Association of Dietary Patterns With Testicular Function in Young Danish Men

Publisher's version (útgefin grein)Importance: Diet may play a role in testicular function, but data on how adherence to different diet patterns influences human testicular function are scarce. Objective: To determine whether adherence to specific dietary patterns is associated with testicular function in young men. Design, Setting, and Participants: This cross-sectional study included 2935 young Danish men unselected regarding fertility status who were enrolled from April 1, 2008, through May 31, 2017. Data were analyzed from July 1, 2017, to January 30, 2019. Exposures: Dietary patterns identified with principal component analysis based on responses to a validated food frequency questionnaire. Main Outcomes and Measures: Standard semen quality assessment; serum concentrations of testosterone, free testosterone, estradiol, inhibin B, follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin; and testicular volume measured with ultrasonography. Results: Among the 2935 participants included in the analysis, median age was 19 (interquartile range, 19-20) years and 2290 (78.0%) had normal body mass index. The 4 dietary patterns identified included Western, prudent, open-sandwich (a traditional Danish eating pattern), and vegetarianlike. The greatest adherence to the prudent pattern was associated with the highest total sperm count (median, 167 [95% CI, 146-183] million), followed by adherence to vegetarianlike (median, 151 [95% CI, 134-168] million) and open-sandwich (median, 146 [95% CI, 131-163] million) patterns. Adherence to the Western pattern was associated with the lowest total sperm count (median, 122 [95% CI, 109-138] million), which was significantly lower than sperm count in the other 3 diet patterns. After adjusting for confounders, the median total sperm count for men in the highest quintile of adherence to the Western pattern was 26 million lower (95% CI, -42 to -9 million) than for men in the lowest quintile of adherence to this pattern. Conversely, the median total sperm count of men in the highest quintile of adherence to the prudent pattern was 43 million (95% CI, 23-63 million) higher than that of men in the lowest quintile. Men with the highest adherence to the Western pattern had a lower median ratio of inhibin B to follicle-stimulating hormone (-12 [95% CI, -20 to -3]) and higher median ratio of free testosterone to luteinizing hormone (10 [95% CI, 2-19]) compared with men with lowest adherence to this pattern. Conclusions and Relevance: In this cross-sectional study, adherence to generally healthy diet patterns was associated with better semen quality, with potentially more favorable fertility potential among adult men.This work was supported by project 2101-08-0058 from the Danish Council for Strategic Research, Program Commission on Health, Food and Welfare, grant 8020-00218B from the Independent Research Fund Denmark, grant 212844 from the European Union, DEER, the Danish Ministry of Health, the Danish Environmental Protection Agency, grant 95-103-72087 from the Kirsten and Freddy Johansen Foundation, and grant P30DK046200 from the National Institutes of Health.Peer Reviewe

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

Prenatal exposure to perfluoroalkyl substances and anogenital distance at 3 months of age in a Danish mother-child cohort

In the Odense child cohort, serum concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 638 pregnant women. Birth weight, head and abdominal circumferences and gestational age were determined. Anogenital distance (AGD), the distance from the anus to the genital organs, and penile width were measured 3 months after expected date of birth in 511 children. PFOS, PFHxS, PFNA and PFDA were associated with a decreased AGD in girls (p-trend < 0.05) after adjusting for age and weight-for-age standard deviation score. PFOS in the highest quartile was associated with a 2.8 mm (95% confidence intervals -4.5; -1.1) reduction in AGD in girls. No such tendencies were seen in boys. However, a tendency toward increased birth weight in girls and reduced birth weight in boys suggests that sex-dimorphic effects may occur from endocrine disrupting effects of these substances

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

Current global status of male reproductive health

BACKGROUND: The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identifying critical questions, collecting pertinent information, and utilizing these data to develop evidence-based strategies. The methods for addressing these questions and the pathways toward their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts. To address these issues, a conjoint ESHRE and Male Reproductive Health Initiative (MRHI) Campus workshop was convened.OBJECTIVE AND RATIONALE: The three objectives were: first, to assess the current state of MRH around the world; second, to identify some of the key gaps in knowledge; and, third, to examine how MRH stakeholders can collaboratively generate intelligent and effective paths forward.SEARCH METHODS: Each expert reviewed and summarized the current literature that was subsequently used to provide a comprehensive overview of challenges related to MRH.OUTCOMES: This narrative report is an overview of the data, opinions, and arguments presented during the workshop. A number of outcomes are presented and can be summarized by the following overarching themes: MRH is a serious global issue and there is a plethora of gaps in our understanding; there is a need for widespread international collaborative networks to undertake multidisciplinary research into fundamental issues, such as lifestyle/environmental exposure studies, and high-quality clinical trials; and there is an urgent requirement for effective strategies to educate young people and the general public to safeguard and improve MRH across diverse population demographics and resources.LIMITATIONS REASONS FOR CAUTION: This was a workshop where worldwide leading experts from a wide range of disciplines presented and discussed the evidence regarding challenges related to MRH. While each expert summarized the current literature and placed it in context, the data in a number of areas are limited and/or sparse. Equally, important areas for consideration may have been missed. Moreover, there are clear gaps in our knowledge base, which makes some conclusions necessarily speculative and warranting of further study.WIDER IMPLICATIONS: Poor MRH is a global issue that suffers from low awareness among the public, patients, and heathcare professionals. Addressing this will require a coordinated multidisciplinary approach. Addressing the significant number of knowledge gaps will require policy makers prioritizing MRH and its funding.STUDY FUNDING/COMPETING INTERESTS: The authors would like to extend their gratitude to ESHRE for providing financial support for the Budapest Campus Workshop, as well as to Microptic S.L. (Barcelona) for kindly sponsoring the workshop. P.B. is the Director of the not-for-profit organization Global Action on Men's Health and receives fees and expenses for his work, (which includes the preparation of this manuscript). Conflicts of interest: C.J.D.J., C.L.R.B., R.A.A., P.B., M.P.C., M.L.E., N.G., N.J., C.K., AAP, M.K.O., S.R.-H., M.H.V.-L.: ESHRE Campus Workshop 2022 (Travel support-personal). C.J.D.J.: Cambridge University Press (book royalties-personal). ESHRE Annual Meeting 2022 and Yale University Panel Meeting 2023 (Travel support-personal). C.L.R.B.: Ferring and IBSA (Lecture), RBMO editor (Honorarium to support travel, etc.), ExSeed and ExScentia (University of Dundee), Bill &amp; Melinda Gates Foundation (for research on contraception). M.P.C.: Previously received funding from pharmaceutical companies for health economic research. The funding was not in relation to this work and had no bearing on the contents of this work. No funding from other sources has been provided in relation to this work (funding was provided to his company Global Market Access Solutions). M.L.E.: Advisor to Ro, Doveras, Next, Hannah, Sandstone. C.K.: European Academy of Andrology (Past president UNPAID), S.K.: CEO of His Turn, a male fertility Diagnostic and Therapeutic company (No payments or profits to date). R.I.M.: www.healthymale.org.au (Australian Government funded not for profit in men's health sector (Employed as Medical Director 0.2 FET), Monash IVF Pty Ltd (Equity holder)). N.J.: Merck (consulting fees), Gedeon Richter (honoraria). S.R.-H.: ESHRE (Travel reimbursements). C.N.: LLC (Nursing educator); COMMIT (Core Outcomes Measures for Infertility Trials) Advisor, meeting attendee, and co-author; COMMA (Core Outcomes in Menopause) Meeting attendee, and co-author; International Federation of Gynecology and Obstetrics (FIGO) Delegate Letters and Sciences; ReproNovo, Advisory board; American Board of Urology Examiner; American Urological Association Journal subsection editor, committee member, guidelines co-author Ferring Scientific trial NexHand Chief Technology Officer, stock ownership Posterity Health Board member, stock ownership. A.P.: Economic and Social Research Council (A collaborator on research grant number ES/W001381/1). Member of an advisory committee for Merck Serono (November 2022), Member of an advisory board for Exceed Health, Speaker fees for educational events organized by Mealis Group; Chairman of the Cryos External Scientific Advisory Committee: All fees associated with this are paid to his former employer The University of Sheffield. Trustee of the Progress Educational Trust (Unpaid). M.K.O.: National Health and Medical Research Council and Australian Research Council (Funding for research of the topic of male fertility), Bill and Melinda Gates Foundation (Funding aimed at the development of male gamete-based contraception), Medical Research Future Fund (Funding aimed at defining the long-term consequences of male infertility). M.H.V.-L.: Department of Sexual and Reproductive Health and Research (SRH)/Human Reproduction Programme (HRP) Research Project Panel RP2/WHO Review Member; MRHI (Core Group Member), COMMIT (member), EGOI (Member); Human Reproduction (Associate Editor), Fertility and Sterility (Editor), AndroLATAM (Founder and Coordinator).</p

Temporal Trends in Fertility Rates:A Nationwide Registry Based Study from 1901 to 2014

Increasing age at first childbirth has been suggested to increase the risk for infertility. Our objective is to determine whether women above thirty years of age historically have been able to sustain fertility rates above replacement level.A descriptive nationwide Danish study using birth registries from 1901-2014.Information on women's age at childbirth was obtained by using records from primary, secondary and tertiary institutions.Mothers to 8,024,969 live births.Mothers were stratified according to age at childbirth to determine total and age specific fertility rates.Total fertility rate (TFR) decreased from 4.1 to 1.8 children per woman and age specific fertility also decreased from 1901 to 2014. Women aged 30-34, 35-39 or 40-44 years in the first decade of the 20th century had higher fertility rates than the corresponding five year younger age groups (25-29, 30-34 and 35-39, respectively) have had for the last 65 years. On average, women gave birth to two children after the age of 30 and one or more child after 35 years of age in the beginning of the 1900s. Furthermore, women more than 40 years of age accounted for 10% of TFR in 1901 compared with 4% in 2014 despite usage of assisted reproduction.This nationwide study shows that women above 30 years of age historically have been able to sustain fertility rates above replacement level. This implies that other factors besides age are strong determinants of fertility in women above 30 years of age

Anogenital distance, male factor infertility and time to pregnancy

BACKGROUND: Anogenital distance (AGD), the distance between the anus and genitals, is in rodents a well‐established marker of early androgen action and has been suggested to be so in humans as well. Thus, a link between human AGD and semen quality and potentially fecundity may exist. OBJECTIVE: The aim of this study was to assess the association between AGD and male factor infertility and among proven fertile men also time to pregnancy (TTP). MATERIAL AND METHODS: All included men were recruited from and examined at Copenhagen University Hospital ‐ Rigshospitalet, Denmark (N = 388). Men with impaired semen quality were included from infertile couples (N = 128), and men with naturally conceived pregnant partners were invited to participate when their partners had their routine second trimester examination (N = 260). All men underwent a physical examination, completed a questionnaire (including TTP for the fertile men), delivered a semen sample and had a blood sample drawn. The primary exposure was AGD(AS) measured from the centre of the anus to the posterior base of the scrotum. Associations between AGD and fertility status as well as between AGD and TTP among the fertile men were calculated using multiple logistic regression adjusted for covariates. RESULTS: AGD did not show a statistically significant association with fertility status. In adjusted logistic regression models, the odds of infertility per 1 cm increase in AGD(AS) were 1.02 (95% confidence interval [CI]: 0.88; 1.19). Among fertile men, a 1‐cm increase in AGD(AS) was associated with an 8% non‐statistically significantly reduced odds of having a longer (>3months) TTP (adjusted odds ratio (OR) = 0.92, 95% CI: 0.76–1.11). CONCLUSION: Our study showed that the clinical application of AGD as a predictor of fertility and fecundity seems to be limited as no associations were observed between AGD and fertility status, nor was the decreased risk of experiencing a longer TTP with longer AGD(AS) statistically significant