Depression in Mid- and Later-Life and Risk of Dementia in Women: A Prospective Study within the Danish Nurses Cohort

BACKGROUND: Depression and dementia confer substantial global health burdens, particularly in women. Understanding the association between depression and dementia may inform new targets for prevention and/or early intervention. OBJECTIVE: To investigate the association between depression in mid- and later-life and dementia (all-cause, Alzheimer's disease (AD) or vascular dementia (VaD)) in women. METHODS: A prospective study design. Nurses were followed from age 60 years or entry into the cohort, whichever came last, until date of dementia, death, emigration, or end of follow-up, whichever came first. Cox regression models with age as the underlying timeline were used to estimate the associations between time-varying depression and incident dementia. RESULTS: The study included 25,651 female Danish nurses (≥45 years) participating in the Danish Nurse Cohort. During an average of 23 years of follow-up, 1,232 (4.8%) nurses developed dementia and 8,086 (31.5%) were identified with at least two episodes of treated depression. In adjusted analyses, nurses with depression were at a statistically significant 5.23-fold higher risk of all-cause dementia (aHR 5.23:95% CI, 4.64-5.91) compared to those with no history of depression. The differential effects of depression were greater for VaD (aHR 7.96:95% CI, 5.26-12.0) than AD (aHR 4.64:95% CI, 3.97-5.42). Later life depression (>60 years) (aHR 5.85:95% CI, 5.17-6.64) and recurrent depression (aHR 3.51:95% CI, 2.67-4.61) elevated dementia risk. Severe depression tripled the risk of all cause dementia (aHR 3.14:95% CI, 2.62-3.76). CONCLUSION: Both later life and severe depression substantially increase dementia risk in women, particularly VaD

Serum Testosterone Levels in 3-Month-Old Boys Predict Their Semen Quality as Young Adults

ContextIt remains unknown how the postnatal activation of the hypothalamic-pituitary-gonadal axis in infancy, also known as "minipuberty", relates to adult testis function.ObjectiveTo investigate how markers of reproductive function in 3-month-old boys correlate with adult reproductive health parameters.MethodsThis population-based birth cohort study (the Copenhagen Mother-Child cohort), conducted at Copenhagen University Hospital, Denmark, included 259 boys examined once around 3 months of age and again at 18 to 20 years. Reproductive hormones, penile length, testis volume, and semen quality were analyzed. Minipubertal markers of testis function (by tertiles, T1-T3) were explored as predictors of adult semen quality using linear regression models. Associations between reproductive outcomes in infancy and young adulthood were estimated by intraclass correlation coefficients (ICCs), describing how well measurements in infancy correlate with those in adulthood.ResultsSerum testosterone concentration in infancy was positively associated with adult total sperm count. Median (IQR) total sperm count was 84 (54-138) million spermatozoa for boys in T1, 141 (81-286) million spermatozoa in T2, and 193 (56-287) million spermatozoa in T3. We found the highest ICC for FSH (0.41; 95% CI, 0.26-0.57), while ICCs for inhibin B, SHBG, penile length, and testis volume ranged between 0.24 and 0.27. ICCs for LH and for total and free testosterone were lower and statistically nonsignificant.ConclusionSerum testosterone in infancy was a predictor of adult total sperm count. Other reproductive hormones and genital measures showed good correlation between infancy and adulthood, suggesting that an individual's reproductive setpoint starts shortly after birth in boys and persists until adulthood.</p

Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome

Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9–20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of tr eatment status. In patients evaluated before and during TRT, a tendency toward a more benefi cial body composition with a significant reduction in the ratio between android fat pe rcentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly low er when compared to the reference. This study confirms that patients with KS have an unf avorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters

Combined exposures to bisphenols, polychlorinated dioxins, paracetamol, and phthalates as drivers of deteriorating semen quality

Background Semen quality in men continues to decline in Western countries, but the contours of the issue remain obscure, in relation to contributing chemicals. Objectives To obtain more clarity about the chemicals that drive the deterioration of semen quality, we conducted a mixture risk assessment based on European exposures. Methods We included chemicals capable of affecting semen quality after prenatal exposures, among them androgen receptor antagonists, substances that disrupt prostaglandin signalling, suppress testosterone synthesis, inhibit steroidogenic enzymes or activate the aryl hydrocarbon receptor. We employed the Hazard Index approach (HI), based on risk quotients of exposures in Europe and reference doses for reductions in semen quality. By summing up the risk quotients of the 29 chemicals included in the assessment we examined fold-exceedances of “acceptable” mixture exposures relative to an index value of 1. For bisphenols A, F, S, phthalates DEHP, DnBP, BBzP, DiNP, n-butyl paraben and paracetamol we relied on biomonitoring studies in which these 9 chemicals were measured together in the same subjects. This allowed us to construct personalised Hazard Indices. Results Highly exposed subjects experienced combined exposures to the 9 chemicals that exceeded the index value of 1 by more than 100-fold; the median was a 17-fold exceedance. Accounting for median background exposures to the remaining 20 chemicals added a Hazard Index of 1.39. Bisphenol A made the largest contribution to the HI, followed by polychlorinated dioxins, bisphenols S and F and DEHP. Eliminating bisphenol A alone would still leave unacceptably high mixture risks. Paracetamol is also a driver of mixture risks among subjects using the drug. Conclusions Tolerable exposures to substances associated with deteriorations of semen quality are exceeded by a large margin. Bisphenols, polychlorinated dioxins, phthalates and analgesics drive these risks. Dedicated efforts towards lowering exposures to these substances are necessary to mitigate risks

Investigation of multiple dose citalopram on the pharmacokinetics and pharmacodynamics of racemic warfarin

Aims An open, controlled, randomized, crossover study was conducted in healthy males to assess the possible occurrence of a pharmacokinetic/pharmacodynamic interaction between warfarin and the selective serotonin re-uptake inhibitor citalopram

Time to pregnancy and life expectancy: a cohort study of 18 796 pregnant couples

International audienceSTUDY QUESTION Is fecundity, measured as time to pregnancy (TTP), associated with mortality in parents?SUMMARY ANSWER Prolonged TTP is associated with increased mortality in both mothers and fathers in a dose-response manner.WHAT IS KNOWN ALREADY Several studies have linked both male and female fecundity to mortality. In women, infertility has been linked to several diseases, but studies suggest that the underlying conditions, rather than infertility, increase mortality.STUDY DESIGN, SIZE, DURATION A prospective cohort study was carried out on 18 796 pregnant couples, in which the pregnant women attended prophylactic antenatal care between 1973 and 1987 at a primary and tertiary care unit. The couples were followed in Danish mortality registers from their child&#039;s birth date until death or until 2018. The follow-up period was up to 47 years, and there was complete follow-up until death, emigration or end of study.PARTICIPANTS/MATERIALS, SETTING, METHODS At the first antenatal visit, the pregnant women were asked to report the time to the current pregnancy. Inclusion was restricted to the first pregnancy, and TTP was categorised into &lt;12 months, &gt;= 12 months, not planned, and not available. In sub-analyses, TTP &gt;= 12 was further categorized into 12-35, 36-60, and &gt;60 months. Information for parents was linked to several Danish nationwide health registries. Survival analysis was used to estimate the hazard ratios (HRs) with a 95% CI for survival and adjusted for age at the first attempt to become pregnant, year of birth, socioeconomic status, mother&#039;s smoking during pregnancy, and mother&#039;s BMI.MAIN RESULTS AND THE ROLE OF CHANCE Mothers and fathers with TTP &gt;60 months survived, respectively, 3.5 (95% CI: 2.6-4.3) and 2.7 (95% CI: 1.8-3.7) years shorter than parents with a TTP &lt;12 months. The mortality was higher for fathers (HR: 1.21, 95% CI: 1.09-1.34) and mothers (HR: 1.29, 95% CI: 1.12-1.49) with TTP &gt;= 12 months compared to parents with TTP &lt;12 months. The risk of all-cause mortality during the study period increased in a dose-response manner with the highest adjusted HR of 1.98 (95% CI: 1.62-2.41) for fathers and 2.03 (95% CI: 1.56-2.63) for mothers with TTP &gt;60 months. Prolonged TTP was associated with several different causes of death in both fathers and mothers, indicating that the underlying causes of the relation between fecundity and survival may be multi-factorial.LIMITATIONS, REASONS FOR CAUTION A limitation is that fecundity is measured using a pregnancy-based approach. Thus, the cohort is conditioned on fertility success and excludes sterile couples, unsuccessful attempts and spontaneous abortions. The question used to measure TTP when the pregnant woman was interviewed at her first attended prophylactic antenatal care: &#039;From the time you wanted a pregnancy until it occurred, how much time passed?&#039; could potentially have led to serious misclassification if the woman did not answer on time starting unprotected intercourse but on the start of wishing to have a child.WIDER IMPLICATIONS OF THE FINDINGS We found that TTP is a strong marker of survival, contributing to the still-emerging evidence that fecundity in men and women reflects their health and survival potential

Serum testosterone levels in three-month-old boys predict their semen quality as young adults

CONTEXT: It remains unknown how the postnatal activation of the hypothalamic-pituitary-gonadal axis in infancy, also known as “minipuberty”, relates to adult testis function. OBJECTIVE: To investigate how markers of reproductive function in 3-month-old boys correlate with adult reproductive health parameters. METHODS: This population-based birth cohort study (the Copenhagen Mother-Child cohort), conducted at Copenhagen University Hospital, Denmark, included 259 boys examined once around 3 months of age and again at 18 to 20 years. Reproductive hormones, penile length, testis volume, and semen quality were analyzed. Minipubertal markers of testis function (by tertiles, T1–T3) were explored as predictors of adult semen quality using linear regression models. Associations between reproductive outcomes in infancy and young adulthood were estimated by intraclass correlation coefficients (ICCs), describing how well measurements in infancy correlate with those in adulthood. RESULTS: Serum testosterone concentration in infancy was positively associated with adult total sperm count. Median (IQR) total sperm count was 84 (54-138) million spermatozoa for boys in T1, 141 (81-286) million spermatozoa in T2, and 193 (56-287) million spermatozoa in T3. We found the highest ICC for FSH (0.41; 95% CI, 0.26–0.57), while ICCs for inhibin B, SHBG, penile length, and testis volume ranged between 0.24 and 0.27. ICCs for LH and for total and free testosterone were lower and statistically nonsignificant. CONCLUSION: Serum testosterone in infancy was a predictor of adult total sperm count. Other reproductive hormones and genital measures showed good correlation between infancy and adulthood, suggesting that an individual’s reproductive setpoint starts shortly after birth in boys and persists until adulthood