Disruption of the hypothalamic luteinizing hormone pulsing mechanism in aging men

2001 ◽  
Vol 281 (6) ◽  
pp. R1917-R1924 ◽  
Author(s):  
Daniel M. Keenan ◽  
Johannes D. Veldhuis
Keyword(s):  
Luteinizing Hormone ◽  
Older Men ◽  
Interpulse Interval ◽  
Deconvolution Analysis ◽  
Age Related ◽  
Aging Men ◽  
Gamma Density ◽  
Lower Amplitude ◽  
Interval Lengths ◽  
Lh Secretion

The incremental nature of neuroendocrine aging suggests that subtle system dysregulation may precede overt axis failure. The present analyses unmask threefold disruption of pulsatile gonadotropin-releasing hormone (GnRH)-luteinizing hormone (LH) secretion in the aging male. First, by way of random effects-based deconvolution analysis, we document an elevated daily GnRH-LH pulse frequency in healthy older men [namely, mean (±SE) 23 ± 1 (older) vs. 15 ± 1 (young) LH secretory bursts/24 h, P < 0.001] and lower mean LH pulse mass [3.73 ± 0.58 (older) vs. 5.46 ± 0.66 (young) IU/l, P = 0.038]. However, total LH secretion rates and two-compartment LH elimination kinetics were comparable in the two age cohorts. Second, using the approximate entropy statistic, we show an equivalently random order-dependent succession of LH interpulse-interval lengths in young and older men, but a marked age-related deterioration of the ad seriatim regularity of LH pulse mass series in older individuals (P = 0.0057). Third, by modeling GnRH pulse-generator output as a Weibull renewal process (generalized Gamma density) to emulate loosely coupled GnRH neuronal oscillators, we identify an age-related reduction in the frequency-independent and order-independent variability of GnRH-LH interpulse-interval sets (P = 0.08). These findings indicate that the GnRH-LH pulsing mechanism in healthy older men maintains an increased mean frequency and lower amplitude of bursting activity, a reduced uniformity of serial LH pulse-mass values, and an impaired variability among interpulse-interval lengths. Thereby, the foregoing order-dependent and order-independent alterations in GnRH-LH signal generation in the aging human suggest a general framework for exploring subtle disruption of time-sensitive regulation of other neurointegrative systems.

Variability of pulsatile luteinizing hormone secretion in young male volunteers

1994 ◽  
Vol 131 (3) ◽  
pp. 263-272 ◽  
Author(s):  
Carl-Joachim Partsch ◽  
Sievert Abrahams ◽  
Niels Herholz ◽  
Michael Peter ◽  
Johannes D Veldhuis ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Half Life ◽  
Hormone Secretion ◽  
Young Male ◽  
Interpulse Interval ◽  
Luteinizing Hormone Secretion ◽  
Individual Subject ◽  
Deconvolution Analysis ◽  
Pulse Detection ◽  
Male Volunteers

Partsch C-J, Abrahams S, Herholz N, Peter M, Veldhuis JD, Sippell WG. Variability of pulsatile luteinizing hormone secretion in young male volunteers. Eur J Endocrinol 1994;131:263–72. ISSN 0804–4643 Characteristics of spontaneous pulsatile luteinizing hormone secretion were compared in ten young healthy men in three 24-h profiles obtained at intervals of 14 days and 3 months. The ages of the volunteers ranged from 19 to 25 years, and heights and weights were within normal limits. Blood samples were taken at 10-min intervals and plasma luteinizing hormone (LH) was determined in the same immunoradiometric assay using monoclonal antibodies. Conventional pulse detection was carried out with PULSAR and CLUSTER programs. In addition, a simultaneous multiple parameter DECONVOLUTION was applied. As a group, no significant differences between the three profile series were found for any of the calculated parameters of LH concentration or LH secretion. However, most parameters showed low correlation coefficients between the three study periods, suggesting that substantial individual variations might contribute to the more reliable group results. Median coefficients of variation (cv) for the individual subject ranged from 9.7% (interpulse interval and endogenous half-life) to 37.7% (mass per burst). However, the maximal individual cv observed was 78.4%. Intra-individual variability was lower than the variability between subjects for quantitative properties of LH concentration and secretion, although not significantly so for all parameters. In conventional pulse detection, the highest individual reliability was found for mean and integrated LH concentrations (median cv 10.2 and 13.7%, respectively), number of pulses per 24 h (CLUSTER, median cv 12.2%), mean pulse amplitude (PULSAR, median cv 10%) and interpulse interval (CLUSTER, median cv 9.7%). In DECONVOLUTION analysis, the endogenous LH half-life (median cv 9.7%), secretory burst amplitude (median cv 14.8%) and interburst interval (median cv 14.5%) revealed the lowest intra-individual variation. In contrast, the half-duration of a secretory episode and the mass of LH secreted per burst proved to be the least reliable measures (median cv 32.7% and 37.7%, respectively). Calculated endogenous LH production rates correlated highly (p < 0.01) across all three sessions. The relative frequencies of the LH peak amplitudes/heights and peak widths (durations) showed almost identical distribution curves for all three sampling periods. In conclusion, a high reproducibility of group results for both integrative parameters and pulse characteristics of LH concentrations and secretion were found in normal men. However, intra-individual reliability was variable and at times considerable, depending on the parameter chosen. These observations suggest caution in the interpretation of single LH profiles from individual subjects or patients unless the variation reported herein is considered. C-J Partsch, Institut für Reproduktionsmedizin, Westfälische Wilhelms-Universität, Steinfurter Straβe 107, D-48149 Münster, Germany

Hypothesis testing of the aging male gonadal axis via a biomathematical construct

2001 ◽  
Vol 280 (6) ◽  
pp. R1755-R1771 ◽  
Author(s):  
Daniel M. Keenan ◽  
Johannes D. Veldhuis
Keyword(s):  
Luteinizing Hormone ◽  
Gonadotropin Releasing Hormone ◽  
Computer Assisted ◽  
Aging Male ◽  
Aging Men ◽  
Model Predictions ◽  
Feedback Networks ◽  
Lh Secretion ◽  
Appl Math ◽  
Dynamic Ensembles

Neuroendocrine axes are feedback- and feedforward-coupled dynamic ensembles. Disruption of selected pathways in such networklike organizations may explicate loss of orderly hormonal output as observed in aging. To test this notion more explicitly, we implemented an earlier computer-assisted biomathematical model of the interlinked male hypothalamo [gonadotropin-releasing hormone (GnRH)]-pituitary [luteinizing hormone, (LH)]-testicular [Leydig cell testosterone (Te)] axis ( Am J Physiol Endocrinol Metab Physiol 275: E157–E176, 1988; Keenan D., W. Sun, and J. D. Veldhuis, SIAM J Appl Math 61: 934–965, 2000). Thereby, we appraise mechanistic hypotheses for more disorderly LH and Te secretion in aging men. We compare model predictions with monitored abnormalities in the older male, namely, irregular patterns of individual and synchronous LH and Te release, reduced 24-h rhythmic Te output, and variably elevated LH secretion. Among the mechanisms examined, the most parsimonious aging hypothesis would entail impaired LH feedforward on Te without or with attenuated Te feedback on GnRH/LH secretion. This investigative strategy should aid in exploring new postulates of disrupted feedback networks in pathophysiology.

scholarly journals Age Attenuates Testosterone Secretion Driven by Amplitude-Varying Pulses of Recombinant Human Luteinizing Hormone during Acute Gonadotrope Inhibition in Healthy Men

2007 ◽  
Vol 92 (9) ◽  
pp. 3626-3632 ◽  
Author(s):  
Paul Y. Takahashi ◽  
Patrick Votruba ◽  
Mohammed Abu-Rub ◽  
Kristi Mielke ◽  
Johannes D. Veldhuis
Keyword(s):  
Half Life ◽  
Medical Center ◽  
Academic Medical Center ◽  
Community Dwelling ◽  
Controlled Study ◽  
Deconvolution Analysis ◽  
Healthy Men ◽  
Age Related ◽  
Aging Men ◽  
The Impact

Abstract Context: Whether testosterone (Te) depletion in aging men reflects deficits in the testis, hypothalamus, and/or pituitary gland is unknown. Objective: Our objective was to quantify the impact of age on gonadal Te secretion driven by amplitude-varying pulses of recombinant human LH (rhLH) in the absence of confounding by endogenous hypothalamo-pituitary signals. Design: This was a double-blind, placebo-controlled study. Setting: The setting was an academic medical center. Subjects: Fifteen healthy community-dwelling men ages 22–78 yr were included in the study. Intervention: Saline or four separate rhLH doses were each infused twice iv in randomized order as one pulse every 2 h over 20 h to stimulate Te secretion, after LH secretion was suppressed by a GnRH-receptor antagonist, ganirelix. Main Outcome: LH and Te concentrations were determined in blood samples collected every 5 min. Maximal and minimal (as well as mean) Te responses were regressed linearly on age to reflect LH peak and nadir (and average) effects, respectively. Results: The ganirelix/rhLH paradigm yielded serum LH concentrations of 4.6 ± 0.22 IU/liter (normal range 1–9). By regression analysis, age was associated with declines in rhLH pulse-stimulated peak and nadir (and mean) concentrations of total Te (P = 0.0068), bioavailable Te (P = 0.0096), and free Te (P = 0.013), as well as lower Te/LH concentration ratios (P &lt; 0.005). Deconvolution analysis suggested that the half-life of infused LH increases by 12%/decade (P = 0.044; R2 = 0.28). Conclusions: Infusion of amplitude-varying pulses of rhLH during gonadal-axis suppression in healthy men unmasks prominent age-related deficits in stimulated total (39%), bioavailable (66%), and free (63%) Te concentrations, and a smaller age-associated increase in LH half-life. These data suggest that age-associated factors reduce the efficacy of LH pulses.

Age-Related Changes in the Regulation of Luteinizing Hormone Secretion by Estrogen in Women

2002 ◽  
Vol 227 (7) ◽  
pp. 455-464 ◽  
Author(s):  
Susanna J. Park ◽  
Laura T. Goldsmith ◽  
Gerson Weiss
Keyword(s):  
Menstrual Cycle ◽  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Luteinizing Hormone Secretion ◽  
Estrogen Regulation ◽  
Lh Surge ◽  
Age Related ◽  
Hypothalamic Pituitary Axis ◽  
The Many ◽  
Lh Secretion

Despite the many studies that have been conducted using both primate and human models to understand the control of the menstrual cycle, there are many aspects of the hormonal dynamics of the menstrual cycle that are not understood. This Minireview summarizes the changes in estrogen regulation of luteinizing hormone (LH) secretion that occur throughout life in women from the time of maturation of the hypothalamic-pituitary axis resulting in the occurrence of the LH surge during puberty, through the reproductive years, to the changes in the regulation of the LH surge during premenopause and, subsequently, menopause.

scholarly journals Long-Term Testosterone Supplementation in Older Men Attenuates Age-Related Decline in Aerobic Capacity

2018 ◽  
Vol 103 (8) ◽  
pp. 2861-2869 ◽  
Author(s):  
Tinna Traustadóttir ◽  
S Mitchell Harman ◽  
Panayiotis Tsitouras ◽  
Karol M Pencina ◽  
Zhuoying Li ◽  
...  
Keyword(s):  
Aerobic Capacity ◽  
Older Men ◽  
Total Testosterone ◽  
Long Term Effects ◽  
Double Blind ◽  
Testosterone Levels ◽  
Age Related ◽  
Aging Men ◽  
The Difference

Abstract Context Testosterone increases skeletal muscle mass and strength, but long-term effects of testosterone supplementation on aerobic capacity, or peak oxygen uptake (V̇O2peak), in healthy older men with low testosterone have not been evaluated. Objective To determine the effects of testosterone supplementation on V̇O2peak during incremental cycle ergometry. Design A double-blind, randomized, placebo-controlled, parallel-group trial (Testosterone’s Effects on Atherosclerosis Progression in Aging Men). Setting Exercise physiology laboratory. Participants Healthy men aged ≥ 60 years with total testosterone levels of 100 to 400 ng/dL (3.5 to 13.9 nmol/L) or free testosterone levels < 50 pg/mL (174 pmol/L). Interventions Randomization to 1% transdermal testosterone gel adjusted to achieve serum levels of 500 to 950 ng/dL or placebo applied daily for 3 years. Main Outcome Measures Change in V̇O2peak. Results Mean (±SD) baseline V̇O2peak was 24.2 ± 5.2 and 23.6 ± 5.6 mL/kg/min for testosterone and placebo, respectively. V̇O2peak did not change in men treated with testosterone but fell significantly in men receiving placebo (average 3-year decrease, 0.88 mL/kg/min; 95% CI, −1.39 to 0.38 mL/kg/min; P = 0.035); the difference in change in V̇O2peak between groups was significant (average 3-year difference, 0.91 mL/kg/min; 95% CI, 0.010 to 0.122 mL/kg/min; P = 0.008). The 1-g/dL mean increase in hemoglobin (P < 0.001) was significantly associated with changes in V̇O2peak in testosterone-treated men. Conclusion The mean 3-year change in V̇O2peak was significantly smaller in men treated with testosterone than in men receiving placebo and was associated with increases in hemoglobin. The difference in V̇O2peak change between groups may indicate attenuation of its expected age-related decline; the clinical meaningfulness of the modest treatment effect remains to be determined.

scholarly journals Hypothalamic-Pituitary-Testicular Axis Disruptions in Older Men Are Differentially Linked to Age and Modifiable Risk Factors: The European Male Aging Study

2008 ◽  
Vol 93 (7) ◽  
pp. 2737-2745 ◽  
Author(s):  
Frederick C. W. Wu ◽  
Abdelouahid Tajar ◽  
Stephen R. Pye ◽  
Alan J. Silman ◽  
Joseph D. Finn ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Men ◽  
Reproductive Hormones ◽  
Community Dwelling ◽  
Modifiable Risk Factors ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Pituitary Dysfunction ◽  
Age Related ◽  
Aging Men

Abstract Context: The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. Objective: The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men. Design: This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40–79 yr from a prospective cohort study in eight European countries. Results: Four predictors were associated with distinct modes of altered function: 1) age: lower free T (FT; −3.12 pmol/liter·yr, P &lt; 0.001) with raised LH, suggesting impaired testicular function; 2) obesity: lower total T (TT; −2.32 nmol/liter) and FT (−17.60 pmol/liter) for body mass index (BMI; ≥ 25 to &lt; 30 kg/m2) and lower TT (−5.09 nmol/liter) and FT (−53.72 pmol/liter) for BMI 30 kg/m2 or greater (P &lt; 0.001–0.01, referent: BMI &lt; 25 kg/m2) with unchanged/decreased LH, indicating hypothalamus/pituitary dysfunction; 3) comorbidity: lower TT (−0.80 nmol/liter, P &lt; 0.01) with unchanged LH in younger men but higher LH in older men; and 4) smoking: higher SHBG (5.96 nmol/liter, P &lt; 0.001) and LH (0.77 U/liter, P &lt; 0.01) with increased TT (1.31 nmol/liter, P &lt; 0.001) but not FT, compatible with a resetting of T-LH-negative feedback due to elevated SHBG. Conclusions: Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men.

Reanalysis of the rat proestrous LH surge by deconvolution analysis

1993 ◽  
Vol 265 (1) ◽  
pp. R240-R245
Author(s):  
J. D. Veldhuis ◽  
M. L. Johnson ◽  
R. V. Gallo
Keyword(s):  
Luteinizing Hormone ◽  
Half Life ◽  
Fold Increase ◽  
Basal Secretion ◽  
Release Rates ◽  
Deconvolution Analysis ◽  
Lh Surge ◽  
Time Profiles ◽  
Burst Amplitude ◽  
Lh Secretion

To evaluate the temporal mechanisms that give rise to the spontaneous proestrous surge of luteinizing hormone (LH) in the rat, we have applied deconvolution analysis to earlier immunoreactive LH concentration vs. time profiles obtained by sampling blood in proestrus at 2- to 3-min intervals in 10 animals over a span of 160-300 min. Six other animals were bled in 6-min intervals on day 1 of diestrus. Deconvolution analysis permitted us to calculate the number, duration, amplitude (maximal release rates), and mass of underlying LH secretory bursts and to simultaneously estimate basal secretion and the half-life of endogenous LH in each animal. Proestrus rats exhibited a significant increase in the number of computer-identified LH secretory bursts per hour (1.8 +/- 0.2 vs. 1.1 +/- 0.01 on diestrus, P < 0.01), with a corresponding reduction in the LH intersecretory burst interval from 61 +/- 6.4 min (diestrus) to 25 +/- 2.7 min (proestrus, P < 0.01). There was a remarkable 16-fold increase in the mass of LH secreted per burst, which rose from 72 +/- 5.2 to 1,230 +/- 200 ng/ml (P < 0.01). This resulted from a sixfold increase in LH secretory burst amplitude and a doubling of burst duration. The total amount of LH released in a burstlike fashion during the proestrous LH surge rose 20-fold, and calculated basal LH secretion increased to approximately 25% of this value. Of interest, the computed half-life of endogenous LH also increased from 10 +/- 1.1 to 19 +/- 3.7 min (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Joint Basal and Pulsatile Hypersecretory Mechanisms Drive the Monotropic Follicle-Stimulating Hormone (FSH) Elevation in Healthy Older Men: Concurrent Preservation of the Orderliness of the FSH Release Process: A General Clinical Research Center Study*

1999 ◽  
Vol 84 (10) ◽  
pp. 3506-3514
Author(s):  
J. D. Veldhuis ◽  
A. Iranmanesh ◽  
L. M. Demers ◽  
T. Mulligan
Keyword(s):  
High Sensitivity ◽  
Approximate Entropy ◽  
Fold Increase ◽  
Older Men ◽  
Older Individuals ◽  
Release Process ◽  
Deconvolution Analysis ◽  
Clinical Research Center ◽  
Lower Amplitude ◽  
Neuroendocrine Mechanisms

Abstract To appraise the neuroendocrine mechanisms that underlie a selective (monotropic) elevation of serum FSH concentrations in healthy older men, we sampled blood in 11 young (ages 21–34) and 8 older men (ages 62–72) men every 2.5 min overnight. Serum FSH concentrations were quantitated in an automated, high-sensitivity, chemiluminescence-based assay. Rates of basal and pulsatile FSH secretion were estimated by deconvolution analysis, and the orderliness of the FSH release process via quantitated the approximate entropy statistic. Statistical analysis revealed that healthy older men manifest dual neuroendocrine hypersecretory mechanisims; specifically, a 2-fold increase in the basel (nonpulsatile) FSH secretion rate, and a concurrent 50% amplification of FSH secretory burst mass (and amplitude). The regularity or orderliness of ad seriatim FSH release is preserved in older individuals. We postulate that higher basel FSH secretion in older men is a consequence of reduced testosterone negative feedback, whereas amplified FSH secretory burst mass reflects net enhanced stimulation of gonadotrope cells by endogenous FSH secretagogues (e.g. GnRH and/or activin). The foregoing specific mechanisms driving heightened FSH secretion in older men contrast with the lower-amplitude pulsatility and more disorderly patterns of LH release in the same individuals. Thus, the present data illuminate an age-dependent disparity in the disruption of FSH neuroregulation in the aging male.

scholarly journals Recombinant Human Chorionic Gonadotropin But Not Dihydrotestosterone Alone Stimulates Osteoblastic Collagen Synthesis in Older Men with Partial Age-Related Androgen Deficiency

2004 ◽  
Vol 89 (6) ◽  
pp. 3033-3041 ◽  
Author(s):  
Christian Meier ◽  
Peter Y. Liu ◽  
Lam P. Ly ◽  
James de Winter-Modzelewski ◽  
Mark Jimenez ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Turnover ◽  
Type I Collagen ◽  
Older Men ◽  
Type I ◽  
Androgen Deficiency ◽  
Age Related ◽  
Aging Men ◽  
To Receive ◽  
Androgen Supplementation

Abstract Several randomized trials of androgen supplementation in older men have been undertaken. However, the relative contributions of testosterone (T) and estrogens on bone metabolism in aging men are controversial. Within the setting of two double-blind, placebo-controlled studies, we evaluated the effect of dihydrotestosterone (DHT) and recombinant human chorionic gonadotropin (rhCG) on bone turnover in healthy, community-dwelling older men with partial androgen deficiency (total T ≤ 15 nmol/liter). In the first study, 35 men (age 68.3 ± 6.8 yr; baseline T, 13.9 ± 3.3 nmol/liter) were randomized to receive either daily transdermal DHT (n = 17) or placebo for 3 months. In the second study, 40 men (age 67.4 ± 5.4 yr; baseline T, 11.4 ± 2.2 nmol/liter) were randomized to receive either rhCG sc (n = 20), two injections weekly, or placebo for 3 months. The following parameters were measured before, monthly during, and 1 month after treatment: serum T, estradiol (E2), and LH; markers of bone formation, serum amino-terminal propeptide of type I procollagen (S-PINP) and osteocalcin; markers of bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline. Compared with placebo, treatment with DHT significantly increased serum DHT and suppressed LH and T levels, whereas E2 concentrations and markers of bone turnover did not change. In contrast, rhCG therapy significantly increased both T and E2, with the increases in E2 being supraphysiological. At the same time, rhCG significantly increased S-PINP concentrations with peak levels after 1 month (Δ40%; P = 0.02 compared with placebo). In contrast, serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change. The change in S-PINP levels correlated with the change in E2 levels (r = 0.59; P = 0.02) but not with a change in T. We conclude that in older men with partial age-related androgen deficiency, rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption. In contrast, treatment with a pure, nonaromatizable androgen (DHT) has no effect on bone turnover despite a 20-fold increase in serum levels. Bone resorption was not accelerated during unchanged (DHT) or increased (rhCG) E2 levels, suggesting that minimal E2 levels are needed to maintain stable resorption, although direct androgen receptor-mediated effects cannot be excluded. If androgen supplementation is required for aging men, aromatizable androgens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone.

scholarly journals Age and time-of-day differences in the hypothalamo–pituitary–testicular, and adrenal, response to total overnight sleep deprivation

SLEEP ◽  
2020 ◽  
Vol 43 (7) ◽  
Author(s):  
Peter Y Liu ◽  
Paul Y Takahashi ◽  
Rebecca J Yang ◽  
Ali Iranmanesh ◽  
Johannes D Veldhuis
Keyword(s):  
Sleep Deprivation ◽  
Older Men ◽  
Pulse Frequency ◽  
Time Of Day ◽  
Regulatory Control ◽  
Sleep Restriction ◽  
Older Individuals ◽  
Deconvolution Analysis ◽  
Age Related ◽  
Adrenal Response

Abstract Study Objectives In young men, sleep restriction decreases testosterone (Te) and increases afternoon cortisol (F), leading to anabolic–catabolic imbalance, insulin resistance, and other andrological health consequences. Age-related differences in the hypothalamo–pituitary–testicular/adrenal response to sleep restriction could expose older individuals to greater or lesser risk. We aimed to evaluate and compare the 24-h and time-of-day effect of sleep restriction on F, luteinizing hormone (LH), and Te in young and older men. Methods Thirty-five healthy men, aged 18–30 (n = 17) and 60–80 (n =18) years, underwent overnight sleep deprivation (complete nighttime wakefulness) or nighttime sleep (10 pm to 6 am) with concurrent 10-min blood sampling in a prospectively randomized crossover study. F, LH, and Te secretion were calculated by deconvolution analysis. Results Sleep deprivation had multiple effects on 24-h Te secretion with significant reductions in mean concentrations, basal, total and pulsatile secretion, and pulse frequency (each p &lt; 0.05), in the absence of detectable changes in LH. These effects were most apparent in older men and differed according to age for some parameters: pulsatile Te secretion (p = 0.03) and Te pulse frequency (p = 0.02). Time-of-day analyses revealed that sleep restriction significantly reduced Te in the morning and afternoon, reduced LH in the morning in both age groups, and increased F in the afternoon in older men. Conclusions These data suggest a time-of-day dependent uncoupling of the regulatory control of the testicular axis and of F secretion. Future studies will need to directly verify these regulatory possibilities specifically and separately in young and older men. Clinical Trial Not applicable.

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