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Anna Ghizzani. Healthy Aging: Well-Being and Sexuality at Menopause and Beyond
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CHAPTER 2. Medical Aspects: Symptoms and Effects in Women. Vasomotor symptoms. Hot flashes, or flushing, are vasomotor symptoms that appear as an immediate response to a reduced level of estrogen in the bloodstream; since this reduction precedes the onset of the changes brought by the menstrual cycle, one or two isolated flashes may occur even when the cycle is still apparently regular. The intensity and frequency vary from woman to woman: for some, they are little more than an annoyance, while for others they represent a real problem, owing to the feelings of awkwardness that come with them. We should not overlook the effects of a hot flash when it comes “in public”, because the redness and sweating are embarrassing, and make evident a situation that one would prefer to keep private. When these occur in the middle of a working day, they limit the ability to concentrate, make one feel inadequate, produce anxiety, and end up interfering in one’s professional life and social relations. It seems that greater acceptance of hot flashes is associated with a positive mental outlook, good family relations, and general emotional well-being. They manifest with brief and sudden episodes of intense heat, located especially in the torso, the neck and the face, accompanied by redness and profuse sweating. Their occurrence is extremely varied; they may represent a fleeting phenomenon, or begin before changes in the cycle, and remain for many years. When symptoms are severe, it becomes necessary to intervene with medication, to lessen the frequency and intensity of the episodes, so as to improve the patient’s quality of social life, or else to allow them an adequate night’s sleep – something not to be underestimated! Hot flashes are caused by the reduction in estrogen, but they present most frequently when a person is going through a stressful time. However, findings from research studies observing patients from various different ethnic groups present us with differing realities. The symptoms of Chinese women are mainly tiredness, muscular pains, irritability, sleep disturbances, and muscular pains, which are also common among Japanese women, who, in turn, complain of memory loss and stress, but do not have hot flashes, instead reporting episodes of cold, which are another aspect of menopausal vasomotor instability. The incidence of hot flashes seems completely different in South American women; indeed, more than half report serious or very serious vasomotor symptoms. Other studies confirm that only 10–20% of Filippino women have hot flashes or episodes of night sweats, unlike 60–90% of women in Europe and the US. Initial observation suggests that ethnic variations cannot easily be explained, even if one takes into account high soya consumption among Asian women, as a protective factor. What do patients ask for? Requests for help for vasomotor symptoms (so difficult to accept) are very common in a gynecology clinic. Before resorting to medicine, it is right and proper for the patient to try to alleviate them with a lifestyle that pays attention to clothing, the environment, and nutrition. General advice valid for all women includes dressing in layers, so as to avoid feeling hot, lowering the temperature in the rooms where one lives, especially in the bedroom, getting mild but constant exercise, and avoiding spicy foods, wine, and cigarettes. It is important to maintain a suitable body weight, because overweight women are those who suffer most from these disturbances. Women who cannot resolve the problem often look to nutritional supplements for a solution. These include soya isoflavones and red clover, which have a bland estrogen action, while cimicifuga (actaea) racemosa (black cohosh) is a serotonin agonist, a substance that regulates the response of the nervous system. Low doses of new-generation antidepressants seem to work better than soya derivatives, but they can have unpleasant secondary effects on sexual behavior, because they slow down orgasm, and so they must be chosen on the basis of individual needs and preferences. Naturally, hormone replacement therapy (HRT), which we will discuss later on, represents the most effective intervention, but a family history of breast cancer and risk factors for cardiocirculatory diseases mean there are contraindications over its use, and it is right that a patient should try possible alternative solutions before resorting to hormonal preparations. Even though vasomotor symptoms do not harm the organism, they are truly irritating. However, the discomfort ultimately proves to be a welcome event, because it leads women to their doctor, giving them the opportunity to get advice about the real conditions, such as genital atrophy or osteoporosis, which must be tackled with preventive measures. Cardiovascular diseases. Cardiovascular pathologies, and in particular coronary disease, are the most frequent cause of death in women. The pathological mechanism is similar to that in men, but with a number of characteristics specific to the female gender, depending on the amount of estrogen3 in circulation, the reduction in which represents an important risk factor. This information is not taken on board by the public at large, and breast cancer, rather than cancer in any other organ, is the event most feared by middle-aged women. This fear is understandable if one thinks of the devastating impact that a cancer diagnosis has for a person, whatever organ is affected, and the special meaning that the breast has for any woman. However, it is not justified by the statistics. Indeed, a cardiovascular event is the most frequent cause of death in women (46% of cases), more than tumors, respiratory conditions, infectious diseases, cerebrovascular events and traumas. After the age of 50, causes of death in women are ischemic conditions, tumors, and neuromuscular degenerative diseases. Progress in the early diagnosis of tumors is improving the chances of survival, and increasing the incidence of ischemic conditions. Up until age 40, ischemic disease is less frequent in women, but after 50 it increases considerably, probably because with menopause one loses the protective effect of estrogen on the cardiovascular system. 3 Female sexual hormones produced by the ovarian follicles. The natural history of cardiac disease in women is different from that in men. Its first manifestation occurs with angina pectoris (chest pain caused by myocardial ischemia), instead of with a heart attack (65% and 35% respectively). The symptoms can remain less severe for years, and indeed women who suffer a heart attack are 7 or 8 years older than men. After the age of 64, hypertension is the most frequent cause of cardiac stroke. Smoking is also an important risk factor in determining coronary disease and atherosclerosis in women without other health problems. Obesity, diabetes, and an altered lipid profile are factors that worsen damage caused by hypertension and smoking. Obesity by itself does not represent a direct risk for cardiovascular disease, but it does cause metabolic conditions such as hypercholesterolemia, and it worsens hypertension, events which have knock-on effects, contributing to coronary damage. Oral contraceptives, such as the pill, only very rarely cause non-fatal heart attacks in women without other risk factors, but who are over the age of 40, or in younger women who are carriers of congenital heart disease, malign hypertension and cardiomyopathy. The most serious side effect caused by these drugs, is phlebothrombosis; for this reason, they are advised against in women with obesity and hypertension, or in women with an altered lipid profile4. 4 Johansson-Vedin-Wilhelmsson, Myocardial infarction in women in “Epidemiologic Reviews”, vol. 5, 1983, pp. 67–95. The association between cigarette smoking and coronary ischemic damage is, however, well known. Around 30% of deaths from heart attacks can be ascribed to smoking, which is the biggest independent risk factor that can be changed, both for men and for women, and it correlates directly to the number of cigarettes smoked. Smoking two packets a day increases the risk by 200% compared to a non-smoker, and when smoking is associated with other factors, such as hypertension, the overall risk becomes greater than the mathematical sum of the two components. The risk of developing coronary disease and atherosclerosis (namely damage to blood vessels) remains significant in women who are smokers without other relevant factors, but in this case, too, the synergic relationship of smoking associated with taking oral contraceptives increases the risk of ischemic disease tenfold, compared to women who do not smoke, and who do not take contraceptives5. 5 Centers for Disease Control, Smoking and cardiovascular disease, in “MMWR”, 1984, pp. 677–679. Differences between women and men. Cardiovascular disease is found to be the leading cause of death among women, despite the fact that it is extremely infrequent up until menopause. Ischemic damage, a heart attack, is between twice and four times as frequent in men than in women, but it is not clear what determines this difference; indeed, the higher incidence in men does not seem to be exclusively related to known risk factors (hypertension, body weight, diabetes, physical activity, and cholesterol levels). Indeed, if one looks at the problem from the point of view of the female gender, it seems that the low incidence of cardiocirculatory illness in pre-menopause ages can be put down to the protective effect that estrogen has on blood vessel function. Other female characteristics include a lower propensity to develop hypercholesterolemia and diabetes, together with less stiffening of the peripheral arteries; this latter condition is to be ascribed to the direct action of estrogens on the vascular system, in which they cause arterial vasodilation and relaxation of the vascular muscles, with a resultant lowering of blood pressure. Together with their action to combat atherosclerosis, these constitute a powerful protective effect against hypertension. The increased risk of cardiovascular disease in postmenopause may be due to hormonal changes and the aging process, although the relationship is not completely clear. In the same way, there is debate over the effect that replacement therapy in menopause has on the cardiocirculatory system, insofar as it has shown positive, negative and neutral effects in the course of many assessments. In any event, although the risk of cardiovascular disease in women increases with menopause, the greater susceptibility of men remains throughout their lives6. 6 Albrektsen, Heuch Løchen, Thelle, Wilsgaard, Njølstad, Bønaa, Lifelong gender gap in risk of incident myocardial infarction: The Tromsø study in “JAMA Internal Medicine”, vol. 176, 2016, pp. 1673–1679. Cardiovascular conditions in menopause. Age is the factor of most importance for cardiovascular health, and women past the age of 50 see a great increase in their risk, although a direct relationship between the menopausal state and the beginning of the condition has never been detected; by contrast, an increased metabolic risk for cardiovascular conditions is recognised in the case of women who arrive at menopause with a diabetic or hypertensive condition. Some findings suggest that there is a higher risk of thromboembolism if menopause sets in at an age above 52, or below 39, while an age of between 40 and 49 at the time of the last menstrual cycle seems to constitute a protective factor. During a woman’s fertile years, estrogen acts on blood coagulation and on the function of arterial vessels, increasing the factors that facilitate coagulation, and reducing the factors that oppose it; furthermore, they promote dilation of the peripheral vessels, thereby helping to control blood pressure. At menopause estrogen reduction and the mechanisms of aging alter this process. Aging influences the function of the arteries by means of the reduction of the vascular lumen, and the capacity to dilate in response to the estrogen stimulus. The loss of elasticity in the walls of the vessels is one component in the rise of blood pressure. The function of coronary arteries seems much better in young women than in men of the same age, and as much as twice as good as that in women in menopause, but differences are not found when one compares women in menopause with men of the same age. Hormone therapy and the cardiovascular system. In view of the protective role played by estrogens during the years of fertility, it has been supposed that taking them in menopause might reduce cardiovascular risk. It has been suggested that hormone replacement therapy might reduce mortality due to cardiovascular causes in postmenopausal women, and that it might have a beneficial effect on the lipid profile, on vasodilation, and on the integrity of the vascular wall, but the hoped-for benefit has not been confirmed. This is because estrogens given systemically increases the risk of thrombosis by acting on the activation of factors of coagulation, and on the greater production of thrombin. The use of estrogens taken through the skin (such as medicated patches) does not appear to be associated with an increase in haemostasis or coagulation, but neither does it offer benefits. Moreover, the scientific literature has not shown any positive effect from administering it with the aim of preventing or delaying a cardiovascular or cerebrovascular accident in women who have had episodes in the past. With the knowledge currently available, neither does it have benefits in the prevention of cardiovascular accidents in women without previous events7. 7 Whayne, Mukherjee, Women, the menopause, hormone replacement therapy and coronary heart disease in “Curr Opin Cardiol”, vol. 30, 2015, pp. 432–438. Given that hormone replacement therapy does not have known benefits in preventing cardiovascular risk, it may be used in a patient who has entered menopause only recently to alleviate vasomotor symptoms, and for the prevention of osteoporosis, if there are no risks of cardiovascular or thromboembolic disease, or of breast cancer. Osteoporosis. Osteoporosis means a weakening of the structure of bones, owing to the rarefaction of the medullary part, and, in my opinion, it is the most important issue to be addressed when a woman enters menopause. Let’s remember that this syndrome is called “the silent killer”, because it does not show itself until it is too late, at least as regards a treatment that has significant benefits, nor can it be prevented in advance. Unfortunately, manifestations of osteoporosis are always very harmful to a woman’s health, with disabling fractures of the femur, the wrists, and the spinal column that are almost always caused by very slight traumas, or even spontaneous ones; the disease is responsible for a permanent state of pain in the spinal column, and the cause of bone deformations and bad posture. The damage is so serious because the loss of bone matrix is not evident, and there is no way to detect it without carrying out a specific examination, a mineralometry, on a regular, repeated basis. If the problem goes unnoticed and is neglected, it is very likely that one will end up suffering from the aforementioned conditions. What is the natural history of the absorption of calcium in bones? Calcium is absorbed from foods and fixed in bones by means of sunlight activating vitamin D in the skin. In optimum conditions, when exposure to sunlight, calcium intake, and estrogens in the bloodstream are sufficient, calcium is fixed to the bone matrix in large quantities up until the age of 20; it continues to be fixed more weakly up until age 30, and thereafter we see the opposite phenomenon: from the age of 30 onwards, calcium content in bones falls at a constant and slow rate until the onset of menopause. Estrogens have a second positive effect on bone metabolism, inasmuch as it maintains the power – ie the capacity for work – of muscle mass, which is a further factor that promotes calcium absorption. When it comes to the functional limitations that a woman perceives as a sign of biological change, the first such involves the loss of muscle power, which in practical terms means that greater effort is needed to perform normal daily tasks; indeed, the extent to which muscle mass and strength are reduced determines how tiring tasks become that were once considered to be almost trivial. As well as diminishing the capacity for work, loss of muscle mass contributes to an associated loss of bone mass because it reduces the demands placed by muscles on the skeleton, which is a factor that encourages calcium absorption. The synergy between muscle work and maintaining bone mass is facilitated by testosterone, and represents one of the reasons why men fix more bone in their youth, and lose it less during aging, and are protected against osteoporosis. Unlike men, women start to lose muscle mass and strength around the age of 50, coinciding with menopause; the functional limitations described are accentuated as the years go by, with the biological phenomena of aging, and with the gradual reduction of steroids. Women who have had surgical menopause are those who suffer most from these phenomena because at the time of the removal of the ovaries, testosterone is suddenly reduced by 50%, making it hard for the biological systems to adapt to a change that, in natural menopause, occurs gradually over a period of many months. Let’s go back over some history: the cradle of mankind is in Africa, a land inundated with sun. Primitive man came into existence with particularly dark skin, which lets through the amount of sunlight necessary to activate the precursor of vitamin D, and at the same time protects against too much sun. Far back in time, man began to migrate towards northern lands, and dark skin represented an evolutionary disadvantage, because too much pigment did not allow the activation of vitamin D; without this, calcium is not fixed, and rickets sets in, with weak and deformed bones. The presence of a flat pelvis, which prevents a woman from giving birth, would have meant the extinction of the human race, had evolutionary mechanisms not determined an advantage in favour of people with pale skin, in which the low content of melanin does not block the sun’s action on vitamin D. In very northern regions, such as Canada, for six months of the year there is not enough sunlight to activate the forerunner of vitamin D, and to ensure good bone metabolism. The commonest foodstuffs, such as milk, have added vitamin D. But sun and vitamin D are not the only factors in bone metabolism. A significant role is also played by sexual hormones: estrogens (that characterize the female phenotype) and testosterone (which characterizes the male phenotype), which act on bone in different ways. Testosterone is the most powerful hormone in ensuring resistent and elastic bones, characteristics needed to be able to absorb shock, ie a trauma, without breaking. Resistence and elasticity are the features that oppose fractures, but testosterone also acts on muscle, promoting the development of muscle mass and the capacity for work (ie contraction) of muscle fibers. The two actions of testosterone, on bone and on muscle, accompany man throughout his life, including in old age, because there is no interruption in production, as happens with menopause. Even in cases of primitive or secondary hypogonadism, there remains at least some androgen production, and bone metabolism is retained; by contrast, in cases of castration of individuals guilty of sex crimes, the scientific literature reports a weakening of the skeleton. Estrogens have a completely different biological action: it acts on bone, but not on muscle, and is often produced on a reduced scale, owing to common conditions such as the removal of an ovary due to cysts, or in the course of a hysterectomy, or reduced production in post-menopause. This marks a crucial difference for the health of bones in women, and suggests that all possible attention should be paid to it. Let us now turn to the natural history of calcium absorption in bones in the presence of adequate amounts of the key factors: sun, calcium from food, and estrogens. In a woman’s lifespan, her evolution reflects variations in estrogens: up to the age of 20, there is maximum uptake, which continues to a lesser degree up until age 30, when the accumulated calcium starts to be slowly lost. During the menopausal transition, the amount of calcium that is lost increases suddenly, as a result of fluctuation in the estrogens in the bloodstream; when estrogen values stabilize, calcium loss from the bones also slows down, although it continues for the rest of one’s life. The metabolic reality is undeniable, and explains why elderly people are so susceptible to bone conditions which, as well as fractures from minimal traumas, also include posture-related deformities and instability, the prime cause of low back pain. What can we do to limit the damage of an event that the extension of the human lifespan makes increasingly serious and disabling? The first step is to safeguard what facilitates positive factors, ie exposure to the sun, albeit with the necessary precautions, together with a diet that includes milk and our wonderful cheeses, to ensure calcium intake, and adequate physical activity that makes demands on muscle and bone at the same time. With the transition of menopause, taking soya isoflavones (phytoestrogens) helps bones to fix calcium, combating, albeit blandly, its reduction in the organism. Much more effective is hormone replacement therapy, the role of which is widely acknowledged. Today people are still unused to thinking that physical exercise may provide so many benefits to bone metabolism and – something not to be overlooked! – that it helps cognitive functions. Race walking, or brisk walking, is the real great remedy, because the constant, regular movement encourages calcium absorption. When women arrive at menopause, they ought to devote an hour a day to brisk walking, without citing the excuse that “we’re always on the go”, because occasional walking does not have the same benefits! With a view to long-term prevention, one must remember that maximum calcium absorption occurs in the first 20 years of life, and thus it is advisable to begin regular physical activity right from adolescence, and keep it up throughout adulthood, in order to store up the largest possible reserves of calcium, to be made use of when it begins to run short. Hormonal effects on cerebral function. Sleep disorders. Sleep disorders are common, affecting around 30% of the adult population (male and female). Sufferers have difficulty in falling asleep, they wake up repeatedly during the night, or early in the morning, and they do not feel rested after having slept. This condition seems to be influenced by aging, alcohol or drug abuse, major life changes, depression, low socioeconomic status, health problems and the female gender8. 8 Nowakowski, Meers, Heimbach, Sleep and women’s health, in “Sleep Med. Res.”, vol. 4, 2013 pp. 1–22. The sleep cycle includes a phase of light sleep, a phase of deep sleep, and a short period called REM (rapid eye movement), which come one after the other, several times during the night. The greatest rest takes place in the phases of deep sleep, while REM sleep is connected to a positive mood and better brain function. This cyclical pattern changes with aging, when the phases of light sleep become dominant, losing the ability to provide rest. The difference between the sexes as regards sleep patterns and sleep quality is noted especially in the years of perimenopause. Sleep can be affected by a variety of disorders that derive from the socio-relational sphere, but men seem to transfer their problems to sleep a lot less than women do, including women in fertile years. Indeed, we know that young women who suffer from premenstrual syndrome have great difficulty in falling asleep, and also getting enough sleep; pregnant women also have difficulty in falling asleep, tend to wake up during the night, and remain dozy during the day; as pregnancy advances, the situation gets worse, especially if there is any anxiety or depression9. In menopause, sleep is influenced by changes in the hormonal balance, and also by more generic aging factors, such as changes in the circadian rhythms, one’s state of health, and unsuitable daily habits. In the distressing accounts that we hear from patients talking about their sleepless nights, there is probably also a touch of anxiety, and feelings linked to uneasiness over the symptom itself. Waking up during the night, which generally happens as a result of hot flashes, is very irritating, but the changes to the architecture of sleep, and losing hours of sleep, do not seem to be major events, in many cases. Insomnia represents a problem for 40–60% of women; in 26% of women in perimenopause, owing to difficulties in their daily and working life, with an obvious decline in their sense of well-being. The consequences of sleep are serious to health and mood, because they make patients more vulnerable emotionally and physically10. Metabolic stress makes vasomotor symptoms worse, and, in the long run, leads to hypertension, diabetes and depression. Nevertheless, it seems that women who develop insomnia in this period have been susceptible ever since their youth to everything that interferes with quality of sleep. In the general population, around 28–35% of young women have difficulties linked to sleep, and are 3.5 times more likely, compared to those who get a good night’s sleep, to develop a full-scale sleep disturbance, once they reach menopause11. According to many women’s experience, the quality of sleep gets worse during the transition to menopause, in other words in the years preceding and following the last menstruation. Alongside women in whom the characteristics of sleep go hand-in-hand with the appearance and worsening of hot flashes, there are patients for whom insomnia is the main disturbance, remaining constant over the years, while vasomotor symptoms are only mild, and transient. The typical picture of insomnia includes repeatedly waking up during the night at least three nights a week, although not all women are the same, and there is a lot of variability in the picture that we find. Those most affected not only wake up during the night, but also experience difficulty in getting to sleep, find themselves waking up too early, and experience more frequent hot flashes. 9 Polo-Kantola, Aukia, Karlsson H., Karlsson L., Paavonen, Sleep quality during pregnancy: associations with depressive and anxiety symptoms, in «”Acta Obstet. Gynecol. Scand.”, vol. 96, 2017, pp. 198–206. 10 Zaslavsky, LaCroix, Hale, Tindle, Shochat, Longitudinal changes in insomnia status and incidence of physical, emotional, or mixed impairment in postmenopausal women participating in the Women’s Health Initiative (WHI) study, in “Sleep Med.”, vol. 16, 2015, pp. 364–71. 11 Freeman, Sammel, Gross, Pien, Poor sleep in relation to natural menopause: A population based 14-year follow up of midlife women, in “Menopause”, vol. 22, 2015, pp. 719–26. Both the quality of sleep described by patients and its architecture, which can be traced from polysomnograms12, suggest that the causes of insomnia display an association between the effects of aging, such as instability of the circardian rhythms, and the effects of menopause, such as hot flashes, night sweats, and frequent awakenings. In women who are overweight, or actually obese, both in their fertile years and in menopause, the characteristics of sleep obtained with home polysomnography show that the distribution of abdominal fat, or the presence of the metabolic syndrome, were associated with high fragmentation of the circadian rhythms. By comparison with women in premenopause, those in postmenopause had less stability in their circadian rhythms, and greater anomalies in their sleep architecture.13. 12 Polysomnography is the recording of physiological parameters during the night. 13 Gomez-Santos, Saura, Lucas, Castell, Madrid, Garaulet, Menopausal status is associated with circadian- and sleep-related alterations, in “Menopause”, vol. 23, 2016, pp. 682–90. It can be hard for the doctor to work out the specific cause of insomnia in a female patient, because the subjective symptoms are a reflection of both vasomotor disorders and mood disturnaces. Hot flashes go hand-in-hand with waking up at night, with sleep that is not rest-giving, daytime sleepiness, and reduced functional capabilities, leading to scenarios that can largely overlap; but one revealing difference is that depression is marked by a difficulty in falling asleep, and by the fact of waking up too early, while hot flashes lead to waking up repeatedly during the night. Hormones and sleep disturbances. Although sleep disturbances are frequent events in women of all ages, and are part of the aging process, it is not yet clear whether, at menopause, their predominant causes are hormonal changes, vasomotor symptoms, anxiety or depressive traits, or altered breathing patterns. Estrogens and progesterone are associated with sleep disruption during reproductive life and pregnancy; the circadian rhythm of cortisol, known as the stress hormone, is related to awakening, as its secretion peak occurs in the early hours of the day14. In turn, ovarian steroid secretion is in synchrony with the circadian rhythm of sleep, while prolactin secretion is sleep-dependent. Polysomnography has shown that changes in sleep architecture occur during the phase preceding that of the menstrual cycle (known as the luteal phase), occurring hand-in-hand with a rise in body temperature. It is evident that ovarian steroids are involved in difficulties in sleeping in menopause which, in turn, correlate with hot flashes and sweating, which are a result of a decline in estrogen levels, in an interdependent circular relationship. We know that ovarian steroids are involved in the occurrence and resolution of breathing disorders, but the mechanism whereby they come into play in the overall process of insomnia is not yet known15. Melatonin takes part in the regulation of the sleep/wakefulness cycle, and its secretion by the pituitary is stimulated by the dimming of light intensity. With aging, the circadian rhythm of its secretion is reduced and changed, contributing to the onset of sleep disorders. The levels of melatonin decline particularly during menopause, but their influence on sleep is determined by individual characteristics. Indeed, melatonin secretion in response to the dimming of light remains essentially the same in postmenopausal women who do not have sleep problems, while its production is lower, and delayed by around fifty minutes, in a woman with a disorder. This would indicate that it is not menopause in itself that alters the melatonin cycle, but a genetic predisposition that is facilitated by the advent of menopause, but affecting only one section of the population. The circadian clock undergoes important changes during the lifespan of every individual, male or female. One example is the disruption of the sleep/wakefulness rhythms that occurs as one ages, rhythms connected to the reduced endogenous production of melatonin. This phenomenon is particularly evident during menopause, and affects all women. However, not all women suffer from it in the same way, because individual sensibility to biological processes is different. 14 Teran-Perez, Arana-Lechuga, Esqueda-Leon et alii, Hormones and sleep regulation, in “Mini Rev. Med. Chem.”, vol.12, 2012, pp. 1040–1048. 15 Epson, Purdie, Effects of sex steroids on sleep, in “Ann. Med.”, vol. 31, 1999, pp. 141–145. How can sleep disorders be dealt. with in women in menopause? Insomnia, as a passing, repeated event, strikes most women during menopause. For some, it is a completely new symptom, while for others it represents the worsening of a function that has always been compromised. Insomnia can be tackled in many ways, ranging from lifestyle changes to an array of medicines; naturally, each of these remedies will be more or less suited to one woman or another; in any event, behavioral interventions are often more effective than medicines, and represent the forefront of treatment; they ought to be administered first, always. Of course, even before thinking about how to treat a patient, it is necessary to know her medical history in order to take action on possible organic conditions involved in the onset of insomnia. These include chronic pain conditions, breathing disorders, incontinence, depression, and anxiety neurosis, which require specific forms of medical intervention. Behavioral therapy interventions specifically designed to foster sleep are regarded as the first-choice form of treatment, able to maintain good results in the long term, compared with medication, which acts immediately, but is addictive. Another advantage not to be underestimated is that these interventions can also be suggested to people who have concomitant conditions, both organic and psychiatric, although not so serious as to prevent normal daily activities. The suggested strategies include interventions in lifestyle, in the environment, and on behavior. When it comes to lifestyle changes that can be suggested, moderate physical activity has shown itself to be effective in improving the quality of sleep in sedentary people. Work programs of 2 to 4 hours a week, comprising activities such as yoga, aerobics, active walking and generic strengthening exercises, lead to a significant improvement, that can be appreciated by the patient in terms of an increased sense of well-being16. Attention to mealtimes and type of diet also has a certain importance: Not having heavy meals, avoiding coffee, and not drinking too much alcohol immediately before going to bed is a commonsense rule that everyone ought to observe, but it becomes more important in people whose sleep is particularly fragile. Other suggestions relate to the need to let go of the worries of the day, not working or watching television in bed, interrupting daily activities for something that is a good preparation for sleep (like an herbal infusion or a bath), choosing a dark room, far from outside noises and not too heated, but especially establishing a habit of going to sleep at a time in keeping with the rhythms of life, and strenuously sticking to these rituals. Obviously, activities incompatible with sleep, activities that increase mental excitement or muscular work, are to be avoided in these patients, while they might be completely neutral in people who do not suffer from insomnia. Intervening in one’s behavior requires a commitment to maintaining a strict time for going to bed, and an equally strict time for getting up, and not staying in bed beyond the agreed time, avoiding naps, and keeping an accurate diary for recording daily variations. Carefully compiling a diary is a commitment that the patient makes with herself to keep a watch on any “bending of the rules” in her behavior, and to record her progress. Negative thoughts, levels of attention and concerns over sleep can be noted down and discussed with the therapist. 16 Hartescu, Morgan, Stevinson, Increased physical activity improves sleep and mood outcomes in inactive people with insomnia: A randomized controlled trial, in “J. Sleep Res.”, vol. 24, 2015, pp. 526–534. Prescriptions are built around cognitive mechanisms: not staying in bed when awake serves to associate the bed only with sleeping time; relaxing activities interrupt worries over not being able to sleep and stimulate pleasant thoughts; getting out of bed (and trying again later) if one has not fallen asleep after half an hour serves to interrupt obsessive thoughts about not managing to sleep. The external contribution of hormones such as melatonin or estrogen and progesterone, in various combinations, is used in treating insomnia. Of these, probably the most effective and most often used treatment is based on ovarian steroids, acting on the phenomenon of broken nights and hot flashes, at one and the same time. Giving exogenous ovarian hormones seems most effective for reducing sleep disorders, using formulations in low doses that can be administered in various different ways. Taking estrogen improves quality of sleep, but it is not clear whether its mechanism of action acts directly on the architecture of sleep or on reducing hot flashes and regulating the breathing pattern17. 17 Moline, Brooch, Zak, Gross, Sleep in women across the life cycle from adulthood through menopause, in “Sleep Medicine Reviews”, vol. 7, 2003, pp 155–177. Despite its effectiveness, hormone replacement therapy is not suitable for all women. It has contraindications in patients with an increased risk of cancer, who have to be advised directly by their specialist about whether or not it is appropriate to take these drugs. It should be noted that the most important negative side effect that must be considered by every woman is that estrogens encourage blood coagulation and increase the risk of thrombosis, including oral contraceptives, and so patients with a personal predisposition or family history of episodes of thrombosis will have to consider other formulations. Melatonin has a positive influence on the sleep/wakefulness cycle. It makes one feel drowsy, and reduces the time it takes to fall asleep after lying down in bed in patients with insomnia. The drug reduces the number of times a patient wakes up at night, and, if need be, it can be used in association with hormonal medications. Moreover, it does not have side effects such as headaches or drowsiness, which are common in the case of many other drugs, and it seems suitable for prolonged use. Antidepressants in low doses are used to alleviate sleep disorders in women who do not have signs of depression (which, if present, would require a different pharmacological approach). Among the more recently formulated antidepressants, low doses seem equally effective in improving the quality of sleep after three months of treatment. The medical literature presents results that are not always uniform regarding the effectiveness of antidepressants, but their use may be considered in cases where other drugs are not advisable.18. 18 Attarian, Hachul, Guttuso, Phillips, Treatment of chronic insomnia disorder in menopause: Evaluation of literature, in “Menopause”, vol. 22, 2015, pp. 674–684. Sleeping pills (anxiolytics, sleep-inducing drugs, and sedatives) are drugs more suited for temporary use than ongoing use, since they may have side effects, and may cause drowsiness during the daytime, and an addiction that restricts their effectiveness. The best use of them is in treating a temporary episode of insomnia. What’s more, they may have side effects, and their sedative action does not seem specific for sleep disorder in. menopause.19. 19 Ibidem. Albeit with the necessary precaution in long-term prescription, sleeping pills have been used extensively since the 1950s by a huge number of patients, offering significant improvement in the quality of sleep, in terms of both reducing the time it takes to fall asleep and reducing broken sleep, and as an increase in the total number of hours slept; their most frequent side effect is residual drowsiness the following morning20. 20 Schroeck, Ford, Conway et alii, Review of safety and efficacy of sleep medicines in older adults, in “Clinical Therapeutics”, vol. 38, 2016, pp. 2340–2372. Acupuncture seems effective in the short term for treating insomnia linked to menopause. Ten-session cycles of acupuncture, carried out in the space of three weeks, have significantly improved the effectiveness of sleep in line with the parameters of the number of hours slept, and the fact the patient wakes up less often during the night. Acupuncture also seems effective in cases of intractable insomnia, especially resistent to every approach in traditional Western medicine21. 21 Fu, Zhao, Liu et alii, Acupuncture improves peri-menopausal insomnia: A randomized controlled trial, in “Sleep”, vol. 40, 2017. Li, Lu, Clinical observation on acupuncture treatment of intractable insomnia, in “Journal of Traditional Chinese Medicine”, vol. 30, 2010, pp. 21–22. Over-the-counter drugs. Valerian is an extract from two plants, Valeriana officinalis and Valeriana edulis, and it is available in various formulas that may contain different concentrations of the active principle. Studies of the effectiveness of valerian on sleep have shown uncertain or conflicting results, with minimal effectiveness of the formulation compared to a placebo; its side effects are also similar to a placebo, and there is no residual drowsiness. Despite the fact there are no studies that analyse the effects of taking it over a prolonged period, the lack of adverse effects means that the drug is considered in the case of older or more fragile patients. Mood changes, depression and anxiety. Depression, in its various stages of severity, is a widespread disorder affecting twice as many women as men; throughout one’s life, the chance of developing a major depressive disorder is 10 to 25% for women, and 5 to 12% in men. The first episode occurs around age 20, and recurrences are variable; in some cases, many months elapse from one episode to the next, in other cases two or three episodes are repeated soon after each other, and as one gets older the frequency tends to increase. Forty percent of patients who have had their first ever episode will have a recurrence within the year, and 50–60% of them should expect a further episode, with a 70% chance of having others in the years to follow. When a major depression occurs for the first time in adult life, it is often triggered by a severe psychosocial event, such as the death of a loved one, a diagnosis of a potentially fatal disease, or a divorce. Scientific studies suggest that stress has a role in precipitating the first or the second episode, but not subsequent ones. The disorder tends to run in the family, and is 1.5-3 times more frequent in the parents or children of people who are ill than in the general population, but it is not in relation with ethnic group, level of education, or socioeconomic status. In clinical settings, the word depression is often used in a general sense, to indicate a non-specific emotional disturbance, a downcast mood, and some difficulties in daily relationships, symptoms which are very different from the more severe condition of major depressive disorder. Depression and menopausal transition. At a time as fragile as menopausal transition, it may happen that many women display signs that suggest a state of depression: a greater tendency to get tired and irritable, and more difficulty in remaining active and maintaining concentration, along with changes in mood, appetite, and sleep patterns. Against this background, anxiety, which always accompanies depression, also increases: She becomes more worried over the things that need to be done, and family organization, and above all for loved ones. Specifically, episodes of unstable mood are relatively common, with a frequency from 2 to 14 times greater than in other moments, and with 75% of women developing hyperreactivity or hypersensibility to unfavorable psychosocial conditions.22. 22 Soares, Menopausal transition and depression: who is at risk and how to treat it?, in “Expert Rev Neurother”, vol. 7, 2007, pp. 1285–93. In the period of the perimenopause, psychcological distress manifests itself more frequently, and there is an increased risk of an initial episode of depression, or a recurrence of it. Why is this? The cause lies in the mutual influence of various different elements, which are all linked to mood changes. The hormonal balance of menopause, the ability to react to a difficulty, social support, lifestyle and the occurrence of a stressful event become interwoven with each other in a complex way, and the balance between them determines a person’s emotional well-being. Although we rarely find ourselves dealing with full-scale, clinical depression, one must be careful in correctly evaluating a patient’s distress, because differential diagnosis is not simple. Indeed, as many doctors know from firsthand experience, it can be difficult to grasp the clinical differences between a mood change that is a reaction to changes in the menopausal transition, that is set to resolve itself, and a state of anxiety or depression that is pre-existing, and intrinsic to the person, and that is accentuated by the pyschosocial stress in this period, and that risks being prolonged. Key symptoms such as an unstable mood, insomnia and difficulty in concentration are common to both conditions, which must be recognized, to make sure that an overlooked psychological condition does not become more serious. The awareness that in the last few years we have been seeing an increased incidence of the psychological condition acts as a spur for timely intervention by the doctor. Going by the statistics in the literature, it seems that 26–33% of women develop clinical symptoms of depression, and that full-blown depression strikes 12–23% of them. The association between menopause and psychopathology is a result, on the one hand, of physical stresses such as hot flashes and insomnia that alter the sleep pattern and cause discomfort, making it impossible to recoup energy; on the other hand, it is also a result of sources of psychosocial stress, such as retirement, financial hardship, and a decline in one’s physical capabilities. Some studies show that depression is more frequent during the menopausal transition than at any other time, regardless of insomnia, hot flashes or anything else. This seems especially true for women who have suffered from it previously; indeed, together with a family history, previous clinical experience of depression is the most important predictive factor; by the same token, it is unlikely that the first episode of major depression will be presented at this time, unless serious traumatizing events take place. Despite the fact that clinical observations do not always agree with each other, all studies show that vulnerability is manifested in the transition period, and not when menopause is stabilized23. 23 Freeman, Associations of depression with the transition to menopause, in “Menopause”, vol. 17, 2010, pp. 823–7. It is significant that mood changes are more frequent when there are concomitant events in reproductive life marked by specific hormonal changes, as in the pre-menstrual phase, in the post partum period, and at menopause. Pre-menstrual syndrome strikes 3–5% of women, and is characterized by a depressive trait, marked anxiety, an unstable mood, and a loss of interest that develops in the last part of the menstrual cycle, and which are repeated for several months in a row. The symptoms disappear at the start of menstruation, and do not present again until the days leading up to the following cycle. Postpartum depression is presented within four weeks after giving birth, with a frequency of 1 in every 500 to 1 in every 1,000 births, and preferentially affects women who have suffered depression, or who have a family history of the illness. The symptoms include especially an unstable mood, acute anxiety, uncontrollable crying and feelings of guilt, or a lack of interest in the newborn baby. A larger number of patients, around 20%, develop a pattern of anxiety in the absence of symptoms of full-scale depression. This can happen later on, within the first year after the baby’s birth, with symptoms such as apprehension, insomnia and irritability, which go beyond the normal stress of becoming a parent. The state can be serious enough to interfere with taking care of the baby, and such as to require medical intervention.24. 24 Toler, et Al., Screening for postpartum anxiety: A quality improvement project to promote the screening of women suffering in silence in “Midwifery”, vol. 62, 2018, pp. 161–170. Menopausal transition is marked by endocrine fluctuations, because the balance between the hormones in the bloodstream is altered. This series of events, occurring one after the other, represents a real source of irritation for the emotional vulnerability of patients who are predisposed toward it25. One should note that mood changes appear more accentuated the bigger the hormonal fluctuations, also when one compares people with a differing predisposition, constituting a stress for the cognitive processes, including short-term memory. By contrast, the phases of life in which hormonal production remains stable, although reduced, as happens in stabilized menopause, seem less susceptible to mood changes. 25 See note 20. Who is at risk? Irritability, pronounced self-criticism, and intolerance towards menopause are traits found in women most susceptible to depression. This period is marked by a rise in irritability, even when a suitable mood is maintained; deterioration of mental equilibrium is 2–4 times more frequent than in reproductive age, even among women who had never been anxious or depressed before, precisely because hormone fluctuations represent a factor of biological vulnerability that lowers the threshold of irritability, to the point of contributing to the onset of depression26. 26 Mauas, Kopala-Sibley, Zuroff, Depressive symptoms in the transition to menopause: The roles of irritability, personality vulnerability, and self-regulation, in “Arch Womens Ment Health”, vol. 17, 2014, pp. 279–289. Life events and previous experiences can lead to a risk of developing a deteriorated mood, albeit outside the limits of full-scale depression. Personal health problems, or relatives’ health problems, a loss of interest in work, and solitude play a negative role, while the ability to overcome unpleasant events, and a satisfying lifestyle, and the fact of having maintained one’s social role and network of relationships with friends and in one’s family (as happens with those women who, after leaving work, find themselves even busier than before, because they take care of their grandchildren) create a sense of well-being, contribute to personal gratification, and represent a factor of protection against psychological uneasiness. If growing old successfully means adding life to one’s years, and not just years to one’s life, which living standards and medical progress ensure we can enjoy, then maintaining gratifying interests is the key to defeating moodiness. How can it be treated? If hormone fluctuations are implicated in mood instability and in the development of depression, it is plausible that taking hormones may improve one’s mood more effectively than classical antidepressants.27. 27 Herrera, Hodis, Mack, Estradiol therapy after menopause mitigates effects of stress on cortisol and working memory, in “J. Clin. Endocrinol. Metab.”, vol. 102, 2017, pp. 4457–4466. Transdermic preparations, especially, seem the best for stabilizing concentrations of hormones, combating the onset of depressive traits, and even alleviating the symptoms of major depression. Metabolic changes. Metabolic syndrome is constituted by a set of clinical characteristics that include abdominal obesity, alterations in the lipid profile, hypertension and diabetes, conditions that are different, but interdependent. Together, these alter the state of health and make the patient more susceptible to cardiovascular disease. The appearance of the syndrome in women in reproductive age is favored by particular endocrine states, as during pregnancy, or altered, as in the case of polycystic ovary syndrome (PCOS). It arises at menopause as a response to reduced estrogens in the bloodstream. Hyperglycemia, hypertension, abdominal obesity and an altered lipid profile constitute risk factors for metabolic syndrome, which is diagnosed when three of these characteristics are present, and occurs with a frequency greater than 50% in women over the age of 56, whose blood pressure tends to increase with age, and in relation to the number of years since her last menstruation. Its appearance also reflects the tendency toward a sedentary lifestyle, which further promotes the accumulation of abdominal fat. It is more common in women than in men, and tends to increase as one gets older. Sex hormones regulate the deposit of fat in tissue by means of the activity of transport proteins. At menopause, the decline in estrogen reduces the availability of these proteins, increases the rate at which abdominal fat is deposited, and increases the propensity toward hyperglycemia, hypertension and altered lipid profile. Abdominal obesity affects around 72% of women after the age of 60, supports metabolic syndrome, and, in the sequence of related biochemical events it is the main cause of cardiocirculatory disease, the risk of which increases by 4 times at a distance of 10 years since the onset of menopause. Conditions that lead to the risk of the syndrome. Metabolic syndrome and obesity are interdependent, and together they can cause considerable health problems. In this connection, an alert comes from the WHO, which shows that the increase in weight in the world’s population is growing at an alarming rate. Currently 35% of adults (men and women) are overweight, and 11% are frankly obese. Body weight that is above limits determined by one’s constitution and age constitutes one of the most serious dangers to health, not least of which is a predisposition to metabolic syndrome. These undeniable facts direct our attention to healthier habits, not only based on a careful diet but also involving constant physical activity, the effectiveness of which is unquestioned in combating the onset of diabetes and cardiocirculatory conditions. Unfortunately, recommendations by themselves are not effective in changing people’s habits, and the remedies, however simple, are not easy to follow without professional help and support from the nearest social environment. A small group of women friends who support each other when they decide to change their eating habits, or a lady who finds empathy in her family to change her lifestyle, will have far greater chances of success than someone embarking on this change by herself. Possible factors leading to an early appearance of the syndrome. Metabolic syndrome originates from a reduction of estrogens in the bloodstream, linked to the age at which menopause arrives; in turn, this is determined by genetic factors and aspects of lifestyle, such as diet, smoking, socioeconomic conditions, the use of oral contraceptives, and the presence of chronic metabolic illnesses. It is not clear whether the age of menopause is also connected to conditions such as eating disorders, ovarian or cardiocirculatory conditions, and hypertension. Since it depends on estrogen reduction, metabolic syndrome is also presented in young women who entered early menopause for whatever reason, and it is important to be aware of this in order to intervene in time in health problems that would be unexpected in an age bracket younger than age 50. For younger women, medical conditions are exacerbated by a psychological state made fragile by the negative experience of untimely menopause. The medical conditions that contribute in bringing forward menopause are:
