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Competing Interests: Competing interests: The authors declare no competing interests.

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 2 (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., (© 2024. The Author(s).)

Objective: Follicle-stimulating hormone (FSH) receptor expression has been reported in many extra-gonadal tissues, raising the question of non-reproductive effects of FSH. Because of increasing usage of FSH in treatment of male infertility, deeper knowledge of possible harmful off-target effects of FSH is warranted., Methods: In total, 33 healthy young men (mean age 30 years) were included in the study. All received an s.c. injection of gonadotropin-releasing hormone (GnRH) antagonist and n = 16 were randomized to 300 IU recombinant FSH (300 IE 3 times/week) for 5 weeks at first visit (V1) whereas n = 17 served as controls. Blood samples were taken at (V1), after 3 weeks (V2), and after 5 weeks (V3), when the study ended. At V2, all subjects received 1000 mg testosterone undecanoate i.m. A standard set of bio- and inflammatory markers were compared between the groups using the Mann-Whitney test adjusted for multiple testing., Results: As compared to controls, the FSH treated men had higher SHBG and albumin concentrations at V2 (p = 0.024 and 0.027, respectively), and lower levels of alanine aminotransferase (p = 0.026) and magnesium (p = 0.028) at V3. However, none of the results remained statistically significant after Bonferroni correction (p > 0.0011)., Conclusions: FSH had no significant effects on non-reproductive organs when given in standard therapeutic doses to young men for 5 weeks. Therefore, the FSH treatment can be considered safe in otherwise healthy young men, constituting candidates for the infertility treatment with FSH., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: The risk of inflammatory diseases is sex-dependent, but it remains unknown whether this is due to the impact of sex hormones or sex chromosomes. Transgender individuals represent a unique cohort for studying the relative influence of endocrine and chromosomal factors. Here we compared serum levels of B-cell activating-factor (BAFF) and tumor necrosis factor (TNF) in transgender men (TM), transgender women (TW), cisgender women (CW) and cisgender men (CM)., Methods: BAFF and TNF were measured in the serum of 26 CW, 30 CM, 27 TM and 16 TW individuals. To determine the responsiveness of immune cells, TNF was measured in bacterial lipopolysaccharide (LPS)-treated peripheral leukocytes., Results: BAFF was higher in CF (998 pg/mL) and TW (973 pg/mL) compared to CM (551 pg/mL) (P < 0.0001) and TM (726 pg/mL) (P < 0.0001). No difference in BAFF levels was shown between subjects grouped according to the number of X chromosomes. TNF was higher in CM (174 pg/mL) than TW (2.3 pg/mL) (P = 0.027) and TM (27.4 pg/mL) (P = 0.028). LPS-induced TNF was higher in CM (2524 pg/mL) and TM (2078 pg/mL) than in CW (1332 pg/mL) (both P < 0.0001) and TW (1602 pg/mL) (both P = 0.009)., Discussion: Sex hormones and sex chromosomes have different impacts on cytokines involved in the sex-dependent inflammatory response. The concentration of BAFF and LPS-stimulated TNF secretion depended on sex hormone levels, whereas basal TNF was regulated by both sex hormone-dependent and -independent factors.

Impaired semen quality is present in approximately 50% of all infertile couples, indicating decreased fertility in the male. The etiology is unknown in 40-60% of the cases and standard semen parameters provide limited information about the cause and the chance for pregnancy in vivo or in vitro. Assessment of sperm DNA strand breaks may therefore be useful for optimal infertility treatment. Since the causes of infertility of the male part are largely unknown, few options for treatment of decreased semen quality are at hand. This applies to pharmacological and surgical methods as well as lifestyle related interventions. There are studies showing that infertile men have a significant risk of hypogonadism and shorter life expectancy due to higher risk of cardiovascular and metabolic diseases as well as certain cancers. Poor fertility can hence be considered as an early marker of general disease. Andrological examination, not only limited to semen analysis, but also including clinical, endocrinological and in some cases genetic evaluation should  be part of the routine work-up of infertile couples.

Dose-response association between level of impairment of semen quality and risk of morbidity or premature death has been reported. Therefore, it can be presumed that men utilizing donated spermatozoa, i.e. patients with non-obstructive azoospermia, are at highest risk for adverse health outcomes. To evaluate the risks of prescription of medications for common metabolic disturbances and testosterone replacement therapy (TRT) among men who father children with donated spermatozoa-who presumably do it due to severe impairment of fertility. We used Swedish nationwide register data on all fathers who had a live-born child between 2007 and 2014 in order to compare men who fathered children with donated spermatozoa to the ones who became fathers by using own gametes. Cox regression analysis was used in order to estimate the post-conception incidence of prescription of medicines for hypertension (HT), diabetes (type 1 and 2), dyslipidaemia (DLE) or TRT. Starting the follow up at time of conception, models were adjusted for age, educational level, and previous cancer treatment. In total 410,119 childbirths were included in the analysis. Among them, for 390 fathers donated spermatozoa were utilized. Fathers to children conceived with donated spermatozoa had higher risk for having TRT prescribed (HR: 18.14; 95%CI: 11.71-28.10; p ≪ 0.001). Same was true for DLE (HR: 2.08; 95%CI: 1.27-3.39; p = 0.003) but not diabetes. Fathers to children conceived by use of donated spermatozoa are at significantly increased risk for testosterone treatment and dyslipidaemia, necessitating stringent follow up and inclusion in prevention programs., (© 2022. The Author(s).)

In parallel with increased survival rates, quality of life (QoL) has become of growing importance in the management of young cancer survivors. Several surveys have indicated that in those subjects, the issue of reproductive function is considered as one of the main QoL aspects. In this article, we summarize the current evidence, as well as gaps of knowledge and research needs, regarding the impact of cancer and cancer treatment on testicular function-including fertility and androgen production. Also, pre and posttherapy clinical management of reproductive issues in male cancer survivors, are given., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2021. The Author(s).)

Based on a nationwide register data we recently reported a link between male infertility and increased risk of early onset prostate cancer. However, mortality due to prostate cancer, which can be regarded as the ultimate proxy for its clinical significance, especially in the context of over-diagnosis and over-treatment, could not be explored in the previous study, since the follow-up period in most cases was too short. Data therefore must be retrieved from other cohorts, with longer follow-up. We sourced data from a population-based prospective cohort including 11,343 men aged over 45 years, enrolled in the 1970s. The results showed that childless men have higher risk for prostate cancer related mortality (HR: 1.49, 95% CI: 1.09-2.03, p  = 0.01) compared to men with children, in particular when only married men, who most probably are involuntary childless, were considered (HR 1.54, 95% CI 1.13 - 2.10, p  = 0.006). However, the prostate cancer incidence did not differ (HR = 1.04, 95% CI: 0.88-1.24). In conclusion, our results show that childless men are at higher risk for dying from prostate cancer, probably due to a more aggressive form of the disease.

In a recent population-based study, an elevated risk of the Metabolic syndrome (MetS) and type 2 diabetes was found in childless men compared to those who have fathered one or more children. Therefore, by using a larger cohort of more than 22 000 men from the Malmo Preventive Project (MPP) we aimed to expand our observations in order to evaluate the metabolic profile of childless men and to evaluate if childlessness is an additional and independent predictor of major adverse cardiovascular events (MACE), mortality and incident diabetes when accounting for well-known biochemical, anthropometric, socio-economic and lifestyle related known risk factors. Logistic regression was used to assess risk of MACE, diabetes and MetS at baseline. Multivariate Cox regression was used to evaluate the risks of MACE and mortality following the men from baseline screening until first episode of MACE, death from other causes, emigration, or end of follow-up (31st December 2016) adjusting for age, family history, marital status, smoking, alcohol consumption, educational status, body mass index, prevalent diabetes, high blood lipids, increased fasting glucose and hypertension. Childless men presented with a worse metabolic profile than fathers at the baseline examination, with elevated risk of high triglycerides, odds ratio (OR) 1.24 (95%CI: 1.10-1.42), high fasting glucose OR 1.23 (95%CI: 1.05-1.43) and high blood pressure, OR 1.28 (95%CI: 1.14-1.45), respectively. In the fully adjusted prospective analysis, childless men presented with elevated risk of cardiovascular mortality, HR: 1.33 (95% CI: 1.18-1.49) and all-cause mortality, HR 1.23 (95%CI: 1.14-1.33), respectively. In conclusion, these results add to previous studies showing associations between male reproductive health, morbidity and mortality. Male childlessness, independently of well-known socio-economic, behavioral and metabolic risk factors, predicts risk of cardiovascular disease and mortality. Consequently, this group of men should be considered as target population for preventive measures., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Male hypogonadism is associated with higher risk of co-morbidity and premature mortality. It is, therefore, of utmost importance to identify young men who are at the highest risk of testosterone deficiency and who may benefit from preventive measures. In this context, infertile men constitute a high-risk group. The extent of testosterone replacement therapy (TRT) among infertile men, defined as men who have to undergo assisted reproduction for fatherhood, is currently unknown. Therefore, we evaluated the pattern of prescription of TRT in the years following child conception among men who have fathered children with the help of intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF)., Design: By sourcing data from national population registries, hazard ratio (HR) for subsequent TRT was assessed for IVF and ICSI-treated men and compared to those who conceived spontaneously with age Cox regression analysis adjusted for age, educational level and previous intake of medicines for metabolic diseases., Results: ICSI and IVF fathers had increased incidence of newly prescribed TRT compared to fathers conceiving spontaneously (ICSI: HR = 3.81, 95% CI = 3.09-4.69, P < 0.001; IVF: HR = 1.54, 95% CI = 1.15-2.05, P = 0.003). After adjustment for prescription of medication for one or more components of the MetS prior to TRT, the risk estimates attenuated but remained robust both for ICSI-treated (HR = 3.17 (95% CI: 2.56-3.9) and IVF-treated men (HR = 1.06 (95% CI: 1.05-1.07)., Conclusion: Men who have to utilise powerful techniques, such as ICSI for fathering children, may be at risk for testosterone deficiency. Routine endocrine evaluation of men seeking fertility treatment is hence warranted.