Evidence map›Paper›PMID 26582516›Full record

ReviewPhysiological reviews2016

Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility.

Niels E Skakkebaek, Ewa Rajpert-De Meyts, Germaine M Buck Louis, Jorma Toppari, Anna-Maria Andersson, Michael L Eisenberg, Tina Kold Jensen, Niels Jørgensen, Shanna H Swan, Katherine J Sapra and 3 more

2 registry-linked trialsOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Physiological reviews, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 396 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
396citing papers in PubMed, 6 pooled it
29.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05212337 phase2active not recruitingnot on this mapstarted 2022, after this paper: background citation

Effect of a Single-dose Denosumab on Semen Quality in Infertile Men (FITMI): A Randomized Controlled Trial

TypeinterventionalSponsorMartin Blomberg JensenRan2022 to 2025Enrolled180ConditionsInfertility, MaleArmsDenosumab, Sodium chloride
NCT06300229 phase1 / phase2completednot on this mapstarted 2024, after this paper: background citation

Novel Approach for Oligospermia (NAPO): A Randomized Controlled Trial

TypeinterventionalSponsorMartin Blomberg JensenRan2024 to 2025Enrolled42ConditionsInfertility, MaleArmsDenosumab, sodium chloride
3 · Its place in the literature

Who cites it

396 citing papers in PubMed, 6 syntheses or guidelines pooled it, 925 citations in OpenAlex.

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  18. Current Applications and Future Prospects of High-ThroughputAnimals : an open access journal from MDPI · 2026
    Review
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336 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 3 countries.

Niels E SkakkebaekDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Ewa Rajpert-De MeytsDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Germaine M Buck LouisDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Jorma ToppariDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Anna-Maria AnderssonDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Michael L EisenbergDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Tina Kold JensenDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Niels JørgensenDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Shanna H SwanDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Katherine J SapraDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Søren ZiebeDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Lærke PriskornDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Anders JuulDepartment of Growth & Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Physiology & Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Male Reproductive Medicine & Surgery Program, Stanford University, Stanford, California; Icahn School of Medicine at Mount Sinai, New York, New York; and The Fertility Clinic, Rigshospitalet, Copenhagen, Denmark.
Icahn School of Medicine at Mount Sinai · USStanford University · USTurku University Hospital · FIUniversity of Copenhagen · DKUniversity of Turku · FI

Funding

The Mount Sinai Transdisciplinary Center on Early Environmental ExposuresP30ES023515 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Robert O Wright · 2014 to 2026
$21.3M
6 · The paper itself

Abstract

It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

Indexed as

Environmental ExposureGene-Environment InteractionLife StyleFertilityGenetic Predisposition to DiseaseHumansIncidenceInfertility, MaleMalePhenotypePopulation DynamicsRisk Factors

Identifiers

PMID26582516
PMCPMC4698396
OpenAlexW2190800365

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.