UMLS:C0600142 - FACTA Search

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)

As ageing progresses the levels of sex hormones decrease in the human body. In the male population, the decrease or absence of testosterone leads to decreased strength and stamina, thin bones and a low sex drive (1). In the female population, the immediate symptoms of menopause include irregular periods, painful sexual intercourse due to vaginal dryness, hot flushes and night sweats (2). Lack of oestrogen also leads to the risk of developing osteoporosis and cardiovascular diseases. In this report, the authors will mainly discuss the effects of hormone therapy (HT) in menopausal women. Available current clinical data on the effects of calcium supplementation with and without HT, exercise, exercise plus calcium and exercise with HT on bone loss are presented. The effects of transdermal and oral oestrogen therapy (OT) on serum lipids are discussed. Commercially-available HT products, their indications, dosages, contra-indications, side-effects and drug interactions are compared. Alternative therapies for menopausal symptoms with Chinese traditional herbs, and a comparison of the molecular structures of phytoestrogens with estradiol and diethylstilbestrol are examined (3, 4). A list of medicinal herbs and foods reported to elicit an oestrogenic response in animals is compiled.
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PMID:Hormone therapy and phytoestrogens. 880 47

Gonadotropin-releasing hormone (GnRH) agonists are widely administered to treat endometriosis, but generally are not prescribed for more than 6 months since they are associated with vasomotor symptoms and bone loss. A GnRH agonist and steroid add-back therapy can be given for longer times without flare-up or significant hypoestrogenic symptoms. We examined the efficacy and safety of a weak estrogenic steroid, OD14, with prolonged goserelin treatment in seven regularly menstruating women (age 26-33 yrs) with laparoscopically diagnosed, symptomatic endometriosis. The women received goserelin 3.65 mg subcutaneously/month and 2.5 mg OD14 2.5 mg/day beginning in the fourth cycle for 18 to 20 months. The frequency and severity of hot flushes, sweating, irritability, loss of libido, nervousness, and sleeplessness were scored by the women on a scale of 0 to 6 and compared. Samples of blood and urine were obtained to measure serum estradiol (E2) levels, lipids, and urinary calcium:creatinine (Ca:Cr) ratios at the start of treatment and monthly thereafter. The vasomotor scores, serum E2 levels, and urine Ca:Cr ratios were consistent with the hypoestrogenism induced by goserelin (24.2 ± 3.1, 18.5 ± 7.2 pg/ml, and 0.063 ± 0.008, respectively). The decreases in vasomotor scoring with regard to hot flushing, sweating, and urinary Ca:Cr ratios were significant after adding OD14 (14.8 ± 2.2, 0.031 ± 0.005, p <0.05), whereas E2 levels remained below 40 pg/ml (23.1 ± 8.2 pg/ml, p >0.05) throughout therapy. The increased low-density:high-density lipoprotein ratio with goserelin improved with OD14, remaining at the lower limit of normal. Thus, OD14 add-back to GnRH agonist therapy enabled us to extend medical therapy of endometriosis longer than 6 months, preventing hypoestrogenic side effects, and with adequate suppression endometriosis symptoms.
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PMID:Effectiveness and Long-Term Safety of Prolonged Gosereline and Tibolone in Women with Endometriosis 907 53

A new class of compounds known as selective estrogen receptor modulators (SERMs) may possess the optimal combination of characteristics desirable in a drug designed for use in postmenopausal women. Among this class of compounds, raloxifene is the most studied and is currently available for clinical use in some countries for the prevention of osteoporosis in post-menopausal women. Raloxifene is a non-steroidal benzotiophene derivative shown to prevent bone loss at axial and appendicular sites and reduce serum cholesterol, like estrogen, in oophorectomized rats and in postmenopausal women. In animal models, unlike estrogen, raloxifene does not stimulate breast or uterine tissues. These appealing attributes make raloxifene a potential treatment for osteoporosis and other menopause related risks in middle aged and elderly women. Multicenter studies have been performed in early postmenopausal women, randomly assigned to receive raloxifene 30, 60, or 150 mg/day or placebo. All subjects received a calcium supplement. Bone mineral density, which was measured twice a year over 24 months by dual X-ray absorptiometry, decreased significantly at all skeletal sites with placebo, and significantly increased with raloxifene at the spine, hip, and total body at the three doses. At 24 months, the mean increase with raloxifene 60 mg compared with placebo was 2.4% at the lumbar spine and at the total hip, and 2% at the total body. Markers of bone formation (serum osteocalcin and bone specific alkaline phosphatase) and of resorption (urinary CrossLaps) decreased significantly to the premenopausal range within 3-6 months of treatment with raloxifene. In addition, total serum and low-density lipoprotein cholesterol decreased significantly in all raloxifene therapy groups in a dose-related fashion. Serum HDL-cholesterol and triglycerides were not significantly changed by therapy. The most commonly observed side-effect was hot flushes, with patients taking raloxifene reporting a slightly higher rate of flushes (25%) than those on placebo (18%). This adverse event usually occurred within the first few months of therapy, was generally mild, and did not result in excess study dropout (raloxifene 1.5%, placebo 2.1%). Preliminary 2-year data indicated that raloxifene is not associated with an increased risk of breast cancer. In summary, the clinical efficacy and safety of raloxifene is very promising and this compound will offer a particularly attractive choice for postmenopausal women.
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PMID:Clinical efficacy of raloxifene in postmenopausal women. 1042 20

The incidence of cardiovascular disease is lower in women before the menopause compared with men, while menopausal women have an incidence of coronary disease similar to that of men of the same age. This is mainly dependent upon oestrogen deficiency. Large-scale epidemiological studies have demonstrated that oestrogen replacement therapy leads to approximately 50 per cent reduction of cardiovascular disease in women taking hormones, compared with untreated women. Multiple mechanisms have been proposed to explain the cardiovascular risk reduction observed in women on oestrogen therapy. Oestrogens positively affect plasma lipids and exert a beneficial effect upon carbohydrate metabolism and the haemocoagulation profile. Oestrogens may also have anti-atherogenic properties. Recent in vitro studies have demonstrated that oestrogens may positively influence all the steps involved in the formation of the atherosclerotic plaque (accumulation of cholesterol in the arterial wall, arterial smooth muscle cell proliferation, platelet aggregation, collagen and elastin production). Angiographic studies conducted in humans have demonstrated that women on oestrogens have significantly less coronary disease and less severe occlusion scores compared with women not taking hormone replacement therapy. Animal and human studies have shown that oestrogens act as vasodilating substances. Endothelium-dependent mechanisms have been identified and imply that oestrogens act through the endothelial release, mainly, of nitric oxide, a potent vasodilating substance which has been identified with EDRF (endothelium derived relaxing factor). More recently, oestrogens have been shown to affect also the vascular tone in the absence of the endothelium. Therefore, endothelium-independent mechanisms could be involved in the pathogenesis of the oestrogens' vascular effects. There is evidence that oestrogens have calcium antagonistic properties; this mechanism may be responsible for the reduction of peripheral vascular resistance observed in women on hormone replacement therapy and may slow the progression of coronary artery disease. The menopausal age is characterized by an imbalance of the neurohormonal system. Sudden increases of plasma catecholamines are evident when women have hot flushes, a typical clinical sign of the menopausal period. The abnormal release of catecholamines may reduce coronary flow reserve and increase peripheral vascular resistance and, therefore, may be dangerous for the heart. It has been shown, by means of the study of heart rate variability, that oestrogens are effective in modulating the neurohormonal system. The reduction of sympathetic tone has beneficial effects on coronary flow reserve and may be important in explaining the cardioprotective effect of oestrogens. Peripheral and coronary vasodilation observed in women on hormone replacement therapy might be also due to the inhibition of the release of vasoconstrictor factors such as endothelin-1 by oestrogens. Therefore, oestrogens protect the heart against coronary artery disease and they are now regarded as being as important as aspirin and antihypertensive drugs were in the past. Hormone replacement therapy should be considered in every menopausal woman to possibly prevent the occurrence of cardiovascular disease or, if already present, to slow its progression.
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PMID:Oestrogens and the heart. 1050 Apr 55

A new drug class called Selective Estrogen Receptor Modulators (SERM) could combine ideal properties for a product designed for menopausal women. The most widely studied member of this class is raloxifene which is currently marketed in several countries for the prevention of osteoporosis in menopaused women. This product is a nonsteroidal derivative of benzothiophene which, like estrogens, has a preventive effect against bone loss involving the spine and peripheral skeleton and a cholesterol lowering effect, both in the ovariectomized rat and in menopausal women. Unlike estrogens, raloxifene does not stimulate breast or uterine tissue. These interesting properties make raloxifene a possible preventive treatment for osteoporosis and other menopause-related risks for menopausal women of all ages. Multicenter studies have been conducted in recently menopausal women who received either raloxifene at the doses of 30, 60, or 150 mg/day or a placebo in a randomized protocol. All subjects were also given calcium supplementation. Bone density was measured twice a year for 36 months by dual X-rays absorptiometry and showed a significant decrease at all sites in the placebo group while there was a significant increase in the spine, the hip and the overall skeleton for all three raloxifen groups. After 24 months of treatment, mean increase over placebo was 2.4% for 60 mg raloxifene measured on the spine and total hip and 2% for the overall skeleton. Markers of bone formation (serum osteocalcin and bone alkaline phasphatase) and resorption (urinary CrossLaps) decreased significantly reaching, after 3 to 6 months of treatment, the levels observed in non menopausal women. In addition, total serum cholesterol as well as LDL-cholesterol decreased significantly in a dose-dependent fashion in all groups treated with raloxifene. Serum HDL-cholesterol and triglycerides did not very significantly during treatment. Hot flashes were the most frequently observed undesirable effect, at a frequency slightly higher in the raloxifene group (25%) than in the placebo group (18%). This undesirable effect was of low intensity and generally occurred during the first months of treatment. It did not cause a higher drop out rate (raloxifen 1.5%; placebo 2.1%). The preliminary data at two years follow-up suggest that raloxifene is not associated with an increased risk of breast cancer. In conclusion, raloxifene is a particularly interesting drug for menopausal women showing very promising efficacy and clinical tolerance.
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PMID:[Results of international clinical trials with raloxifene]. 1052 Apr 16

Three hundred and one healthy women between 45 and 65 yr of age and at least 1 yr postmenopausal were randomly assigned to 12-month double-blind therapy with levormeloxifene [1.25 (n = 51), 5, 10, or 20 mg/day], low dose continuous combined hormone replacement therapy [HRT; 1 mg 17 beta-estradiol and 0.5 mg norethisterone acetate/day], or placebo (all n = 50). All of the women were also given a daily supplement of calcium (500 mg). Serum CrossLaps decreased by about 50% in the levormeloxifene groups, with no dose-response effect. The group receiving HRT decreased more (>60%), and the placebo group (500 mg calcium alone) decreased by about 10%. The pattern was similar for bone alkaline phosphatase, except that the decreases were smaller, about 30% for the levormeloxifene groups and 50% for the HRT group. Serum osteocalcin also showed highly significant decreases, of the same magnitude in the levormeloxifene and HRT groups. Spinal bone mineral density (BMD) decreased by less than 1% in the placebo group and increased by about 2% in the levormeloxifene groups and by almost 5% in the HRT group (P < 0.001 for the difference between levormeloxifene and HRT vs. placebo). BMD of the total hip and total body changed in the same direction, although differences between groups were not as pronounced as those for BMD spine. Total cholesterol decreased by about 13--20% during levormeloxifene therapy, whereas daily doses of 1 mg estradiol and 0.5 mg norethisterone acetate produced a decrease of only about 8%. Levormeloxifene decreased low density lipoprotein cholesterol by about 22-30% compared with about 12% in the low dose HRT group. High density lipoprotein cholesterol was unchanged in all groups. Endometrial thickness increased both clinically and statistically significantly in the levormeloxifene groups independently of the dose; the difference from the placebo and HRT groups was significant (P < 0.001). There was no significant difference between the HRT and placebo groups. Other adverse events of interest include hot flushes, which did not occur more frequently in the levormeloxifene than the placebo groups, but occurred significantly less frequently in the HRT group (P < 0.05). Breast tenderness was much more common in the HRT group (<0.001) than in all other groups. In conclusion, the study shows that levormeloxifene, a new selective estrogen receptor modulator, has positive effects on BMD and bone turnover and apparently strong estrogenic effects on the serum concentrations of different cholesterol subfractions. Levormeloxifene at the doses tested had an estrogen-like effect on endometrium and no effect on hot flushes. The study was unable to differentiate between the effects of the different doses of levormeloxifene.
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PMID:Efficacy of levormeloxifene in the prevention of postmenopausal bone loss and on the lipid profile compared to low dose hormone replacement therapy. 1115 42

Tibolone, a steroid with tissue-specific activities, can reduce the bone resorption that takes place after the menopause. The present calcium-controlled, 2-year study aimed to evaluate the effect of two doses of oral tibolone, 1.25 mg and 2.5 mg, on bone loss in early postmenopausal women. The subjects were randomly allocated to one of the three groups, namely tibolone 2.5 mg (n = 30), tibolone 1.25 mg (n = 30) and a control group (n = 30). All subjects received 1000 mg of calcium per day. In the control group, vertebral and femur bone mineral density (BMD) decreased significantly (p < 0.05) after 12 and 24 months. In both tibolone groups, vertebral and femur BMD increased significantly (p < 0.05) increased after 12 and 24 months. In the control group, bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin levels) remained constant, while in both tibolone groups these markers showed similar significant decreases (p < 0.05) after 12 and 24 months. After 24 months, body weight increased in the control group (p < 0.05), while smaller increments were evident in the tibolone groups. Symptom scores in the control group did not show any significant modification during the study. In contrast, the administration of 2.5 mg tibolone was significantly (p < 0.05) effective in reducing hot flushes and other symptoms. The tibolone 1.25 mg group yielded similar results (even if it was proportionally less efficient) to the higher dose. It is concluded that tibolone is effective, even at lower doses, in relieving climacteric symptoms and preventing a decrease in spine and femur BMD in early postmenopausal women.
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PMID:A longitudinal evaluation of the effect of two doses of tibolone on bone density and metabolism in early postmenopausal women. 1510 59

In this semiar, I propose to describe the pharmacological properties of raloxifene that provide a basis for its role in the treatment of postmenopausal osteoporosis. These pharmacological properties can be described as providing therapeutic benefits in the following three areas: 1) reduction in bone turnover, 2) increases in bone mineral density, and 3) risk reduction in fractures. While reloxifene shares these effects with conventional bisphosphonates that are in common use for postmenopausal osteoporosis, it exerts its antiresorptive effects through a different mechanism of action from those of the bisphosphonates. Furthermore, raloxifene exerts its stimulatory or inhibitory effects on estrogen in a tissue-specific fashion as a selective estrogen-receptor-modulator (SERM), thereby providing a wide range of clinical benefits that result from its ability to exert estrogen-like beneficial effects in tissues other than bone while at the same time inhibiting estrogen-like deleterious effects in other tissues. I therefore propose to define the role of raloxifene as a viable therapeutic option in the treatment of postmenopausal osteoporosis in light of these unique pharmacological features. Current data suggests that raloxifene can be positioned somewhere in between hormone replacement therapy (HRT) and bisphosphonates, and is highly likely to be suitable for use in patients between the ages of 55 and 70, while other agents may be indicated in special populations, such as premenopausal patients, postmenopausal patients with hot flushes, or elderly patients who may be placed at accelerated risk of developing femoral neck fractures. Thus, as a novel therapeutic option with unique clinical benefits, a far greater role may be expected for raloxifene in the treatment of postmenopausal osteoporosis than for other conventional therapeutic agents.
Clin Calcium 2004 Oct
PMID:[Defining the role of raloxifene as a therapeutic agent for postmenopausal osteoporosis: focus on its pharmacological properties]. 1557 35

Selective estrogen receptor modulators (SERMs) are a diverse group of non-steroidal (non hormonal) compounds developed to offer the postmenopausal women many of the advantages of estrogen therapy (ET) while avoiding undesired effects on reproductive and other tissues. Tamoxifen and toremifene, first generation SERMs are used for the adjuvant treatment of breast cancer worldwide, but their stimulatory effect on the uterus prevents their widespread use in other indications. A second generation SERM, raloxifene hydrochloride, a benzothiophene SERM is fully safe for the uterus and significantly reduces the risk of vertebral fractures in postmenopausal women with osteoporosis. The safety and efficacy of raloxifene in postmenopausal women have been studied extensively in more than 40,000 women over 50 clinical trials in 30 countries. The majority of the trials have been large double-blind placebo-controlled trials, including Asia and Japan. Raloxifene is well tolerated, with the only common side effects significantly higher than placebo being hot flushes and minor leg cramps. Venous thromboembolism was the only adverse events of clinical significance but rare associated with raloxifene in Caucasian women, but was not observed so far in Asian countries.
Clin Calcium 2004 Oct
PMID:[Safety profile of raloxifene]. 1557 39

The effects of Ginkgo biloba leaf extract (GBE), a widely used herbal dietary supplement in Japan, on the pharmacokinetics and pharmacodynamics of nifedipine (NFP), a calcium-channel blocker, were studied using 8 healthy volunteers. Simultaneous oral ingestion of GBE (240 mg) did not significantly affect any of the mean pharmacokinetic parameters of either NFP or dehydronifedipine, a major metabolite of NFP, after oral administration of NFP (10 mg). However, the maximal plasma NFP concentrations in 2 subjects were approximately doubled by GBE, and they had severer and longer-lasting headaches with GBE than without GBE, with dizziness or hot flushes in combination with GBE. The mean heart rate after oral administration of NFP with GBE tended to be faster than that without GBE at every time point. Accordingly, it was concluded that GBE and NFP should not be simultaneously ingested as much as possible, and careful monitoring is needed when administering NFP concomitantly with GBE to humans.
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PMID:Studies on interactions between functional foods or dietary supplements and medicines. IV. Effects of ginkgo biloba leaf extract on the pharmacokinetics and pharmacodynamics of nifedipine in healthy volunteers. 1557 21

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