Low grade systemic inflammation (LGSI) as well as androgen deficiency has in older men been associated with several pathologies, including cardiovascular disease (CVD). We wanted to investigate ...whether low testosterone levels are linked to biomarkers of LGSI already in young age, before any concurrent manifestations of CVD or other systemic diseases.
Nested cross-sectional study.
Forty subfertile biochemically hypogonadal (n = 20) or eugonadal (n = 20) men (mean age 37 years, SD = 4.3) and 20 age-matched controls were randomly selected from an ongoing study on male subfertility. Subjects comprised male partners in infertile couples in whom also subnormal sperm concentration was present. Blood sampling, interviews, and anthropometric measures were undertaken. Serum levels of testosterone, LH, estradiol, SHBG, and 21 LGSI-markers were assessed.
Among 21 inflammatory markers, macrophage inflammatory protein 1-alpha (MIP1a) (ß = -0.025; p = 0.028), 1-beta (MIP1B) (ß = -0.015; p = 0.049) and tumor necrosis factor alpha (TNFa) (ß = -0.015; p = 0.040) showed negative association to total testosterone (TT) levels. MIP1a (ß = -1.95; p = 0.001) and TNFa (ß = -0.95; p = 0.014) showed negative association to calculated free testosterone (cFT) levels. Compared to men with normal TT and cFT levels, TNFa levels were higher in men with subnormal levels of TT (mean ratio 1.61; p = 0.006) and cFT (mean ratio 1.58; p = 0.007). Also, MIP1a levels were higher in men with subnormal levels of TT (mean ratio 1.84; p = 0.030).
Subnormal testosterone may already in young age associate to LGSI, which might be a part of the mechanism underlying adverse health outcomes of male hypogonadism.
To determine whether high DNA stainability (HDS), as assessed by the sperm chromatin structure assay (SCSA), predicts the risk of early miscarriage after in vitro fertilization with intracytoplasmic ...sperm injection (IVF-ICSI).
Retrospective cohort study of consecutive pregnancies after IVF and ICSI treatment.
Reproductive medicine center.
A total of 1,602 pregnancies after 832 IVF and 770 ICSI treatments.
HDS measured using SCSA.
Early miscarriage (≤12 weeks).
The HDS represents the proportion of immature spermatozoa lacking the normal exchange of histone for protamine-complexed DNA, and the outcome parameter was early miscarriage (≤12 weeks). For all treatments, the odds ratio (OR) and 95% confidence interval (CI) for early miscarriage was 1.41 (1.07-1.85) if HDS >15% compared with HDS ≤15%. When comparing the two HDS categories, for ICSI, the OR was 1.44 (1.01-2.04) whereas for IVF the results were not statistically significant.
There is a small but increased risk of early miscarriage if HDS >15% compared with HDS ≤15%. This increased risk is seen only after ICSI, not after IVF. These findings suggest that HDS can be used as a predictor of an increased risk of miscarriage in ICSI treatments.
Abstract Context New data regarding the diagnosis and treatment of male infertility have emerged and led to an update of the European Association of Urology (EAU) guidelines for Male Infertility. ...Objective To review the new EAU guidelines for Male Infertility. Evidence acquisition A comprehensive work-up of the literature obtained from Medline, the Cochrane Central Register of Systematic Reviews, and reference lists in publications and review articles was developed and screened by a group of urologists and andrologists appointed by the EAU Guidelines Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence summary These EAU guidelines are a short comprehensive overview of the updated guidelines of male infertility as recently published by the EAU ( http://www.uroweb.org/guidelines/online-guidelines/ ), and they are also available in the National Guideline Clearinghouse ( http://www.guideline.gov/ ).
Childless men are reported to have a higher risk of cardiovascular disease (CVD) and mortality. Information on inherited genetic risk for CVD has improved the predictive models. Presuming that ...childlessness is a proxy of infertility we aimed to investigate if childless men inherit more often genetic traits for CVD and if combining genetic and parenthood information improves predictive models for CVD morbidity and mortality. Data was sourced from a large prospective population-based cohort where genetic risk score (GRS) was calculated using two sets of either 27 (GRS 27) or 50 (GRS 50) single nucleotide polymorphisms (SNPs) previously found to be associated with CVD. Part of the participants (n = 2572 men) were randomly assigned to a sub-cohort with focus on CVD which served as an exploratory cohort. The obtained statistically significant results were tested in the remaining (confirmatory) part of the cohort (n = 9548 men). GRS distribution did not differ between childless men and fathers (p-values for interaction between 0.29 and 0.76). However, when using fathers with low GRS as reference high GRS was a strong predictor for CVD mortality, the HR (95% CI) increasing from 1.92 (1.10-3.36) for GRS 50 and 1.54 (0.87-2.75) for GRS 27 in fathers to 3.12 (1.39-7.04) for GRS50 and 3.73 (1.75-7.99) for GRS27 in childless men. The confirmatory analysis showed similar trend. Algorithms including paternal information and GRS were more predictive for CVD mortality at 5 and 10 years follow-ups when compared to algorithms including GRS only (AUC 0.88 (95% CI 0.84-0.92) and 0.86 (95% CI 0.84-0.90), and, AUC 0.81 (95% CI 0.75-0.87) and 0.78 (95% CI 0.73-0.82), respectively). Combining information on parental status and GRS for CVD may improve the predictive power of risk algorithms in middle-aged men. Childless men and those with severe infertility problem may be an important target group for prevention of CVD.
Male reproductive impairment has been linked with an increased risk of numerous non-communicable diseases. Yet, epidemiological data on renal disease among subfertile men is scarce. Therefore, by ...using male childlessness as a proxy for male infertility, we aimed to investigate its association with renal function. Data was sourced from a population-based cohort including 22,444 men. After exclusion of men aged < 45 years (n = 10,842), the remaining men were divided into two groups: these being childless (n = 5494) and fathers (n = 6108). Logistic regression was applied to explore the association between male childlessness and renal impairment. Childless men as compared to fathers, were more likely to have an estimated-glomerular filtration rate < 60 ml/min/1.73m
(OR 1.36, 95 CI 1.08-1.70; p = 0.008). After adjustment for age, marital status, smoking habits, diabetes, hypertension and other components of metabolic syndrome, childless men were also more likely to have dipstick proteinuria (OR 1.85, 95 CI 1.16-2.95; p = 0.01). With the growing panorama of disease associated with male reproductive impairment, men with fertility issues may constitute a target population with potential benefit from closer follow-up of their renal function.
Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a ...variety of consumer products during the twentieth century. Wildlife and animal studies have long suggested adverse effects of exposure to these compounds on human reproductive health, which, according to the endocrine disrupter hypothesis, are ascribed to the compounds＇ potential to interfere with endocrine signaling, especially when exposure occurs during certain phases of fetal and childhood development. An extensive number of epidemiological studies have addressed the possible effects of exposure to POPs on male reproductive health, but the results are conflicting. Thus far, most studies have focused on investigating exposure and the different reproductive health outcomes during adulthood. Some studies have addressed the potential harmful effects of fetal exposure with respect to malformations at birth and/ or reproductive development, whereas only a few studies have been able to evaluate whether intrauterine exposure to POPs has long-term consequences for male reproductive health with measurable effects on semen quality markers and reproductive hormone levels in adulthood. Humans are not exposed to a single compound at a time, but rather, to a variety of different substances with potential divergent hormonal effects. Hence, how to best analyze epidemiological data on combined exposures remains a significant challenge. This review on POPs will focus on current knowledge regarding the potential effects of exposure to POPs during fetal and childhood life and during adulthood on male reproductive health, including a critical revision of the endocrine disruption hypothesis, a comment on pubertal development as part of reproductive development and a comment on how to account for combined exposures in epidemiological research.
Diagnosis of male infertility has mainly been based on the World Health Organization (WHO) manual-based semen parameter's concentration, motility and morphology. It has, however, become apparent that ...none of these parameters are reliable markers for evaluation of the fertility potential of a couple. A search for better markers has led to an increased focus on sperm chromatin integrity testing in fertility work-up and assisted reproductive techniques. During the last couple of decades, numerous sperm DNA integrity tests have been developed. These are claimed to be characterized by a lower intraindividual variation, less intralaboratory and interlaboratory variation and thus less subjective than the conventional sperm analysis. However, not all the sperm chromatin integrity tests have yet been shown to be of clinical value. So far, the test that has been found to have the most stable clinical threshold values in relation to fertility is the sperm chromatin structure assay (SCSA), a flow cytometric test that measures the susceptibility of sperm DNA to acid-induced DNA denaturation in situ. Sperm DNA fragmentation as measured by SCSA has shown to be an independent predictor of successful pregnancy in first pregnancy planners as well as in couples undergoing intrauterine insemination, and can be used as a tool in investigation, counseling and treatment of involuntary childlessness. More conflicting data exist regarding the role of sperm DNA fragmentation in relation to fertilization, pre-embryo development and pregnancy outcome in in vitro fertilization and intracytoplasmic sperm injection (ICSI).
Preliminary published data depict a much greater prevalence of males with laboratory‐confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) referred for intensive care unit admission ...and severe sequelae in several countries. In this context, males seem to not only be more susceptible to the infection compared to female subjects, at least in Western countries, but their case fatality rate attributable to SARS‐CoV‐2 infection is also highest. Therefore, we may speculate that the different hormonal milieu could have a more profound pathophysiological role in association with SARS‐CoV‐2, with endogenous testosterone leaving men more prone to develop more serious complications related to the SARS‐CoV‐2 infection. Another option is that SARS‐CoV‐2 infection per se causes an acute stage of male hypogonadism, the depletion of androgenic action triggering serious or an even fatal course of the disease. Therefore, we strongly advocate the development of a prospective multidimensional andrological translational research project in men, which we called the PROTEGGIMI study. In this Opinion Article, we will not only highlight novel research activity in this area but also invite other researchers and learned scientific societies to join us in our efforts to understand an important and very newly discovered gap in knowledge, which may have serious implications for the lives of millions of men.
The number of the X chromosome–linked genes has been previously suggested to influence immune responses and the development of autoimmune diseases. In the present study, we aimed at evaluating the ...level of expression of CD40L (an X‐linked gene involved in adaptive immunity) and TLR7 (an X‐linked gene involved in innate immunity) in a variety of different karyotypes. Those included males, females and patients with X chromosome aneuploidy. Healthy females (46, XX; n = 10) and healthy males (46, XY; n = 10) were compared to females with Turner syndrome (TS) (45, X; n = 11) and males with Klinefelter syndrome (KS) (47, XXY; n = 5). Stimulation of peripheral blood mononuclear cells (PBMCs) with PMA and ionomycin resulted in higher percentage of CD3 + CD40L+ T cells (P < 0.001) and higher level expression of CD40L in T cell (P < 0.001) in female and KS patients compared with male and TS patients. TLR7‐mediated IFN‐alpha production by HLADR + CD3− CD19− cells was significantly upregulated in healthy women compared with healthy males, TS and KS patients (P < 0.001). TLR7 agonist‐stimulated PBMCs from healthy females and KS patients expressed significantly higher levels of TLR7 mRNA than those from male and TS patients (P < 0.05). The increased expression of the X‐linked genes TLR7 and CD40L in healthy females and KS patients suggests that the presence of two X chromosomes plays a major role in enhancing both innate and adaptive immune responses. These results may contribute to the explanation of sex‐based differences in immune biology and the sex bias in predisposition to autoimmune diseases.
The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset ...hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level.
We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses.
In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter 2.3 to 3.7 ng per milliliter for total testosterone and 160 to 280 pmol per liter 46 to 81 pg per milliliter for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism.
Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).
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