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CLINICAL STUDY
A cohort effect on serum testosterone levels in Finnish men
A Perheentupa
1,2
,JMa¨kinen
3
, T Laatikainen
5
, M Vierula
1
, N E Skakkebaek
6
, A-M Andersson
6
and J Toppari
1,4
1
Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FI 20520 Turku, Departments of
2
Obstetrics and
Gynaecology,
3
Medicine and
4
Paediatrics, University of Turku, Turku, Finland,
5
National Institute for Health and Welfare, Mannerheimintie 166, Helsinki
FI 00300, Finland and
6
Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen DK-2100, Denmark
(Correspondence should be addressed to A Perheentupa at Department of Physiology, Institute of Biomedicine, University of Turku;
Email: antti.perheentupa@utu.fi)
Abstract
Objective: To investigate whether a population-level decline in serum testosterone exists in Finnish men.
In comparison with other European populations, Finnish men have compared well in the studies
of reproductive health (i.e. semen quality, incidence of cryptorchidism and testicular cancer); thus,
we expected no significant cohort-dependent decrease in serum testosterone.
Methods: We analysed serum levels of testosterone, gonadotrophin and sex hormone binding globulin
(SHBG) in 3271 men representing different ages (25–74 years) and birth cohorts within three large
Finnish population surveys conducted in 1972, 1977 and 2002.
Results: Serum testosterone levels decreased (from 25.3 nmol/l in 25- to 29-year-old men gradually to
16.9 nmol/l in 70- to 74-year-old men), whereas SHBG and gonadotrophin levels increased with
increasing age. In addition, a significant secular trend in testosterone (total and free), SHBG and
gonadotrophin levels was observed with lower levels in more recently born age-matched men. Serum
testosterone level decreased in men aged 60–69 years from 21.9 nmol/l (men born 1913–1922) to
13.8 nmol/l (men born 1942–1951). These decreases remained significant following adjustment
for BMI. An age-independent birth cohort effect existed on reproductive hormones measured in the
Finnish men. In concert with the lower free testosterone levels, we observed lower gonadotrophin
levels, suggesting that while there may be detrimental changes at the gonad level, the hypothalamus–
pituitary–axis is not responding appropriately to this change.
Conclusions: The more recently born Finnish men have lower testosterone levels than their earlier
born peers. This study offers no explanation for this substantial recent adverse development.
European Journal of Endocrinology 168 227–233
Introduction
Serum testosterone decreases with age in men, and
longitudinal estimates of this phenomenon are signi-
ficantly greater than cross-sectional estimates (1, 2, 3).
Low serum testosterone has been associated with a
number of compromised health conditions such as
obesity, diabetes, dyslipidemia, decreased bone and
muscle mass and decreased quality of life (4). The
number of elderly men will significantly increase in
the near future and hence their well-being and quality
of life are of general concern for public health. Two
recent studies reported a population-level decline in
serum testosterone in American and Danish men (5, 6).
This would partly explain the observed difference in
age-related serum testosterone decline between cross-
sectional vs longitudinal studies, and it may also reflect
an ongoing adverse trend in male reproductive health.
By contrast, the recent analysis of National Health and
Nutritional Examination Surveys (NHANES) from 1988
to 1991 and from 1999 to 2004 failed to show any
decline in testosterone in USA males (7).
Compared with Danishmen, the Finnish men have
compared well in recent evaluations of reproductive
health (i.e. incidence of cryptorchidism, hypospadias and
testicular cancer and semen quality) (8,9,10,11,12);
we questioned whether population-level changes in
testosterone levels would also be apparent in Finnish
men and therefore not specific to men from Denmark
and New England.
Subjects and methods
Study population
Testosterone, gonadotrophin and sex hormone binding
globulin (SHBG) were analysed in sera of men from
three Finnish population surveys conducted in 1972,
1977 and 2002 by the National Public Health Institute
(presently the National Institute for Health and
Welfare). Data collection and blood sampling were
carried out within the national cardiovascular disease
risk factor surveys named the National FINRISK
European Journal of Endocrinology (2013) 168 227–233 ISSN 0804-4643
q2013 European Society of Endocrinology DOI: 10.1530/EJE-12-0288
Online version via www.eje-online.org
Study (13). For each survey, an independent random
sample was drawn from the national population
register, i.e. the same individuals did not contribute
to different surveys. To obtain comparable data, the
methodology of the data collection has been kept as
similar as possible throughout the survey years. Since
1982, the survey methodology has closely followed the
WHO MONICA protocol (14). In 2002, some more
detailed recommendations of the European Health
Risk Monitoring Project were adopted (15). The surveys
included a self-administered questionnaire, physical
measurements and blood tests. The health question-
naire, together with the invitation to the health
examination, was sent by mail to all the selected
subjects. Trained nurses carried out the physical
measurements and blood sampling in the local
health centres.
Venous blood samples were drawn during office
hours following a minimum of 4-h fasting. Samples
were then centrifuged in the field survey sites and
the sera were mailed daily to the Laboratory of
Analytical Biochemistry in the National Public Health
Institute. Upon arrival, they were immediately frozen
and later stored at K20 8C. For this study, we received
serum samples from this Bio bank from 3271 men. The
men were divided into six age groups: 25–29, 30–39,
40–49, 50–59, 60–69 and 70–74 years). They were
also divided into seven birth cohort groups according to
their year of birth: 1913–1922, 1923–1932, 1933–
1941, 1942–1951, 1952–1959, 1960–1969 and
1970–1977. The number of men in each category in
the age–birth year matrix is shown in Table 1. Although
the number of men in each cell is quite different, the
distribution of ages within each age group and cell is
rather even.
Hormone measurements
Testosterone, SHBG, LH and FSH levels were
measured by time-resolved fluoroimmunoassays
(DELFIA; Wallac Oy, Turku, Finland) with detection
limits 0.23, 0.23 nmol/l, 0.05 and 0.06 IU/l respect-
ively. The intra- and interassay coefficients of variation
were !12% for testosterone, 8% for SHBG and 5% for
gonadotrophins.
All samples were analysed during the same period
and mixed in the different assay runs to eliminate any
influence of assay variation. Free testosterone was
calculated from the testosterone and SHBG concen-
trations using the method by Vermeulen et al.(16),
with the assumption of an average serum albumin
concentration of 43 g/l.
Statistical analysis
Hormone levels across age and birth cohort groups were
compared using one-way ANOVA with Bonferroni’s
post hoc test. The effect of age, BMI and birth cohort on
the hormone levels was compared using multiple
regression models adjusting for the other respective
variables.
Ethics
The study was approved by the Joint Ethics Committee of
the Turku University and Turku University Central Hospital.
Table 1 Number of participants in each age and cohort group and the respective serum testosterone concentrations in nanomoles per litre
(median, 5th–95th percentiles) in birth cohorts of Finnish men.
Birth year 1970–1977 1960–1969 1952–1959 1942–1951 1933–1941 1923–1932 1913–1922 All
Age (years)
25–29 nZ63 nZ289 nZ352
19.1
(8.7–27.3)
26.4
‡
(15.1–44.0)
25.3
(13.3–43.5)
30–39 nZ51 nZ127 nZ57 nZ624 nZ859
17.2
(7.7–37.6)
16.1
(8.6–28.3)
20.5*
,‡
(11.1–38.6)
22.0
‡
(11.6–38.6)
20.5*
(10.3–37.6)
40–49 nZ62 nZ143 nZ682 nZ887
15.7
(7.5–25.8)
14.6
(8.5–29.8)
22.6
‡
(11.2–39.6)
20.9*
(9.5–38.4)
50–59 nZ28 nZ204 nZ519 nZ751
17.4
(8.7–30.9)
15.3*
,†
(7.5–30.4)
22.6
‡
(11.3–40.9)
19.9*
(8.7–39.9)
60–69 nZ23 nZ192 nZ130 nZ345
13.8*
,†
(7.7–27.8)
14.4
(8.0–31.3)
21.9
‡
(10.3–40.9)
17.0*
,†
(8.1–36.4)
70–74 nZ77 nZ77
16.9
(8.4–28.3)
16.9*
,†
(8.4–28.3)
*
,†
Depict statistical significance compared with the above values in each column.
‡,§
Depict statistical significance compared with the values to the left across
each row. The significance in all of the cases is P!0.05.
228 A Perheentupa and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2013) 168
www.eje-online.org
Results
Testosterone
Serum total testosterone concentration modestly
decreased with age in the study population from on
average 25.3 nmol/l in the youngest men (25–29 years)
to 16.9 nmol/l in the oldest men (70–74 years).
Testosterone levels declined over ages as follows:
25–29O30–39Z40–49Z50–59O60–69Z70–74
years (Bonferroni’s post hoc test). In addition to the
overall age-related decrease, significantly lower serum
testosterone levels were observed in men of the same
age born in more recent decades. This was true in all
age groups for which two or more groups existed with
at least a decade’s difference in time of birth (Fig. 1).
For more detailed data, see Table 1.
Sex hormone binding globulin
Serum SHBG concentrations increased clearly with age
in the study population: 25–29Z30–39!40–49!50–
59Z60–69Z70–74 years. Within age groups, a clear
trend of men born earlier (at least a decade’s difference)
displaying higher SHBG concentrations was observed
(Table 2).
Free testosterone
A more pronounced decrease was observed in serum
free testosterone with age compared with the total
testosterone (Table 3). The cohorts of men born earlier
displayed significantly higher free testosterone concen-
trations, although not all pair-wise comparisons
between two consecutive cohorts reached statistical
significance.
Gonadotrophins
In response to the age-related decreasing testosterone,
serum LH concentrations increased significantly with
age in the entire study population, being highest in the
oldest group (25–29Z30–39Z40–49!50–59Z60–
69!70–74 years). By contrast, LH did not seem to
respond to the birth year-related decrease of testoster-
one levels, but LH levels were significantly lower in men
born later (Table 4). Similarly, serum FSH concen-
trations showed an age-related increase (25–29Z30–
39!40–49!50–59Z60–69Z70–74 years), but a
birth year-related decrease within age groups with
lower levels was measured in the cohort born later
(Table 5).
Hormone level in relation to BMI
The BMI was higher in the older men. When stratified
according to age and birth cohort, serum testosterone,
SHBG and LH concentrations were significantly corre-
lated with BMI (Table 6).
Both age and BMI were statistically significant
variables affecting testosterone levels (P!0.0001), but
the effect of birth cohort on serum testosterone remained
significant when data were stratified according to age-
related changes and BMI (P!0.0001 in cohorts born
by 1951 in comparison with 1970–1974; Table 6).
However, this cohort effect is not significant when the
three most recently born age groups are compared each
with each other (PZ0.0931 and PZ0.6625 for men
born in 1952–1959 and 1960–1979 respectively).
A
g
e (
y
ears)
25–29
14
16
18
20
22
24
26
30–39 40–49 50–59
1933–1941
1923–1932
1913–1922
1970–1977
1960–1969
1952–1959
1942–1951
60–69 70–74
Serum testosterone concentrations (nmol/l)
Birth cohort
Figure 1 Serum testosterone concentrations (nmol/l; median
values) in Finnish men of different ages (X-axis) born in different
decades. Note that the Y-axis does not start from 0.
Table 2 Serum SHBG concentrations in nanomoles per litre (median, 5th–95th percentiles) in birth cohorts of Finnish men.
Birth year 1970–1977 1960–1969 1952–1959 1942–1951 1933–1941 1923–1932 1913–1922 All
Age (years)
25–29 26 (15–53) 33
‡
(17–57) 32 (16–56)
30–39 28 (17–59) 28 (14–50) 28 (14–54) 35
‡
(17–56) 33 (16–56)
40–49 34 (14–51) 33 (19–60) 41
‡
(20–75) 38* (19–72)
50–59 42* (16–66) 36* (19–71) 47
‡
(24–85) 44*
,†
(21–81)
60–69 38 (18–78) 38* (24–84) 50
‡
(26–94) 40*
,†
(22–91)
70–74 50* (26–77) 50*
,†
(26–77)
*
,†
Depict statistical significance compared with the above values in each column (P!0.05, ANOVA).
‡,§
Depict statistical significance compared with the values
to the left across each row.
Declining testosterone levels in Finnish men 229EUROPEAN JOURNAL OF ENDOCRINOLOGY (2013) 168
www.eje-online.org
Likewise, the cohort effect on serum LH, FSH and
SHBG levels is significant in cohorts born earlier when
data were stratified according to age-related changes
and BMI (P!0.0001; Table 6). Similar to serum
testosterone, the significance of the cohort effects in
LH, FSH and SHBG levels is lost in the more recently
born men (Table 6).
Discussion
In this study, we observed a clear age- and BMI-
independent birth cohort effect on serum testosterone
concentrations measured in Finnish men. Our study is
the third large population study to demonstrate a
declining trend in serum testosterone of men in a
similar fashion as seen in a USA and Danish population.
Men born more recently have also been shown to have a
higher risk of testicular cancer compared with men
born in previous decades (17). Furthermore, several
studies have indicated that sperm concentrations
among men in Europe have decreased (18). Taking
these findings together with the cohort effect observed
in this and the previous studies, serum testosterone
concentrations appear to follow a similar pattern and
these changes together may well reflect a detrimental
change in the overall reproductive health in men.
Finnish men have previously displayed better repro-
ductive health compared with Danish men as they show
better semen quality (9, 10) and markedly lower
incidences of testicular cancer (19), cryptorchidism
and hypospadias (8, 11, 12). If the cohort effect in
serum testosterone levels observed in Danish men
reflects their overall reproductive health (5), the Finns
would be expected to show little or no cohort effect.
This, however, was not the case, as the cohort effect we
observed in the Finnish men was as evident as
previously observed in other countries including Den-
mark (5, 6). Thus, although the reproductive health of
Finnish men may be better compared with Danish men
judged by the above-mentioned criteria, a birth cohort-
related decrease in serum testosterone levels seems to
have taken place over several decades. More recent data
on reproductive health of Finnish men show that the
Table 3 Serum free testosterone concentrations in picomoles per litre (median, 5th–95th percentiles) in birth cohorts of Finnish men.
Birth year 1970–1977 1960–1969 1952–1959 1942–1951 1933–1941 1923–1932 1913–1922 All
Age (years)
25–29 410
(212–704)
610
s
(350–1010)
570
(310–1000)
30–39 390
(170–675)
370
(190–587)
490
(280–986)
470
(270–859)
450*
(240–840)
40–49 320
(172–607)
320
(190–617)
430
s
(240–720)
400*
,†
(220–710)
50–59 330
(174–523)
285*
(160–490)
390
s
(189–661)
360*
,†,‡
(170–630)
60–69 270*
(181–509)
260*
(8.0–31.3)
370
s
(190–620)
310*
†,‡,§
(160–558)
70–74 260*
(158–450)
260*
,†,‡,§
(158–450)
*
,†,‡,§
Depict statistical significance compared with the above values in each column (P!0.05, ANOVA).
s,¶
Depict statistical significance compared with the
values to the left across each row.
Table 4 Serum LH concentrations in international units per litre (median, 5th–95th percentiles) in birth cohorts of Finnish men.
Birth year 1970–1977 1960–1969 1952–1959 1942–1951 1933–1941 1923–1932 1913–1922 All
Age (years)
25–29 3.16
(1.67–5.14)
3.85
‡
(1.81–7.96)
3.74
(1.79–7.65)
30–39 3.32
(1.01–6.2)
3.28
(1.35–8.41)
3.99
‡
(1.75–7.28)
3.80
‡
(1.74–7.63)
3.76
(1.6–7.48)
40–49 3.60
(1.41–5.78)
3.42
(1.67–7.96)
4.10
‡
(1.9–9.17)
3.91
(1.86–9.05)
50–59 3.67
(1.98–7.78)
3.91
(1.61–8.11)
4.87
‡
(2.04–12.6)
4.53*
(1.95–11.44)
60–69 4.57*
(1.81–9.53)
4.40*
(2.01–10.28)
5.51*
,‡
(2.21–18.34)
4.73*
(2.06–12.86)
70–74 5.57*
(2.28–11.61)
5.57*
,†
(2.28–11.61)
*
,†
Depict statistical significance compared with the above values in each column (P!0.05, ANOVA).
‡,§
Depict statistical significance compared with the values
to the left across each row.
230 A Perheentupa and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2013) 168
www.eje-online.org
incidence of testicular cancer has increased and the
semen quality has decreased in the more recently born
Finnish men (20). Together, these observations suggest
that the adverse trends in the parameters of repro-
ductive health may have lagged behind in the Finnish
men compared with e.g. Danish men, but that the same
trends nevertheless occur in Finland. Changes in serum
testosterone may be an early sentinel for adverse trends
in reproductive health as the decline in serum
testosterone was also observed between the earliest
birth cohorts included in this study.
Several studies have shown that serum testosterone
concentration decreases in men with ageing. The cross-
sectional studies report a decrease of !1%/year,
whereas a more dramatic decrease is observed in the
longitudinal studies (21). Our current study is well in
agreement with these findings as, the decrease of serum
testosterone is of similar magnitude. The magnitude
of the cohort effect is similar when comparing different
cohorts within each age group (2–4 nmol/l per decade).
Although greater in magnitude, the changes in
calculated serum free testosterone reflect the changes
in total testosterone.
In our study population, the gonadal–pituitary
feedback system reacted appropriately to the age-
related decrease in serum testosterone, with a typical
increase in LH levels. Analysis of all the age groups
(irrespective of birth decade) supports the compensatory
age-dependent LH increase associated with decreasing
testosterone in our study. But, within each age group,
Table 5 Serum FSH concentrations in international units per litre (median, 5th–95th percentiles) in birth cohorts of Finnish men.
Birth year 1970–1977 1960–1969 1952–1959 1942–1951 1933–1941 1923–1932 1913–1922 All
Age (years)
25–29 3.17
(1.5–5.9)
3.60
‡
(1.42–11.24)
3.43
(1.47–10.85)
30–39 3.12
(1.37–6.61)
3.58
(1.4–7.7)
3.49
(1.72–11.42)
4.21
‡
(1.74–10.66)
4.00
(1.66–10.31)
40–49 3.72
(1.58–9.25)
3.92
(2.04–11.14)
4.92
‡
(2.17–16.3)
4.56*
(2.05–15.17)
50–59 3.71
(1.97–8.65)
4.58*
(1.97–11.58)
6.52
‡
(2.4–23.7)
5.64*
,†
(2.2–18.84)
60–69 6.05*
,†
(2.67–25.82)
5.60*
(2.03–17.43)
6.37
(1.46–21.36)
5.92*
,†
(2.02–18.68)
70–74 6.43
(2.88–27.13)
6.43*
,†
(2.88–27.13)
*
,†
Depict statistical significance compared with the above values in each column (P!0.05, ANOVA).
‡,§
Depict statistical significance compared with the values
to the left across each row.
Table 6 The effect and significance of age, BMI and birth cohort studied in multivariate regression models adjusted for the other two
respective factors. The study population is divided into seven birth cohorts by their birth years. In the analyses, the birth cohorts are
compared with the most recent birth cohort (individuals born in 1970–1974); hence, this is the point of reference and given value 1
(significant comparisons are highlighted by bolding, with the respective Pvalue below).
Variables
Testosterone
(bGS.E.M.)
SHBG
(bGS.E.M.)
Free testosterone
(bGS.E.M.)
LH
(bGS.E.M.)
FSH
(bGS.E.M.)
Age K0.182G0.015 0.432G0.027 K0.007G0.001 0.031G0.005 0.066G0.010
P!0.0001 P!0.0001 P!0.0001 P!0.0001 P!0.0001
BMI K0.776G0.041 K1.842G0.075 K0.006G0.001 K0.069G0.015 K0.028G0.027
P!0.0001 P!0.0001 P!0.0001 P!0.0001 PZ0.294
Birth cohort
(1913–1922) 9.460G0.914 8.540G1.687 0.164G0.019 1.900G0.337 3.176G0.596
P!0.0001 P!0.0001 P!0.0001 P!0.0001 P!0.0001
(1923–1932) 6.957G0.853 5.425G1.573 0.125G0.017 0.847G0.314 2.048G0.556
P!0.0001 PZ0.0006 P!0.0001 PZ0.0071 PZ0.0002
(1933–1941) 4.969G0.828 1.552G1.528 0.109G0.017 0.599G0.305 1.427G0.540
P!0.0001 PZ0.310 P!0.0001 PZ0.050 PZ0.0008
(1942–1951) 4.947G0.839 0.979G1.549 0.120G0.017 0.636G0.309 0.974G0.548
P!0.0001 PZ0.527 P!0.0001 PZ0.040 PZ0.076
(1952–1959) 1.692G1.007 K1.199G1.858 0.041G0.020 0.050G0.371 0.204G0.657
PZ0.093 PZ0.519 PZ0.044 PZ0.894 PZ0.756
(1960–1979) K0.420G0.964 K2.659G1.779 K0.001G0.020 0.056G0.355 K0.032G0.629
PZ0.663 PZ0.135 PZ0.950 PZ0.874 PZ0.959
(1970–1974) 1111 1
Declining testosterone levels in Finnish men 231EUROPEAN JOURNAL OF ENDOCRINOLOGY (2013) 168
www.eje-online.org
the more recently born men with lower testosterone
also displayed lower LH levels. Obese ageing men may
display signs of hypogonadotrophic hypogonadism,
perhaps due to the feedback effect of adipose
tissue-derived oestrogen (3). Unfortunately, we did not
have oestradiol measurements of these samples.
However, although the later-born cohorts in our study
had higher BMIs, this alone could not explain the
relative decline in gonadotrophin levels in later birth
cohorts. Previous studies have not reported gonado-
trophin levels in association with the testosterone
changes. It is clear that this birth cohort effect makes
the evaluation of both cross-sectional and longitudinal
studies more complex. Health consequences of the
declining testosterone levels would be associated with
deteriorating reproductive health. The reasons for
these changes need to be identified in order to prevent
reproductive problems. Furthermore, several studies
have shown that decreased serum testosterone levels
are associated with increased morbidity and adverse
health conditions (4, 22). Our finding reflects a relative
decrease in serum testosterone on a population level,
and the values for most men remain well within the
normal reference range. However, a shift of the total
population will consequently increase the number
of individuals who become hypogonadal and
experience effects of low testosterone, particularly with
increasing age.
Unfortunately, in a cohort study of this nature, it was
not possible to ensure similar group size in the different
age groups or in the different cohort groups. Whereas
our study population is relatively large, the small size
of some groups weakens the statistical power and makes
the analysis of these groups less reliable. Collection of
the blood samples for testosterone analysis should
optimally be performed during the morning hours.
Variable collection times may affect individual testoster-
one levels. However, as the samples were collected
similarly in the different surveys, this is very unlikely
to have affected the cohort effect studied.
Our study cannot reveal the causes of the adverse
trends in male reproductive hormone levels. However,
the fact that the changes occurred over a relatively
short period suggests that changes in lifestyle or
environment – or both – are involved. The reasons for
these changes need to be identified in order to prevent
further deterioration of male reproductive health.
Declaration of interest
The authors declare that there is no conflict of interest that could be
perceived as prejudicing the impartiality of the research reported.
Funding
This work was supported by research grants from the Academy
of Finland, Sigrid Juse
´lius Foundation, Turku University Hospital and
the European Commission (QLK4-2002-00603, DEER 212844 FP7-
ENV-2007-1).
Acknowledgements
The authors thank M.Sc. Jaakko Matoma¨ki for assistance in the
statistical analyses of this study.
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Received 1 April 2012
Revised version received 18 September 2012
Accepted 15 November 2012
Declining testosterone levels in Finnish men 233EUROPEAN JOURNAL OF ENDOCRINOLOGY (2013) 168
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