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)

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

Estrogens and progestins influence rates of cell proliferation in the breast and endometrium. Current oral contraceptives (OCs) inhibit endometrial cell division and protect against ovarian cancer. Findings of a 1991-1992 pilot trial of a prototype contraceptive show that the addition of a gonadotropin releasing hormone agonist [GnRHA] significantly reduces the doses of estrogen and progestin to a point lower than that of current OCs. The prototype includes the GnRHA and 0.625 mg of conjugated estrogen (CE) (6 days/week) and 10 mg medroxyprogesterone acetate (13 days/4 months). The subjects were 25-40 year old premenopausal women with a 5-fold greater than normal risk of breast cancer who did not want to become pregnant within the next 2 years and who lived in California. The women began the contraceptive regimen during the luteal phase of the menstrual cycle. Women in the treatment group had fewer symptoms than those in the control group because the regimen eliminated symptoms associated with the luteal phase (i.e., premenstrual syndrome). A small increase of the estrogen dose to 0.9 mg CE eliminated the few instances of hot flushes or vaginal dryness. Few subjects had unscheduled bleeding or spotting, and its incidence fell with time. Women in the treatment group experienced a beneficial increase in high density lipoprotein cholesterol. They lost bone mineral density (BMD) (measured at the lumbar spine) at an annual rate of 1.9% which was near significance (p = .07), even though 0.625 mg CE is enough to prevent loss of BMD in normal postmenopausal women. Women in the treatment group experienced a greater reduction in mammographic densities than did those in the control group. This is promising, since decreased densities are believed to be linked to a decreased risk of breast cancer. It appears that this regimen reduces the amount of breast cell mitotic activity. Researchers are developing a combined depot form of the complete regimen administered every 3-4 months.
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PMID:Contraception and cancer prevention. 1228 45

This article is focused on the use of norethisterone acetate as progestogen in hormone replacement therapy. Emphasis is made on the fact that the primary reason for adding a progestogen to hormone replacement therapy is to protect the endometrium against hyperplasia. In this paper we review data that demonstrate that hormone replacement therapy that includes norethisterone acetate has positive effects on the postmenopausal bone metabolism and that it increases bone mass more than expected and more than treatment with alendronate. All available evidence is reviewed to show that norethisterone acetate, if given in the correct dosage, does not influence serum lipids and lipoproteins in any negative way. It is furthermore shown that norethisterone acetate seems to be superior compared to other progestogens to provide optimum bleeding control and endometrial protection. Also, hormone replacement therapy combinations with norethisterone acetate efficiently alleviate hot flushes. Hormone replacement therapy and the risk of breast cancer and the role of progestogens are discussed.
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PMID:Norethisterone acetate in combination with estrogen: effects on the skeleton and other organs. A review. 1238 12

Hot flashes affect about three fourths of postmenopausal women and are one of the most common health problems in this demographic group. Dysfunction of central thermoregulatory centers caused by changes in estrogen levels at the time of menopause has long been postulated to be the cause of hot flashes. Treatment should begin with a careful patient history, with specific attention to the frequency and severity of hot flashes and their effect on the individual's function. For mild symptoms that do not interfere with sleep or daily function, behavioral changes in conjunction with vitamin E (800 IU/d) use is a reasonable initial approach. For more severe symptoms, the next step is to determine whether there is a contraindication or a personal reservation to estrogen replacement therapy. For women who are able and willing to use estrogen, it will successfully relieve symptoms by about 80% to 90%. In patients with a history of breast or uterine cancer, treatment with the progestational agent megesterol acetate appears to be a safe alternative that also decreases hot flashes by approximately 80%. For women unwilling or unable to use hormone therapy, one of the newer antidepressant agents can be prescribed. Venlafaxine decreases hot flashes by about 60%. Gabapentin is another drug that appears promising as therapy for women unable or unwilling to use estrogen, and the results of ongoing trials to determine its efficacy are eagerly awaited. The use of clonidine, methyldopa, and belladonna should be discouraged because of their modest efficacy and adverse effects.
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PMID:Pathophysiology and treatment of hot flashes. 1263 May 92

For the past 25 years, the estrogen antagonist tamoxifen has been considered the 'gold standard' for the treatment of breast cancer, despite certain tolerability issues and the risk of developing resistance. The aromatase inhibitors work by blocking the conversion of androgens to estrogen and were developed for use in patients where ovarian function had ceased (naturally, surgically or pharmacologically). Anastrozole, a third-generation nonsteroidal aromatase inhibitor that is a highly potent and selective inhibitor of the aromatase enzyme, has been shown to be superior to the gold standard tamoxifen for the first-line treatment of postmenopausal women with advanced breast cancer. As second-line therapy, anastrozole has shown superior survival compared with megestrol acetate and is also efficacious as neoadjuvant treatment in postmenopausal women and in combination with goserelin for the treatment of premenopausal women with advanced breast cancer. More recently, the results of the ATAC (anastrozole, tamoxifen, alone or in combination) trial, a large study in 9366 patients, demonstrated that anastrozole was significantly superior to tamoxifen for the treatment of postmenopausal women with early breast cancer, with regards to disease-free survival (p = 0.013) and incidence of contralateral breast cancer (p = 0.007). In addition, anastrozole was shown to be significantly better tolerated than tamoxifen with respect to endometrial cancer (p = 0.02), vaginal bleeding/discharge (p < 0.0001 for both), ischaemic cerebrovascular events (p = 0.0006), thromboembolic events (p = 0.0006) and hot flushes (p < 0.0001), while tamoxifen was associated with significantly less musculoskeletal disorders and fractures than anastrozole (p < 0.0001 for both). This review focuses on both the clinical pharmacology and the clinical data of anastrozole with emphasis on its future applications.
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PMID:Anastrozole (Arimidex) in clinical practice versus the old 'gold standard', tamoxifen. 1250 8

To evaluate the efficacy of a long-acting preparation of medroxyprogesterone acetate for hot flash management, 3 men receiving androgen ablation therapy for prostate cancer and 15 women with a history of breast cancer were treated as part of clinical practice with three biweekly intramuscular injections of 500 mg depomedroxyprogesterone. A review of hot flash diaries and patient charts were completed to evaluate the effectiveness and tolerability of these injections for managing hot flashes. Treatment was associated with an approximate 90% decrease in hot flashes (95% CI 82-97%). Daily hot flash frequency decreased from a mean of 10.9 on the first day of treatment (95% CI 8.0-13.8 hot flashes per day) to a mean of 1.1 hot flashes 6 weeks later (95% CI 0.5-1.8 hot flashes) and to a mean of 0.7 hot flashes 12 weeks following therapy initiation (95% CI 0.1-1.2). Improvement in the hot flashes remained for months after discontinuing the injections in many patients. Reported side effects were minimal. This experience suggests that treatment with depomedroxyprogesterone may be an effective and well-tolerated option for the treatment of hot flashes.
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PMID:Depomedroxyprogesterone acetate for hot flashes. 1255 11

Clinical and experimental studies indicate that combined unique conjugated estrogens and medroxyprogesterone acetate moderately increase the risk of breast cancer in postmenopausal women. Classically, hormone replacement therapy is contra-indicated in women with a past history of breast cancer due to the fear of recurrence. However, these postmenopausal patients complain about hot flushes and adjuvant hormonal therapies (such as aromatase inhibitors, SERMs and Tamoxifen...) aggravate their symptoms. Observational studies and their meta-analyses do not show a deleterious effect but rather a beneficial impact of hormone replacement therapy among women with a past history of breast cancer. We summarise all these studies and their biological, clinical and epidemiological interpretations. We conclude that short term hormone replacement therapy is safe among those women requesting a replacement therapy after complete information. It is however advisable to conclude definitely only when prospective randomised trials with estradiol or tibolone (a promising alternative) will be available. Such ongoing studies will allow to conclude definitely the possible benefits and risks of hormone replacement therapy among patients with a past history of breast cancer.
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PMID:[Hormone replacement therapy after breast cancer. Yes...or no?]. 1269 7

Over 24-25 February 2003 in Funchal, Madeira, Novo Nordisk gathered together 25 of the top international hormone replacement therapy (HRT) experts, in order to debate the results of the Women's Health Initiative (WHI) and interpret its possible implications for the future use of HRT. The meeting covered many interesting and controversial areas, addressing the complex and multifaceted issues with insight and realism. Some of the areas covered at the meeting were the use of HRT as a short- or long-term therapy for hot flushes, for general menopausal symptom relief and in osteoporosis prevention; the overall risk-benefit profile and specific breast cancer concerns were also discussed. The WHI data were reviewed and summarized, and, although it was generally agreed that the study was well designed and executed, its relevance to standard hormone therapy for clinical practice must be seriously called into question. The target population used in the WHI is not representative of the target population for whom menopausal HRT is normally considered. It is important to note that randomized controlled trials such as the WHI are really scientific tools for a group of research participants, not a form of individualized medical management. Since their publication, the relevance of the WHI study results for everyday clinical practice has been the subject of controversy. The WHI targeted a group of women who were much older than those normally treated and who had numerous other risk factors. These were not women for whom a practicing clinician would think about initiating hormone therapy with the regimen that was used. Putting a high-risk 70-year-old woman on 0.625 mg conjugated equine estrogens (CEE) plus 2.5 mg medroxyprogesterone acetate would not seem appropriate for any indication. With this in mind, we reviewed statements and guidance that followed the release of the WHI to the media, putting them in context with the actual results. Focusing on data taken out of context and without reference to subject profiles, the media created an emotive wave of uncertainty for patients and physicians, which needs to be addressed through realistic, factual communication. It is clear that hormone therapy is effective for postmenopausal symptoms and osteoporosis prevention. Timing is critical for the initiation of therapy and length of treatment. The individual's unique personal profile must be assessed. This leads to the paradox of osteoporosis prevention: therapy should be long-term, but it is long-term therapy that may increase breast cancer risk. The meeting reviewed the uncertain nature of the risks for breast cancer, although the evidence is becoming stronger that combinations of estrogen and progestogen cause a modest increase in risk after 5 years, while this seems not to be true for estrogen alone. Cardiovascular disease issues were also reviewed and discussed. This is perhaps the most misinterpreted result that came out of the WHI, given the population of women studied. Considering the vascular biology and effects of early interventions, the WHI finding that hormone therapy has no place in primary cardiovascular protection is an unwarranted conclusion. Other issues regarding the risk-benefit profile of HRT for the individual patient were also discussed. Additionally, presenters explored the possibility of class effects against the potential risk factors associated with particular estrogen and progestogen types. It is quite clear that CEE and 17beta-estradiol differ with respect to their source and composition; pharmacokinetic and metabolic data indicate that they differ in their total estrogenic potency, with CEE possessing greater estrogenic potency. Using 17beta-estradiol at the lowest dosage level can provide safe and effective therapy for most indications. The evidence for progestogen differences is even more clear. Medroxyprogesterone acetate and norethisterone acetate have different pharmacokinetic profiles and different activities on steroid receptors. Evidence from preclinical and clinical studies supports the conclusion that these differences result in different pharmacological and clinical effects in favor of norethisterone acetate. Having comprehensively discussed and reviewed all available evidence, a consensus was achieved with regard to appropriate therapy: HRT should be given to women with menopausal complaints to meet their individual needs, taking into account their individual risk profile and the overall therapeutic objectives.
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PMID:Hormone replacement therapy in the post-Women's Health Initiative era. Report a a meeting held in Funchal, Madeira, February 24-25, 2003. 1294 98

Hormone replacement therapy (HRT) is effective for relieving vasomotor symptoms such as hot flash and vaginal atrophy and for preventing bone loss in postmenopausal and bilaterally ovariectomized women. However, compliance with HRT was reported to be low despite the benefits of HRT. In addition, results of several recent large-scale randomized clinical trials have demonstrated that protection from cardiovascular disease is not an indication for treatment with estrogen and progestin in postmenopausal women. Recent studies have demonstrated that low-dose HRT is safe and effective for prevention of postmenopausal bone loss. Low-dose HRT has also been shown to be effective for reducing the number and severity of hot flashes, improving vaginal atrophy, and inducing favorable changes in lipids, lipoproteins and hemostatic factors. Moreover, low-dose regimens of CEE (conjugated equine estrogen) and MPA (medroxyprogesterone acetate) result in higher rates of amenorrhea and endometrial protection compared with the conventional dose of HRT. Low-dose HRT may improve the compliance rate and may be more effective than conventional-dose HRT for reducing the risk of breast cancer. On the other hand, it has been shown that transdermal estrogen treatment reduces the incidence and severity of hot flashes and that long-term treatment with transdermally administered estrogen is effective for protection against osteoporosis. Transdermal administration of estrogen is recommended in postmenopausal women with hypertriglycemia because this treatment has little effect on lipid metabolism. The serum estradiol level was reported to be closely related to estrogenic effects on various tissues. An HRT regimen should be based on the needs of each patient. Serum estradiol levels in women should be maintained at appropriate levels for benefits and not be excessively high in order to prevent side effects. Selection of the most appropriate regimen of HRT (dose, route of administration and schedule) for the needs of the individual are important factors to increase the rate of continuation with HRT.
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PMID:Hormone replacement therapy in postmenopausal women. 1367 82

A combination of 2 mg estradiol valerate with 2 mg dienogest (E2V/DNG) (Climodien, Schering AG, Berlin, Gemany) is the first continuous combined postmenopausal hormone replacement therapy (HRT) preparation to contain a progestogen with substantial antiandrogenic activity. A study of its clinical efficacy and safety in a comparative study versus a combination of 2 mg estradiol with 1 mg norethisterone acetate (E2/NETA) has shown both preparations to be highly effective in achieving a rapid response in women with postmenopausal symptoms, in terms of hot flushes and the Kupperman index. Biopsy and ultrasound studies have demonstrated that E2V/DNG quickly and effectively achieved endometrial atrophy in the vast majority of subjects, suggesting a protective role in endometrial proliferation. Data on PP-14 (glycodelin) levels may indicate that E2V/DNG is even more effective than E2/NETA in maintaining endometrial atrophy. No-bleed rates with E2V/DNG at 1, 6 and 12 months were at least as favorable as those with other standard HRT products, with evidence that the no-bleed state is attained more quickly with E2V/DNG. The proportions of women with the no-bleed state in a large-scale study (n = 1501) at 1, 6 and 12 months were 71.8%, 76.6% and 86.4%, respectively. Women with irregular bleeding before treatment responded to E2V/DNG in a manner similar to those without bleeding; this concordance was especially marked after five cycles of treatment. In the comparative study, the mean number of days of bleeding over 12 cycles was significantly lower for E2V/DNG than for E2/NETA. Overall, the profiles of adverse events recorded in clinical use were similar in the two preparations, whilst the safety profile of E2V/DNG in the large-scale study was similar to that of other HRT preparations and gave no cause for clinical concern. The 2 mg E2V/2 mg DNG preparation was associated with a favorable lipid profile, whilst a similar combination (2 mg E2V/3 mg DNG) showed no impact on carbohydrate metabolism or hemostasis, compared to placebo. In summary, 2 mg E2V/2 mg DNG is a novel continuous combined HRT preparation that is effective in treating postmenopausal symptoms rapidly, and has a highly favorable bleeding profile. Studies of the safety of 2 mg E2V/2 mg DNG in clinical use have uncovered no factors likely to be disadvantagous in comparison with other HRT products in widespread use.
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PMID:Clinical efficacy and safety of combined estradiol valerate and dienogest: a new no-bleed treatment. 1466 41


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