Endogenous Melatonin Production Research Articles

The dark side of apnea: altered 24-hour melatonin secretion in obstructive sleep apnea (OSAS) is disease severity dependent

PurposeMelatonin aids in the synchronization of the circadian rhythm to the external environment. Few studies have tried to elucidate the relationship between melatonin and obstructive sleep apnea syndrome (OSAS). These often include few patients, do not differentiate between OSAS severity and/or do not analyse a 24-h melatonin profile. This study set out to investigate disease severity dependent differences in 24-h salivary melatonin secretion of OSAS patients compared to a reference population in a retrospective design.Methods24-h salivary melatonin profiles of 169 OSAS patients were analysed (55 light, 66 moderate, 48 severe) as well as 91 reference patients. Several aspects of the melatonin curve were analysed and stratified according to OSAS severity. Parameters included: dim light melatonin onset (DLMO), time of returning below DLMO (DLMOoff), peak melatonin concentration and time, and total melatonin exposure.ResultsSignificant effects were corrected for confounding by age and sex using linear regression. Our analysis shows that, compared to reference and in a disease dependent manner, OSAS patients have a significantly lower 24-h melatonin curve, lower melatonin peak concentration, lower total melatonin exposure and a smaller proportion of patients reach DLMO. The differences in peak melatonin production and total melatonin exposure were resistant to confounding by age and/or sex.ConclusionThis study describes clear OSAS severity dependent abnormalities in melatonin production in OSAS patients, independent of sex and/or age. Future research should indicate whether oral melatonin supplementation has beneficial effects in OSAS patients with attenuated endogenous melatonin production.

Overcoming poor ovarian response in assisted reproductive technology programs in patients of late reproductive age

Objective: to increase the effectiveness of in vitro fertilization in patients of late reproductive age by optimizing prepregnancy preparation for the IVF program.Materials and methods: The study included 67 patients of late reproductive age with a history of unsuccessful IVF attempts, divided into two groups at the second stage of the study, depending on the volume of prepregnancy preparation: group 1 (33 patients), group 2 (34 patients). The control group (50 patients) were healthy women of reproductive age. Immunohistochemical examination of the endometrium and microbiological examination of the uterine cavity, hormonal status of peripheral blood, study of the concentration of melatonin in peripheral blood and follicular fluid, antioxidant status of follicular fluid, expression of leukemia inhibitory factor (LIF) in the cervical secretion were performed.Results: in patients with age-related dysregulation of the hypothalamic-pituitary-ovarian axis and impaired fertile function, a systemic and local (in follicles) decrease in melatonin levels was revealed. The studied effects of melatonin suggested that its use in patients of late reproductive age with reduced follicular reserve and a "poor" response to ovarian stimulation may increase the effectiveness of in vitro fertilization (IVF).Conclusions: The inclusion in the pre-gravidar preparation of a complex of water-soluble polypeptide fractions of the epiphysis, stimulating the production of endogenous melatonin, made it possible to increase the effectiveness of IVF in patients by an average of 3.1 times according to the criterion of "clinical pregnancy" and 4.1 times according to the criterion of "live birth".

The amelioration of salt stress-induced damage in fenugreek through the application of cold plasma and melatonin

Nowadays, it is increasingly crucial to combine innovative approaches with established methods to enhance plant tolerance and maximize the production of beneficial compounds. With this aim in view, a study was carried out to investigate how different melatonin concentrations (0, 30, and 60 ppm), cold plasma treatment (at 3000 and 4000 V), and varying exposure durations (0, 1, 2, and 4 min) affect the physiological and biochemical attributes of fenugreek plants, as well as the levels of diosgenin under salinity stress. This study revealed that the application of 3000 V cold plasma for 2 min with 60 ppm melatonin by establishing cellular redox homeostasis in salinity-treated fenugreek plants, effectively prevented the destruction of pigments and reduced the electrolyte leakage index of malondialdehyde content. The utilization of these two elicitors has the potential to trigger multiple pathways, including the enzymatic and non-enzymatic antioxidants biosynthesis, and abscisic acid-dependent pathways. This activation results in an enhanced production of abscisic acid, auxin, and endogenous melatonin, along with the regulation of signal transduction pathways. Surprisingly, applying these two treatments increased the expression of SQS, CAS, SSR, BGL, SEP, SMT, and diosgenin content by 13, 22.5, 21.6, 19, 15.4, 12, and 6 times respectively. The findings highlight the intricate interplay between these treatments and the positive impact of their combined application, opening up avenues for further research and practical applications in improving plant tolerance to environmental stresses.

Comparative Quality Analysis of Three Marketed Melatonin Containing Products in Spain for the Improvement of Sleep

Background: Exogenous melatonin may effectively improve the sleep-wake cycle and sleep quality in subjects with age or disease related decrease in endogenous melatonin production or response. A controlled release melatonin-based medication, Circadin® has been developed and licensed for insomnia; in addition to several food supplements available on the market. However, the quality and release profile of these melatonin containing products may vary.
 Aims: The current study aimed to compare three melatonin containing products, all of them marketed in Spain: a licensed medicine prolonged release tablet, Circadin® 2 mg, and two food supplements, Aquilea® 1,95mg and Oniria® 1,98 mg.
 Materials and Methods: Three batches of each product were analyzed for melatonin content, inter-batch variability and dissolution profile.
 Results: Our results confirm a large gap in quality control of the two melatonin containing food supplements, where Aquilea® and Oniria® showed poorer quality control as demonstrated by high variability between batches in melatonin content compared to Circadin®. Moreover, the extended release characteristics of Circadin® were evident in its profile, which exhibited an initial release of 70% at the 4-hour mark, followed by a consistent and sustained release lasting up to 8 hours.
 Conclusion: In terms of the dissolution profile, only Circadin® provides the prolonged release profile as indicated in the specifications, with proven efficacy and safety for the improvement of sleep-onset, sleep maintenance and quality throughout the whole night.

The role of exogenous melatonin in the regulation of sleep

Melatonin is a natural hormone produced by the pineal gland and is a derivative of serotonin. One of the key properties of melatonin is its chronobiological ability, realized by multilevel synchronization of biological processes. Physiologically, melatonin secretion increases at night and decreases in the morning. At present, the role of melatonin in the regulation of sleep, circadian rhythms, and adaptation of the body to a rapid change in time zones has been proven. With a decrease in the production of endogenous melatonin in a number of people (with a disorder of daily biorhythms due to long-distance flights, shift work, insomnia), the use of exogenous melatonin improves the quality of sleep.

The pancreatic clock is a key determinant of pancreatic fibrosis progression and exocrine dysfunction.

Chronic pancreatitis (CP) is characterized by progressive fibrosis and exocrine dysregulation, which have long been considered irreversible. As a peripheral oscillator, the pancreas harbors autonomous and self-sustained timekeeping systems in both its endocrine and exocrine compartments, although the role of the latter remains poorly understood. By using different models of CP established in mice with dysfunctional pancreatic clocks, we found that the local clock played an important role in CP pathology, and genetic or external disruption of the pancreatic clock exacerbated fibrogenesis and exocrine insufficiency. Mechanistically, an impaired retinoic acid receptor-related orphan receptor A (Rora)/nuclear receptor subfamily 1, group D, member 1 (Nr1d1)/aryl hydrocarbon receptor nuclear translocator-like (Arntl or Bmal1) loop, called the circadian stabilizing loop, resulted in the deficiency of pancreatic Bmal1, which was responsible for controlling the fibrogenic properties of pancreatic stellate cells (PSCs) and for rewiring the function of acinar cells in a clock-TGF signaling-IL-11/IL-11RA axis-dependent manner. During PSC activation, the antagonistic interaction between Nr1d1 and Rora was unbalanced in response to the loss of cytoplasmic retinoid-containing lipid droplets. Patients with CP also exhibited reduced production of endogenous melatonin. Enhancing the clock through pharmacological restoration of the circadian stabilizing loop using a combination of melatonin and the Rora agonist SR1078 attenuated intrapancreatic pathological changes in mouse models of CP. Collectively, this study identified a protective role of the pancreatic clock against pancreatic fibrosis and exocrine dysfunction. Pancreatic clock-targeted therapy may represent a potential strategy to treat CP.

The efficacy of subcutaneous slow-release melatonin implants in the prevention of canine flank alopecia recurrence is uncertain: A double-blind, randomized, placebo-controlled study.

Canine flank alopecia (CFA) is characterized by seasonally recurring noninflammatory, occasionally hyperpigmented alopecia predominantly in the thoracolumbar area. Previous studies suggest that reduced production of endogenous melatonin may play a role in the pathogenesis of this condition, and placebo-controlled studies on the efficacy of preventative melatonin treatment are lacking. To evaluate the efficacy of subcutaneous slow-release melatonin implants in the prevention of CFA recurrence. Twenty-one client-owned dogs with a history of CFA were included in the study. At time (T)0, a general physical and dermatological examination was performed on each dog, blood was collected for serum biochemistry analysis and two skin biopsies were taken from alopecic areas on the nonsedated affected dogs after subcutaneous injection with 2% lidocaine. Dogs with normal blood work and histological results compatible with CFA were included in the study. Participating dogs were randomly assigned to receive either placebo or 18 mg melatonin subcutaneously in the interscapular area, approximately 2 months before expected CFA onset (T1). CFA recurrence was scored qualitatively as complete, ≤50% recurrence, or no recurrence at 5 and 7 months after the intervention (T2 and T3, respectively). At T3, in dogs treated with placebo (nine of 17), the percentages for complete recurrence, ≤50% recurrence and no recurrence were 44%, 0% and 56%, respectively. In dogs treated with melatonin (eight of 17), these percentages were 25%, 50% and 25%, respectively. There were no statistically significant differences in the scores between melatonin-treated dogs and placebo-treated dogs (p=0.40). In three of eight melatonin-treated dogs, mild transient swelling was observed at the injection site. This study did not provide evidence that an 18 mg melatonin implant treatment, although well-tolerated, is efficacious in preventing recurrence of CFA in affected dogs.

Melatonin Supplementation in Undetermined Pediatric Deaths.

Since 2015, the North Carolina Office of the Chief Medical Examiner has investigated seven deaths of infants and toddlers, aged 2 months to 3 years, with exogenous melatonin detected upon toxicological analysis. Melatonin concentrations ranged from 3 to 1,400 ng/mL in postmortem whole blood. While the cause and the manner of all seven deaths were classified as undetermined, the analytical findings are noteworthy. Melatonin is generally considered a safe, natural product appearing in many over-the-counter supplements geared toward young children to facilitate calmness and improve sleep. Melatonin is a neurohormone, which regulates not only circadian rhythms and natural sleep but also other physiological functions. Endogenous melatonin production, derived from essential amino acid metabolism, does not begin until pineal gland maturation at ∼3 months of age with concentrations in plasma peaking during periods of darkness at ∼0.2 ng/mL. Administering commercially available melatonin supplements to infants results in levels substantially greater than endogenous sources, which should not be assumed to be safe just because of their endogenous nature. The finding of exogenous concentrations in some postmortem pediatric cases warrants attention. Several topics of interest surrounding these postmortem melatonin findings will be considered, such as minimal regulatory control over commercial products as well as the potential impact on hazardous sleeping conditions. This manuscript will outline the physiological effects of melatonin and detail the case studies from the North Carolina medical examiner system. Forensic toxicology laboratories should consider including melatonin at exogenous concentrations in their testing schemes for appropriate postmortem infant and toddler cases.

Endogenous melatonin delays sepal senescence and extends the storage life of broccoli florets by decreasing ethylene biosynthesis

Although previous work has revealed that exogenous melatonin (MT) improves the storage life and quality of broccoli, whether endogenous MT has similar effects and the mechanism of MT action remains uncertain. We discovered that during storage of broccoli, endogenous MT was impaired. Supplementation with 100 μmol L-1 MT enhanced endogenous MT production, whereas 10 μmol L-1 luzindole (LD, an MT receptor inhibitor) decreased endogenous MT production. Differences in sepal yellowing, storage life, and chlorophyll degradation were observed, such that the senescence of broccoli was delayed by MT but accelerated by LD. Further results revealed that the decreased storage life and accelerated senescence induced by LD were blocked by MT administration, and endogenous MT homeostasis was re-established. These beneficial roles of MT were verified by the alleviation of senescence-induced ethylene production and the increased activities of ethylene biosynthesis enzymes. Compared with those of LD alone, the expressions of chlorophyll degradation-related and ethylene biosynthesis-related genes were also downregulated when MT was added. Overall, the above results imply that endogenous MT homeostasis prolongs the storage life and delays the senescence of broccoli by decreasing ethylene biosynthesis.

The Improved Milk Quality and Enhanced Anti-Inflammatory Effect in Acetylserotonin-O-methyltransferase (ASMT) Overexpressed Goats: An Association with the Elevated Endogenous Melatonin Production.

Background: Transgenic animal production is an important means of livestock breeding and can be used to model pharmaceutical applications. Methods: In this study, to explore the biological activity of endogenously produced melatonin, Acetylserotonin-O-methyltransferase (ASMT)-overexpressed melatonin-enriched dairy goats were successfully generated through the use of pBC1-ASMT expression vector construction and prokaryotic embryo microinjection. Results: These transgenic goats have the same normal phenotype as the wild-type goats (WT). However, the melatonin levels in their blood and milk were significantly increased (p < 0.05). In addition, the quality of their milk was also improved, showing elevated protein content and a reduced somatic cell number compared to the WT goats. No significant changes were detected in the intestinal microbiota patterns between groups. When the animals were challenged by the intravenous injection of E. coli, the ASMT-overexpressed goats had a lower level of pro-inflammatory cytokines and higher anti-inflammatory cytokines compared to the WT goats. Metabolic analysis uncovered a unique arachidonic acid metabolism pattern in transgenic goats. Conclusions: The increased melatonin production due to ASMT overexpression in the transgenic goats may have contributed to their improved milk quality and enhanced the anti-inflammatory ability compared to the WT goats.

The association between pineal gland calcification and intracranial atherosclerotic disease in older adults

Abstract Background: This study assesses whether pineal gland calcification (PGC) – a surrogate for reduced endogenous melatonin production – is associated with significant stenosis of large intracranial arteries – a biomarker of intracranial atherosclerotic disease (ICAD). Methods: Individuals aged ≥60 years enrolled in the Three Villages Study received head CT to assess PGC and MRA to estimate stenosis of large intracranial arteries. Multivariate logistic regression models were fitted to assess the association between PGC and ICAD, after adjusting for relevant confounders. Inverse probability of exposure weighting was used to estimate the effect of PGC on ICAD. Results: A total of 581 individuals were enrolled. PGC and ICAD were associated in a fully-adjusted logistic regression model (p=0.032). Inverse probability of exposure weighting showed an estimate for the proportion of ICAD among those without PGC of 3.7% and the adjusted-effect coefficient was 5.7% higher among those with PGC (p=0.031). Conclusions: PGC is associated with ICAD. Study results provide grounds for evaluating the role of melatonin deficiency in ICAD progression. Keywords: Pineal gland calcification, intracranial atherosclerosis, stenosis of large intracranial arteries, melatonin; population study, older adults

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

Obstructive sleep apnea syndrome: association of serum melatonin, increased daytime sleepiness, and intermitting night hypoxemia

The relevance of studies related to the features of respiratory disorders during sleep is undeniable due to the steady growth of the worldwide prevalence of apnea syndrome, which leads to a decrease in quality of life, the risk of early cardiovascular diseases together with cerebrovascular, endocrine, and pulmonary disorders.The aim of this study was to determine the relationship between the morning serum melatonin, blood oxygen saturation (SрO2), and increased daytime sleepiness in patients with SOAS, as well as to assess changes in the production of endogenous melatonin after eliminating clinical manifestations of nocturnal hypoxemia, through a 3-month course of non-invasive continuous positive airway pressure (CPAP) therapy. The study enrolled 30 male patients who came to the Federal State Public Scientific Institution “Scientific Centre of Family Health and Human Reproduction Problems” because of snoring, sleep apnea, and increased daytime sleepiness.Methods. Polysomnography, questionnaire, HPLC-MS/MS analysis of serum melatonin levels, CPAP-therapy for the respiratory support at home for 3 months, monitoring of the sleep scores, serum melatonin, and daytime sleepiness after the treatment.Results. A comparative assessment of the sleep scores before and after the respiratory support for 3 months revealed a significant improvement in sleep structure, elimination of the apnea episodes, and restoration of blood SрO2 after the therapy. Analysis of the serum melatonin vales confirmed a statistically significant increase of melatonin level against baseline in patients with SOAS after the treatment. A correlation analysis showed a relationship between the melatonin level, daytime sleepiness, and blood SрO2.Conclusion. The results of this study and the data of other researchers demonstrate that the elimination of intermittent nocturnal hypoxia in patients with SOAS allows reducing the morning serum melatonin level, thereby reducing the daytime sleepiness and subsequently improving the quality of life.

Functional interplay of melatonin in the bile duct and gastrointestinal tract to mitigate disease development: An overview

Prevalence of bile duct and gastrointestinal (GI) tract associated diseases is increasing globally. Commonly, the bile duct epithelial cell (cholangiocytes) malfunction and its uncontrolled proliferation often cause liver fibrosis and tumorigenesis, particularly the cholangiocarcinoma. Specifically, GI tract is constantly under diverse endogenous and exogenous stressors which interrupt GI physiological functions and promote inflammation, tissue damage, ulceration, gastrointestinal bleeding, gastroesophageal reflux disease (GERD), irritable bowel disease (IBD) and gastritis. On the other hand, melatonin exhibits important functions in both cholangiocyte and GI tract. The abundance of melatonin generated in the GI tract and its widely distributed receptors facilitate its protective effects in GI tissues. In the most of the cases, the disease progression in GI tract, particularly in bile duct, is associated with endogenous melatonergic system suppression. Therefore, to increase the endogenous melatonin production appears a suitable strategy to retard the disease development in these tissues. Melatonin administration or, exposure to prolonged darkness not only reverse the detrimental biochemical alterations, but also inhibit cholangiocyte proliferation as well as ulceration in the GI tract. Thus, use of melatonin as a natural therapeutic agent is beneficial and exhibits advantages over other contemporary drugs in prevention and treatment of bile duct and gastrointestinal tract associated diseases.

Myopia, or near-sightedness, is associated with delayed melatonin circadian timing and lower melatonin output in young adult humans.

Myopia, or near-sightedness, is the most common refractive vision disorder and predisposes the eye to many blinding conditions in adulthood. Recent research has suggested that myopia is associated with increased endogenous melatonin production. Here we investigated the differences in melatonin circadian timing and output in young adult myopes and non-myopes (or emmetropes) as a pathogenesis for myopia. A total of 18 myopic (refractive error [mean ± standard deviation] -4.89 ± 2.16 dioptres) and 14 emmetropic participants (-0.09 ± 0.13 dioptres), aged 22.06 ± 2.35 years were recruited. Circadian timing was assessed using salivary dim light melatonin onset (DLMO), collected half-hourly for 7 h, beginning 5 h before and finishing 2 h after individual average sleep onset in a sleep laboratory. Total melatonin production was assessed via aMT6s levels from urine voids collected from 06:00 pm and until wake-up time the following morning. Objective measures of sleep timing were acquired a week prior to the sleep laboratory visit using an actigraphy device. Myopes (22:19 ± 1.8 h) exhibited a DLMO phase-delay of 1 hr 12 min compared with emmetropes (21:07 ± 1.4 h), p = 0.026, d = 0.73. Urinary aMT6s melatonin levels were significantly lower among myopes (29.17 ± 18.67) than emmetropes (42.51 ± 23.97, p = 0.04, d = 0.63). Myopes also had a significant delay in sleep onset, greater sleep onset latency, shorter sleep duration, and more evening-type diurnal preference than emmetropes (all p < 0.05). These findings suggest a potential association between circadian rhythms and myopia in humans.

Elevated serum melatonin under constant darkness enhances neural repair in spinal cord injury through regulation of circadian clock proteins expression

We investigated the effects of environmental lighting conditions regulating endogenous melatonin production on neural repair, following experimental spinal cord injury (SCI). Rats were divided into three groups randomly: the SCI + L/D (12/12‐h light/dark), SCI + LL (24‐h constant light), and SCI + DD (24‐h constant dark) groups. Controlled light/dark cycle was pre‐applied 2 weeks before induction of spinal cord injury. There was a significant increase in motor recovery as well as body weight from postoperative day (POD) 7 under constant darkness. However, spontaneous elevation of endogenous melatonin in cerebrospinal fluid was seen at POD 3 in all of the SCI rats, which was enhanced in SCI + DD group. Augmented melatonin concentration under constant dark condition resulted in facilitation of neuronal differentiation as well as inhibition of primary cell death. In the rostrocaudal region, elevated endogenous melatonin concentration promoted neural remodeling in acute phase including oligodendrogenesis, excitatory synaptic formation, and axonal outgrowth. The changes were mediated via NAS‐TrkB‐AKT/ERK signal transduction co‐regulated by the circadian clock mechanism, leading to rapid motor recovery. In contrast, exposure to constant light exacerbated the inflammatory responses and neuroglial loss. These results suggest that light/dark control in the acute phase might be a considerable environmental factor for a favorable prognosis after SCI.Support or Funding InformationNational Research Foundation (NRF‐2013R1A2A2A01067169, NRF‐2015R1C1A2A01055691, NRF‐2017R1D1A1B03029565), Korea.

Exogenous melatonin alleviates cadmium uptake and toxicity in apple rootstocks.

To examine the potential roles of melatonin in Cd uptake, accumulation and detoxification in Malus plants, we exposed two different apple rootstocks varying greatly in Cd uptake and accumulation to either 0 or 30 μM Cd together with 0 or 100 μM melatonin. Cd stress stimulated endogenous melatonin production to a greater extent in the Cd-tolerant M. baccata than in the Cd-susceptible M. micromalus ‘qingzhoulinqin’. Melatonin application attenuated Cd-induced reductions in growth, photosynthesis, and enzyme activity, as well as ROS and MDA accumulation. Melatonin treatment more effectively restored photosynthesis, photosynthetic pigments, and biomass in Cd-challenged M. micromalus ‘qingzhoulinqin’ than in Cd-stressed M. baccata. Exogenous melatonin lowered root Cd2+ uptake, reduced leaf Cd accumulation, decreased Cd translocation factors (Tfs), and increased root, stem, and leaf melatonin contents in both Cd-exposed rootstocks. Melatonin application increased both antioxidant concentrations and enzyme activities to scavenge Cd-induced ROS. Exogenous melatonin treatment altered the mRNA levels of several genes regulating Cd uptake, transport, and detoxification including HA7, NRAMP1, NRAMP3, HMA4, PCR2, NAS1, MT2, ABCC1, and MHX. Taken together, these results suggest that exogenous melatonin reduced aerial parts Cd accumulation and mitigated Cd toxicity in Malus plants, probably due to the melatonin-mediated Cd allocation in tissues, and induction of antioxidant defense system and transcriptionally regulated key genes involved in detoxification.

Sleep Parameters and Overnight Urinary Melatonin Production in Children With Persistent Post-concussion Symptoms

BackgroundSleep disturbance is common after a mild traumatic brain injury (mTBI) in children, yet its biology is poorly understood. We aimed to explore sleep-related problems (SRPs), sleep-activity patterns, and endogenous melatonin production in children with different recovery trajectories following mTBI. We hypothesized that children with delayed recovery would have more SRPs and abnormal sleep-activity patterns, which would correlate with lower overnight melatonin production. MethodsIn this prospective controlled cohort study, we enrolled 83 children with persistent symptoms, 26 children who had clinically recovered following mTBI, and 25 healthy controls. SRPs were evaluated using the sleep subscale of the Post-Concussion Symptom Inventory. Sleep actigraphy was performed for five to seven days at 37 (S.D. 7) days post-injury. Health-related quality of life and mood disturbance was assessed using the Child Health Questionnaire and the Behavior Assessment System for Children, respectively. Endogenous melatonin production was assessed using overnight urine collection. ResultsThe groups were similar in age (13.9 [S.D. 2.6] years) and sex (52% female). Regression analysis demonstrated increased SRP in the symptomatic group (9.0; 95% confidence interval: 7.6, 11.1) compared with the recovered group (1.6; 95% confidence interval: 1.0, 2.4) and controls (2.0; 95% confidence intervals: 1.2, 3.2). Actigraphy parameters and urinary melatonin levels were not significantly different between groups. Neither SRPs nor actigraphy parameters correlated with anxiety and depression scores. ConclusionsAlthough children with persistent post-concussion symptoms reported more SRPs, this was not related to actigraphy sleep parameters or melatonin production. Further research is warranted to understand the pathophysiology of post-traumatic sleep disturbance.

Does night work affect age at which menopause occurs?

To delineate the current state of evidence on the impact of night shift work on age at natural menopause. The only direct evidence is from a single observational study, which indicates that women who work night shifts are at moderately higher risk for earlier menopause and that this risk is more pronounced among younger women. Underlying biological mechanisms have yet to be sufficiently substantiated. A long-held line of inquiry, most strongly propagated by the observed link between night shift work and female breast cancer, is the 'Light at Night' hypothesis, which suggests melatonin-mediated circadian disruption as a potential regulator of reproductive signaling in women. Supporting evidence is found from observations of changes in endogenous melatonin production among night working women or in response to light exposure, and corresponding changes in endogenous ovarian hormone levels and modulated menstrual patterns, among other indications of altered central ovulation-governing processes. Susceptibility to night shift work may be modified by chronotype. This review summarizes the literature related to night work and ovulatory regulation in humans, prioritizing population-based evidence to provide motivation for the study of circadian disruption and night shift work as a regulator of menopausal timing.

Protective Effects of Melatonin on the Skin: Future Perspectives.

When exposed to hostile environments such as radiation, physical injuries, chemicals, pollution, and microorganisms, the skin requires protective chemical molecules and pathways. Melatonin, a highly conserved ancient molecule, plays a crucial role in the maintenance of skin. As human skin has functional melatonin receptors and also acts as a complete system that is capable of producing and regulating melatonin synthesis, melatonin is a promising candidate for its maintenance and protection. Below, we review the studies of new metabolic pathways involved in the protective functions of melatonin in dermal cells. We also discuss the advantages of the topical use of melatonin for therapeutic purposes and skin protection. In our view, endogenous intracutaneous melatonin production, together with topically-applied exogenous melatonin and its metabolites, represent two of the most potent defense systems against external damage to the skin.