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HUMAN SEMEN QUALITY IN THE NEW MILLENIUM: A MATTER OF CONCERN?
Rigshospitalet
Copenhagen
Denmark
Niels Jørgensen, Ulla N. Joensen, Tina K. Jensen, Martin B.
Jensen, Kristian Almstrup, Inge A. Olesen, Elisabeth Carlsen,
Jørgen H. Petersen, Jorma Toppari and Niels E. Skakkebæk
Semen quality a matter of concern
• Lower than two-three generations ago
• In European countries
• Only 25% have optimal semen quality
• 20-30% at risk of prolonged waiting time to pregnancy
• 10-15% at risk for need of fertility treatment
• Other implications
• Marker of reduced general health status?
Carlsen et al: BMJ, 1992
Historical data
• Mainly European and US
• 50% decrease in 50 yrs
Evidence for decreasing quality of semen during past 50 years
0
20
40
60
80
100
120
140
160
180
200 S
perm
co
nc
en
trati
on
(m
ill/m
L)
Jørgensen et al: BMJ Open, 2012
45 mill/mL
43 mill/mL 45 mill/mL 48 mill/mL
Year of investigation
0
5
10
15
20
25
30
35
40
45
50
% o
f m
en
Sperm concentration (million/mL)
0
10
20
30
40
50
60
70
% o
f m
en
Total sperm count (million)
Men from infertile couples (1940-1943) Men from general population (1996-2010)
Jørgensen et al: BMJ Open, 2012
0
2
4
6
8
10
12
% o
f m
en
Sperm concentration (million/mL)
0
5
10
15
20
25
30
% o
f m
en
Total sperm count (million)
0
5
10
15
20
25
30
35
40
0 >0-2 2-5 5-9 9-12 12-15 >15
% o
f m
en
Morphologically normal spermatozoa (%)
Jørgensen et al: BMJ Open, 2012
Fertile men (1996-1998)
Men from the general population (1996-2010) 45 mill/mL 61 mill/mL
143 mill 215 mill
6.5% 8.5%
Bonde et al.: Lancet, 1998.
Probability of pregnancy within one menstrual cycle
Sperm concentration, mill/ml
%
4,867 men from Copenhagen area in Denmark
Results compatible with decrease since early 1940’s
Slight increase in sperm concentration and total sperm
count 1996-2010
Only 23% had sperm concentration >40 mill/ml AND
>9% morphologically normal spermatozoa
Approx. 15% had a sperm concentration that indicate a
high risk of needing future fertility treatment, and
another 27% will be at risk of a prolonged waiting time
to pregnancy
41
Normal young men
Sperm conc. (mill/ml)
55 63
63
55
44
43-48
67 48
(62)
Jørgensen et al (2002, 2011),
Richthoff et al (2000),
Axelsson et al (2011)
Punab et al (2002),
Tsarev et al (2003),
Paasch et al (2008)
Fernandez et al (2010)
Semen quality studies
Decrease in Finnish men (and maybe also in French)
Geographical differences, lowest levels in Norway,
Denmark, Germany (and maybe Switzerland)
High frequency of men with low sperm counts in all
(investigated) European countries
Many men at risk of impaired fertility
Also low among young Americans?
Testicular Cancer
”Association of Nordic Cancer Registries” and ”Cancer in Germany”
0
2
4
6
8
10
12
1943
1947
1951
1955
1959
1963
1967
1971
1975
1979
1983
1987
1991
1995
1999
2003
Inc
ide
nc
e r
ate
s (
pe
r 1
00
,00
0),
WS
P
Denmark
Norway
Germany
Sweden
Finland
Semen quality
• Reduced semen quality may cause fertility problems
and have an impact on fertility rates
• Semen quality is a risk factor for
• reduced capacity for testosterone production
• testicular cancer
• morbidity and mortality?
Should reduced semen quality be seen as a warning
of general health problems?
Testicular Dysgenesis Syndrome
TESTICULAR
DYSGENESIS
DISTURBED
SERTOLI
CELL
FUNCTION
DECREASED
LEYDIG CELL
FUNCTION
IMPAIRED
GERM
CELL
DIFFEREN-
TIATION
ANDROGEN
INSUFFICIENCY
REDUCED SEMEN
QUALITY
TESTICULAR
CANCER
HYPOSPADIAS
TESTICULAR
MALDESCENT
Environmental factors
incl. endocrine
disrupters
Genetic defects
incl. 45,X/46,XY and
point mutations
CIS
Prenatal period Postnatal period
Prenatal vs. adulthood exposures
TESTICULAR
DYSGENESIS
REDUCED SEMEN
QUALITY
Environmental factors
incl. endocrine
disrupters
Genetic defects
incl. 45,X/46,XY and
point mutations
Prenatal period Adulthood
Environmental factors
incl. endocrine
disrupters
Irradiation
Chemotherapy
Occupational events
(toxic events)
Postnatal period
?
TESTICULAR
CANCER
HYPOSPADIAS
TESTICULAR
MALDESCENT
CIS
Conclusions
• Semen quality has approached levels that may
impair fertility
• Testicular cancer incidence is increasing in
many European countries
• Genital malformations of newborn boys have
increased in some European countries
• May all be symptoms of a Testicular
Dysgenesis Syndrome (TDS) of fetal origin
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