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Biomedical subjects

Tina Kold Jensen

Publications and source records attributed to Tina Kold Jensen.

18 recordsLinked to original sources

Primary testicular failure in Klinefelter's syndrome: the use of bivariate luteinizing hormone-testosterone reference charts.

BACKGROUND: The diagnosis of androgen deficiency is based on clinical features and confirmatory low serum testosterone levels. In early primary testicular failure, a rise in serum LH levels suggests inadequate androgen action for the individual's physiological requirements despite a serum testosterone level within the normal range. The combined evaluation of serum LH and testosterone levels in the evaluation of testicular failure has not been widely advocated. PATIENTS: Seven hundred and six healthy males and 39 patients with known primary hypogonadism due to Klinefelter's syndrome and SRY-positive 46,XX karyotypes were included in the study. DESIGN: Testosterone, oestradiol and LH serum concentrations were measured in all individuals. Based on the 706 healthy males two-dimensional bivariate LH-testosterone reference charts were constructed. RESULTS: Despite a median serum total and free testosterone and oestradiol levels being reduced (P < 0.001) and LH levels elevated (P < 0.001) in Klinefelter's syndrome and 46,XX-males, many subjects (69%) had total testosterone within the reference range. However, using the bivariate charts all subjects lay outside the 97.5 percentile. CONCLUSION: Bivariate LH and testosterone charts are useful in the evaluation of men with known primary testicular failure due to sex chromosomal aneuploidy in whom evaluation based on testosterone measurement in isolation underestimates the prevalence of hypogonadism. It is, however, important to emphasize that isolated use of the bivariate evaluation should not form the basis for androgen substitution therapy. Further studies are needed in order to evaluate the use of bivariate LH and testosterone charts in the assessment of any younger man with possible primary testicular failure.

Adult↗

Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population.

Little is known the about the reproductive health of offspring after fertility treatment. In 2001-2005, the authors approached young Danish men attending a compulsory physical examination to determine their fitness for military service. A total of 1,925 men volunteered, delivered a semen sample, had a physical examination performed and a blood sample drawn, and responded to a questionnaire. Their mothers were questioned about whether they had received fertility treatment in order to conceive their sons. Forty-seven mothers reported having received fertility treatment to conceive the index subject. After control for confounders, men whose mothers had received fertility treatment to conceive them had a 46% lower sperm concentration (95% confidence interval (CI): -63, -20) and a 45% lower total sperm count (95% CI: -64, -16). They had a smaller testis size (-0.9 ml, 95% CI: -2.2, 0.4), fewer motile sperm (-4.0%, 95% CI: -8.0, -0.1), and fewer morphologically normal spermatozoa (-2.0%, 95% CI: -4.1, 0.0). They also had a lower serum testosterone level and free androgen index (results not statistically significant). These findings should be viewed in light of the increasing use of fertility treatments. Although the cause of these findings is unknown, they raise concern about possible late effects of fertility treatment. Larger-scale studies of children born after fertility treatment should be performed.

Adult↗

The influence of occupational exposure on male reproductive function.

Recently, many studies have found a decrease in semen quality which has increased the focus on male reproductive health. Occupational hazards are by far the best documented in reproductive epidemiological research. Generally, occupational exposures have been divided into physical exposures (heat and radiation), chemical exposures (solvents and pesticides), psychological exposures (distress), exposure to metals and welding. The recent and/or most important epidemiological studies exploring the effect of occupational exposures on semen quality and fecundity, the ability to conceive, are reviewed. The evidence for an adverse effect on male reproduction of several occupational and environmental exposures and toxicants, such as heat, ionizing radiation, inorganic lead, dibromochloropropane, ethylene dibromide, some ethylene glycol ethers, carbon disulfide and welding operations, is strongly supported in well-designed epidemiological studies. For other agents, the association is only suspected or suggested and needs further evaluation before conclusions can be drawn. It is also important to bear in mind that many workers in the non-Western world still are exposed to substances that are banned in the Western world, sometimes in high concentrations.

Fertilization↗

Is human fecundity declining?

Summary The decreasing trends in fertility rates in many industrialized countries are now so dramatic that they deserve much more scientific attention. Although social and behavioural factors undoubtedly play a major role for these trends, it seems premature, and not based on solid information, to conclude that these trends can be ascribed to social and behavioural changes alone. There is evidence to suspect that changing lifestyle and increasing environmental exposures, e.g. to endocrine disrupters, are behind the trends in occurrence of male reproductive health problems, including testis cancer, undescended testis and poor semen quality. These biological factors may also contribute to the extremely low fertility rates. However, the necessary research is complex and requires non-traditional collaboration between demographers, epidemiologists, clinicians, biologists, wild life researchers, geneticists and molecular biologists. This research effort can hardly be carried out without major support from governments and granting agencies making it possible to fund collaborative projects within novel research networks of scientists.

Environmental Pollutants↗

Increased risk of precocious puberty in internationally adopted children in Denmark.

BACKGROUND: Studies have indicated that internationally adopted children have an increased risk of developing precocious puberty, but no epidemiologic risk estimates have previously been calculated. We aimed to assess the risk of developing precocious puberty in intercountry adoptees, children immigrating with their family, and descendants of immigrants living in Denmark. METHODS: Patients who were registered with the diagnosis of precocious puberty during the period 1993-2001 were identified through the national patient registry. The background population of children born from 1983 to 2001 were identified through the unique Danish Civil Registration System and subsequently categorized as being Danish (N = 1,062,333), adopted (N = 10,997), immigrating with their family (N = 72,181), or being descendants of immigrants (N = 128,152). The incidence rate ratio of precocious puberty was estimated by log-linear Poisson regression. All rate ratios were adjusted for age and its interaction with gender and calendar year. P values were based on likelihood ratio tests, and 95% confidence intervals were calculated by Wald's test. RESULTS: In the study period, 655 children developed precocious puberty during 5,627,763 person-years at risk. Adopted children were followed during 39,978 person-years at risk, during which 45 girls and 6 boys developed precocious puberty. The risk of developing precocious puberty was significantly increased 10 to 20 times in adopted girls compared with girls with Danish background. The risk of developing precocious puberty depended on the country of origin. In children immigrating with their family, the risk of developing precocious puberty was only marginally increased. Older age at adoption significantly increased the risk of precocious puberty in adoptees independent of region of origin. The incidence rate ratio was significantly higher in children adopted after the age of 2. In children immigrating with their family, we found no effect of age at migration. DISCUSSION: In this large, nationwide, register-based study including 655 cases of precocious puberty, we found that intercountry boys and girls were 10 to 20 times more likely to develop precocious puberty compared with the Danish reference group. Older age at adoption significantly increased the risk of precocious puberty. Uncertainty of the exact age is a well-known problem in adopted children, and systematic underestimation of age might bias the result. However, using the worst-case scenario that all children who according to the Danish Civil Registration System were adopted after 2 years of age were in fact 1 year older, we still observed a highly increased risk of precocious puberty associated with adoption and especially with adoption after 2 years of age. Surprisingly, the risk of precocious puberty was not increased in the large group of children adopted from Korea. One case of precocious puberty was identified among Korean children, whereas > 20 cases of precocious puberty would have been expected if the risk for a Korean child was at the same level as observed among adopted children from India and South America. In the study population, 99% of Korean children were adopted before 2 years of age, which may contribute to explaining our finding. In Korea, children appointed for adoption are often living in foster care settings from birth to adoption, whereas most other countries are reported to take care of the children in orphanages before adoption. It can only be speculated whether a relation between preadoption living conditions and later risk of precocious puberty exists. Genetic factors play a key role in the timing of puberty, and large variations in age at menarche are observed worldwide. Age at menarche is reported to be in the same age range in South Korea as in well-off populations in other parts of the world, indicating that the different risk of precocious puberty observed between Korean and other adoptees probably cannot be explained by genetic factors alone. The finding that the risk of precocious puberty was significantly increased among adoptees in contrast to what was seen in children immigrating with their families contradicts a direct effect of migration. An increasing number of studies have shown long-term effects of certain prenatal and postnatal growth patterns, including advancement in pubertal maturation after poor intrauterine growth and catch-up growth during childhood. Different growth patterns and dietary habits between adoptees and children immigrating with their families might contribute to explain our findings. It has been hypothesized that stressful psychosocial factors in infancy and childhood may lead to earlier pubertal maturation. In general, adoptees have experienced several traumatic life events, and it may be speculated that these events alter the susceptibility for developing precocious puberty. CONCLUSIONS: Foreign-adopted children originating from regions other than Korea had a 15- to 20-fold increased risk of precocious puberty compared with Danish-born children, whereas adoptees originating from Korea had no increased risk of precocious puberty. In addition, children immigrating with their families had no increased risk of precocious puberty. The effect of country of origin might be explained by genetic factors or by different environmental exposures and living conditions in the different countries. Older age at adoption increased the risk for premature onset of puberty, which may suggest that environmental factors influence the risk of precocious pubertal development in adopted children.

Adoption↗

Studying time to pregnancy by use of a retrospective design.

Biologic fertility can be measured using time to pregnancy (TTP). Retrospective designs, although lacking detailed timed information about behavior and exposure, are useful since they have a well-defined target population, often have good response rates, and are simpler and less expensive to conduct than prospective studies. This paper reviews retrospective TTP studies from a methodological viewpoint and shows how methodological problems can be avoided or minimized by appropriate study design, conduct, and analysis. Sensitivity analyses using data from four European retrospective TTP studies are presented to explore the issues. Although the identified biases tend to have small impacts, the effects are not systematic across studies, and sensitivity analyses are recommended routinely. Planning bias can be checked by comparing propensity to report contraceptive failures in different exposure groups. Medical intervention bias can be avoided by censoring and inclusion of unsuccessful pregnancy attempts. Truncation bias can be a serious problem if unrecognized, but it is avoidable with appropriate study design and/or analysis. Behavior change bias can be minimized by assessing the covariates at the beginning of unprotected intercourse. More complete inference is possible if the study design covers the whole population, not just those who achieve a pregnancy.

Bias↗

Time trends in waiting time to pregnancy among Danish twins.

BACKGROUND: Little is known about time trends in fecundity because few population-based data are available. In a survey among female twins born from 1953 to 1976, their time to pregnancy did not differ from singletons and can be considered to represent the fecundity of the general population. METHODS: Information was collected by interview about waiting time to first pregnancy (TTP) and any periods of subfecundity among both male and female twins born between 1931 and 1952. Trends were analysed by considering the year of birth of the index person (birth cohort effect) or year at which the first attempt started (period effect). RESULTS: Eighty-five percent of male and 81.3% of female eligible twins participated. A total of 1598 male twins and 1653 female twins reported a TTP value and 1671 men and 1715 women had a value for their first attempt to conceive including unsuccessful attempts. No overall trends in either male or female TTP were observed with increasing year of birth or of starting time, after adjustment for confounders, but for attempts fecundity increased among female twins by year of birth or of starting the attempt. A decreasing risk of severe infertility with increasing year of birth or year for start of the attempt was observed among male twins, but this observation was based on only 81 men and was not seen among female twins. CONCLUSION: No decreasing trend in fecundity was observed among Danish twins born between 1931 and 1952 who had completed their reproduction. Female twins had a slight increase in fecundity, and men a decrease in severe infertility. In addition, TTP was apparently well reported and recalled for up to 50 years among both male and female twins.

Adult↗

Effects of breast feeding on neuropsychological development in a community with methylmercury exposure from seafood.

Breastfeeding has been associated with an advantage to infant neurobehavioral development, possibly in part due to essential nutrients in breast milk. However, breast milk may be contaminated by environmental neurotoxicants, such as methylmercury. In the Faroe Islands, where maternal consumption of pilot whale may cause transfer of marine toxicants into breast milk, a cohort of 1022 consecutive singleton births was generated during 1986-87. Methylmercury exposure was assessed from mercury concentrations in cord blood and in the hair of the child at age 12 months, and the duration of breastfeeding was recorded. At approximately 7 years of age, 917 (90%) of the children underwent detailed neurobehavioral examination. After adjustment for confounders, breastfeeding was associated with only marginally better neuropsychological performance on most tests. These associations were robust even after adjustment for cord-blood and hair mercury concentration at age 1 year. Thus, in this cohort of children with a relatively high prenatal toxicant exposure and potential exposure to neurotoxicants through breast milk, breastfeeding was associated with less benefits on neurobehavioral development than previously published studies though not associated with a deficit in neuropsychological performance at age 7. Although the advantage may be less, Faroese women can still safely breastfeed their children.

Adult↗

Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries.

OBJECTIVE: To our knowledge, no population-based epidemiologic studies on the incidence and prevalence of precocious pubertal development have been published. Danish national registries provide sufficient data for estimating the prevalence and incidence of this condition. The aim of this study was to estimate the prevalence and incidence of precocious pubertal development in Denmark in a 9-year period. METHODS: The age- and gender-specific incidence rates as well as prevalence rates of precocious pubertal development in Denmark were estimated using data from the Danish National Patient Registry and Statistics Denmark from 1993 to 2001. RESULTS: Overall, 670 children with precocious pubertal development were registered with a diagnosis of precocious puberty (PP) from 1993 to 2001, corresponding to 50 to 70 new cases of PP per year in Denmark. The incidence of PP was constant during the study period from 1993 to 2001. The incidence of PP subdivided by gender and age at diagnosis was approximately 0.5 per 10000 in girls who were younger than 2 years, decreasing to levels below 0.05 per 10000 in girls aged 2 to 4 years, thereafter gradually rising to 8 per 10000 for girls aged 5 to 9 years. For boys who were younger than 8 years, the incidence was very low (<1 per 10000) and increased only slightly to 1 to 2 per 10000 in boys aged 8 to 10 years. The prevalence of PP was approximately 20 to 23 per 10000 in girls, whereas the prevalence was fivefold lower for boys (<5 per 10000). CONCLUSIONS: From this first epidemiologic study based on national registries, we estimated that 0.2% of all Danish girls and <0.05% of Danish boys had some form of precocious pubertal development.

Age Distribution↗

Alcohol consumption at the time of conception and spontaneous abortion.

The authors studied the association between female and male alcohol intakes at the time of conception and the risk of spontaneous abortion, including early pregnancy loss detected by urinary human chorionic gonadotropin. After a nationwide mailing to about 50,000 members of four trade unions in Denmark in 1992-1994, 430 couples without previous pregnancy attempts were enrolled when birth control was discontinued, and they were followed until a clinically recognized pregnancy or for six menstrual cycles. Alcohol intake and potential confounding factors were reported in monthly questionnaires. Women collected morning urine for 10 days from the first day of vaginal bleeding in each cycle. The authors detected 186 pregnancies: 131 resulted in childbirth, and 55 resulted in spontaneous abortion (34 detected by urinary human chorionic gonadotropin). Depending on the intake in the cycle of conception and the adjustment factors, female alcohol intake was associated with 2-3 times the adjusted risk of spontaneous abortion compared with no intake, and male alcohol intake was associated with 2-5 times the adjusted risk. Only the adjusted relative risks for 10 or more drinks/week compared with no intake were statistically significant. Both male and female alcohol intakes during the week of conception increased the risk of early pregnancy loss.

Abortion, Spontaneous↗

Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries.

Between 1996 and 1999, the authors invited all young men from five European countries who were undergoing compulsory medical examination for possible military service to participate in a study on male reproductive health. The participation rate was 19% in two cities in Denmark (n = 889), 17% in Oslo, Norway (n = 221), 13% in Turku, Finland (n = 313), 14% in Kaunas, Lithuania (n = 157), and 19% in Tartu, Estonia (n = 190). Each man provided a semen sample, was examined by a physician, and, in collaboration with his mother, completed a questionnaire about general and reproductive health, current smoking habits, and exposure to smoking in utero. After adjustment for confounding factors, men exposed to smoking in utero had a reduction in sperm concentration of 20.1% (95% confidence interval (CI): 6.8, 33.5) and a reduction in total sperm count of 24.5% (95% CI: 9.5, 39.5) in comparison with unexposed men. Percentages of motile and morphologically normal sperm cells were 1.85 (95% CI: 0.46, 3.23) and 0.64 (95% CI: -0.02, 1.30) percentage points lower, respectively, among men exposed in utero, and exposed men had a 1.15-ml (95% CI: 0.66, 1.64) smaller testis size. The associations were present when data from the study centers were analyzed separately (though not in Lithuania, where only 1% of mothers smoked during pregnancy), although the strength of the association varied. Maternal smoking may have long-term implications for the reproductive health of the offspring. This is another good reason to advise pregnant women to avoid smoking.

Adolescent↗

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.

Adolescent↗

Frequent polymorphism of the mitochondrial DNA polymerase gamma gene (POLG) in patients with normal spermiograms and unexplained subfertility.

BACKGROUND: Male fertility largely depends on the quality of sperm production, which may be affected by environmental and genetic factors. In this study, we explored a possible role of the polymerase gamma (POLG) gene polymorphism, recently reported to be associated with male infertility in some populations. METHODS: The polymorphic CAG repeat (usually 10 codons long) in the POLG gene was studied in 1298 male subjects: 429 patients with infertility/subfertility, and 869 controls (495 men from the general population with unknown fertility and 374 recent fathers). In all subjects, the POLG polymorphism was assessed in relation to their semen quality, and--in the fertile controls--with biological fecundity measured as waiting time-to-pregnancy (TTP) for the couples. In the patients lacking the common POLG allele, the outcome of the assisted reproductive techniques (ART) for the couples was evaluated. RESULTS: The absence of one (10/ not equal to 10) or both common POLG alleles (not equal to 10/not equal to 10) was more frequent among the subfertile patients than among fertile controls (P=0.021 and P=0.04 respectively). The estimated predictive value for infertility in a man homozygous for the POLG polymorphism was 15.5% (95% CI: 4.8-51%). There was a positive association with sperm concentration: 14.3% of the normospermic subfertile patients were homozygous for the absence of the common POLG allele (not equal to 10/not equal to 10), in comparison with 2.3% of unselected controls (P=0.001) and 0.9% of the fertile men (P=0.0001). No association with sperm motility, morphology and TTP was found. Spermatozoa of the three not equal to 10/not equal to 10 patients treated with IVF retained the ability to penetrate the egg, but the fertilization rate was low. Nine homozygous not equal to 10/ not equal to 10 patients were treated with ICSI, resulting in pregnancy in seven couples. CONCLUSIONS: The POLG gene polymorphism should be considered as a possible contributing factor in patients with unexplained subfertility and normal spermiograms. The oocyte penetration ability of sperm may be partially impaired in the not equal to 10/not equal to 10 patients but most of them can be successfully treated with ICSI.

Adult↗

Poor semen quality may contribute to recent decline in fertility rates.

During past decades, we have witnessed a remarkable decline in fertility rates (number of births per 1000 women of reproductive age) in the industrialized world. It seems beyond doubt that the enormous social changes of our societies play the major role in this decline, but can it be attributed to changing social structures alone or is a reduced fecundity in the population also a factor? To address this we have focused on trends in teenage pregnancies (which to a large extent are unplanned). During the period in question fertility rates among 15-19 year old Danish women have been falling and the decline in fertility rate is not counterbalanced by an increase in the rate of induced abortion. When seen together with recent results from Denmark, which have shown that more than 30% of 19 year old men from the general population now have sperm counts in the subfertile range, we argue that this fall may not be attributable to social factors, changes in conception practices or diminished sexual activity alone. It seems reasonable also to consider widespread poor semen quality among men as a potential contributing factor to low fertility rates among teenagers. Due to the concern caused by the low sperm count among younger Danish men, the Danish Ministries of Health and Environment have launched a surveillance programme which includes an annual examination of the semen quality in 600 young Danes from the general population. We propose that researchers in other countries with low and falling fertility rates among young women should consider the possibility that semen quality of their younger male cohorts may also have deteriorated.

Adolescent↗

East-West gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland.

BACKGROUND: Denmark and Norway have a three-fold higher incidence of testicular cancer than Estonia and Finland. Groups of young men from Denmark, Norway, Finland and Estonia were investigated to elucidate whether semen parameters and other related parameters follow a gradient between these countries, as does the gradient in incidence of testicular cancer. METHODS: In total, 968 young men from the general population in these four countries were investigated according to the same protocol. Possible confounders were evaluated, and included in the statistical analysis when appropriate. Inter-laboratory differences in assessment of sperm concentrations were controlled by an external quality control programme and morphology assessment was centralized to one person. RESULTS: The Finnish and Estonian men had an adjusted median sperm concentration of 54 and 57 x 10(6)/ml, respectively and the Norwegian and Danish men 41 x 10(6)/ml. The corresponding total sperm counts were 185, 174, 133 and 144 x 10(6). The frequency of normal sperm in men from Finland was 8.9%, Estonia 9.2%, Norway 6.9% and Denmark 6.4%. Within all four groups of men, a relationship between increasing levels of inhibin-B and increasing sperm counts was observed. However, inhibin-B levels were not predictive of sperm count differences between countries. CONCLUSIONS: It is believed that the men examined were representative of the normal population of young men in all four countries as they were recruited from groups attending a compulsory medical examination, and not selected for known fertility or semen quality. Moreover, the majority of participants had no prior knowledge of their fertility potential. It appears that an east-west gradient exists in the Nordic-Baltic area with regard to semen parameters, this being in parallel with the incidences of testicular cancer. Further investigations are required to determine whether these findings are due to genetic differences, to different environments, or perhaps to a combination of both factors.

Adult↗