Indiana University-Purdue University Indianapolis (IUPUI) / Menopausal symptoms, primarily hot flashes, are a pressing clinical problem for both naturally menopausal women and breast and ovarian cancer patients, with a high societal and personal cost. Hot flashes are poorly understood, and animal modeling has been scarce, which has substantially hindered the development of non-hormonal treatments. An emerging factor in the hot flash experience is the role of anxiety and stress-related stimuli, which have repeatedly been shown to influence the bother, frequency, and severity of hot flashes. Causal relationships are difficult to determine in a clinical setting, and the use of animal models offers the ability to elucidate causality and mechanisms. The first part of this work details the development and validation of novel animal models of hot flashes using clinically relevant triggers (i.e., compounds or stimuli that cause hot flashes in clinical settings), which also increase anxiety symptoms. These studies revealed that these triggers elicited strong (7-9 °C) and rapid hot flash-associated increases in tail skin temperature in rats. In a surgical ovariectomy rat model of menopause, which typically exhibit anxiety-like behavior, hot flash provocation revealed an ovariectomy-dependent vulnerability, which was attenuated by estrogen replacement in tested models. An examination of the neural circuitry in response to the most robust flushing compound revealed increased cellular activity in key thermoregulatory and emotionally relevant areas. The orexin neuropeptide system was hyperactive and presented as a novel target; pretreatment with selective and dual orexin receptor antagonists significantly diminished or eliminated, respectively, the response to a hot flash provocation in ovariectomized rats. The insertion/deletion polymorphism of the serotonin transporter has been linked to increased anxiety-associated traits in humans, and subsequent studies prolonged hot flashes in SERT+/- rats, which also caused hot flashes in highly symptomatic women. These studies indicate the orexin system may be a novel non-hormonal treatment target, and future studies will determine the therapeutic importance of orexin receptor antagonists for menopausal symptoms.

No description available.

<p>According to the salutogenic theory put forth by Antonovsky, an individual’s sense of coherence (SOC) is central for maintaining health. The present study used data from middle-aged women being part of a longitudinal research program to investigate how SOC relates to health status (in terms of self-rated health and medicine consumption) and a set of lifestyle factors (physical exercise, alcohol consumption, nicotine consumption and dietary habits). Women with a strong SOC were hypothesized to exhibit better health profiles, consume less medication, and lead a healthier lifestyle than women with a weak SOC. The findings partly confirmed the hypotheses in showing that women with a strong SOC had better self-rated overall health, better psychological well-being, fewer self-reported diseases and lower medicine consumption. Contrary to the hypothesis, women with stronger SOC had more self-reported psychological and physical symptoms. Of the lifestyle factors, only dietary habits were significantly associated with SOC. The study shows that SOC is related to differences in health and medicine consumption in a homogeneous group of middle-aged women, while the association between SOC and lifestyle was found to be less prominent.</p>

According to the salutogenic theory put forth by Antonovsky, an individual’s sense of coherence (SOC) is central for maintaining health. The present study used data from middle-aged women being part of a longitudinal research program to investigate how SOC relates to health status (in terms of self-rated health and medicine consumption) and a set of lifestyle factors (physical exercise, alcohol consumption, nicotine consumption and dietary habits). Women with a strong SOC were hypothesized to exhibit better health profiles, consume less medication, and lead a healthier lifestyle than women with a weak SOC. The findings partly confirmed the hypotheses in showing that women with a strong SOC had better self-rated overall health, better psychological well-being, fewer self-reported diseases and lower medicine consumption. Contrary to the hypothesis, women with stronger SOC had more self-reported psychological and physical symptoms. Of the lifestyle factors, only dietary habits were significantly associated with SOC. The study shows that SOC is related to differences in health and medicine consumption in a homogeneous group of middle-aged women, while the association between SOC and lifestyle was found to be less prominent.

No description available.