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)

Third-generation aromatase inhibitors are able to reduce circulating plasma estrogen concentrations in postmenopausal women to below detectable limits and significantly inhibit aromatase, the enzyme responsible for estrogen synthesis, in normal breast tissue and breast tumors. Their role in the treatment of advanced breast cancer is well established and their use in adjuvant therapy is currently being explored. On the basis of these trials, evaluation of these inhibitors in the prevention of breast cancer may be appropriate. Aromatase inhibitors have non-specific toxic side effects including (but not limited to): asthenia, headache, nausea, peripheral edema, fatigue, vomiting and dyspepsia. In addition, certain endocrinological side effects in postmenopausal women are notable, namely hot flushes and vaginal dryness. In advanced breast cancer, these side effects result in treatment withdrawal in few (<4%) women. Of concern, however, are the potential long-term endocrinological side effects in women receiving treatment as first-line adjuvant therapy or in sequence or combination with tamoxifen or other selective estrogen receptor modulators (SERMs). Current studies of adjuvant treatments for breast cancer in healthy women are carefully evaluating, in addition to general toxicities, the effects on bone, lipid metabolism, cardiovascular risk, quality of life and menopausal symptoms. Careful evaluation of all-cause morbidity and mortality is necessary to plan trials and justify long-term use of aromatase inhibitors in the treatment or prevention of breast cancer in healthy women.
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PMID:Risks versus benefits in the clinical application of aromatase inhibitors. 1073 Nov 26

Most women in developed countries will live a third of their lives after the menopause. Vasomotor symptoms (hot flushes, night sweats, irritability, sleep disturbances, mood swings), and urogenital complications (atrophic vaginal irritation and dryness, dyspareunia) occur frequently during this period of life, but their severity and duration may vary widely between individuals. The menopause also induces accelerated bone loss and is the principal risk factor for osteoporosis. Hormone replacement therapy (HRT; estrogen or estrogen plus progestogen) alleviates these symptoms and can be administered orally, transdermally, topically, intranasally, or as subcutaneous implants. HRT is also effective for prevention and treatment of postmenosausal osteoporosis throughout the time that it is used. It is not surprising that HRT use has increased substantially during the past decade. Nevertheless, there are still considerable variations in use between different countries within the European community. This presentation will analyze: the frequency of menopausal symptoms among women in different European countries and the factors that influence them; the frequency of other postmenopausal women's health issues in Europe; the use of HRT in Europe as well as the type of HRT and its evolution during the last decade; and possible reasons explaining heterogeneity between countries.
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PMID:The menopause in Europe. 1083 Nov 88

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

In a multicenter observational study, the efficacy and acceptance of two different regimens of postmenopausal hormone replacement therapy in the form of a combination of 17 beta-estradiol in percutaneous gel application and micronized oral progesterone were evaluated. Forty-eight patients (aged 40-66 years) received 2.5 g estradiol gel plus either continuously micronized progesterone 100 per day (group A) or, sequentially, 200 mg per day between day 16 and 25 of a monthly cycle (group B) for two months. A significant reduction in typical menopausal symptoms, especially vasomotor complaints like hot flushes or sweating, was observed in both groups (score average at the beginning for hot flushes: 2.0 in group A and 1.8 in group B; after two months of treatment, 0.7 in group A and 0.4 in group B). Cholesterol levels were slightly reduced but statistically significant (235.9 +/- 49.55 mg/dl vs. 226.3 +/- 52.24 mg/dl; p < 0.05) only in group A; a trend towards lower cholesterol was observed in group B (236.5 +/- 47.82 mg/dl vs. 227.4 +/- 44.72 mg/dl). Lipoprotein (a) was also significantly reduced in group A (32.57 +/- 36.52 mg/dl vs. 28.28 +/- 31.03 mg/dl in group A; 31.7 +/- 28.42 mg/dl vs. 28.34 +/- 23.71 in group B; p < 0.05). The overall acceptance of this therapy was excellent or good in 91.3% of group A and 92.8% of group B patients.
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PMID:[Hormone replacement therapy with a transdermal estradiol gel and oral micronized progesterone. Effect on menopausal symptoms and lipid metabolism]. 1100 25

Raloxifene is a selective oestrogen receptor modulator (SERM) that has anti-oestrogenic effects on breast and endometrial tissue and oestrogenic actions on bone, lipid metabolism and blood clotting. In postmenopausal women raloxifene decreases bone turnover and increases bone mineral density, reducing the incidence of vertebral fractures. Unlike tamoxifen, raloxifene does not cause endometrial hyperplasia or cancer, as demonstrated by endometrial monitoring with ultrasonography and biopsy during treatment. Evidence suggests that raloxifene lowers total low-density lipoprotein cholesterol levels behaving like oestrogens, but does not increase high-density lipoprotein cholesterol levels. In randomised clinical trials on postmenopausal women with osteoporosis, raloxifene reduced the risk of newly diagnosed ER-positive invasive breast cancer by 76% during a median of 40 months of treatment. However, raloxifene does not alleviate early menopausal symptoms, such as hot flushes and urogenital atrophy, and may even exacerbate some of them. In conclusion, raloxifene may be an alternative for the prevention of long-term effects of oestrogen deficiency (osteoporosis and heart diseases) in women with previous breast cancer not having hot flushes. For symptomatic patients, the association of raloxifene with different drugs which have demonstrated efficacy in the control of vasomotor symptoms is now under evaluation.
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PMID:How to manage the menopause following therapy for breast cancer. is raloxifene a safe alternative? 1105 28

The object of this study is to determine the status of an urban Malaysian woman in her menopause age group with reference to her menopausal symptoms, lipid profile, breast, pelvis and bone. One hundred and sixty four women attending the Menopause Clinic of University Hospital, Kuala Lumpur who had not previously been on hormone replacement therapy were studied. Forty nine women were perimenopausal, 74 women were in early menopause (within 5 years of menopause) and 41 women were in late menopause (after 5 years of menopause). The most common symptoms were hot flushes (56%) and generalised tiredness (49%). Eighty four percent (84%) of women had high cholesterol levels. Serum triglycerides were highest in the late menopause group. There were 2 cases of intraductal carcinoma diagnosed on routine mammography, with 8 cases of fibrocystic breast disease and 7 cases of suspicious breast lumps. Routine ultrasound (pelvic and abdominal) revealed two women with ovarian cysts, 6 women with an endometrial thickness of more than 5 mm and 8 women with uterine fibroids. Eighty five women (51.8%) had mild osteoporosis while four women had moderate osteoporosis on dual photon measurements for bone mineral density. Menopause clinics should aim at investigating a woman in her menopause as a whole. Vasomotor symptoms were common in the urban Malaysian menopausal woman. There was a high incidence of lipid abnormalities. Routine mammography, pelvic ultrasound examinations and bone mineral density tests detected significant pathology and abnormalities.
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PMID:Profile of a menopause clinic in an urban population in Malaysia. 1119 15

Hot flashes are a primary reason that midlife women seek medical care, but there is little information about the onset or the predictors of hot flashes in the years before the menopause. This study examines women's experience of hot flashes in the late reproductive years, comparing African American and Caucasian women, and identifies hormonal, behavioral, and environmental risk factors for hot flashes associated with ovarian aging. Data are from a population-based prospective cohort study of ovarian aging in women who were ages 35--47, in general good health, and had regular menstrual cycles at study enrollment. Hot flashes were assessed by subject report in a structured interview at the first follow-up period and correlated highly with previous prospective daily ratings of hot flashes (p = 0.0001). Blood samples were obtained in the first 6 days of the menstrual cycle in two consecutive cycles at enrollment and two consecutive cycles at follow-up. Predictor variables include hormone measures, structured interview, and standard questionnaire data. Thirty-one percent of the sample (n = 375) reported hot flashes (mean age 41 years). In bivariate analysis, more African American than Caucasian women reported hot flashes (38% vs. 25%, p = 0.01). Significant predictors of hot flashes in the final multivariable logistic regression model were higher follicle-stimulating hormone (FSH) levels (odds ratio [OR] 3.19), anxiety (OR 1.06), baseline menopausal symptoms (OR 4.91), alcohol use (OR 1.09), body mass index (BMI) (OR 1.04), and parity (OR 1.20). Race did not predict hot flashes after adjusting for these variables. Hot flashes commonly occur before observable menstrual irregularities in the perimenopause and are associated with both hormonal and behavioral factors. The association of hot flashes with increased body mass (BMI) challenges the current "thin" hypothesis and raises important questions about the role of BMI in hormone dynamics in the late reproductive years.
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PMID:Hot flashes in the late reproductive years: risk factors for Africa American and Caucasian women. 1122 46

An unanticipated onomatopoeic expression emerged during ethnographic interviews with Japanese women about menopausal symptoms. At the same time, a newly coined term for hot flush, derived from English, started appearing in Japanese media. These two independent linguistic phenomena led me to speculate on what linguistic expression of physical sensations may reveal about social forces in a given society. This report examines the complexities involved in studying physiological symptoms. The multiple and intertwined variables--including economics, politics, social organization, and language--involved in translating physiological symptoms cross-culturally have been well recognized. But how to study these variables remains a challenge. This article offers a case study of what careful attention to verbal expression may tell us. My argument underscores the social fact that the expressions people choose to use vary according to their reasons for communicating and that their motivations for verbalizing symptoms (hot flush, in this case) depend on the priorities and sanctions of the society in which they live. These factors must be given due consideration when assessing any symptoms of the individual body.
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PMID:How Japanese women talk about hot flushes: implications for menopause research. 1145 27

The major biologically active circulating estrogen in both males and females is estradiol (E(2)). Circulating E(2) is a product of the ovarian granulosa cell and the testicular Leydig cell. Its gonadal formation is dependent on A-ring aromatization of its immediate precursor, testosterone, by a particular isoform of the enzyme aromatase, which also catalyses the conversion of the much weaker androgen, androstenedione, to the weak estrogen, estrone. E(2) is also formed in non-gonadal tissues, such as adipose tissue, liver, muscle and brain. Only adipose tissue makes significant extra-gonadal contributions to circulating estrogen. Loss of ovarian function during reproductive life, as a result of loss of gonadotropin secretion (secondary hypogonadism) or as a result of premature ovarian failure (generally defined as cessation of ovarian function prior to age 40), results in loss of the majority of circulating E(2) and of luteal progesterone. Loss of ovarian function at the menopause likewise results in a 90% loss of circulating E(2). The consequences of loss of ovarian function during reproductive life may be severe. Symptoms include hot flushes, night sweats, vaginal dryness and dyspareunia, loss of libido, loss of bone mass with subsequent osteoporosis and abnormalities of cardiovascular function, including a substantial increase in the risk of ischemic heart disease. Various regimens of estrogen replacement have been employed, aiming to eliminate symptoms, restore well-being and avert the consequences of estrogen depletion. The commonly adopted form of replacement is with the low-dose oral contraceptive pill for reasons of convenience, cost, efficacy, general freedom from side effects and the psychological advantage that many of the patient's peer group are also "taking the pill". An often neglected aspect of hormone therapy in the reproductive age group is the therapeutic use of testosterone. The application of such principles to the postmenopausal period is more problematic, as there is a common perception that the menopause is a normal physiological occurrence and that it is therefore not physiological to offer hormone therapy at that time. The pragmatic approach is to recommend standard therapy with estrogen and progestogen for the management of menopausal symptoms and to recommend longer term hormone replacement in the light of the individual's needs and current data with regard to efficacy for protection from osteoporosis and cardiovascular disease.
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PMID:Physiological principles of endocrine replacement: estrogen. 1178 92

Selective oestrogen receptor modulators (SERMs) are compounds that interact with the oestrogen receptor and have tissue-specific effects distinct from those of oestradiol, acting as an oestrogen agonist in some tissues and as an antagonist in others. The development of SERMs that selectively interact with specific receptors, coactivators and corepressors in different organ systems offers the possibility of improving the risk:benefit profile relative to hormone replacement therapy. Tamoxifen is a SERM that acts as an oestrogen antagonist in breast tissue and is currently being used for the treatment and prevention of breast cancer. Tamoxifen also exhibits oestrogen-agonistic properties in the endometrium and increases the risk of endometrial cancer. Oestrogen and another SERM, raloxifene, have been shown to prevent osteoporosis. The effects of oestrogens on cognitive functions are currently being investigated. Recent data reveal the lack of secondary prevention of coronary heart disease with oestrogen. Oestrogen has been used to treat menopausal symptoms, whereas the SERMs have been shown to induce hot flushes. Current research is focused on producing the ideal SERM, which would have benefits over existing SERMs in terms of preventing cancer, cardiovascular disease, osteoporosis and menopausal symptoms, improving cognitive functions, and have a significantly better toxicity profile in terms of endometrial cancer and thromboembolic events.
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PMID:The search for the ideal SERM. 1203 7


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