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Background Carlsen and coworkers (1992) reviewed 61 heterogeneous observational studies on semen quality published between 1938 and 1990. This review indicates that mean sperm density decreased significantly between 1940 and 1990. An extended meta-analysis with 101 studies confirmed a decline in sperm density for the period from 1934 to 1996 (2000). The key message of the meta-analyses is that sperm counts have decreased globally by about 50% over the past decades. This assessment has been questioned. Discussion A major methodological problem of the meta-analysis is the use of data collected in different countries, at different times, on different populations and with different methods of semen analysis. Furthermore, the results of studies concerning semen analysis are frequently biased e.g. by selection criteria of volunteers. In most studies on human semen characteristics the populations under study are insufficiently defined and the study participants are not a representative population sample. The incidence of testicular cancer has increased in Caucasian men worldwide. The investigation of common risk factors for male reproductive disorders requires well designed epidemiological studies and the collection of individual data. Summary Former meta-analyses of sperm count data show a global downward trend. This conclusion should be interpreted with caution. The included studies are of great heterogeneity due to geographical and/or ethnical variation, different study designs and different methodological standards. Population-based prospective studies are needed to investigate secular trends in male reproductive disorders.

Purpose Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany. Methods A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account. Results After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85–1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88–1.25). Conclusions Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.

Background This study aimed to compare the quality of life (QoL) reported by childhood cancer survivors (CCS) drawn from a cohort of the German Childhood Cancer Registry with a representative general population sample and, within CCS, to test associations between QoL and health behavior, health risk factors, and physical illness. Methods CCS ( N  = 633, age at diagnosis M  = 6.34 ( SD  = 4.38), age at medical assessment M  = 34.92 ( SD  = 5.70)) and a general population sample (age-aligned; N  = 975) filled out the EORTC QLQ-C30. Comparisons were performed using General linear models (GLMs) (fixed effects: sex/gender, group (CCS vs. general population); covariates: age, education level). CCS underwent an extensive medical assessment (mean time from diagnosis to assessment was 28.07 ( SD  = 3.21) years) including an objective diagnosis of health risk factors and physical illnesses (e.g., diabetes and cardiovascular disease). Within CCS, we tested associations between QoL and sociodemographic characteristics, health behavior, health risk factors, and physical illness. Results CCS, especially female CCS, reported both worse functional QoL and higher symptom burden than the general population. Among CCS, better total QoL was related to younger age, higher level of education, being married, and engaging in active sports. Both health risk factors (dyslipidemia and physical inactivity) and manifest physical illnesses (cardiovascular disease) were associated with lower total QoL. Conclusions In all domains, long-term CCS reported worse QoL than the comparison sample. The negative associations with risk factors and physical illnesses indicate an urgent need for long-term surveillance and health promotion.

We investigated the association between social inequality and participation in a mammography screening program (MSP). Since the German government offers mammography screening free of charge, any effect of social inequality on participation should be due to educational status and not due to the financial burden. The 'Gutenberg Health Study' is a cohort study in the Rhine-Main-region, Germany. A health check-up was performed, and questions about medical history, health behavior, including secondary prevention such as use of mammography, and social status are included. Two indicators of social inequality (equivalence income and educational status), an interaction term of these two, and different covariables were used to explore an association in different logistic regression models. A total of 4,681 women meeting the inclusion criteria were included. Only 6.2% never participated in the MSP. A higher income was associated with higher chances of ever participating in a mammography screening (odds ratios (OR): 1.67 per [euro]1000; 95%CI:1.26-2.25, model 3, adjusted for age, education and an interaction term of income and education). Compared to women with a low educational status, the odds ratios for ever participating in the MSP was lower for the intermediate educational status group (OR = 0.64, 95%CI:0.45-0.91) and for the high educational status group (0.53, 95%CI:0.37-0.76). Results persisted also after controlling for relevant confounders. Despite the absence of financial barriers for participation in the MSP, socioeconomic inequalities still influence participation. It would be interesting to examine whether the educational effect is due to an informed decision.

Background Self-administered health-status questionnaires are important tools in epidemiology. The objective of the presented validation study is to measure the agreement between breast cancer patients’ self-reports and their physicians’ information on late cardiac events, and to investigate determinants of agreement. To estimate possible misclassification is an important requirement for observational studies on cardiovascular endpoints. Methods A retrospective, multi-center cohort study included 11,982 women diagnosed with breast cancer in Germany in 1998–2008. In 2014, a questionnaire survey assessed cardiovascular risk factors and incident cardiac events after therapy. A validation study was conducted, based on a sample of 3091 breast cancer patients from two university hospitals. Among them, 2261 women (73%) sent back the questionnaire on cardiovascular events, and 1316 women gave consent to request medical records from their general practitioners. A total of 1212/1316 (92.1%) medical records could be obtained for validation. Cohen’s kappa coefficient was calculated, and multivariate regression was applied to study the influence of patient characteristics on agreement between both data sources. Results Overall agreement for the composite endpoint of any cardiac event was 84.5% (kappa 0.35). Of 1055 breast cancer patients reporting no cardiac event, 950 (90%) had no such diagnosis in physicians’ medical records. A total of 157 breast cancer survivors indicated a cardiac event, and the same diagnosis was confirmed by GPs for 74 (47%) women. For specific diagnoses, moderate to substantial agreement of self-reports was found for myocardial infarction (kappa 0.54) and stroke (kappa 0.61). Poor to fair agreement was present for angina pectoris, valvular heart disease, arrhythmia, and congestive heart failure. Younger age, higher education and a more recent cancer diagnosis were found to be associated with greater total agreement. Conclusions For the composite endpoint, survivors of breast cancer report the absence of cardiac disease accurately. However, for specific diagnoses, self-reported morbidity data from breast cancer patients may not fully agree with information from physicians. The agreement is moderate for acute events like myocardial infarction and stroke, but poor to fair for chronic diseases.

Background Computed tomography (CT) is a major source of ionizing radiation exposure in medical diagnostic. Compared to adults, children are supposed to be more susceptible to health risks related to radiation. The purpose of a cross-sectional survey among office-based physicians in Germany was the assessment of medical practice in paediatric CT referrals and to investigate physicians' knowledge of radiation doses and potential health risks of radiation exposure from CT in children. Methods A standardized questionnaire was distributed to all paediatricians and surgeons in two defined study areas. Furthermore, the study population included a random sample of general practitioners in the two areas. The questionnaire covered the frequency of referrals for paediatric CT examinations, the medical diagnoses leading to paediatric CT referrals, physicians' knowledge of radiation doses and potential health risks of radiation exposure from CT in children. Results A total of 295 (36.4%) physicians responded. 59% of the doctors had not referred a child to CT in the past year, and approximately 30% referred only 1-5 children annually. The most frequent indications for a CT examination in children were trauma or a suspected cancer. 42% of the referrals were related to minor diagnoses or unspecific symptoms. The participants underestimated the radiation exposure due to CT and they overestimated the radiation exposure due to conventional X-ray examinations. Conclusions In Germany, the frequency of referrals of children to computed tomography is moderate. The knowledge on the risks from radiation exposure among office-based physicians in our sample varied, but there was a tendency to underestimate potential CT risks. Advanced radiological training might lead to considerable amendments in terms of knowledge and practice of CT referral.

Computed tomography (CT) is an essential tool in modern medicine and is frequently used to diagnose a wide range of conditions, particularly in industrial countries, such as Japan and Germany. However, markedly higher doses of ionizing radiation are delivered during CT imaging than during conventional X-ray examinations. To assess pediatric CT practice patterns, data from three university hospital databases (two in Japan and one in Germany) were analyzed. Anonymized data for patients aged 0 to 14 years who had undergone CT examinations between 2008 and 2010 were extracted. To assess CT practice, an interdisciplinary classification scheme for CT indications, which incorporated the most common examination types and radiosensitive tissues, was developed. The frequency of CT examinations was determined according to sex, age at examination, and indications. A total of 5182 CT examinations were performed in 2955 children. Overall, the frequency of CT examinations at the Japanese university hospitals did not differ significantly from that at the German hospital. However, differences were detected in the age distribution of the patients who underwent CT examinations (the proportion of patients <5 years of age was significantly higher in Japan than in Germany) and in the indications for CT. Substantial practice differences regarding the use of CT in pediatric health care were detected between the three hospitals. The results of this study point towards a need for approaches such as clinical guidelines to reduce unwarranted medical radiation exposures, particularly abdominal and head CT, in the Japanese health system.

Background Vascular alterations induced by antineoplastic treatment might be considered as a possible underlying mechanism of increased cardiovascular (CV) sequelae in childhood cancer survivors (CCS). Therefore, we thought to evaluate the changes in arterial stiffness (AS) among long-term CCS compared to the general population. Methods AS was assessed by digital photoplethysmography (Stiffness Index (SI); m/s) among 1,002 participant of “Cardiac and Vascular late Sequelae in long-term Survivors of childhood cancer” study, diagnosed with neoplasia prior to an age of 15 years (1980–1990). A population-based subsample from the Gutenberg Health Study (GHS) (n = 5,252) was used for comparison. All subjects underwent a comprehensive, standardized clinical examination in the same study center. Results Compared to the population subsample with similar age range, CCS had higher SI in multivariable linear regression analysis with adjustment for cardiovascular risk factor and comorbidities (β = 0.66[0.51/0.80]; p < 0.0001). Moreover, SI was varying according to tumor entity with highest values in bone tumors. Interestingly, CCS demonstrated stiffer vessels than individuals from the population even in absence of a history of chemo- or radiotherapy (β = 0.56[0.16/0.96]; p = 0.0066) or prevalent hypertension (β = 0.66[0.50/0.81]; p < 0.0001) in fully-adjusted models. Finally, a 5.2-fold [3.9; 7.0] higher prevalence of SI values exceeding age-specific, population-based reference limits was observed among CCS compared to individuals from the population. Conclusions This is the first study demonstrating increased AS among long-term CCS. The data suggest that AS promotion might differ in individuals with childhood cancer: Cancer development and antineoplastic treatment might be relevant determinants.

Long-term childhood cancer survivors (CCS) are at risk for adverse late effects. However, not all of them are well understood. The present study addressed loneliness, a previously under-researched mental health risk in cancer survivor populations. We assessed the prevalence of loneliness and its impact on psychological symptoms over time. Method: A registry-based sample of N=633 adult long-term CCS underwent medical and psychological assessments and took part in a follow-up survey 2.5 years later. Psychological symptoms (somatic, anxiety, depression symptoms, and suicidal ideation) were measured using the Patient Health Questionnaire. We calculated linear regression models of symptoms at follow-up to investigate the impact of loneliness over time (controlling for symptoms at baseline and relevant confounders). Results: Loneliness was reported by 17.70% of CCS. In multivariate linear regression analyses, loneliness was still predictive of more severe anxiety symptoms and suicidal ideation over two years later. Loneliness did not predict somatic and depression symptoms at follow-up (which increased with age). Conclusions: Loneliness affected a significant number of CCS and was a risk factor for persistent anxiety symptoms and suicidal ideation. The extent to which young cancer patients’ re-integration into society is successful could thus have important implications for well-being in adulthood. Los sobrevivientes a largo plazo de cáncer infantil (SCI) están en riesgo de sufrir efectos tardíos. Evaluamos la prevalencia de la soledad y su impacto en los síntomas psicológicos a lo largo del tiempo. Método: Una muestra de N=633 adultos con un pasado de SCI se sometió a evaluaciones médicas y psicológicas y participó en una encuesta de seguimiento 2,5 años después. Los síntomas psicológicos se midieron mediante el Patient Health Questionnaire. Calculamos modelos de regresión lineal de síntomas en el seguimiento para investigar el impacto de la soledad a lo largo del tiempo (controlando los síntomas al inicio y los factores de confusión relevantes). Resultados: La soledad fue reportada por el 17,70% de SCI. La soledad seguía siendo predictiva de síntomas de ansiedad más graves e ideación suicida dos años después. La soledad no predijo los síntomas somáticos y de depresión durante el seguimiento (que aumentaron con la edad). Conclusiones: La soledad fue un factor de riesgo para síntomas de ansiedad persistente e ideación suicida. La medida en que la reintegración de los pacientes jóvenes con cáncer en la sociedad tenga éxito podría tener importantes implicaciones para el bienestar en la edad adulta.

Purpose In breast cancer patients treated in the 1970s and 1980s, radiation therapy (RT) for left-sided tumors has been associated with an elevated risk of cardiac mortality. In recent years, improved RT techniques have reduced radiation exposure of the heart and major coronary vessels, but some exposure remains unavoidable. In a retrospective cohort study, we investigated the long-term cardiac mortality risk of breast cancer survivors treated with modern RT in Germany. Methods A total of 11,982 women were included who were treated for breast cancer between 1998 and 2008. A systematic mortality follow-up was conducted until December 2012. The effect of breast cancer laterality on cardiac mortality and on overall mortality was investigated as a surrogate measure of exposure. Using Cox regression, we analyzed survival time as the primary outcome measure, taking potential confounding factors into account. Results We found no evidence for an effect of tumor laterality on mortality in irradiated patients ( N  = 9058). For cardiac mortality, the hazard ratio was 0.94 (95% CI 0.64–1.38) for left-sided versus right-sided tumors. For all causes of death, the hazard ratio was 0.95 (95% CI 0.85–1.05). A diagnosis of cardiac illness prior to breast cancer treatment increased both cardiac mortality risk and overall mortality risk. Conclusions Contemporary RT seems not to be associated with an increased risk of cardiac mortality or overall mortality for left-sided breast cancer relative to right-sided RT. However, an extended follow-up period and exact dosimetry might be necessary to confirm this observation.