The impact of hormones on menopausal sexuality: a literature review

Menopause is associated with physiological and psychological changes that influence sexuality. During menopause, the primary biological change is a decrease in circulating estrogen levels. Estrogen deficiency initially accounts for altered bleeding and diminished vaginal lubrication. Continual estrogen loss often leads to numerous signs and symptoms, including changes in the vascular and urogenital systems. Alterations in mood, sleep, and cognitive functioning are common as well. These changes may contribute to lower self-esteem, poorer self-image, and diminished sexual responsiveness and sexual desire. Other important nonhormonal factors that affect sexuality are health status and current medications, changes in or dissatisfaction with the partner relationship, social status, and cultural attitudes toward older women. The problems in sexual functioning related to estrogen deficiency can be treated with hormone therapy that includes estrogens alone and estrogens combined with androgens. Vaginal lubricants and moisturizers also may be useful in ameliorating postmenopausal sexual complaints. This article reviews the literature on the impact of menopausal estrogen loss on sexuality and on the effect of hormone therapy on sexual function during menopause.     

Stress, immunity and illness--a review

Psychological factors have long been thought to play a contributing role in either the predisposition, onset or course of various physical illnesses. Recently, rapid advances in immunology have created interest in the interaction between psychosocial factors, behaviour and the immune system. This paper reviews some of the models proposed to explain the relationship between psychological variables and physical illness and presents evidence for a contribution of psychological factors to certain illnesses in which abnormalities in immunologic state are thought to be important. From a somewhat different perspective, animal studies have demonstrated complex effects of stress, on disease susceptibility. Recent human studies have demonstrated consistent immunologic changes in people undergoing acute naturally occurring psychological stress such as bereavement or an important examination. In humans, the effects of chronic stress may be different from acute stress, corresponding to the findings in animals. Abnormalities in immunologic functioning and physical illness are reviewed for different psychiatric disorders--depression, anorexia nervosa and schizophrenia; depression is the only disorder which consistently demonstrated immunologic changes. Possible mechanisms for the stress/immune-change relationship are suggested.     

Relations of caregiving stress and health depend on the health indicators used and gender

Extensive research has evaluated relations between stress and health. These studies have varied in the type of stress examined (acute vs. chronic) and in the way in which health has been operationalized. Here we examine relations between chronic stress and 25 indicators of various health dimensions (e.g., physiological indexes, medical records, and self-reports of global health; symptoms, functional status, health service utilization, and psychosocial distress/quality of life). We also assessed whether such relations are moderated by gender, an individual difference variable that is important to health and longevity. Samples included 157 community-residing older adults (M age = 69.4 years, 31.8% men), approximately half of whom were caregivers for a spouse with Alzheimer’s disease, and half were demographically similar noncaregiver spouses. Principal component analyses on the 25 health measures resulted in 5 factors that met standard criteria for acceptance. In women, caregivers reported worse physical health and psychological health than noncaregivers, but their physiological risk was similar. In men, caregivers had greater physiological risk, but they reported better physical health than did men noncaregivers. Researchers who study chronic stress and health should consider the possibility that the relation between chronic stress and health may vary for men and women depending on the type of health being assessed.     

Experience-dependent plasticity in hypocretin/orexin neurones: re-setting arousal threshold

The neuropeptide hypocretin is synthesized exclusively in the lateral hypothalamus and participates in many brain functions critical for animal survival, particularly in the promotion and maintenance of arousal in animals – a core process in animal behaviours. Consistent with its arousal-promoting role in animals, the neurones synthesizing hypocretin receive extensive innervations encoding physiological, psychological and environmental cues and send final outputs to key arousal-promoting brain areas. The activity in hypocretin neurones fluctuates and correlates with the behavioural state of animals and intensive activity has been detected in hypocretin neurones during wakefulness, foraging for food and craving for addictive drugs. Therefore, it is likely that hypocretin neurones undergo experience-dependent changes resulting from intensive activations by stimuli encoding changes in the internal and external environments. This review summarizes the most recent evidence supporting experience-dependent plasticity in hypocretin neurones. Current data suggest that nutritional and behavioural factors lead to synaptic plasticity and re-organization of synaptic architecture in hypocretin neurones. This may be the substrate of enhanced levels of arousal resulting from behavioural changes in animals and may help to explain the mechanisms underlying the changes in arousal levels induced by physiological, psychological and environmental factors.     

Corticotropin-releasing hormone receptor type 1-deficiency enhances hippocampal serotonergic neurotransmission: an in vivo microdialysis study in mutant mice.

Corticotropin-releasing hormone plays an important role in the coordination of various responses to stress. Previous research has implicated both corticotropin-releasing hormone and the serotonergic system as causative factors in the development and course of stress-related psychiatric disorders such as major depression. To delineate the role of the corticotropin-releasing hormone receptor type 1 (CRH-R1) in the interactions between corticotropin-releasing hormone and serotonergic neurotransmission, in vivo microdialysis was performed in CRH-R1-deficient mice under basal (home cage) and stress (forced swimming) conditions. Hippocampal dialysates were used to measure extracellular levels of serotonin and its metabolite 5-hydroxyindoleacetic acid, and free corticosterone levels to monitor the status of the hypothalamic-pituitary-adrenocortical axis. Moreover, behavioural activity was assessed by visual observation and a scoring paradigm.Both wild-type and heterozygous mutant mice showed a clear diurnal rhythm in free corticosterone. Free corticosterone concentrations were, however, lower in heterozygous mutant mice than in wild-type animals and undetectable in homozygous CRH-R1-deficient mice. Homozygous CRH-R1-deficient mice showed enhanced hippocampal levels of 5-hydroxyindoleacetic acid but not of serotonin during the light and the dark phase of the diurnal cycle, which may point to an enhanced synthesis of serotonin in the raphe-hippocampal system. Moreover, the mutation resulted in higher behavioural activity in the home cage during the light but not during the dark period. Forced swimming caused a rise in hippocampal serotonin followed by a further increase after the end of the stress paradigm in all genotypes. Homozygous and heterozygous mutant mice showed, however, a significantly amplified serotonin response to the forced swimming as compared to wild-type control animals.We conclude that CRH-R1-deficiency results in reduced hypothalamic-pituitary-adrenocortical axis activity, in enhanced synthesis of serotonin during basal conditions, and in an augmented response in extracellular levels of serotonin to stress. These data provide further evidence for the intricate relationship between corticotropin-releasing hormone and serotonin and the important role of the CRH-R1 herein.     

Psychological factors in surgical stress: Implications for management

To regard surgery as an instance of psychological stress can provide a framework for integrating knowledge about psychological and physiological processes in recovery. Within this broad framework this review considers three issues. First, different measures of recovery, including indexes of emotional state, pain, or physiological changes, do not covary. Whereas some of these measures are clinically ambiguous, others, such as hormonal changes, may provide both clinically and theoretically important indexes of the impact of surgery. Second, the importance of psychological factors in recovery remains unclear, partly because of discrepancies between results with physiological and psychological measures. Third, psychological management of surgical stress has been used to change preoperative emotional state or mode of coping. The evidence is, however, ambiguous as to whether effects are beneficial or even harmful. Moreover, the mechanisms that mediate the effects of these procedures remain unclear. An alternative, but less explored, strategy is to target, not the patient, but features of the surgical ward likely to influence the response to stress. These include deficits in social support and restriction of the opportunity for active coping. Psychological procedures must, however, be carefully evaluated for their physiological and psychological effects before being adopted routinely.     

Stress and changing lifestyles in the Pacific: Physiological stress responses of Samoans in rural and urban settings

The lifestyles and social environments of Pacific Islanders have changed profoundly as a result of local development and migration to urban, cosmopolitan centers. These changes have often been accompanied by an increase in chronic diseases, alcoholism, and suicide. As a result, the health effects of psychological and physiological stress have become an increasing concern in Pacific Island nations and in countries with significant Pacific migrant communities. Several studies in the Samoan Studies Project have examined catecholamine excretion rates in order to understand how the behavioral, psychological, and environmental changes of modernization affect the physiological stress responses of young Samoan adults. The results of studies in rural and urban Western Samoa, American Samoa, and Honolulu, Hawaii show that several complex factors associated with urban, more cosmopolitan lifestyles tend to increase stress hormone levels. Specifically, lifestyle differences in physical activity, diet, and social interaction have significant independent and interactive contributions. These behavioral factors can lead to a high degree of day-to-day variability in catecholamine excretion. The implications of these findings for future research designs are discussed. However, the data suggest that it is a complex interaction of lifestyle factors, not any specific single factor, that determines the physiological stress responses of Samoans in different environments. © 1993 Wiley-Liss, Inc.     

Existing and Training Induced Differences in Aerobic Fitness: Their Relationship to Physiological Response Patterns During Different Types of Stress

Aerobic fitness has been associated with various desirable psychological and physiological characteristies. Recently, attenuation of physiological reactivity during stressful situations was added to this list, although comparison of the stress responses of sportsmen and sedentary subjects has yielded equivocal results. The present study examined cardiovascular patterns rather than single variables, and tried to clarify these matters. Tasks were used that were known to increase blood pressure through different combinations of changes in cardiac output and vascular resistance. Autonomic nervous system dynamics underlying these response patterns were studied using preejection period as an index of β-adrenergic activity, and respiratory sinus arrhythmia as an index of vagal activity. Pre-existing differences in aerobic fitness in a sample of sedentary subjects were related to their responses during the stressful tasks and the recovery periods afterwards. This approach prevented confounding of the relationship between fitness and stress-reactivity with the psychological effects of regular exercise. Furthermore, it excluded the bias in psychological makeup that is introduced when subjects spontaneously engaged in sports are compared to non-exercising persons. To rule out a third (hereditary?) factor underlying both stress-reactivity and fitness, physiological responses before and after a seven-week training program were compared to those of subjects in a waiting list control group. Substantial individual differences in aerobic fitness were found in spite of the fact that all subjects reported low levels of habitual activity. During two active coping tasks, diastolic blood pressure reactivity and vagal withdrawal were negatively related to these pre-existing differences in fitness. No such relation was seen during a cold pressor test or during recovery from the tasks. Neither β-adrenergic cardiac reactivity nor heart rate responses were related to fitness, but the absolute heart rate during the tasks was lower in the more fit subjects. Seven weeks of training were not effective in changing either reactivity or recovery of any of the variables. The discrepancy between cross-sectional and longitudinal results in the present study suggests that training of longer duration is necessary to induce the psychological or physiological changes underlying reduced reactivity. The latter may include changes in cardiac vagal/sympathetic balance or in adrenoceptor sensitivity. Alternatively, both psychological and physiological determinants of stress-reactivity may be related to aerobic fitness at a dispositional level.     

Frailty in older women

It is a truth universally acknowledged that although men tend to have better health in old age, women live longer lives. Here, we briefly review the biological, social and behavioural factors that may contribute to women's greater longevity. We consider in particular factors that might result in a greater frailty burden in women, focusing on frailty being measured by a Frailty Index. The Frailty Index represents the burden of health deficits, expressed for an individual as the proportion of deficits present - from 0 (no deficits) to 1.0 (the theoretical maximum, if all deficits were expressed). A greater frailty burden in women might first represent a male "fitness-frailty pleiotropy", resulting in men having lower physiological reserves in old age so that health deficits are more lethal. In short, the price of more optimal physiological functioning during youth is a lower threshold for system failure in old age. Conversely, a female "fertility-frailty pleiotropy" might result in greater physiological reserves in women. Child birth and child rearing necessitate high levels of energetic and nutritional investment: women who have children live shorter lives. Women currently are limiting the number of children they bear and their life expectancies may be longer than predicted by evolutionary design. Third, though the Frailty Index captures physical, cognitive and psychological vulnerability, it may not include all factors that impact life expectancy in older people; these factors may be present more in men than in women. While these hypotheses seek to explain how frailty impacts men and women in different ways, there is clearly much to be done to understand frailty in older people.     

Exercise and the immune system: regulation, integration, and adaptation

Stress-induced immunological reactions to exercise have stimulated much research into stress immunology and neuroimmunology. It is suggested that exercise can be employed as a model of temporary immunosuppression that occurs after severe physical stress. The exercise-stress model can be easily manipulated experimentally and allows for the study of interactions between the nervous, the endocrine, and the immune systems. This review focuses on mechanisms underlying exercise-induced immune changes such as neuroendocrinological factors including catecholamines, growth hormone, cortisol, beta-endorphin, and sex steroids. The contribution of a metabolic link between skeletal muscles and the lymphoid system is also reviewed. The mechanisms of exercise-associated muscle damage and the initiation of the inflammatory cytokine cascade are discussed. Given that exercise modulates the immune system in healthy individuals, considerations of the clinical ramifications of exercise in the prevention of diseases for which the immune system has a role is of importance. Accordingly, drawing on the experimental, clinical, and epidemiological literature, we address the interactions between exercise and infectious diseases as well as exercise and neoplasia within the context of both aging and nutrition.     

Hormonal replacement therapy and the skeletal system

The two most important risk factors for maintaining skeletal health are the bone mass obtained at skeletal maturity (peak bone mass) and the subsequent bone loss. Those women with a low peak bone mass and a rapid bone loss are thus at increased risk of developing osteoporosis in the future, and should be identified. This may be accomplished by determination of the bone mass combined with an estimate of the rate of the postmenopausal bone loss. The bone mass can be accurately assessed in the forearm by single photon absorptiometry. The postmenopausal bone loss can be estimated by three or four biochemical markers of bone turnover. The women at highest risk of developing osteoporosis should be offered preventive therapy, e.g., hormonal replacement therapy (HRT). HRT arrests the bone loss not only in early, but also in elderly postmenopausal women. The effect lasts as long as the therapy is continued. Several epidemiological studies have demonstrated that HRT decreases the number of osteoporotic fractures.     

Relationship among plasma cortisol, catecholamines, neuropeptide Y, and human performance during exposure to uncontrollable stress

OBJECTIVE: Although many people are exposed to trauma, only some individuals develop posttraumatic stress disorder; most do not. It is possible that humans differ in the degree to which stress induces neurobiological perturbations of their threat response systems, which may result in a differential capacity to cope with aversive experiences. This study explored the idea that differences in the neurobiological responses of individuals exposed to threat are significantly related to psychological and behavioral indices. METHODS: Individual differences in neurohormonal, psychological, and performance indices among 44 healthy subjects enrolled in US Army survival school were investigated. Subjects were examined before, during, and after exposure to uncontrollable stress. RESULTS: Stress-induced release of cortisol, neuropeptide Y, and norepinephrine were positively correlated; cortisol release during stress accounted for 42% of the variance in neuropeptide Y release during stress. Cortisol also accounted for 22% of the variance in psychological symptoms of dissociation and 31% of the variance in military performance during stress. CONCLUSIONS: Because dissociation, abnormalities in the hypothalamic-pituitary-adrenocortical axis, and catecholamine functioning have all been implicated in the development of stress disorders such as posttraumatic stress disorder, these data suggest that some biological differences may exist before index trauma exposure and before the development of stress-related illness. The data also imply a relationship among specific neurobiological factors and psychological dissociation. In addition, the data provide clues about the way in which individuals' psychobiological responses to threat differ from one another.     

Inflammaging: The driving force in osteoporosis?

With advancing age, the balance between the amounts of old bone removed and new bone formed during the remodelling process becomes negative. In the past, it was commonly thought that skeletal involution was the result of age-related changes in other organs, and in particular from the decline in ovarian function in women at menopause. Nonetheless, with regard to emerging epidemiologic studies, the hypothesis suggesting that age-related changes such as inflammatory modifications importantly account for age-related bone loss is gaining increasing interest. Aging is indeed associated with immune dysfunction that coexists with a chronic subclinical inflammatory status. The latter is illustrated by a 2-4-fold increase in the levels C-reactive protein (CRP) or interleukin (IL)-6. This inflammatory status, which has been referred to by the neologism "inflammaging", is of sufficient magnitude to impact health and survival time, and correlates with age-related diseases such as atherosclerosis, insulin resistance and Alzheimer's disease. In this article, we first present the factors that condition inflammaging, and propose the hypothesis that inflammaging may be the driving force in age-related bone loss and may even be responsible for osteoporosis due to estrogen deficiency. Finally, we discuss the possibility that pro-inflammatory biomarkers may be used to provide clinical information for identifying patients at risk for osteoporosis, and the possibility that inflammatory cytokines may be targeted to improve bone formation in aged patients undergoing orthopaedic surgery.     

Lipids in psychological research: the last decade.

We review the recent literature examining lipid changes during stressful experiences, and the psychological and constitutional differences that influence lipid levels at rest and that may modulate lipid response to stress. Mild forms of chronic or episodic stress are apparently not associated with alterations in lipids and lipoproteins, but severe forms of real or perceived stress do appear to alter lipid levels. Acute laboratory stress is frequently associated with short-term alterations in lipids and lipoproteins, but the significance of these changes is unclear. Several individual characteristics, such as heightened neuroendocrine or autonomic reactivity to stressors, Type A component behavior, and other aspects of personality, appear to be associated with an atherogenic lipid profile. Stress may influence lipid concentrations and metabolism through a variety of physiological and behavioral mechanisms, but none have been clearly elucidated. Future research should concentrate on understanding these mechanisms.     

Individual differences and the stress response

Amid the deleterious consequences of prolonged stress, there is tremendous variability in how readily various stressors provoke stress responses in different individuals. This review covers some of the underpinnings of such differences, heavily emphasizing adrenocortical secretion of glucocorticoids during stress, and responsiveness to psychological, rather than physical stressors. Psychological stress is shown to involve loss of control or of predictability, an absence of outlets for frustration, an absence of social support, and a perception of events worsening; some powerful studies show that the physiological and pathophysiological responses to identical physical stressors will vary dramatically as a result of manipulating some of those psychological variables. Those findings are then used to interpret a literature concerning differences in the stress response among individuals of different ranks among a variety of social animal species. In a broad manner, social dominance in a stable hierarchy, with its attendant psychological rewards, is associated with a more adaptive stress response, as measured by a number of physiological endpoints. However, considerable subtleties in this relationship exist, transcending the mere issue of rank. Instead, rank and its physiological correlates are sensitive to the society in which the rank occurs, the individual's experience of both that rank and that society, and personality factors that color the perception of external events. Finally, these primate studies are used to interpret data in the health psychology field concerning individual differences and coping mechanisms in humans.     

Nociceptin/orphanin FQ regulates neuroendocrine function of the limbic-hypothalamic-pituitary-adrenal axis

We examined the effects of the neuropeptide nociceptin/orphanin FQ on activity of the limbic-hypothalamic-pituitary-adrenal axis (also known as the stress axis) in rats. This axis regulates important metabolic functions, and initiates critical neuroendocrine responses that cope with environmental threats and challenges to homeostatic functioning. Disregulation of the limbic-hypothalamic-pituitary-adrenal axis is associated with impaired physical and psychological health. In the present experiments, rats were treated with intracerebroventricular injections of nociceptin/orphanin FQ in the presence or absence of acute stressors. Plasma adrenocorticotrophic hormone and corticosterone concentrations were assayed 15 or 30min after injections. In the rats that were not exposed to stress, nociceptin/orphanin FQ produced dose-orderly elevations of circulating adrenocorticotrophic hormone and corticosterone concentrations. These effects were also found after administration of the nociceptin/orphanin FQ analogues, des-Phe orphanin FQ and [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin((1-13))NH(2). In rats that were exposed to the mild stress of a novel environment, nociceptin/orphanin FQ administration enhanced the stress-induced elevations of plasma adrenocorticotrophic hormone concentrations and prolonged the stress-induced elevations of plasma corticosterone concentrations. In rats that were exposed to restraint stress, nociceptin/orphanin FQ administration did not augment the stress-induced elevations in plasma hormones, perhaps because of a ceiling effect. We conclude that administration of nociceptin/orphanin FQ activates neuroendocrine activity of the limbic-hypothalamic-pituitary-adrenal axis even in the absence of a stressor, and may delay the shutdown of these physiological responses after exposure to acute mild stress. In light of the known functions of this axis, it appears that nociceptin/orphanin FQ participates in the regulation of important metabolic functions, and may be implicated in physiological responses to stress. This interaction between nociceptin/orphanin FQ and the limbic-hypothalamic-pituitary-adrenal axis implicates nociceptin/orphanin FQ in important aspects of physiological and psychological well-being.     

Effects of maternal prenatal stress on offspring development: a commentary

Pregnancy is associated with major physiological changes and adaptation to these changes is crucial for normal fetal development. Heightened emotional stress during pregnancy may interfere with the necessary adaptation and lead to dysregulation of the two major stress response systems: the Hypothalamic-Pituitary-Adrenal (HPA) Axis and the Autonomic Nervous System (ANS). Negative effects on the fetus of such maladaptation have been documented in both animals and humans and range from poor birth outcomes to negative impacts on neurodevelopment, as well as long term emotional and behavioural disturbances. Conversely, it has been hypothesized that low levels of maternal prenatal stress may actually have an adaptive value for the offspring. Investigation of these associations employing physiological markers and repeated measures throughout pregnancy and postpartum of both the mother and the offspring, is required in order to understand the various effects of prenatal stress on the development of the offspring. It is also crucial to explore the possibility of variable periods of vulnerability throughout gestation. The aim of this commentary is to reexamine the current literature on the ill-effects of maternal stress during pregnancy on the offspring and to explore avenues for future treatment and prevention.     

Posttraumatic stress disorder and pregnancy health: preliminary update and implications

Posttraumatic stress disorder (PTSD) is pervasive among women of childbearing age. The cascade of behavioral health and neuroendocrine changes commonly associated with PTSD may adversely affect perinatal health. The authors examined the relationship between PTSD and perinatal health in a sample of 101 women seeking prenatal care on the island of Oahu, Hawaii. Trauma, PTSD, and psychological and behavioral health were assessed during prenatal care. Pregnancy health, labor and delivery information, and birth outcomes were abstracted from medical records post-partum. Findings suggest that women with PTSD entering pregnancy are at increased risk for engaging in high-risk health behaviors, such as smoking, alcohol consumption, substance use, poor prenatal care, and excessive weight gain. Authors discuss clinical and research implications.     

Interpretation of elevated FSH in the regular menstrual cycle

In reproductive medicine, abnormal elevation of serum follicle stimulating hormone (FSH) concentrations during the luteofollicular transition is associated with low response in infertility treatment. Increasing levels of serum FSH in the early follicular phase is a characteristic of reproductive ageing and has become very popular for the determination of diminished ovarian oocyte reserve. In the case of elevated FSH in premenopausal women, many more (patho)physiological mechanisms other than ageing may be responsible and should be considered also. FSH concentrations may vary considerably due to a number of factors. Next to intra-, inter- and between different assays variation there is hourly-, cycle day dependent-, intercycle and life time variation. Furthermore, physiological conditions such as during puberty, in hereditary dizygotic twinning, after use of oral contraceptives and during lactation also elevated FSH levels can be found. Pathological conditions associated with significant increases in FSH are after unilateral ovariectomy, during recovery from hypothalamic amenorrhea and with excessive smoking. It should be kept in mind, that with the interpretation of an abnormal high FSH value, just as with any other abnormal laboratory result, one should be aware, that there may be a variety of underlying causes other than the one where was aimed at.     

Mapping causal interregional influences with concurrent TMS–fMRI

Transcranial magnetic stimulation (TMS) produces a direct causal effect on brain activity that can now be studied by new approaches that simultaneously combine TMS with neuroimaging methods, such as functional magnetic resonance imaging (fMRI). In this review we highlight recent concurrent TMS–fMRI studies that illustrate how this novel combined technique may provide unique insights into causal interactions among brain regions in humans. We show how fMRI can detect the spatial topography of local and remote TMS effects and how these may vary with psychological factors such as task-state. Concurrent TMS–fMRI may furthermore reveal how the brain adapts to so-called virtual lesions induced by TMS, and the distributed activity changes that may underlie the behavioural consequences often observed during cortical stimulation with TMS. We argue that combining TMS with neuroimaging techniques allows a further step in understanding the physiological underpinnings of TMS, as well as the neural correlated of TMS-evoked consequences on perception and behaviour. This can provide powerful new insights about causal interactions among brain regions in both health and disease that may ultimately lead to developing more efficient protocols for basic research and therapeutic TMS applications. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.