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However, research on the impacts of light, body temperature, and circadian/circannual rhythms is relatively lacking, although some correlations have been demonstrated. Growing evidence has shown that the circadian clock is tightly connected to male fertility, and circadian perturbations contribute to infertility. Because all physiological activities occur at a specific time, circadian rhythm disturbances can lead to various pathological disorders and diseases. Disruptions to these rhythms due to low testosterone can lead to sleep disturbances, fatigue, and mood changes. Low testosterone levels have been linked to sleep disturbances, decreased energy levels, and mood changes.
It doesn’t tick with gears or hands but with pulses of hormones, oscillations of proteins, and rhythmic cycles of genes turning on and off. Therefore, a more accurate dose regimen can be proposed to minimize the impact of the circadian behavior of testosterone in hypogonadal men. As expected, the simulations evidenced that lower levels of testosterone would be easier observed in an old subject compared to a young subject. Therefore, the modeled typical hypogonadal patient would always be considered as a hypogonadal subject, even at the peak testosterone concentration. In this study, a cutoff of 300 ng/dL was used to consider a subject with low levels of testosterone. Base baseline value, tmax time at which the peak of testosterone is reached, tmin time at which the nadir of testosterone occurs Diagnostic plots of the model developed to characterize testosterone kinetics in hypogonadal men.
Previous studies have highlighted the tissue-specific nature of this mechanism, revealing that skeletal muscle possesses its own inherent circadian clock output—a phenomenon observed in various tissue types . Given that sporting events occur across different time zones and times of day, adapting training strategies to align with circadian regulation is essential. Optimizing sport and exercise performance requires adapting training to time-of-day-dependent fluctuations in physiological regulation . Wearable devices that monitor sleep, light exposure, and activity are providing real-time insights into circadian health. Smart lighting systems that mimic the changing spectrum of sunlight throughout the day are also being developed to support healthier rhythms.
Using tools like the MEQ and RB-UB chronometric tests to identify an individual’s diurnal preference can help develop personalized training schedules aligned with internal biological clocks. Researchers should also develop practical interventions to mitigate the effects of circadian disruptions, such as travel-induced jet lag, to enhance adaptability and maintain optimal performance. The importance of managing circadian disruptions caused by societal demands, such as travel across time zones and irregular competition schedules, cannot be overstated. Diurnal fluctuations in physiological parameters such as hormonal levels, core body temperature, and individual chronotypes provide valuable insights for optimizing training schedules and recovery strategies. Based on these assessments, staggered training sessions or flexible practice schedules may be implemented to align with players’ peak performance windows .
Where L1 is the length of the first interval, in other words the time that it takes from the peak of testosterone to the nadir modulo 24 h as well. This function allows the time between the peak of testosterone (tmax) and the nadir (tmin) to be different from 12 h in order to capture this non-symmetric behavior. The model fitted a total of 859 baseline profiles of testosterone consisting of 4556 observations. Where Tobs is the observed testosterone level, Tpred is the corresponding model prediction, and ε is a parameter quantifying the residual variability, assumed to follow an independent Gaussian distribution with mean zero and variance σ2. Since testosterone is an endogenous substance with a circadian behavior, the assessment of the therapeutic effect of TRT results is challenging. The normal range for early morning total testosterone in healthy adult males ranges from approximately 300 to 1000 ng/dL (4,5). This discrepancy may be due to differences in the oscillation amplitude and phase of clock gene expression in different types of cells within the testis.
The SCN perceives ambient light through the retinal hypothalamic pathway, then converts photoperiodic signals into endocrine signals and transmits the signals to Leydig cells through various hormones, including melatonin and LH.33,36 In mammals, most circulating melatonin originates from the pineal gland,61 where the SCN plays a regulatory role in melatonin secretion.62 Once synthesized by the pineal gland, melatonin has high diffusivity and will be rapidly released into the cerebrospinal fluid and blood. Spermatogenic cells mainly consist of spermatogonia, spermatocytes, and spermatids. We also examined the specific effects of these genes on the occurrence, development, and treatment of common male diseases, including late-onset hypogonadism, erectile dysfunction, male infertility, and prostate cancer.
Studies have shown that late-night screen use delays sleep onset, shortens sleep duration, and lowers sleep quality. Morning sunlight is especially effective at anchoring the SCN and reinforcing the wake-sleep cycle. Blood pressure normally dips at night during sleep—a phenomenon known as nocturnal dipping. In fact, chronotherapy—using light exposure and sleep timing—has become an effective treatment strategy for mood disorders. Circadian rhythms regulate neurotransmitters such as serotonin and dopamine, which influence mood and cognition. Shift workers, who often eat at odd hours and sleep during the day, are particularly vulnerable. This mismatch between internal time and external environment is known as circadian misalignment, and it has been linked to a broad range of health problems.
Importantly, the SCN responds to light, the primary cue—or zeitgeber—that entrains the circadian clock. The present model manages to well characterize the population and individual kinetics of the testosterone levels, making it suitable to compare the efficacy between different TRT. The proposed stretched cosine function might also be useful in all those situations where a non-symmetric circadian rhythm is observed in order to improve model predictions. Simulation of the time course of the testosterone levels based on typical patient values. This fact might show the clinicians the optimal time for the TRT to be administrated in order to maintain the testosterone levels within the normal range of 300 and 1000 ng/dL.
The National Sleep Foundation has suggested a sleep period of 7–9 h for people aged 18–64 years and 7–8 h for those over 65 years (68, 69). Considering this discrepancy, further studies with large prospective populations are necessary to verify the impact of shiftwork on male fertility before providing suggestions to shiftwork schedules. However, whether such recovery of sperm quality could be observed in shift workers requires more evidence. Furthermore, prolonged light exposure increased the expression of Per1/2 and decreased Bmal1, while darkness exposure upregulated Per1/2, Clock, and Rer-erab (57). Moreover, LL reduced glutathione reductase (GR) levels in the epididymis but increased the enzymatic activity of glutathione S-transferase (GST) and glutathione peroxidase (GPx) in the testis (57).
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