Genetic factors underlying insomnia and ovarian insufficiency.

Premature ovarian insufficiency (POI) is characterized by a loss of regular hormone production and egg release in women below the age of 40 years, which often leads to infertility, vaginal dryness and dysfunctional sleep. Acknowledging the common co-occurrence of insomnia and POI, we tested the overlap between POI and insomnia-associated genes, which were implicated in previous large-scale populational genetics efforts. Among the 27 overlapping genes, three pathways were found as enriched: DNA replication, homologous recombination and Fanconi anemia. We then describe biological mechanisms, which link these pathways to a dysfunctional regulation and response to oxidative stress. We propose that oxidative stress may correspond to one of the convergent cellular processes between ovarian malfunction and insomnia pathogenic etiology. This overlap might also be driven by cortisol release associated with dysregulated DNA repair mechanisms. Benefiting from the enormous advances in populational genetics studies, this study provides a novel outlook on the relationship between insomnia and POI. The shared genetic factors and critical biological nodes between these two comorbidities may lead to identification of putative pharmacological and therapeutical targets, which can leverage novel approaches to treat or alleviate their symptoms.

Impact of insomnia on pain in postmenopausal women.

BACKGROUND: Sleep disturbances and pain are assumed to be reciprocally linked. Insomnia and pain are central symptoms of the postmenopausal period and are closely related. Insomnia affects quality of life, increases pain sensitivity, the risk of pain-related disability, and other health problems. OBJECTIVE: To investigate whether insomnia influences aspects of pain (pain intensity and the effect of pain on daily function) in postmenopausal women, and to evaluate the objective sleep pattern of insomniacs with pain. METHODS: Fifty-seven women completed questionnaires about insomnia, climacteric symptoms, and pain. Polysomnography data were collected as well as their medical history. Patients were allocated into three groups: control, subthreshold insomnia, and insomnia. Pain intensity, climacteric symptoms and objective sleep pattern were compared between groups. RESULTS: Postmenopausal women with insomnia had statistically significant higher pain interference in their activities (e.g. relationships with other people, enjoyment of life and sleep) than controls, and had more severe climacteric symptoms. There were no statistically significant differences in pain intensity and objective sleep pattern between groups. CONCLUSIONS: Insomnia status affected climacteric symptoms and pain interference, but not pain intensity in postmenopausal women. Women with insomnia had higher rates of climacteric symptoms than those without insomnia or those with subthreshold insomnia. No changes in objective sleep pattern were found.

Musculoskeletal pain and the reproductive life stage in women: is there a relationship?

Objectives To investigate the association between reproductive life stage, pain perception and musculoskeletal pain complaint in a representative sample of women from São Paulo, Brazil. Methods A population-based survey was carried out with 574 women who were classified as being in the premenopausal or postmenopausal stage. They answered questions about pain perception and musculoskeletal pain. Follicle stimulating hormone was collected to confirm menopausal condition along with clinical evaluation. Results In the whole sample, we found a prevalence of 56% for pain perception and 20.2% for complaints of musculoskeletal pain. Regarding the topography of musculoskeletal pain, the distributions were similar among the premenopausal and postmenopausal groups. No significant association was found between reproductive life stage and pain perception, as 58.1% of the premenopausal group and 52.0% of the postmenopausal group reported pain. Similarly, there was no significant association between menopausal stage and musculoskeletal pain, as 19.5% and 21.6% of the premenopausal and postmenopausal women, respectively, complained of musculoskeletal pain. There was no significant association of postmenopausal stage (early or late) with pain perception or musculoskeletal pain. The use of analgesics was significantly higher in postmenopausal compared to premenopausal women (p < 0.001). Conclusion A high prevalence of pain was found in women from the city of São Paulo. However, neither the presence of musculoskeletal pain nor pain perception were associated with the reproductive life stage, showing that both parameters was independent from the menopausal status in the studied women.

Vitamin E supplementation inhibits muscle damage and inflammation after moderate exercise in hypoxia.

BACKGROUND: Exercise under hypoxic conditions represents an additional stress in relation to exercise in normoxia. Hypoxia induces oxidative stress and inflammation as mediated through tumour necrosis factor (TNF)-α release that might be exacerbated through exercise. In addition, vitamin E supplementation might attenuate oxidative stress and inflammation resulting from hypoxia during exercise. The present study aimed to evaluate the effects of vitamin E supplementation (250 mg) on inflammatory parameters and cellular damage after exercise under hypoxia simulating an altitude of 4200 m. METHODS: Nine volunteers performed three sessions of 60 min of exercise (70% maximal oxygen uptake) interspersed for 1 week under normoxia, hypoxia and hypoxia after vitamin E supplementation 1 h before exercise. Blood was collected before, immediately after and at 1 h after exercise to measure inflammatory parameters and cell damage. RESULTS: Percentage oxygen saturation of haemoglobin decreased after exercise and recovered 1 h later in the hypoxia + vitamin condition (P < 0.05). Supplementation decreased creatine kinase (CK)-TOTAL, CK-MB and lactate dehydrogenase 1 h after exercise (P < 0.05). The exercise in hypoxia increased interleukin (IL)-6, TNF-α, IL-1ra and IL-10 immediately after exercise (P < 0.05). Supplementation reversed the changes observed after exercise in hypoxia without supplementation (P < 0.05). CONCLUSIONS: We conclude that 250 mg of vitamin E supplementation at 1 h before exercise reduces cell damage markers after exercise in hypoxia and changes the concentration of cytokines, suggesting a possible protective effect against inflammation induced by hypoxia during exercise.

Reduction in saturated fat intake improves cardiovascular risks in obese adolescents during interdisciplinary therapy.

BACKGROUND/OBJECTIVES: Obesity is related to inflammation and cardiovascular disease. The increase in saturated fatty acid intake (SFA) can potentiate cardiovascular risks. The aim of this study was to assess the influence of change in SFA on carotid intima-media thickness (cIMT), metabolic profile and anti/pro-inflammatory adipokines in obese adolescents. METHODS: Sixty obese adolescents were subjected to 1 year of interdisciplinary intervention (nutrition, psychology, physical exercise and clinical therapy). Blood glucose, insulin, lipid profile, leptin and adiponectin were analysed. Insulin resistance was estimated by HOMA-IR and HOMA-AD. cIMT was measured by ultrasonography. Dietetic intake was calculated by 3-day dietary record. Volunteers were analysed according to tertiles of change (Δ) in SFA intake: Low-SFA reduction<3.68 g; Moderate-SFA reduction 3.68-13.67 g; and High-SFA reduction>13.67 g. RESULTS: Moderate and High-SFA tertiles presented reduction in insulin, leptin/adiponectin ratio, cIMT and increase in adiponectin and adiponectin/leptin ratio. Adiponectin/leptin ratio was predictor of cIMT. HOMA-IR, total cholesterol and LDL-cholesterol reduced only in High-SFA tertile, and was associated with SFA independent of visceral fat. Negative correlations between Δ of SFA and adiponectin and adiponectin/leptin ratio were observed. CONCLUSION: Obese adolescents with moderate and high reduction in SFA presented improvements on pro/anti-inflammatory biomarkers and cIMT, leading to reduction in cardiovascular risks.

Saturated fatty acid intake can influence increase in plasminogen activator inhibitor-1 in obese adolescents.

The aim of this study was to verify if saturated fatty acid intake adjusted by tertiles can influence metabolic, inflammation, and plasminogen activator inhibitor-1 (PAI-1) in obese adolescents. Body mass, height, body mass index, waist circumference, blood pressure, and body composition of 108 obese adolescents were obtained. Fasting glucose, insulin, PAI-1, and CRP were determined. Insulin resistance was assessed by Homeostasis Model Assessment (HOMA-IR) and insulin sensitivity by Quantitative Insulin Sensitivity Check Index (QUICKI). Dietetic intake was estimated by a 3-day dietary record, and volunteers were divided according to consumption of saturated fatty acids: tertile 1 [Low Saturated Fatty Acid Intake (Low-SFA): ≤12.14 g], tertile 2 [Moderate Saturated Fatty Intake (Moderate SFA intake): 12.15-20.48 g], and tertile 3 [High Saturated Fatty Acid Intake (High-SFA Intake); >20.48 g]. Statistical analysis was performed using STATISTICA 7.0 software and the significance level was set at p<0.05. The most important finding in the present study is that Moderate and High-SFA intakes presented significantly higher values of PAI-1 than Low-SFA Intake. PAI-1 was positively associated with saturated fatty intake, waist circumference, mean blood pressure, and HOMA-IR. SFA intake was predictor of PAI-1 independent of body fat, HOMA-IR and total-cholesterol. In addition, PAI-1 was an independent predictor of blood pressure. HOMA-IR and QUICKI presented significantly higher and lower, respectively, in High-SFA compared to Moderate-SFA intake. High-SFA influenced cardiovascular disease risks, since it increased PAI-1 and insulin resistance, and decreased insulin sensibility, leading to vicious cycle among food ingestion, pro-thrombotic state, and cardiovascular risks in obese adolescents.

Complementary and alternative therapies for treatment of insomnia in women in postmenopause.

Menopause is an important episode in the life of women and, for the great majority of women, occurs in their fifties. The climacteric period, which is often associated with insomnia, represents one of the most important changes in the female reproductive cycle because it marks the end of reproductive capacity. Hormonal therapy has been considered the most useful and standardized method for treating menopause and climacteric-associated symptoms despite its side-effects. The present study is a review of the scientific literature about the efficacy, toxicity and safety of complementary and alternative therapies used as alternatives to hormone therapy to treat insomnia in menopausal women. Mind-body therapies and the use of isoflavonoids have exhibited promise as interventions for treating insomnia in the climacteric at our Walk-In Clinic of Sleep Disturbance at the Universidade Federal de São Paulo. This review will describe the use of complementary and alternative therapies and their effectiveness in treating insomnia in this period of a woman's life.

Moderate acute exercise (70% VO2 peak) induces TGF-ß, α-amylase and IgA in saliva during recovery.

Strenuous exercise promotes changes in salivary IgA and can be associated with a high incidence of upper respiratory tract Infections. However, moderate exercise enhances immune function. The effect of exercise on salivary IgA has been well studied, but its effect on other immunological parameters is poorly studied. Thus, this study determined the effect of moderate acute exercise on immunological salivary parameters, such as the levels of cytokines (TGF-ß and IL-5), IgA, α-amylase and total protein, over 24 h. Ten male adult subjects exercised for 60 min at an intensity of 70% VO2 peak. Saliva samples were collected before ('basal') and 0, 12 and 24 h after an exercise session. The total salivary protein was lower after 12 and 24 h than immediately after exercise, whereas α-amylase increased at 12 and 24 h after exercise compared with basal levels. The IgA concentration was increased at 24 h after exercise relative to immediately after exercise, and there was no difference in the IL-5 while TGF-ß concentration increased in recovery. In conclusion, 70% VO2 peak exercise does not induce changes immediately after exercise, but after 24 h, it produces an increase in salivary TGF-ß without changing IL-5.

Cardiovascular function alterations induced by acute paradoxical sleep deprivation in rats.

Sleep loss has been implicated in triggering the hypertension. The goal of the present study was investigated the possible mechanisms underlying cardiovascular alterations after acute paradoxical sleep deprivation (PSD). Male Wistar rats were assigned in two experimental groups: (1) control and (2) PSD for 24 h using the modified single platform method. Paradoxical sleep deprived rats exhibited higher blood pressure, heart rate (HR) and impaired baroreceptor sensitivity. After pharmacological autonomic double blockade (propranolol and methylatropine administration), intrinsic heart rate was decreased after PSD. The PSD rats showed a reduction in the vagal tone without affecting sympathetic tone. Isoproterenol administration (0.001, 0.01 and 1 µg/kg) induced an increase in ΔHR responses in PSD group. Electrocardiographic analysis in response to ß-adrenergic stimulation indicated that PSD contributed to ventricular cardiac arrhythmias. Our findings suggest that acute paradoxical sleep loss induce cardiovascular alterations, autonomic imbalance accompanied by impaired baroreflex sensitivity and increased arrhythmia susceptibility.

Is lack of sleep capable of inducing DNA damage in aged skin?

Skin naturally changes with age, becoming more fragile. Various stimuli can alter skin integrity. The aim of this study was to evaluate whether sleep deprivation affects the integrity of DNA in skin and exacerbates the effects of aging. Fifteen-month old female Hairless mice underwent 72 h of paradoxical sleep deprivation or 15 days of chronic sleep restriction. Punch biopsies of the skin were taken to evaluate DNA damage by single cell gel (comet) assay. Neither paradoxical sleep deprivation nor sleep restriction increased genetic damage, measured by tail movement and tail intensity values. Taken together, the findings are consistent with the notion that aging overrides the effect of sleep loss on the genetic damage in elderly mice.

Effects of different physical exercises on leptin concentration in obese adolescents.

In order to compare the effects of leisure physical activity (LPA), aerobic training (AT) and aerobic plus resistance training (AT + RT) as part of a 6-month interdisciplinary therapy in body composition, insulin resistance and leptin concentrations in obese adolescents, 72 volunteers (n = 24 in each group) ages 15-19 years were evaluated. Delta (Δ) body mass (kg) and Δ BMI (kg/m(2)) was different between AT and LPA groups and in AT + RT group compared to both LPA and AT groups; Δ body fat mass (kg and %) was different only in AT + RT group compared to both LPA and AT; Δ body lean mass (%) was different only in AT + RT group; Δ body lean mass (kg) was negative only in AT and positive and different from AT in AT + RT group; ΔHOMA-IR did not differ among groups; Δ leptin (ng/ml) was negative and different from LPA for both AT and AT + RT groups. In conclusion, both AT and AT + RT promoted a reduction on leptin levels, however, the adolescents subjected to AT + RT presented better results in body composition than the AT group. These results highlight the importance of associating aerobic and resistance training with nutritional and psychological approaches in the treatment of obese adolescents.

Sleep patterns and acute physical exercise: the effects of gender, sleep disturbances, type and time of physical exercise.

AIM: Aim of the study was to determine which factors influence sleep patterns after a single session of physical exercise. METHODS: Adult sedentary volunteers (N.=221; 104 men and 117 women) aged 31.40±9.40 were randomised into groups with three different types of physical exercise (resistance, aerobic and interval). After the exercise protocol was explained, each volunteer was given the first polysomnographic (PSG) and performed the acute session of physical exercise (resistance: based on a 1RM test; aerobic: based on a maximum effort test (MET) and interval: 10 series with 4-minute intervals between series). The second PSG was performed the day after the acute session of physical exercise. RESULTS: A negative correlation was found between sleep latency and the acute physical exercise session practiced in the evening, and a positive correlation was found between the total sleep time and female gender. The REM sleep stage (%) was positively correlated with the control, obstructive sleep apnea (OSA) and periodic leg movement (PLM) groups and the acute physical exercise session practiced in the morning. Positive correlations were observed in the arousal index and the PLM group and female gender; the PLM index and the control and OSA groups; minimum oxygen saturation and the OSA and PLM groups. CONCLUSION: Therefore, these results suggested that such factors as gender, the presence of sleep disturbance (PLM and/or OSA), type of physical exercise (aerobic, resistance or interval) and the time that it was practiced (morning, afternoon or evening) can influence sleep patterns after a single session of physical exercise. However, the gender seems to be the most important factor to influence sleep pattern in the situation studied.

Sleep deprivation alters gene expression and antioxidant enzyme activity in mice splenocytes.

Cellular defence against the formation of reactive oxygen species (ROS) involves a number of mechanisms in which antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) play an important role. The relation between sleep deprivation and oxidative stress has not yet been completely elucidated. Although some authors did not find evidence of this relationship, others found alterations in some oxidative stress markers in response to sleep deprivation. Thus, the objective of this study was to identify changes induced by sleep deprivation in the activity and gene expression of antioxidant enzymes in mice splenocytes, ideally corroborating a better understanding of the observed effects related to sleep deprivation, which could be triggered by oxidative imbalance. Splenocytes from mice sleep deprived for 72 h showed no significant difference in CAT and CuZnSOD gene expression compared with normal sleep mice. However, sleep-deprived mice did show higher MnSOD gene expression than the control group. Concerning enzymatic activity, CuZnSOD and MnSOD significantly increased after sleep deprivation, despite the expression in CuZnSOD remained unchanged. Moreover, CAT activity was significantly lower after sleep deprivation. The data suggest that the antioxidant system is triggered by sleep deprivation, which in turn could influence the splenocytes homoeostasis, thus interfering in physiological responses.

Acupuncture improves sleep in postmenopause in a randomized, double-blind, placebo-controlled study.

BACKGROUND: Insomnia increases in frequency as women approach and pass through menopause. Studies have not shown acupuncture efficacy for insomnia in postmenopausal women. OBJECTIVES: The aim of this study was to evaluate the effectiveness of acupuncture therapy on sleep parameters, depression symptoms and quality of life in postmenopausal women with insomnia. METHODS: This study included 18 postmenopausal women aged 50-67 years old. Participants had a body mass index ≤ 30 kg/m(2), presented a diagnosis of insomnia according to the DSM-IV criteria, had experienced at least 1 year of amenorrhea and had a follicle stimulating hormone level ≥ 30 mIU/ml. Participants were not using antidepressants, hypnotics or hormonal therapy. This study was randomized, double-blind and placebo-controlled. The sample was divided into two groups: acupuncture and 'sham' acupuncture. We performed ten sessions of acupuncture and 'sham' acupuncture during a period of 5 weeks. A polysomnography exam (PSG) and questionnaires (WHOQOL-BREF, Beck Depression Inventory and Pittsburgh Sleep Quality Index) were completed by all patients before and after the treatment period. RESULTS: Anthropometric, polysomnographic, and questionnaire data were similar among the groups at baseline. Comparison of baseline and post-treatment data of the acupuncture group showed that treatment resulted in significantly lower scores on the Pittsburgh Questionnaire and an improvement in psychological WHOQOL. The acupuncture group had a higher percentage of the N3 + 4 stage than the sham group in PSG findings. CONCLUSION: Acupuncture was effective in improving reported sleep quality and quality of life in postmenopausal women with insomnia.

Does menopause influence nocturnal awakening with headache?

OBJECTIVE: The aim of the present study was to assess whether menopausal status influences the occurrence of nocturnal awakening with headache (NAH) in the female population of Sao Paulo, Brazil. We also examined the relationship of this complaint to sociodemographic determinants, hot flushes, sleep quality and parameters, anxiety and depressive symptoms, somnolence and fatigue according to menopausal status. METHODS: The female population of the Sao Paulo Epidemiologic Sleep Study (EPISONO) (n = 576) was divided according to menopausal status (pre-, peri-, early and late menopause) based on questionnaires and hormonal blood measures. The complaint of waking up because of a headache at least once a week was assessed by the UNIFESP Sleep questionnaire. Additionally, hot flushes, sleep complaints, anxiety and depressive symptoms, somnolence and fatigue were assessed by specific questionnaires. A full-night polysomnography assessed sleep parameters. RESULTS: The prevalence of NAH in women in the Sao Paulo population was 13.3%. Perimenopause was associated with a higher risk of having NAH (odds ratio 13.9; 95% confidence interval 4.3-45.2). More complaints of NAH were observed in obese women. All the groups with NAH showed more hot flushes, worse subjective sleep quality, more complaints of insomnia, anxiety symptoms and fatigue. CONCLUSIONS: We observed a constellation of symptoms in women according to menopausal status and NAH that included hot flushes, sleep complaints, more anxiety symptoms and fatigue. Moreover, some of these symptoms were more frequent in perimenopausal women with NAH. Therefore, we concluded that menopausal status influences NAH and the women in perimenopause presented a high risk of having this complaint.

Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery.

Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

Moderate exercise training modulates cytokine profile and sleep in elderly people.

Aging causes several physiological alterations, including alterations in sleep. It is possible that difficulty sleeping can be exacerbated by increased inflammation in older individuals. Moderate exercise training may be a modality of non-pharmacological treatment for sleep disorders and inflammation. We aimed to assess the effects of moderate exercise training on sleep in elderly people as well as their cytokine profiles. Additionally, we examined the effect of exercise training on quality of life parameters using a SF-36 questionnaire. Twenty-two male, sedentary, healthy, elderly volunteers performed moderate training for 60 min/day, 3 days/week for 24 week at a work rate equivalent to their ventilatory aerobic threshold. The environment was kept at a temperature of 23 ± 2°C, with a humidity of 60 ± 5%. Blood and polysomnograph were collected twice: at baseline (1 week before training began) and after 6 months of training. Training increased aerobic capacity parameters (p<0.0001), decreased REM latency (p<0.02), and decreased time awake (p<0.05). After training, the levels of IL-6 (p<0.0001) and TNF-α (p<0.0001) and the ratio of TNF-α/IL-10 (p<0.0001) were decreased, whereas IL-10 levels were increased after training (p<0.001). Furthermore, exercise training was shown to improve quality of life parameters. Our results suggest that 6 months of training can improve sleep in the elderly and is related to the anti-inflammatory effect of moderate training, which modifies cytokine profiles.