Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the menopause transition, ovarian steroid production is gradually inhibited and around 35% of women will seek medical help for postmenopausal symptoms. The hot flush is a characteristic manifestation occurring in about 70% of women; it is associated with oestrogen withdrawal and disappears with oestrogen-based hormone replacement therapy. The exact mechanism behind it is still unclear but is probably related to heat loss mechanisms. The flush often occurs in parallel to changes in skin temperature, blood flow, pulse rate and pulses of luteinizing hormone (LH). These are probably secondary to a disturbance in the thermoregulatory centre of the CNS, which is anatomically close to neurons containing gonadotropin-releasing hormone. Depression is no more frequent in the menopausal transition than at other times in life. After surgical menopause, however, oestrogen improves low mood over placebo. In women with premenstrual syndrome, an increased feeling of well-being is associated with the pre-ovulatory oestrogen peak. Progestogens are associated with negative mood changes during the menstrual cycle, oral contraception and postmenopausal replacement therapy. Certain progesterone metabolites are anaesthetic and have anti-epileptic and anxiolytic properties, effects which are mediated via the type A gamma-aminobutyric acid (GABAA) receptor. Oestrogen is associated with increased sensory perception, locomotory activity, limb coordination and balance: this may help explain the increased frequency of bone fractures in the early postmenopausal period. Oestrogen improves memory and performance in patients with mild Alzheimer's dementia and increases epileptic activity in patients with partial epilepsy. These effects can be related to amplifying effects of oestrogen on excitatory amino acids in the CNS.
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PMID:Symptoms related to the menopause and sex steroid treatments. 858 96

The continuing growth of female life expectancy has resulted in a marked increase of women in years beyond the menopause. Women can nowadays expect to live one-third of their lives in a potential hormonal deficiency state. Women over 50 comprise 17% of the total population of any country in the modern western world. Any decision regarding their health issues will have a great impact on our limited health care resources. There is no doubt that estrogen replacement therapy effectively mitigates hot flushes and other vasomotor symptoms and more effectively so than other treatment modalities. Vasomotor symptoms affect more than half of the female population around the menopause with a mean duration of 2-3 years. When used to treat vasomotor symptoms hormone replacement therapy has repeatedly been shown to be cost effective. It is also well documented that hormone replacement therapy effectively prevents bone loss and osteoporotic fractures as well as heart disease. The majority of cases of both fractures and heart disease occur at ages over 75 and concern has been expressed if treatment from the menopausal age to the onset of fractures or heart disease is cost effective with regard to the perceived increase in risk of side effects, especially breast cancer. One important aspect in this scenario is the control system that we impose on women on HRT. Given our present preparations women are recommended an annual check-up. If the number of office procedures and visits to the clinic cannot be substantially reduced long-term therapy with HRT is not cost effective. An exception from this rule is the treatment of urogenital estrogen deficiency using low dose vaginal estrogens. Systemic concentrations of estrogens following such administration are negligible. Hence, low dose estrogen topical applications can be made an OTC preparation. As no control system is needed this therapy seems to be highly cost effective. The pharmaceutical industry is urged to produce better products so that side effects such as bleeding problems leading to a number of visits to the clinic and fear of cancer among women can be avoided. Recent data also imply that estrogen treatment may confer protection against Alzheimer's disease. Breast cancer is the remaining controversy even if recent data imply that estrogens could be given to women operated on for breast cancer without increasing the risk of a relapse.
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PMID:The menopause revisited. 858 12

As life expectancy increases and members of the postwar generation settle into their fifth decade of life, hormone replacement therapy--estrogen or an estrogen-progestin combination--has become a major research interest. An extensive, but often confusing and even contradictory, literature exists on the uses of hormone replacement for the treatment and prevention of a multitude of difficulties that may be associated with the perimenopausal and postmenopausal periods. These include hot flushes, vaginal changes, urinary tract changes, changes in sexuality, affective or emotional symptoms, changes in the oral mucosa and skin, loss of memory and Alzheimer's disease, bone loss and osteoporosis, and cardiovascular disease. This article reviews the literature in each of these areas. It also reviews studies relating to possible side effects of hormone therapy, including endometrial cancer, gall bladder disease, and breast cancer. The article outlines principles for practitioners to follow in assisting women to make informed and individualized decisions about this therapy. Part II of this article, which will appear in the May/June 1996 issue of the Journal of Nurse-Midwifery, will cover specific therapeutic regimens and their management, as well as alternative therapies and preventive measures.
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PMID:Perimenopausal and postmenopausal hormone replacement therapy. Part 1. An update of the literature on benefits and risks. 870 9

Menopause is primary determined by the estrogen deficit. Neuropeptides and neurotransmitters such as opioid peptides, serotonin, noradrenaline, dopamine secreted within the central nervous system also plays significant role in the patho-physiology of menopausal symptoms. They are under regulatory influence of sex steroid hormones, mainly estrogens. It is appeared that estrogen may act within central nervous system through the genomic and nongenomic effect. In this article the mechanisms of estrogen influence on the function and metabolism of neuronal cells have been presented. The neuroendocrine background of some menopausal symptoms also has been discussed. Particularly the etiopathogenesis of hot flushes and cognitive functions has been analyzed. Contemporary views on the role of estrogens in the etiopathogenesis of Alzheimer disease have been presented.
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PMID:[Neuroendocrine aspects of menopause]. 968 73

Menopausal loss of ovarian estradiol production has numerous unfavourable effects on woman's health. Frequency and intensity of hot flushes mostly decline after some years. However, urogenital atrophy, incontinence, bone loss and rising risk for cardiovascular disease and probably for M. Alzheimer are of greatest importance as their incidence increases after menopause and because they play a major role in causing morbidity and mortality in elderly women. We discuss the pathophysiology of hot flushes, estradiol's effects on bone turnover, on the arterial vessel wall, on serum lipids and some aspects of estradiol action in the brain.
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PMID:[Menopause and its sequelae: an interdisciplinary syndrome]. 984 69

Ever since the discovery of estradiol and the elucidation of its chemical structure, there has been a great deal of interest in its mechanism of action and its potential therapeutic value. It is now well established that estrogens have many different functions in many different cell-types. With respect to the potential use of estrogens as therapeutics, there is an interest in controlling reproductive function, bone metabolism, cardiovascular disease, as well as in the prevention of hot flushes, mood changes and Alzheimer s disease. For over a decade, it was believed that estrogens signal through a a single estrogen receptor, now referred to as ERalpha, which belongs to a family of ligand-activated transcription factors. More recently, however, a second estrogen receptor ERbeta was identified. The current review describes similarities as well as differences between these two distinct estrogen receptors. Both ERalpha and ERbeta bind 17beta-estradiol with high affinity and they bind to classical estrogen response elements in a similar if not identical fashion. However, there are also major differences between ERalpha and ERbeta for instance with respect to their tissue distribution, the phenotype of the corresponding knock-out mice and their transcriptional activities. It is anticipated that a better understanding of these two receptors will eventually lead to more selective ways of modulating physiological processes which are influenced by estrogens. For this purpose, the development of ERalpha and ERbeta specific ligands, both agonists as well as antagonists, will be of great importance.
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PMID:Estrogen receptors alpha and beta: two receptors of a kind? 1070 25

In the menopause transition, around 35% of women will seek medical help for menopausal symptoms. At the climacteric, various symptoms such as forgetfulness, anxiety, depressive neurosis, abnormal sensation, hot flush and sleeplessness are often observed due to hypofunction of the ovaries. There is some indication that women become more anxious during times of relatively low level of estrogen and progesterone such as premenstrual syndrome, premenstrual dysphoric disorder, maternity blues and menopausal state. The exact mechanism behind it is still unclear but is probably related to the decrease of ovarian hormones, which may be triggering psychiatric mood disorders. It is known that ovarian hormones act on specific areas of the brain and appear to act as anxiolytics. Certain progesterone metabolites are anesthetic and have antiepileptic and anxiolytic properties. These steroids modulate the type A gamma-aminobutyric acid (GABAA)/benzodiazepine receptor. This may help explain the increased frequency of anxiety disorders and mood disorders in the early postmenopausal period. In addition, estrogen also improves memory and performance in patients with mild Alzheimer's dementia. These effects can be related to amplifying effects of estrogen on excitatory amino acids in the brain. This is suggested that gonadal steroidal hormones seemed to be one of the essential substances for the maintenance of the limbic system and forebrain function which regulated anxiety, mood, memory and cognitive functions in menopausal women.
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PMID:[Menopause and anxiety: focus on steroidal hormones and GABAA receptor]. 1087 12

Estrogens have been convincingly shown to be highly effective in preventing and reversing menopause-related conditions, such as hot flushes, urogenital complaints, and postmenopausal bone loss. Observational studies report that long-term, estrogen-containing, postmenopausal hormone replacement therapy (HRT) leads to a substantial reduction in hip fractures, myocardial infarction, and possibly colonic cancer, with important consequences for health and quality of life. Estrogen replacement may postpone the onset of Alzheimer's disease and extend life. While many of these effects are biologically plausible, with a variety of cellular mechanisms being involved, only ongoing and future large-scale randomized clinical trials can and should define the effects of HRT more precisely. Long-term compliance is a key issue for long-term benefits, and offering women a choice of administration routes and regimens can only be beneficial in this respect. Pills, patches, gels, and implants are all widely prescribed. Intravaginal or intranasal forms of administration, which are very easy to use and adaptable on an individual level, are among the new options which could improve long-term continuation of HRT use. Fear of breast cancer and recurrence of vaginal bleeding are real concerns for many women considering HRT. This has led to research into lower-dose, estrogen-containing regimens, into continuous combined regimens, and into the potential of estrogen receptor alpha or beta binding molecules that may help to prevent such problems from arising. The prospects for safe and effective postmenopausal HRT with either estrogens or estrogen-like drugs are very promising when these drugs are used in a patient-tailored, risk profile-based manner.
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PMID:Perspectives in hormone replacement therapy. 1139 Jan 23

All androgens and estrogens in post-menopausal women are synthesized locally in peripheral target tissues by tissue-specific steroidogenic enzymes according to the intracrine process. The importance of the intracrine or peripheral formation of sex steroids is illustrated by the success of aromatase inhibitors and antiestrogens in the prevention and treatment of breast cancer in post-menopausal women. On the other hand, a large series of problems are associated with the deficiency of sex steroids accompanying menopause and the decreased secretion of DHEA, osteoporosis being the best defined example. In this context, an important observation is that women at menopause are not only deprived from ovarian estrogens but are also lacking androgens due to the marked decrease of DHEA. In order to achieve a more physiological and tissue-specific hormone replacement therapy, DHEA, in combination with a SERM (selective estrogen receptor modulator) having pure antiestrogenic activity in the mammary gland and uterus could possibly meet the most important needs of women at menopause, namely control of hot flushes and, most importantly, prevent breast cancer, uterine cancer, ovarian cancer and osteoporosis with a potential improvement of cognitive functions and memory and prevention of Alzheimer's disease.
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PMID:Extragonadal synthesis of sex steroids: intracrinology. 1277 42

The Women's Health Initiative Study and other reports have created major uncertainty among postmenopausal women and physicians concerning hormone replacement therapy. We have thus investigated the possibility of replacing the progestin in hormone replacement therapy by a novel selective estrogen receptor (ER) modulator having potent and pure antiestrogenic activity in the mammary gland and uterus. As measured by changes in histology and Cdc47 labeling in the rat model, the present study shows that the stimulatory effect of estradiol in the mammary gland and uterus is efficiently blocked by simultaneous administration of the novel selective ER modulator EM-652, but bone mineral density is preserved and serum cholesterol is decreased. After the administration of 14C-labeled EM-652, we observed that there is no detectable radioactivity in the brain. Moreover, ER alpha immunoreactivity remained constant in the hypothalamus after EM-652 treatment, whereas ER alpha became almost undetectable in the mammary gland and uterus. The present data show the poor or absent access of EM-652 to the brain, whereas the effects of estrogens are efficiently neutralized in the mammary gland and uterus. Such data support the exciting possibility of a novel approach that could meet most of the needs of women's health at menopause, namely control of hot flushes and prevention of breast, uterine, and ovarian cancer as well as osteoporosis and potentially helping brain function and preventing Alzheimer's disease with no identifiable risk or negative effect.
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PMID:The combination of a novel selective estrogen receptor modulator with an estrogen protects the mammary gland and uterus in a rodent model: the future of postmenopausal women's health? 1457 21


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