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)

The mechanisms underlying menopausal hot flushes are poorly understood, although it is generally assumed they result from disturbances of thermoregulatory centres in the hypothalamus. 8-Prenylnaringenin (8-PN) has been identified as a potent phytoestrogen in hops (Humulus lupulus) and there are claims that hop-containing preparations can reduce hot flushes. We have investigated the site of action of 8-PN in a rat model of menopausal hot flushes, in which the tail skin temperature (TST) is increased after oestrogen withdrawal induced by ovariectomy. Daily s.c. administration of either 17beta-oestradiol (E2; 4 microg/kg) or 8-PN (400 microg/kg) significantly reduced the elevated TST after 2 days of treatment. Subcutaneous co-administration of either E2 or 8-PN with the oestrogen receptor (ER) antagonist, ICI 182,780 (200 microg/kg), which is thought not to cross the blood-brain barrier, completely blocked the effect of E2 and 8-PN on TST. The ERalpha- and ERbeta-specific agonists, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (100 microg/kg) and 2,3-bis(4-hydroxyphenyl)-propionitrile (60 microg/kg) respectively, both significantly reversed the raised TST in ovariectomised rats. These observations suggest that the regulation of the vasomotor response by oestrogens and phytoestrogens is mediated, at least in part, by peripheral mechanisms involving both ERalpha and ERbeta.
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PMID:The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes. 1708 9

Although the hot flush is generally recognised by women and the medical profession as the most characteristic and often a very distressing symptom of the climacteric, it remains an enigma. The physiological changes associated with the hot flush are different from any other flushing condition, with an increased peripheral blood flow, increased heart rate and in particular a decrease in galvanic skin resistance, which is unique to the flush. Flushing occurs as a result of disturbance of the temperature regulating mechanism situated in the hypothalamus, and probably a reduction in the thermoneutral zone, within which fluctuations of basal body temperature do not provoke compensatory vascular responses. Many factors have been implicated, including hormone releasing factors, gonadotrophins and neurohumorals. However, the role of oestrogen is critical and the clinical value of oestrogen therapy is well established and has been confirmed by a Cochrane review. Nevertheless, the precise mechanism by which reduced circulating levels of oestrogen are involved in causing the flush has not yet been established. Priming with oestrogen seems to be an essential pre-requisite for flushing, as young women with ovarian dysgenesis and very low circulating levels of oestrogen never have hot flushes unless they are given oestrogen replacement therapy, which is later discontinued. Oestrogen antagonist activity by selective oestrogen receptor modulators such as tamoxifen and raloxifene can also cause flushing. A link with gonadotrophins is demonstrated by a temporal association of flushes with the pulsatile release of luteinising hormone (LH). However, if LH pulses are eliminated by GnRH analogue, the frequency of flushing is not altered, which confirms that LH is merely associated with the flush rather than being causative. It is probable that the flush is initiated by a supra-pituitary mechanism which is influenced by the hypothalamic factors responsible for pulsatile LH release. A variety of chemical pathways have been proposed involving serotonin, noradrenalin and dopamine. Trials of drugs that selectively inhibit the re-uptake of serotonin and noradrenalin have shown some beneficial effects, as also has gabapentin, but often the results have been disappointing, and certainly less than the response seen with oestrogen or tibolone. The prevalence of hot flushes varies considerably around the world and is less in the Far East than in the west. Differences in diet and in particular the intake of phytoestrogens has been implicated and many studies have tried to establish whether dietary supplementation with phytoestrogens might be a suitable alternative to conventional hormone replacement therapy (HRT). So far, the results are disappointing. Other lifestyle measures such as avoiding alcohol, caffeine and spicy foods, keeping the core body temperature cool, paced respiration, taking exercise and even acupuncture may help. Hot flushes remain a major cause of reduced quality of life in a large proportion of menopausal women, but perhaps because they are not fatal and are usually self-limiting, there has been rather limited research or clinical interest. However, for the increasing number of women being treated with tamoxifen for breast cancer, and for whom oestrogen will usually be contra-indicated or unsuitable, there is an urgent need to identify the underlying mechanism so that appropriate, specific and safe non-oestrogen therapy can be offered to improve their quality of life.
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PMID:The menopausal hot flush--anything new? 1880 29

The health benefits associated with soya food consumption have been widely studied, with soya isoflavones and soya protein implicated in the protection of CVD, osteoporosis and cancers such as those of the breast and prostate. Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman), a metabolite of the soya isoflavone daidzein, is produced via the formation of the intermediate dihydrodaidzein, by human intestinal bacteria, with only approximately 30-40% of the adult population having the ability to perform this transformation following a soya challenge. Inter-individual variation in conversion of daidzein to equol has been attributed, in part, to differences in the diet and in gut microflora composition, although the specific bacteria responsible for the colonic biotransformation of daidzein to equol are yet to be identified. Equol is a unique compound in that it can exert oestrogenic effects, but is also a potent antagonist of dihydrotestosterone in vivo. Furthermore, in vitro studies suggest that equol is more biologically active than its parent compound, daidzein, with a higher affinity for the oestrogen receptor and a more potent antioxidant activity. Although some observational and intervention studies suggest that the ability to produce equol is associated with reduced risk of breast and prostate cancer, CVD, improved bone health and reduced incidence of hot flushes, others have reported null or adverse effects. Studies to date have been limited and well-designed studies that are sufficiently powered to investigate the relationship between equol production and disease risk are warranted before the clinical relevance of the equol phenotype can be fully elucidated.
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PMID:Is equol production beneficial to health? 2109 66

Estradiol (E2) plays a key role in human reproduction through the induction of vascular endothelial growth factor (VEGF) and T-regulatory cells (T-Regs), which are also important in breast cancer (BC) growth. The primary endpoint of the present study was the investigation of whether E2 suppression, chemotherapy and radiation therapy decreased the levels of VEGF and T-Regs of premenopausal patients with high-risk early BC. The secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Between April 2003 and July 2008, 100 premenopausal women with early, high-risk BC were entered into the study. The characteristics of the patients were as follows: median age, 43 years (range, 26-45); median number of positive axillary nodes, 3.3; median Ki-67, 33%. Plasma E2, VEGF and T-Reg were measured at baseline and every year. Treatment comprised luteneizing hormone-releasing hormone (LH-RH) analogue, tailored chemotherapy, radiation therapy and hormonal therapy in oestrogen receptor-positive (ER+) tumours. At 4 years, a statistically significant decrease in E2, VEGF and T-Reg levels was observed; the PFS and OS rates were 94 and 98%, respectively. Hot flushes and G1 osteopenia occurred following LH-RH analogue administration, while no unexpected toxicity was observed following chemotherapy. E2 deprivation with an LH-RH analogue, tailored chemotherapy, radiation therapy and hormonal therapy in ER+ tumours decreased plasma VEGF levels and T-Regs numbers in premenopausal high-risk ER+ and ER- BC patients. In addition, a favorable impact on PFS and OS was observed.
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PMID:Vascular endothelial growth factor expression and T-regulatory cells in premenopausal breast cancer. 2359 49

Tamoxifen is a selective oestrogen receptor modulator used for the treatment of oestrogen/progesterone receptor positive breast cancer. It possess antagonistic or agonistic activity depending on the tissue location i.e., antagonistic action on breast but agonist action on endometrium and bones. The side effects of tamoxifen include hot flushes, gynaecologic symptoms (vaginal dryness, vaginal discharge), depression, forgetfulness, sleep alterations, weight gain, alteration of lipoprotein metabolism, thromboembolic disorder. Tamoxifen, like oestrogens, increases the plasma level of triglycerides and liver secretion of Very Low Density Lipoprotein (VLDL). Moreover, it inhibits the key enzymes of triglyceride metabolism. However, there are few cases of severe tamoxifen induced hypertriglyceridemia and pancreatitis. Hypertriglyceridemia is one of the risk factor for acute pancreatitis. Here we present a case of tamoxifen-induced hypertriglyceridemia and acute pancreatitis in a 50-year-old female without any comorbidity. She was treated with supportive antibiotics and supportive therapy. About one week after discharge, patient was started on letrozole 2.5 mg once a day. Clinicians must be aware of this rare side effect of tamoxifen, so baseline and periodic testing of triglyceride level must be done to avoid such complications.
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PMID:Tamoxifen Induced Pancreatitis: An Unusual Complication of Commonly used Drug. 2896 60


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