Tina Kold Jensen

Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men

Objectives Considerable interest and controversy over a possible decline in semen quality during the 20th century raised concern that semen quality could have reached a critically low level where it might affect human reproduction. The authors therefore initiated a study to assess reproductive health in men from the general population and to monitor changes in semen quality over time. Design Cross-sectional study of men from the general Danish population. Inclusion criteria were place of residence in the Copenhagen area, and both the man and his mother being born and raised in Denmark. Men with severe or chronic diseases were not included. Setting Danish one-centre study. Participants 4867 men, median age 19 years, included from 1996 to 2010. Outcome measures Semen volume, sperm concentration, total sperm count, sperm motility and sperm morphology. Results Only 23% of participants had optimal sperm concentration and sperm morphology. Comparing with historic data of men attending a Copenhagen infertility clinic in the 1940s and men who recently became fathers, these two groups had significantly better semen quality than our study group from the general population. Over the 15 years, median sperm concentration increased from 43 to 48 million/ml (p=0.02) and total sperm count from 132 to 151 million (p=0.001). The median percentage of motile spermatozoa and abnormal spermatozoa were 68% and 93%, and did not change during the study period. Conclusions This large prospective study of semen quality among young men of the general population showed an increasing trend in sperm concentration and total sperm count. However, only one in four men had optimal semen quality. In addition, one in four will most likely face a prolonged waiting time to pregnancy if they in the future want to father a child and another 15% are at risk of the need of fertility treatment. Thus, reduced semen quality seems so frequent that it may impair the fertility rates and further increase the demand for assisted reproduction.

Endocrine-disrupting chemicals and obesity development in humans: A review

This study reviewed the literature on the relations between exposure to chemicals with endocrine‐disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine‐disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta‐hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors.

Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

BACKGROUND More than half of pregnant women in the Western world report intake of mild analgesics, and some of these drugs have been associated with anti-androgenic effects in animal experiments. Intrauterine exposure to anti-androgens is suspected to contribute to the recent increase in male reproductive problems, and many of the anti-androgenic compounds are like the mild analgesics potent inhibitors of prostaglandin synthesis. Therefore, it appears imperative to further investigate the potential endocrine disrupting properties of mild analgesics. METHODS In a prospective birth cohort study, 2297 Danish and Finnish pregnant women completed a questionnaire and 491 of the Danish mothers participated in a telephone interview, reporting on their use of mild analgesics during pregnancy. The testicular position of newborns was assessed by trained paediatricians. In rats, the impact of mild analgesics on anogenital distance (AGD) after intrauterine exposure was examined together with the effect on ex vivo gestational day 14.5 testes. RESULTS In the Danish birth cohort, the use of mild analgesics was dose-dependently associated with congenital cryptorchidism. In particular, use during the second trimester increased the risk. This risk was further increased after the simultaneous use of different analgesics. The association was not found in the Finnish birth cohort. Intrauterine exposure of rats to paracetamol led to a reduction in the AGD and mild analgesics accordingly reduced testosterone production in ex vivo fetal rat testes. CONCLUSION There was an association between the timing and the duration of mild analgesic use during pregnancy and the risk of cryptorchidism. These findings were supported by anti-androgenic effects in rat models leading to impaired masculinization. Our results suggest that intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders.

Low concentration of circulating antimüllerian hormone is not predictive of reduced fecundability in young healthy women: a prospective cohort study.

OBJECTIVE To evaluate whether circulating levels of antimüllerian hormone (AMH) predict fecundability in young healthy women. DESIGN Prospective cohort study. SETTING General community. PATIENT(S) A total of 186 couples who intended to discontinue contraception to become pregnant were followed until pregnancy or for six menstrual cycles. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Fecundability was evaluated by the monthly probability of conceiving (i.e., fecundability ratio [FR]). In addition, circulating levels of LH, FSH, T, and sex hormone-binding globulin (SHBG) were evaluated in 158 of 186 women. RESULT(S) Fifty-nine percent of couples conceived during the study period. Compared to the reference group of women with medium AMH (AMH quintiles 2-4), fecundability did not differ significantly in women with low AMH (AMH quintile 1) (FR 0.81; 95% confidence interval [CI] 0.44-1.40). In contrast, women with high AMH (AMH quintile 5) had reduced fecundability (FR 0.62; 95% CI 0.39-0.99) after adjustment for covariates (womans age, body mass index [BMI], smoking, diseases affecting fecundability, and oligozoospermia). Irregular menstrual cycles were more prevalent in women with high AMH compared with women with low or medium AMH levels, and they had higher levels of LH (geometric mean: 8.4 vs. 5.3 IU/L) and LH:FSH ratio (2.4 vs. 1.8). After exclusion of women with irregular cycles, women with high AMH still had reduced fecundability (FR 0.48; 95% CI 0.27-0.85) and elevated LH:FSH ratio (2.4 vs. 1.7). CONCLUSION(S) Low AMH in healthy women in their mid-20s did not predict reduced fecundability. Even after exclusion of women with irregular cycles, the probability of conceiving was reduced in women with high AMH.

Association between Pregnancy Loss and Urinary Phthalate Levels around the Time of Conception

Background: Animal studies indicate that some phthalate metabolites may harm female reproductive function. Objectives: We assessed the associations between exposure to phthalate metabolites and pregnancy loss. Methods: Using a previously established cohort of couples planning their first pregnancy, we analyzed four primary and two oxidized secondary phthalate metabolites in urine samples collected on day 10 after the first day of the last menstrual period before conception occurred (n = 128) and during the previous cycle (if any, n = 111). Subclinical embryonal loss was identified by repeated measurement of urinary human chorionic gonadotropin, and information on clinical spontaneous abortions was obtained by telephone interview with the mother. Results: Pregnancy loss (n = 48) was increased among women with urinary concentration of monoethylhexyl phthalate (MEHP) in the upper tertile in the conception sample compared with women in the lowest tertile [adjusted odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.1, 7.6]. The corresponding OR for subclinical embryonal loss (n = 32) was 40.7 (95% CI: 4.5, 369.5). Conclusions: The phthalate metabolite MEHP was associated with higher occurrence of pregnancy loss. Because this is the first human study to show this association and the sample size is small, the findings need to be corroborated in independent studies.

The Relationship Between Anogenital Distance and Reproductive Hormone Levels in Adult Men

PURPOSE Anogenital distance is a marker for endocrine disruption in animal studies in which decreased distance has been associated with testicular dysfunction. In this study we investigated whether anogenital distance was associated with reproductive hormone levels in adult men. MATERIALS AND METHODS A total of 116 men (mean age 36.1 ± 8.0 years) were evaluated at an andrology clinic in Houston. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length were measured using digital calipers. Testis size was estimated by physical examination. Linear regression was used to determine correlations between genital measurements and hormone levels. RESULTS Anogenital distance (r = 0.20, p = 0.03) and penile length (r = 0.20, p = 0.03) were significantly associated with serum testosterone levels while total testis size was not (r = 0.17, p = 0.07). No relationship between genital length and luteinizing hormone, follicle-stimulating hormone or estradiol was identified. After adjusting for age the serum testosterone increased by 20.1 ng/dl (95% CI 1.8, 38.4; p = 0.03) for each 1 cm increase in anogenital distance. On multivariable models no statistically significant relationship existed between penile length and testosterone levels. Moreover men with hypogonadal testosterone levels (less than 300 ng/dl) had a significantly shorter anogenital distance compared to men with higher testosterone levels (31.6 vs 37.3 mm, p = 0.02). CONCLUSIONS Anogenital distance may provide a novel metric to assess testicular function in men. Assuming that anogenital distance at birth predicts adult anogenital distance, our findings suggest a fetal origin for adult testicular function.

Caffeine Intake and Semen Quality in a Population of 2,554 Young Danish Men

The authors examined the association between semen quality and caffeine intake among 2,554 young Danish men recruited when they were examined to determine their fitness for military service in 2001-2005. The men delivered a semen sample and answered a questionnaire including information about caffeine intake from various sources, from which total caffeine intake was calculated. Moderate caffeine and cola intakes (101-800 mg/day and < or =14 0.5-L bottles of cola/week) compared with low intake (< or =100 mg/day, no cola intake) were not associated with semen quality. High cola (>14 0.5-L bottles/week) and/or caffeine (>800 mg/day) intake was associated with reduced sperm concentration and total sperm count, although only significant for cola. High-intake cola drinkers had an adjusted sperm concentration and total sperm count of 40 mill/mL (95% confidence interval (CI): 32, 51) and 121 mill (95% CI: 92, 160), respectively, compared with 56 mill/mL (95% CI: 50, 64) and 181 mill (95% CI: 156, 210) in non-cola-drinkers, which could not be attributed to the caffeine they consumed because it was <140 mg/day. Therefore, the authors cannot exclude the possibility of a threshold above which cola, and possibly caffeine, negatively affects semen quality. Alternatively, the less healthy lifestyle of these men may explain these findings.

Prenatal and adult exposures to smoking are associated with adverse effects on reproductive hormones, semen quality, final height and body mass index

BACKGROUND Exposure to tobacco smoking prenatally is a risk factor for reduced semen quality, but whether the exposure has adverse effects on reproductive hormones, pubertal development or adult BMI remain largely unexplored. The aim of this study was to investigate the associations between these factors while controlling for the effects of current smoking in young adulthood. METHODS This cross-sectional study (1996-2006) included 3486 Danish men (median age: 19 years), participating in a semen-quality study. Data were obtained from questionnaires, physical examinations, semen analyses and assessments of reproductive hormones. The main outcome measures were markers of pubertal onset, BMI, reproductive hormones and semen variables. RESULTS Maternal smoking during pregnancy was associated with earlier onset of puberty (e.g. early pubic hair development in 25.2 versus 18.9% of unexposed subjects), lower final adult height (median: 1.80 versus 1.82 cm), higher BMI (22.9 versus 22.4), smaller testicles (14.0 versus 14.5 ml), lower total sperm counts (119 versus 150 million), reduced spermatogenesis-related hormones (e.g. inhibin-B/FSH 66 versus 73 pg/mU) and higher calculated free testosterone (free-T, 2.38 versus 2.33 nmol/l). If not exposed prenatally, mens own smoking was associated with increased total testosterone but unchanged free-T. For smokers who had been exposed prenatally, total testosterone was increased but free-T was reduced (2.30 versus 2.38 nmol/l, P = 0.003) due to higher levels of sex hormone-binding globulin. CONCLUSIONS Prenatal exposure to tobacco may lead to faster pubertal development possibly caused by a higher free-T, and to higher adult BMI and impairment of testicular function. The findings may not be clinical relevant for the individual but are of public health importance, and add to the knowledge of effects of tobacco smoking.

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.

Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: a prospective study

BackgroundEndocrine disrupting chemicals have been hypothesized to play a role in the obesity epidemic. Long-term effects of prenatal exposure to non-persistent pesticides on body composition have so far not been investigated. The purpose of this study was to assess possible effects of prenatal exposure to currently used pesticides on childrens growth, endocrine and reproductive function.MethodsIn a prospective study of 247 children born by women working in greenhouses in early pregnancy, 168 were categorized as prenatally exposed to pesticides. At three months (n = 203) and at 6 to11 years of age (n = 177) the children underwent a clinical examination and blood sampling for analysis of IGF-I, IGFBP3 and thyroid hormones. Body fat percentage at age 6 to11 years was calculated from skin fold measurements. Pesticide related associations were tested by linear multiple regression analysis, adjusting for relevant confounders.ResultsCompared to unexposed children birth weight and weight for gestational age were lower in the highly exposed children: -173 g (-322; -23), -4.8% (-9.0; -0.7) and medium exposed children: -139 g (-272; -6), -3.6% (-7.2; -0.0). Exposed (medium and highly together) children had significantly larger increase in BMI Z-score (0.55 SD (95% CI: 0.1; 1.0) from birth to school age) and highly exposed children had 15.8% (0.2; 34.6) larger skin folds and higher body fat percentage compared to unexposed. If prenatally exposed to both pesticides and maternal smoking (any amount), the sum of four skin folds was 46.9% (95% CI: 8.1; 99.5) and body fat percentage 29.1% (95% CI: 3.0; 61.4) higher. There were subtle associations between exposure and TSH Z-score -0.66(-1.287; -0.022) and IGF-I Z-score (girls: -0.62(-1.0; -0.22), boys: 0.38(-0.03; 0.79)), but not IGFBP3.ConclusionsOccupational exposure to currently used pesticides may have adverse effects in spite of the added protection offered to pregnant women. Maternal exposure to combinations of modern, non-persistent pesticides during early pregnancy was associated with affected growth, both prenatally and postnatally. We found a biphasic association with lower weight at birth followed by increased body fat accumulation from birth to school age. We cannot rule out some residual confounding due to differences in social class, although this was adjusted for. Associations were stronger in highly exposed than in medium exposed children, and effects on body fat content at school age was potentiated by maternal smoking in pregnancy.