentration, motility, and morphology. Hormones levels were also analyzed in case and control subjects. RESULT(S) In the logistic regression, control subjects had a significantly higher intake of carbohydrates, fiber, folate, vitamin C, and lycopene and lower intakes of proteins and total fat. CONCLUSION(S) A low intake of antioxidant nutrients was associated with a poor semen quality in this case-control study of Spanish men attending infertility clinics.

Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study

BackgroundAnimal studies have shown the reproductive toxicity of a number of heavy metals. Very few human observational studies have analyzed the relationship between male reproductive function and heavy metal concentrations in diverse biological fluids.MethodsThe current study assessed the associations between seminal and hormonal parameters and the concentration of the 3 most frequent heavy metal toxicants (lead, cadmium and mercury) in three different body fluids. Sixty one men attending infertility clinics that participated in a case-control study to explore the role of environmental toxins and lifestyles on male infertility were analyzed. Concentration of lead, cadmium and mercury were measured in blood and seminal plasma and whole blood using anodic stripping voltammetry and atomic absorption spectrophotometry. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone and testosterone. Semen analyses were performed according to World Health Organization criteria. Mann-Whitney test and Spearmans rank correlations were used for unadjusted analyses. Multiple linear regression models were performed controlling for age, body mass index and number of cigarettes per day.ResultsThere were no significant differences between cases and controls in the concentrations of heavy metals in any of the three body fluids. In multivariate analyses using all subjects no significant associations were found between serum hormone levels and metal concentrations. However there was a significant positive association between the percentage of immotile sperms and seminal plasma levels of lead and cadmium.ConclusionsOur results suggest that the presence of lead and cadmium in the reproductive tract of men may be related to a moderate alteration of their seminal parameters.

Anogenital distance is related to ovarian follicular number in young Spanish women: a cross-sectional study.

BackgroundIn animals, anogenital distance (AGD) at birth reflects androgen levels during pregnancy and predicts adult AGD. Little is known about AGD in relation to female reproductive characteristics in humans, a question this study was designed to explore.MethodsWe used multiple linear and logistic regression analyses to model the relationships between adult female reproductive system characteristics (e.g. ovarian morphology, menstrual cycle) and two measures of AGD [anus-fourchette (AGDAF) and anus-clitoris (AGDAC)] in 100 college-age volunteers in Spain. Ovarian morphology was classified as having < 6 or ≥ 6 follicles per ovary.ResultsBoth AGD measures were positively associated with ovarian follicle number, with AGDAF being more strongly associated. Women in the upper tertile of the AGDAF and AGDAC distributions were more likely to have ≥ 6 ovarian follicles [OR: 6.0 (95% CI 2.0, 17.6) and 3.0 (95% CI 1.1, 8.6), respectively] compared to women in the lowest tertile.ConclusionsIncreased follicular recruitment has been related to excess androgen exposure in utero in toxicological studies. Our results suggest that the androgenic environment during early fetal life may influence reproductive system development, including AGD, in human females.

Sperm counts may have declined in young university students in Southern Spain

Several studies have investigated temporal trends in semen quality in Northern Europe, but none has examined this question in Southern Europe. A prior study conducted in Almeria Province (Southern Spain) reported higher sperm count and concentration among Spanish young men recruited from 2001 to 2002 compared with young men from Northern Europe. The aim of this new study was to examine whether semen quality has changed among Spanish young men in the last decade. In this cross‐sectional study, questionnaires and semen samples were collected from 215 healthy young university students from Murcia Region between 2010 and 2011. The 273 men from the Almeria study previously studied were included in a trend analysis of the two populations from Southern Spain. Descriptive statistics were calculated for the Murcia study population and these and semen variables for the Murcia and Almeria study populations were compared. Study methods and population characteristics were similar across the two studies. Therefore, we used multiple linear regression analyses on the combined population (controlling for study centre, age, ejaculation abstinence time, season, smoking, medication during the last 3 months, Body mass index (BMI), presence of varicocoele and prenatal exposure to tobacco) to look for a birth‐cohort effect over the combined study period (2001–2011). Sperm concentration and total sperm count declined significantly with year of birth in the pooled analysis (β = −0.04 and β = −0.06, respectively, both p < 0.01). Sperm counts were significantly lower in Murcia study subjects than in the Almeria participants; sperm concentration median (5th–95th) = 44.0 (8.9–129) million/mL vs. 51.0 (5.0–206) million/mL; p < 0.01 and total sperm count = 121 (17.8–400) million vs. 149 (8.0–599) million; p < 0.01. Other semen variables did not differ significantly between the two studies. Our study suggests that total sperm count and sperm concentration may have declined in young Spanish men over the last decade.

Physical activity and television watching in relation to semen quality in young men

Background Semen quality appears to have declined over the past decades but reasons for this decline are unresolved. The concurrent increase in sedentary behaviour may be a contributing factor. The objective of this study was to evaluate the relationship of physical activity and television (TV) watching with sperm parameters in a population of young, healthy men. Methods Men aged 18–22 years (n=189) from the Rochester Young Mens Study (2009–2010) participated in this analysis. Physical activity (h/week of moderate and vigorous exercise) and TV watching (h/week of TV, video or DVD watching) over the past 3 months were assessed via questionnaire. Semen quality was assessed by sperm concentration, motility, morphology and total sperm count. Results Sperm concentration and total sperm count were directly related to physical activity after multivariable adjustment (p-trend=0.01 and 0.04); men in the highest quartile of moderate-to-vigorous activity (≥15 h/week) had 73% (95% CI 15% to 160%) higher sperm concentration than men in the lowest quartile (<5 h/week). TV watching was inversely associated with sperm concentration and total sperm count in multivariable analyses (p-trend=0.05 and 0.06); men in the highest quartile of TV watching (>20 h/week) had 44% (95% CI 15 to 63%) lower sperm concentration than men in the lowest quartile (0 h/week). These measures of physical and leisure time activities were not significantly associated with sperm motility or morphology. Conclusions In this population of healthy men, higher moderate-to-vigorous activity and less TV watching were significantly associated with higher total sperm count and sperm concentration.

Urinary Concentrations of Di(2-ethylhexyl) Phthalate Metabolites and Serum Reproductive Hormones: Pooled Analysis of Fertile and Infertile Men

Urinary concentrations of metabolites of the anti-androgenic xenobiotic di-(2-ethylhexyl) phthalate (DEHP) were previously shown to be weakly associated with serum levels of several hormones in 2 disparate US populations: partners of pregnant women participating in the Study for Future Families and partners in infertile couples from Massachusetts General Hospital infertility clinic. The observed associations between phthalate metabolites and reproductive hormones were robust and insensitive to the characteristics of the subpopulation or the laboratory in which the hormones were measured, despite the fact that these 2 populations span a range of fertility, urinary phthalate metabolites, and reproductive hormone levels. We therefore examined associations between urinary metabolites of DEHP and reproductive hormones-follicle-stimulating hormone, luteinizing hormone, testosterone (T), inhibin B, and estradiol (E(2))-and sex hormone-binding globulin (SHBG) in the pooled population. The magnitude of the associations seen were similar to those reported for each population separately, but effect estimates were more precise because of the increased sample size and the greater range of phthalate metabolite concentrations and hormone levels. Urinary concentrations of 3 metabolites of DEHP [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were inversely associated with the free androgen index (FAI = T/SHBG) and calculated free testosterone. Urinary concentrations of MEHHP and MEOHP were positively associated with SHBG, and MEHP was inversely associated with E(2). No other phthalate metabolites were associated with serum hormones, consistent with results in each population. Our results in this diverse population suggest that DEHP exposure is robustly associated with some male sex steroid hormones.

Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men

Widely used man-made chemicals, including phthalates, can induce hormonal alterations through a variety of cellular and molecular mechanisms. A number of rodent and observational studies have consistently demonstrated the anti-androgenic effect of several phthalates. However, there are only limited data on the relationship between exposure to these chemicals and reproductive hormone levels in men. All men (n=425) were partners of pregnant women who participated in the Study for Future Families in five US cities and provided urine and serum samples on the same day. Eleven phthalate metabolites were measured in urine and serum samples were analysed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and oestradiol and sex hormone-binding globulin (SHBG). Pearson correlations and parametric tests were used for unadjusted analyses, and multiple linear regression analysis was performed controlling for appropriate covariates. We observed weak or no associations with urinary phthalates other than di(2-ethylhexyl) phthalate (DEHP). All measures of testosterone [total, calculated free testosterone and the free androgen index (FAI)] were inversely correlated with the urinary concentrations of four DEHP metabolites. After adjustment by appropriate covariates, there was no longer an association between urinary DEHP metabolite concentrations and total testosterone levels; however, FAI was significantly associated with the urinary concentrations of several DEHP metabolites. SHBG was positively related to the urinary concentrations of mono(2-ethylhexyl) phthalate, but not with other DEHP metabolites, an association that was attenuated after adjustment. Our results suggest that DEHP exposure of fertile men is associated with minor alterations of markers of free testosterone.