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The Journal of Clinical Endocrinology & Metabolism 88(7):3160 –3166
Copyright © 2003 by The Endocrine Society
doi: 10.1210/jc.2002-021920
Middle-Aged Men Secrete Less Testosterone at Night
Than Young Healthy Men
RAFAEL LUBOSHITZKY, ZILA SHEN-ORR,
AND
PAULA HERER
Endocrine Institute, Haemek Medical Center (R.L.), Afula 18101, Israel; and Endocrine Laboratory, Rambam Medical
Center (Z.S.-O.), and Sleep Research Center, Technion, Israel Institute of Technology (P.H.), Haifa 32000, Israel
Aging men largely maintain their testicular androgen production. Cross-sectional studies have demonstrated that after
the age of 40 yr a 0.2–2% annual decline is observed in morning
total testosterone. In elderly males, the coordinate release of
LH and testosterone became asynchronous despite normal
serum levels of these hormones.
The aim of this study was to test the reproductive hormone
rhythm at night in middle-aged men. We studied seven healthy
middle-aged (46.6 ⴞ 6.7 yr) and six healthy young (23.9 ⴞ 2.4 yr)
men by determining their serum levels of LH and testosterone
levels every 15 min from 1900 – 0700 h with simultaneous sleep
recordings. The nocturnal rise in testosterone occurred earlier in young men (2235 ⴞ 0022 h) and at 2331 ⴞ 0057 h in
middle-aged men (P < 0.04). In young men, the mean testosterone level at night (5.0 ⴞ 1.3 ng/ml; 17.4 ⴞ 4.4 nmol/liter) and
the integrated nocturnal secretion [area under the curve
(AUC); 60.6 ⴞ 8.9 ng/ml䡠h; 210 ⴞ 31 nmol/liter䡠h] were significantly higher compared with the values (3.6 ⴞ 1.1 and 31.1 ⴞ
7.2 ng/ml䡠h; 12.6 ⴞ 3.8 and 108 ⴞ 24.8 nmol/liter䡠h, respectively)
observed in middle-aged men (P < 0.04 and P < 0.01, respectively). The mean (3.5 ⴞ 0.3 mIU/ml; 3.5 ⴞ 0.3 IU/liter) and AUC
(43.4 ⴞ 8.3 mIU/ml䡠h; 43.4 ⴞ 8.3 IU/liter䡠h) LH values in middleaged men were significantly higher than the values observed
in young men (2.0 ⴞ 0.7 and 30.8 ⴞ 6.1 mIU/ml䡠h; 2.0 ⴞ 0.7 and
30.8 ⴞ 6.1 IU/liter䡠h; P < 0.05 and P < 0.01, respectively). Young
I
N YOUNG ADULT males testosterone is secreted in an
episodic fashion in response to an LH stimulus (1). An
overall diurnal rhythm is seen for testosterone, which is
maximal in the early morning hours and minimal in the
evening (2). The nocturnal testosterone rhythm is related to
deep sleep (3) and to rapid eye movement (REM)/non-REM
sleep cycles (4). Peaks in testosterone coincide with the onset
of REM sleep (5). In young men the sleep-related testosterone
rise is linked with the appearance of the first REM sleep
episode (6).
Androgen production declines with age in men, resulting
in decreased serum levels of both total and bioavailable testosterone (7). The circadian rhythmicity in serum testosterone levels found in young men was attenuated, and the mean
24-h testosterone levels were lower in elderly men (8). The
pathophysiological mechanisms underlying this hypoandrogenemia are not known. Several cross-sectional studies measuring fasting morning hormone levels have revealed that
testosterone and dehydroepiandrosterone sulfate undergo a
gradual decline after the age of 40 yr, associated with increases in LH, FSH, and SHBG levels (9 –12). Older men
Abbreviations: AUC, Area under the curve; BMI, body mass index;
CV, coefficient of variation; REM, rapid eye movement.
men had significantly more testosterone pulses at night (6.7 ⴞ
1.6/12 vs. 3.8 ⴞ 1.1/12 h in middle-aged men; P < 0.005) of shorter
interpulse interval (88.5 ⴞ 23.6 vs. 137.4 ⴞ 46.4 min; P < 0.02).
LH pulse characteristics and sleep quality were similar in
both groups. However, the first rapid eye movement (REM)
sleep episode occurred earlier in middle-aged men (2303 ⴞ
0034 h) vs. young men (0010 ⴞ 0054 h; P < 0.04). As a consequence, the testosterone rise antedated the first REM episode
by 90 min in young men. The link between testosterone rise
and REM sleep episode was not observed in middle-aged men.
Linear regression analysis revealed that the LH AUC was significantly related to age (P < 0.02). Analysis of covariance
revealed that the two groups differed significantly in testosterone AUC (P < 0.04).
Comparison of LH and testosterone concentrations showed
significant and positive cross-correlations between LH and
testosterone only in young men, with the testosterone rise
lagging 60 min after the rise in LH. Our findings suggest that
in middle-aged men, less pulsatile testosterone and more LH
are secreted at night than in young men, with disruption of the
association between testosterone rhythm and REM sleep. The
decline in nocturnal testosterone secretion appears to involve
a combination of testicular and pituitary hypogonadism.
(J Clin Endocrinol Metab 88: 3160 –3166, 2003)
exhibit blunted peak serum testosterone levels in response to
human chorionic gonadotropin stimulation (13). Also, the
administration of recombinant human LH after an LHdown-regulating dose of leuprolide acetate revealed that
older men had delayed initial and reduced maximal serum
testosterone levels compared with young men (13). These
data suggested primary testicular failure. In middle-aged
men the mean and integrated LH values did not differ from
those observed in young men, although LH pulse frequency
increased, suggesting relative hypogonadotropic hypogonadism (14).
Recent studies have reported that a decline in deep sleep
already occurs in middle-aged men (15). We have demonstrated that in young men, the sleep-related rise in serum
testosterone levels is linked with the appearance of the first
REM sleep. Fragmented sleep disrupted the testosterone
rhythm, with attenuation of the nocturnal rise in men who
did not experience REM sleep. These findings suggested that
a single circadian oscillator that controls REM sleep, core
body temperature, and melatonin is related to LH-testosterone secretion (6). In older men decreases in sleep efficiency
and number of REM episodes and an increase in REM latency
were associated with lower testosterone levels (4). Others
have suggested that the interactive coupling between repro-
3160
Luboshitzky et al. • Testosterone in Middle-Aged Men
ductive axis, brain sleep-wake cycles, and neural nocturnal
penile tumescence oscillations are disrupted in aging men (3).
As many differences in LH and testosterone secretory patterns have been described with aging, the present study was
undertaken to determine the dynamics of nocturnal LH and
testosterone secretion in middle-aged men and to examine
whether changes in sleep with aging are related to changes
in the secretion of these hormones. To address these issues
we analyzed nocturnal pulsatile serum LH and testosterone
levels, obtained at 15-min intervals, with simultaneous sleep
recordings.
Subjects and Methods
Participants
Seven healthy middle-aged (46.6 ⫾ 6.7 yr) and six healthy young
(23.9 ⫾ 2.4 yr) men volunteered to participate in the study. All were in
good health, nonsmoking, and nonobese and received no medications.
The study was approved by the Helsinki Committee of the Afula Medical Center (Afula, Israel). All participants gave their informed consent
before the onset of the study.
J Clin Endocrinol Metab, July 2003, 88(7):3160 –3166 3161
is the elimination of all peaks for which either the increment (difference
between the peak and the preceding trough) or the decrement (difference between the peak and the next trough) does not exceed a certain
threshold related to measurement error. The sd of the error associated
with each calculated secretory rate was calculated following the theory
of error propagation, assuming normally distributed errors on plasma
levels. For each significant pulse, the amplitude was defined as the
difference between the level at the peak and the level at the preceding
trough. We determined the number and interpulse interval of LH and
testosterone pulses, the absolute increment of the pulse and the half-life,
using a threshold of 2 CVs. Independent two-sample t tests were used
to compare the mean LH and testosterone levels, the AUC, the 0700 h
testosterone level, pulse characteristics, and sleep data between the two
groups. A repeated measure ANOVA was performed to test the difference between the two age groups’ mean hourly LH and testosterone
levels. The relationship between age and the mean LH and testosterone
concentrations as well as LH and testosterone AUC were analyzed by
linear regression. Analysis of covariance, using mean LH or LH AUC as
the covariate, was used to examine the relationship between age group
and the mean and AUC of testosterone. Cross-correlation analysis was
used to measure the strength of the tendency of LH and testosterone to
vary in the same or opposite directions over time. Pearson correlation
(r) was computed over 12 lag units, with the higher absolute value of r
taken to be the lag time. The lag time and correlations of the two groups
were compared by two independent sample t and z tests.
Study protocol
Subjects were admitted to the Sleep Research Center at 1800 h. They
slept between 2200 and 0700 h for habituation, with electrodes attached
for sleep recordings. During the experimental night, at 1800 h, an iv
catheter was inserted into an antecubital vein, kept patent by a slow
infusion of 0.9% NaCl. Blood samples (3 ml) were collected every 15 min
from 1900 – 0700 h. Between 2200 – 0700 h lights were off, and subjects
remained in bed and attempted to fall asleep. Polysomnographic sleep
recordings were conducted between 2200 – 0700 h.
Analysis of sleep stages
Electrodes were attached for the following electrophysiological recordings: two electroencephalograms (C3-A2 and C4-A1), two electrooculograms, and one electromyogram of the mentalis. Sleep stages
were recorded in 30-sec epochs using conventional methods (16).
The following parameters were determined: total recording time, real
sleep time (total recording time ⫺ sleep latency ⫺ waking periods), sleep
latency (time from lights off until 3 consecutive min of stage 2), sleep
efficiency (real sleep time/total recording time), REM latency (time to
first REM), first REM sleep episode (time from beginning of sleep to the
first REM episode).
Hormone measurements
Blood was centrifuged, immediately separated, and stored at 22 C
until assayed. Serum LH and testosterone levels were determined in
each sample in duplicate using an immunoradiometric technique (Biodata Diagnostics, Rome, Italy). The intraassay coefficients of variation
(CV) were 6.0% and 3.0% for low (0.6 –1.1 ng/ml; 2.2– 4.0 nmol/liter) and
high (8.5–17.9 ng/ml; 29.4 – 62.0 nmol/liter) testosterone concentrations,
respectively. The interassay CV were 1.9% and 1.6%, respectively. The
sensitivity of the assay was 0.04 ng/ml (0.15 nmol/liter). The LH intraassay CV were 2.1% and 3.2% for low (2.2–3.3 m IU/ml; 2.2–3.3
IU/liter) and high (27– 41 mIU/ml; 27– 41 IU/liter) concentrations, respectively. The interassay CV were 3.7% and 0.8%, respectively. The
sensitivity of the assay was 0.15 mIU/ml (0.15 IU/liter).
Statistical analysis
Mean and integrated [area under the curve (AUC)] serum LH and
testosterone levels from 1900 – 0700 h were determined in the two
groups. The onset of the testosterone rise was defined as the time of the
first occurrence of at least three consecutive samples exceeding the mean
levels obtained between 1900 and 2200 h by more than 1 sd. Significant
LH and testosterone secretory pulses were identified using the pulse
detection program ULTRA (17). The general principle of this algorithm
Results
Sleep quality and sleep stage data were similar in middleaged and young men (Table 1). All participants had REM
sleep episodes during the experimental night. The first REM
sleep episode was observed at 0010 ⫾ 0054 h in young men
compared with 2303 ⫾ 0034 h in middle-aged men (P ⬍ 0.04).
All subjects had a well defined nocturnal testosterone rise
(Table 2). In young men the testosterone onset antedated the
appearance of the first REM sleep episode by 95 min. In
middle-aged men, no association was observed between the
nocturnal rise in testosterone and the appearance of the first
REM sleep. The middle-aged men had significantly higher
mean and AUC LH values compared with young men
(Table 2 and Fig. 1). The mean nocturnal and 0700 h testosterone levels were significantly higher in young men compared with middle-aged men. The testosterone AUC in
young men (60.6 ⫾ 8.9 ng/ml䡠h; 210 ⫾ 31 nmol/liter䡠h) was
significantly higher than that in middle-aged men (31.2 ⫾ 7.2
ng/ml䡠h; 108 ⫾ 24.8 nmol/liter䡠h; P ⬍ 0.01). As shown in
Table 3, young men had significantly more testosterone
pulses (6.7 ⫾ 1.6 pulses/12 h) than middle aged men (3.8 ⫾
1.1 pulses/12 h; P ⬍ 0.005) of shorter interpulse interval
(88.5 ⫾ 23.6 vs. 137.4 ⫾ 46.6 min, respectively; P ⬍ 0.05). The
TABLE 1. Characteristics of nocturnal (2200 – 0700 h) sleep
quality data in middle aged and young healthy men
Parameter
Middle aged
men
Young men
P
Awakening (%)
Real sleep duration (h)
Sleep latency (min)
REM latency (h)
Sleep efficiency (%)
Stage 1 (%)
Stage 2 (%)
Stage 3/4 (%)
REM sleep (%)
First REM episode (h)
27.4 ⫾ 11.9
5:37 ⫾ 01:15
24.0 ⫾ 12.5
1:19 ⫾ 0:49
69:0 ⫾ 3.9
3.5 ⫾ 2.6
47.1 ⫾ 10.1
13.0 ⫾ 4.0
12.8 ⫾ 4.3
23:03 ⫾ 0:34
21.7 ⫾ 12.8
5:49 ⫾ 1:18
27.4 ⫾ 15.4
1:10 ⫾ 0:33
79.2 ⫾ 4.2
1.8 ⫾ 0.4
63.4 ⫾ 4.1
17.9 ⫾ 5.4
16.9 ⫾ 3.1
00:10 ⫾ 0:54
NS
NS
NS
NS
NS
NS
NS
NS
NS
0.04
NS, Not significant.
3162
J Clin Endocrinol Metab, July 2003, 88(7):3160 –3166
Luboshitzky et al. • Testosterone in Middle-Aged Men
TABLE 2. Pituitary-gonadal hormones status in middle aged and young healthy men
LH
Subject
Middle-aged men
1
2
3
4
5
6
7
Mean ⫾ SD
Young men
1
2
3
4
5
6
Mean ⫾ SD
P
Testosterone
First REM (h)
Mean
(IU/liter)
AUC
(IU/liter ⫻ h)
Onset
(h)
Onset
(nmol/liter)
0700-h level
(nmol/liter)
Mean
AUC
(nmol/liter) (nmol/liter ⫻ h)
22:52
22:04
23:43
23:21
22:38
23:29
23:16
23:03 ⫾ 0:34
4.9
2.7
3.3
3.1
3.3
3.5
3.1
3.5 ⫾ 0.3
36.7
37.5
58.9
39.7
41.5
40.2
32.8
43.4 ⫾ 8.3
21:40
24:00
23:20
24:20
24:20
24:00
23:00
23:31 ⫾ 0:57
10.4
18.7
20.7
13.0
7.1
8.4
10.9
12.7 ⫾ 5.2
11.2
19.3
21.8
19.6
8.5
10.5
13.5
14.9 ⫾ 4.3
9.9
16.2
19.0
13.2
8.5
10.5
10.6
12.6 ⫾ 3.8
99.8
111.0
160.2
99.2
87.3
92.1
96.5
108 ⫾ 24.8
23:21
01:57
00:24
23:54
23:26
01:13
00:10 ⫾ 0:54
0.04
1.5
1.2
2.1
3.3
1.8
2.3
2.0 ⫾ 0.7
0.05
22.3
20.1
33.9
36.1
33.2
39.3
30.8 ⫾ 6.1
0.01
22:15
23:15
22:15
22:45
22:45
22:15
22:35 ⫾ 0:22
0.04
18.8
10.3
24.1
18.2
12.9
15.6
16.7 ⫾ 4.4
NS
22.0
11.6
25.3
18.9
19.3
18.9
19.3 ⫾ 4.1
0.05
20.4
19.3
23.4
16.9
17.4
15.7
17.4 ⫾ 4.4
0.04
241
129
277
201
204
205
210 ⫾ 31
0.01
NS, Not significant; AUC, area under the curve. To convert testosterone units to ng/ml, divide by 3.467. To convert LH units to mIU/ml
divide by 1.
FIG. 1. Nocturnal LH and testosterone secretion in
middle-aged and young healthy men. An arrow indicates the first REM sleep episode. Between 2200 –
0700 h, lights were off, and subjects were asleep. To
convert testosterone units to nanograms per milliliter,
divide by 3.467. To convert LH units to milliinternational units per milliliter, divide by 1.
two groups had similar numbers of LH pulses of similar
interpulse intervals. The ratio between the number of LH and
testosterone pulses was 0.9 in young men compared with 1.4
in middle-aged men. Individual nocturnal profiles of LH and
testosterone secretory rates in young and middle-aged men
are shown in Fig. 2.
Luboshitzky et al. • Testosterone in Middle-Aged Men
J Clin Endocrinol Metab, July 2003, 88(7):3160 –3166 3163
Repeated measures analysis of testosterone levels revealed
that there was a time effect (F ⫽ 15.48; P ⬍ 0.001) and an
interaction between time and age group (F ⫽ 3.02; P ⬍ 0.001).
Post hoc testing (Duncan’s multiple range test) of the time
effect revealed that testosterone levels were lower before
2300 h than after 2300 h. Bonferroni post hoc test revealed that
young men had higher testosterone levels than middle-aged
men (t ⫽ 1.86; P ⬍ 0.04). Repeated measures analysis of LH
levels revealed a time effect (F ⫽ 1.86; P ⬍ 0.05). Bonferroni
post hoc test revealed that middle-aged men had higher LH
levels than young men (t ⫽ 2.26; P ⬍ 0.02). Analysis of
TABLE 3. Characteristics of pulsatile LH and testosterone
nocturnal secretion in middle aged and young healthy men
Parameter
Testosterone
No. of pulses (/12 h)
Duration (min)
Increment (nmol/liter)
Half-life (min)
LH
No. of pulses (12 h)
Duration (min)
Increment (IU/liter)
Half-life (min)
Middle-aged men
Young men
P
3.8 ⫾ 1.1
137.4 ⫾ 46.6
4.4 ⫾ 1.2
178.7 ⫾ 98.2
6.7 ⫾ 1.6
88.5 ⫾ 23.6
5.2 ⫾ 1.1
144.2 ⫾ 47.7
0.005
0.03
NS
NS
5.2 ⫾ 1.6
128.4 ⫾ 24.9
2.8 ⫾ 0.5
91.5 ⫾ 26.0
6.0 ⫾ 1.9
105.7 ⫾ 29.1
2.3 ⫾ 0.9
92.8 ⫾ 21.3
NS
NS
NS
NS
NS, Not significant. To convert testosterone units to ng/ml, divide
by 3.467. To convert LH units to mIU/ml divide by 1.
covariance, using LH AUC as a covariate, revealed that there
was a statistically significant difference between the two age
groups in testosterone AUC (P ⬍ 0.04). Cross-correlation
analysis revealed that an increase in testosterone concentration occurred 50.0 ⫾ 18.2 min before a rise in LH concentration in young men and 127.5 ⫾ 84.7 min before the LH rise
in middle-aged men (Fig. 3). This was a statistically significant difference (P ⬍ 0.05). Middle-aged men had lag times
of 30 –240 min, whereas young men had lag times of 15– 60
min. No positive correlation was found in one middle-aged
man. There was no statistically significant difference in the
strength of the correlation (r ⫽ 0.49 in young men and r ⫽
0.26 in middle-aged men; P ⬎ 0.50). A comparison of LH and
testosterone concentrations in young men showed significant and positive cross-correlations between LH and testosterone when the later lagged by 9 –96 min. In fact, LH and
testosterone were positively correlated, with the testosterone
rise lagging 60 min after the rise in LH. No extended positive
cross-correlations between LH and testosterone were found
in middle-aged men.
Discussion
In this study we demonstrated that in middle-aged men
less pulsatile testosterone and more LH are secreted at night,
with disruption of the association between testosterone rise
FIG. 2. Individual nocturnal profiles of LH and testosterone secretory rates in young men (left) and middle-aged men (right). Asterisks denote
a significant pulse of secretion. To convert testosterone units to nanograms per milliliter, divide by 3.467. To convert LH units to milliinternational units per milliliter, divide by 1.
3164
J Clin Endocrinol Metab, July 2003, 88(7):3160 –3166
Luboshitzky et al. • Testosterone in Middle-Aged Men
FIG. 3. Cross-correlation between testosterone and LH in middle-aged (A) and young (B) men. A positive lag means lagged LH, and a negative
lag means lagged testosterone. The dots show the cross-correlation for each individual. The solid line is an average for the population. The dotted
lines define the range outside which correlations are significantly at the 5% level.
Luboshitzky et al. • Testosterone in Middle-Aged Men
and the appearance of first REM sleep. Cross-correlation
analysis revealed a significant positive correlation between
LH and testosterone only in young men, with the testosterone rise lagging 60 min after the rise in LH. The diminution
in testosterone secretion seen in middle-aged men combined
with a compensatory increase in LH levels and the asynchrony between LH and testosterone observed in our study
may suggest relative testicular and pituitary hypogonadism.
Over the last 15 yr several studies have investigated the
nocturnal LH-testosterone rhythms in elderly men by measuring serum hormone levels over a 24-h period. Frequent
sampling (every 10 min) studies revealed reduced serum
testosterone concentrations with decreases in LH and testosterone pulse frequency (13). Intense sampling (every 2.5
min) over a period of 7 h disclosed normal mean LH and
testosterone levels, but increased LH pulse frequency and
reduced testosterone secretory bursts (3). In agreement with
our findings, these studies suggested that reduced testosterone secretion in elderly men results from both pituitary and
testicular defects. However, in these reports the association
between LH-testosterone secretion and sleep patterns was
not studied.
In healthy elderly men a blunted testosterone response to
human chorionic gonadotropin together with an elevation of
basal LH levels indicated a defect in Leydig cell steroidogenesis (18, 19). Low testicular volume was described in
elderly men and was associated with a decrease in inhibin
B/FSH and testosterone/LH ratios, suggesting a combined
Leydig cell and Sertoli cell dysfunction (20). On the other
hand, Korenman et al. (21) have suggested that almost all
elderly men with reduced testosterone levels have evidence
of hypothalamic-pituitary dysfunction, as reflected by low
basal LH levels and blunted LH response to GnRH stimulation. Pulsatile LH release in elderly men is marked by lower
amplitude and more frequent secretory events (22). GnRH
infusion for 2 wk in elderly men restored LH pulsatile values
to levels achieved in young men. The synchrony between LH
and testosterone secretion is disrupted in the elderly, suggesting an impaired output of the GnRH-LH axis (14).
Age-related changes in sleep quality were nonconclusive,
as sleep stages were similar in middle-aged and elderly subjects and between young and elderly subjects (23), whereas
others reported that older men spent more time awake and
displayed decreased REM latency (24). Among the most
common sleep changes detected in middle-aged subjects are
decreased sleep stages 3 and 4 (deep sleep) and increased
number and duration of nocturnal awakening. In our study
middle-aged men tended to have more awakening periods
and less sleep stages 3 and 4, although this was not statistically significantly different from young men. The effect of
aging on REM sleep is variable and occurs later in life. This
may be due to the fact that REM sleep is regulated by the
circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (25, 26). It was assumed that LH-testosterone
rhythms are dependent on specific phase relationship between sleep and the underlying circadian oscillator rather
than on the circadian oscillator per se (27). In young men the
first REM period appears after 90 min of non-REM sleep. The
characteristics of the REM/non-REM cycle during sleep were
shown to be age dependent (28).
J Clin Endocrinol Metab, July 2003, 88(7):3160 –3166 3165
Aging in men is associated with decreases in bone mineral
density and muscle mass and strength and an increase in
adiposity (29 –32). The age-associated decline in testosterone
levels was linked with abdominal obesity and insulin resistance (33, 34). Epidemiological studies have demonstrated
higher cardiovascular risks in men with lower testosterone
levels (35, 36). Over the last decade several clinical studies
have been undertaken to determine whether testosterone
supplementation in aging is beneficial. Significant improvement in bone mineral density, muscle mass and strength,
plasma lipids, and insulin sensitivity was observed only in
elderly men with subnormal testosterone levels (29, 37).
Other studies failed to demonstrate changes in serum lipids
during testosterone treatment (31). It is not yet clear whether
androgen supplementation affects cardiovascular morbidity
and mortality (30). The increased prevalence of metabolic
syndrome (obesity, insulin resistance, dyslipidemia, and hypertension) and consequently cardiovascular disease is frequently observed in middle-aged men (38). The associated
decline in nocturnal testosterone secretion in a similar age
group observed in the present study suggests that testosterone treatment is indicated in middle-aged men to determine
whether its supplementation is beneficial.
In conclusion, middle-aged men secrete less testosterone
and more LH at night than young healthy men. The synchrony between LH and testosterone and the link between
the nocturnal rise in testosterone and the appearance of the
first REM sleep episode are disrupted. These findings suggest that hypoandrogenemia in middle-aged men results
from combined testicular, pituitary, and central nervous system dysfunctions.
Acknowledgments
Received December 5, 2002. Accepted April 4, 2003.
Address all correspondence and requests for reprints to: Prof. R.
Luboshitzky, Endocrine Institute, Hemeek Medical Center, Afula 18101,
Israel. E-mail: [email protected].
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