Increasing Trends in Male Reproductive Disorders, Environmental Exposures, and Implications for...
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Transcript of Increasing Trends in Male Reproductive Disorders, Environmental Exposures, and Implications for...
Increasing Trends in Male ReproductiveDisorders, Environmental Exposures, andImplications for Human HealthNiels E. SkakkebaekDepartment of Growth and ReproductionInternational Center for Research and Research Training in Endocrine Disruption of MaleReproduction and Child Health (EDMaRC), Rigshospitalet,University of Copenhagen, Denmark
Teleconference 20 April, 2016
Nothing to declare
Total Fertility Rates (TFR), European Union, Japan and United States, 1960–2013
Skakkebaek et al. Physiol Rev 2016;96:55-97©2016 by American Physiological Society
InallthedataaboutGermany,it'stheonestatisticthatbucksthetrend.Itseconomyisstrong,itscitiesareregularlycitedasamongthebestintheworldtolivein– butGermanyisashrinkingAccordingtothenationalstatisticsoffice,fewerbabieswerebornin Germany lastyearthanatanytimeinitshistory.Atotalof663,000childrenwereborn,15,000fewerthanin2010andinstarkcontrastto1964whenGermanbirths(eastandwest)peakedatjustunder1.4 million.Therateforyoungerwomeninparticularfelllastyear,
Increasing political focuson low fertility
50% fewer childrenand young people!
Possible Reasons for Declining Fertility Rates
• Some social scientists and demographers:a. people just plan to have fewer kids andb. use of modern contraception and induced abortions
Total Fertility Rate (TFR), Denmark 1901–2014
Skakkebaek et al. Physiol Rev 2016, Blomberg Jensen et al PLoS One, 2015©2016 by American Physiological Society
45% Unintended Pregnancy Rate in USAFiner & Zolna, NEJM, 2016
Pregnancy eitherMistimed -not wanted at the time that pregnancy
occcurred but at a later timeor
Unwanted – not wanted then or at any time in thefuture
Possible Reasons for Declining Fertility Rates
• Some social researchers (demographers):a. people intend to have fewer kids andb. use of modern contraception and induced abortion
• Gynecologists: Women are too old when theystart trying to become pregnant
Mean ages of Danish women delivering from 1901–2014.
Blomberg Jensen et al, PLoS One, 2015; Skakkebaek et al. Physiol Rev 2016;96:55-97©2016 by American Physiological Society
Possible Reasons for Declining Fertility Rates
• Social researchers (demographers):a. people intend to have fewer kids andb. use of modern contraception and induced abortion
• Gynecologists: Women are too old when theystart trying to become pregnant
• Fecundity (ability to conceive) has declined,male or female, or both
Fewer Unintended Pregnanciesand Widespread Infertility
• 40-50% of children in US and Europe are bornafter sex where pregnancy was not planned.
• But previously a higher number.• Hypothesis I will discuss is: Does a general
decline in male reproductive health play a rolefor birth rates by causing a reduction in thenumber of unintended pregnancies and moreinfertility?
Testicular germ cellcancer (TGCC)
Congenitaldisorders of
genitalia
Reduced fecundityand childlessness
Lower T-levels
Links and Trends in Male Reproductive DisordersA Square
From Møller, Hum Reprod2001
Testicular Cancer
Prostate Cancer
Age-standardized incidence in DK, around 1995
Well diagnosedand registrationclose to complete
Testicular germ cellcancer (TGCC)
Congenitaldisorders of
genitalia
Reduced fecundityand childlessness
Lower T-levels
Links and Trends in Male Reproductive DisordersA Square
casescontrols
454035302520
2.5
2.0
1.5
1.0
0.5
0.0
Age
Number of children
Møller & Skakkebæk, Br Med J, 1999
Evidence for decreased fertility in menprior to development of testicular cancer
Testicular germ cellcancer (TGCC)
Congenitaldisorders of
genitalia
Reduced fecundityand childlessness
Lower T-levels
Links and Trends in Male Reproductive Disorders
Sperm count of 4867 young men from the general populationJørgensen et al, BMJ Open, 2012
Adjusted for duration of ejaculation abstinence
Sperm concentration, young Danish men
0
2
4
6
8
10
12
0
>0- <
10
10- <2
0
20- <3
0
30- <4
0
40- <5
0
50- <6
0
60-<7
0
70- <8
0
80- <9
0
90- <1
00
100-
<110
110-
<120
120-
<130
130-
<140
140-
<150
Categories of sperm concentration (mio/ml)
No.
ofm
en(%
)
Similar results from Finland, Germany, USA, Japan and Australia
21%<20 mill/ml43% < 40 mill/ml
Should we be concerned about thesepublications on low sperm counts ?
Some people may think:
”….after all, only one sperm is necessary forfertilization….“
Bonde et al.: Lancet, 1998
Probability of pregnancy within one menstrual cycle
Sperm concentration, mill/ml
%
Increasing need for assisted reproduction
Most recent data (2015) from Danish Fertility Societyshows that:
8 % of the 2012 national birth cohort conceived after assistedreproduction
(IVF,ICSI,IUI-H or IUI-D)http://www.fertilitetsselskab.dk/
In addition, almost 1% of children adopted
Testicular germ cellcancer (TGCC)
Congenitaldisorders of
genitalia
Reduced fecundityand childlessness
Lower T-levels
Links and Trends in Male Reproductive DisordersRoots in fetal development
Testicular Dysgenesis Syndrome (TDS)
©2016 by American Physiological Society Skakkebaek et al. Physiol Rev 2016;96:55-97
WHO-UNEP: Strong evidence that EDCs can haveadverse effects on male reproduction at the level of
the pituitary, the testicle and the gamete
• Effects in wild life• Effects in experimental settings• Potential effects in humans• We are all exposed• Possible transgenerational effects
Conclusions• Testicular cancer is an important marker of endocrine disruption of
the fetal human testis.• Worldwide increases in testicular cancer incidence.• Semen quality of young men now rarely meets all criteria of the WHO
standard.• Extremely low fertility rates below replacement levels have previously
been seen as a result of womens choices.• However, an increasing number of data suggest that male infertility
also contributes to low birth rates.• We and others are testing the hypothesis that environmental
exposures contribute to the current epidemic of subfertility andinfertility, which likely is associated with decreasing populations inmany industrialized countries.
• Good news: Exposures can be reduced by better regulation ofchemicals!