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ABSTRACT PRESENTATO al CONGRESSO INTERNAZIONALE dell'INTERNATIONAL MENOPAUSE SOCIETY-ROMA GOUGNO 2011 ed AL CONGRESSO ANTIAGING AL FEMMINILE DI ROMA NOV.2012-


   Dott. ASCANIO POLIMENI 
Spec.Neuroendocrinology,Chronobiology,
Codirector of ‘’Regenera Research Group’’ (www.regeneragroup.com)
 
MENOPAUSE,SLEEP DISORDERS,AGING and AGING RELATED DISEASES.
 
Complaints of sleep disturbance are more prevalent among women than men across the entire life span. Among women, the prevalence of insomnia rises sharply by approximately 40% during the period of transition to menopause and after menopause.Therefore, it is not surprising that menopausal women are more likely to take hypnotic medications than younger women or men (National Sleep Foundation Women and Sleep Poll, 1998).
Exploring he neuroendocrineimmune imbalancement of sleep disorders of menopausal period.
 Four sets of sleep disorders are associated with menopause:insomnia/depression, sleep disordered breathing(SDB),restless leg syndrome and fibromyalgia. These are promoted by the deep and integrated neuroimmunendocrine imbalancement that is a key factor in perimenopause,menopause and postmenopause related disorders.Many hormones are produced during sleep; melatonin, growth hormone,leptin, ghrelin are released mainly during the first part of the night, while during the second part of the night are produced wake up hormones like CRH-ACTH-cortisol and thyroid hormones.Viceversa, there are many hormones that affect various stages of sleep and wakefulness in different ways such as sex hormones, prolactin,galanin , NPY, oxytocin, vasopressin, thyroid hormones melatonin, GH and cortisol. As woman ages , the secretion of hormones is altered. Around or during menopause, women’s estrogen levels decrease and hot flashes occur. As a result, skin temperature rises and women may experience increased heart rates and sweating that disrupts sleep. Also the lack of progesterone the hormone that enhances sleep acting on Gaba system is involved in the promotion of sleep disorders while testosterone and Dhea deficiency is related to REM phase  flattening.A key sleep-promoting hormone, melatonin, is often released in the evening during darkness. As we age, we may not produce as much melatonin, and this makes it more difficult to fall asleep and promotes distruption of sleep architecture. We release less growth hormone, which normally is secreted during deep sleep and is particularly important to our muscles and tissue repair. The release of cortisol, that normally helps us become alert in the morning hours, increases in the evening around the 5th decade of life.This evening production  of cortisol  is  also associated to the nocturnal increase of adrenaline and noradrenaline release that distrupts sleep promoting night awakenings and hot flashes.This endocrinological disharmony is concomitant with imbalancement between excitatory (glutamate,epinephrine,norepinephrine,dopamine,pea) and inhibitory neurotransmitters(gaba,glycine,taurine,serotonin) that characterizes menopausal transition.The disharmony of cytokines (th1-th2   immune branches imbalancement) is an other feature of sleep disorders and is the main factor in the pathogenesis of sonnolence and fatigue during day,inability to perform well during the day and inflammaging related diseases.In addition, the physical changes associated with chronic medical conditions such as arthritis and other musculoskeletal problems, gastrointestinal problems such as heartburn and any pain add to the litany of sleep disruptions that can occur as we age. Medications taken for the symptoms of these conditions may also lead to difficulties sleeping. Aging women like men  are also more sensitive to environmental factors, particularly if they have more light sleep. While noise, light and temperature may have minimally  effects affecting  us as young adults, these factors have a greater impact on our sleep, causing arousals and further disruptions as we age.
The role of sleep in aging and aging related diseases.
We know that sleep plays a vital role in our health and  well being like that exerted by nutrition,stress controll ,physical activity etc. and  many published studies have proved that the quantity and  quality of sleep is  related to the quality and  expectancy of life.Sleep exerts different functions,the most important are: energy conservation, the consolidation of memory,hormonal and immune systems regulation and body-mind restoration. The primary predictor of disturbed sleep architecture in menopausal age  is the presence of vasomotor symptoms. This subset of women has lower sleep efficiency and more sleep complaints. The same group is at higher risk of insomnia and depression.Sleep disordered breathing (SDB) increases markedly at menopause for reasons that include both weight gain and unclear hormonal mechanisms. A recent analysis of the Wisconsin Sleep Cohort data showed that menopause was an independent risk factor for sleep apnea-hypopnea. Fibromyalgia has gender, age and probably hormonal associations. Sleep complaints are almost universal in FM. We know today that,  sleep disorders are cofactors  of many age-related diseases and increase the risk of mortality for various causes.Among the diseases promoted by insomnia and by other sleep disorders, are reported obesity, diabetes, cardiovascular disease and metabolic syndrome.Sleep disturbances that characterize the  peri,menopause and postmenopause period would also be an important cofactor of cognitive and mood disorders of varios degree, of immunosenescence, inflammaging and cancer.Several studies have proved that chronic insomnia and other sleep disorders can promote an increased risk of mortality for cardiovascular disease in menopause and postmenopause women. Consideration of the many potential causes of insomnia and specific therapeutic approaches provides an excellent opportunity to improve health and quality of life in women during menopausal age who are affected by sleep disturbances.
Evaluation of Insomnia in Perimenopausal ,Menopausal and Postmenopausal Patients
The recognition that the etiology of insomnia is often multifactorial rather than attributing sleep problems only to the absence of estrogen, is key to the evaluation and subsequent treatment of "menopausal insomnia." Hot flashes, medical disorders, medications, mood disorders, other sleep disorders, and lifestyle factors should be considered. In addition to the patient's own sleep habits, it is important to inquire about the bed partner's snoring or movements during sleep that can disturb the patient's sleep. Key questions in the history can help uncover these causes and conditions.When obtaining a history, all patients should be asked the following questions: Do you have difficulty falling or staying asleep, and are you excessively sleepy during the day? If the answer is "yes," then a more careful history can be investigated regarding hot flashes, depression, anxiety, pain, medications, sleep environment, snoring (herself and partner), and symptoms of restless legs (such as uncomfortable sensations in the limbs at rest and/or leg kicks during sleep). For patients with hot flashes, in addition to the assessment of menopause, night sweats due to metabolic disorders, such diabetes mellitus and thyroid dysfunction, should be considered in the differential diagnosis. A sleep diary during a 2-week period can provide a more detailed assessment of sleep and wake behavior. When sleep apnea, restless legs syndrome, or periodic leg movements of sleep are suspected, an overnight sleep study (polysomnogram) is a useful diagnostic tool.
Managing Insomnia in Perimenopausal,Menopausal and  and Postmenopausal Patients
Successful management often requires a comprehensive approach that addresses neuro-hormonal- immune related changes in sleep, hot flashes, poor sleep habits, disruptive environmental factors, stress management, underlying medical and psychiatric conditions, and sleep disorders (such as primary insomnia, restless legs syndrome, and sleep apnea).General informations about safe sleep habits are suggested in this lecture and about the treatment of the neuroendocrine imbalancement that characterizes menopausal sleep disorders.
The use of safe bioidentical hormones replacement therapy and of supplements and herbs as alternative to benzodiazepines is in particular suggested.For patients with restless legs syndrome, following evaluation for possible causes, such as iron deficiency, diabetes mellitus, or thyroid disease, dopamine agonist medications are effective and are preferred to the benzodiazepine medications. For patients with sleep apnea, the most commonly used medical treatment is nasal continuous positive pressure.
To conclude we can say that,sleep disturbances, disharmony of circadian rhythms, in particular those of meurotransmitters, hormones and of cytokines that characterize  pre,menopausal and post menopausal age,should be considered as an important biomarker of unsuccessfull aging and of decreased life expectancy .
Treating them in a safe way, is one of the  strategies in the promotion of health, wellness and of successful aging. 
 
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06 Novembre 2012