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)

Seventy-three healthy, postmenopausal women, aged 45-54 years, were randomly assigned to one of three groups for 2 years of treatment: 17 beta-oestradiol 1.5 mg on days 1-12 and 17 beta-oestradiol 1.5 mg + desogestrel 150 micrograms on days 13-24 (E2/DG) or oestradiol valerate 2 mg on days 1-11 and oestradiol valerate 2 mg + medroxyprogesterone acetate 10 mg on days 12-21 (E2V/MPA) or placebo. Fifty-seven women (78%) completed the study. Bone mineral content of the distal regions of the forearms (measured by single photon absorptiometry, SPA) and bone mineral density of the spine (measured by dual energy X-ray absorptiometry, DXA) showed increases of 0.5-1% and 4-5%, respectively, in the hormone groups over 2 years. The placebo group exhibited a decrease in spinal bone density of 2% per year, and in the forearm of 2.5-3.5% per year. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium) decreased significantly to premenopausal levels in the hormone groups but remained unchanged in the placebo group. In both hormone groups total cholesterol decreased by about 9% (P less than 0.001), whereas low density lipoprotein cholesterol decreased by 16% in the E2/DG group and 20% in the E2V/MPA group (P less than 0.001). High density lipoprotein cholesterol showed only minor, insignificant changes in the hormone groups. The placebo group had virtually unchanged values. Climacteric symptoms, including hot flushes, were significantly reduced in both hormone groups. Bleeding occurred regularly in about 80% of the women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Desogestrel in hormone replacement therapy: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding. 183 79

The effect transcutaneous oestradiol for four months supplemented by medroxyprogesterone (Perlutex) from the 12th to 26th day of every month was assessed in an open uncontrolled prospective investigation in 34 women with menopausal symptoms and follicle stimulating hormone greater than 40 international units and luteinizing hormone greater than 25 international units. A marked effect was found on sweating and hot flushes and other menopausal complaints as expressed by Kupperman's menopausal index. Serum oestradiol increased during the first two months to follicular phase values and this was followed by an unexplained decrease after the fourth month which did not, however, result in aggravation of the symptoms. No alterations were found in steroid-hormone-binding globulin, lipids and body weight. Whether the patients placed the plasters in the hip or abdominal regions was found to be of no significance. Seventeen patients had no side effects of the treatment. Nine patients had transient skin symptoms which disappeared spontaneously. Five patients had mastalgia which disappeared after reduction of the Perlutex dose. One patient developed metrorrhagia. A total of three patients abandoned the treatment: one on account of skin symptoms, one on account of high blood pressure and a third on account of psychiatric symptoms which were unrelated to the treatment. A total of 28 patients wanted to continue treatment after the fourth month.
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PMID:[Transcutaneous estradiol treatment in the climacteric]. 240 44

Ninety-five healthy women who had been amenorrheic for at least 6 months were randomly assigned to one of four cyclic, sequential hormone regimens for 1 year. Groups A and C received 0.625 or 1.25 mg conjugated equine estrogen (Premarin), respectively, from days 1-25 and 5 mg medroxyprogesterone acetate (Provera) from days 15-25. Groups B and D were given 0.625 or 1.25 mg conjugated equine estrogen, respectively, from days 1-25 and placebo from days 15-25. Plasma estrone levels were physiologic after the lower dose of conjugated equine estrogen and supraphysiologic after ingestion of the higher dose. All four treatment regimens successfully controlled hot flushes, but patients who received 1.25 mg conjugated equine estrogen with or without medroxyprogesterone acetate had a higher energy level and a more enhanced sense of well-being (P less than .05). The four treatments all had favorable effects on lipid metabolism, albeit in a dose-related manner: After 1 year of treatment, high-density lipoprotein levels increased 4.3, 13.7, 13.4, and 19% in groups A, B, C, and D, respectively, compared with pre-treatment values. The high-density lipoprotein/low-density lipoprotein ratios, an antiatherogenic index, increased by 7.3, 13.6, 24, and 43% in groups A, B, C, and D, respectively. The findings of this study on the relative effects of different doses of oral estrogen and progestin, administered sequentially, on clinical symptoms and lipid metabolism provide guidelines for the treatment of postmenopausal women.
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PMID:A prospective one-year study of estrogen and progestin in postmenopausal women: effects on clinical symptoms and lipoprotein lipids. 270 4

Combination oral contraceptive (COC) users have reduced risks of ovarian and endometrial cancer, but COCs have not reduced breast cancer risk. We have previously argued that a hormonal contraceptive with substantially lower doses of sex-steroids should reduce breast cancer risk by decreasing the breast epithelial cell proliferation below usual premenopausal levels. We report here the preliminary results of a pilot trial with such a prototype contraceptive consisting of an agonist of gonadotropin releasing hormone (GnRHA) administered with low doses of an oral estrogen (0.625 mg of conjugated estrogen, CE, for 6 days every week) and intermittent oral progestogen (10 mg of medroxyprogesterone acetate, MPA, for 13 days every 4 months). Eighteen subjects at five-fold or greater increased breast cancer risk were entered and randomized -12 to the contraceptive arm and 6 to a control arm. The principal endpoints included tolerance of the regimen, vaginal bleeding patterns, and the regimen's effect on the endometrium, bone metabolism, and lipids. A symptom questionnaire was used to assess tolerance; the contraceptive subjects had fewer symptoms following initiation of the regimen. This results from the elimination of symptoms associated with the luteal phase of the menstrual cycle, commonly referred to collectively as premenstrual syndrome, PMS. The few occurrences of hot flushes or vaginal dryness that did occur were eliminated by small increases in estrogen dose (0.9 mg CE). Scheduled vaginal bleeding occurred associated with most periods of progestogen administration. Unscheduled bleeding or spotting was infrequent and decreased with time on the regimen. A beneficial rise in high-density lipoprotein cholesterol was evident in the contraceptive subjects. Despite the use of an estrogen dose which is known to prevent loss of bone mineral density in normal postmenopausal women, an annualized loss of 1.9% was seen in contraceptive subjects. It is hypothesized that this is secondary to inhibition of ovarian androgen production by the GnRHA, which may additionally account for changes in libido occasionally reported with GnRHA. The study continues with the addition of a small dose of androgen to replace that lost by the action of the GnRHA.
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PMID:Pilot trial of a gonadotropin hormone agonist with replacement hormones as a prototype contraceptive to prevent breast cancer. 839 Mar 40

In order to determine the usual dose in the first line therapy and a high dose in the second or third line therapy, a dose finding study of a novel antiestrogen NK 622 (toremifene citrate) was performed in patients (pts) with advanced or recurrent breast cancer. NK 622 was orally administered daily once for more than 8 weeks. In pts without previous drug therapy or in pts with cancer relapse after adjuvant therapy, the response rates [(CR + PR)/total] were 24.1% (7/29), 13.8% (4/29), 20.0% (1/5) and 40.0% (2/5) at doses of 40, 60, 120 and 240 mg/day, respectively. A 40 mg/day dose showed an objective response only in postmenopausal pts with estrogen receptor (ER) positive or unknown cancer. At a dose of 60 mg/day, some of the responding cases were premenopausal pts or pts with ER(-) cancer. In pts with cancer relapse during adjuvant therapy or in those with previous therapy and/or radiation, response rates were 25.0% (2/8), 0% (0/4), 13.5% (5/37) and 10.3% (4/39) at doses of 40, 60, 120 and 240 mg/day, respectively. Response was more frequent in pts with ER (+) cancer than with ER (-) cancer. The response rates in pts with previous therapy including tamoxifen (TAM) except medroxyprogesterone (MPA) were 14.3% (4/28) at a 120 mg/day dose and 6.1% (2/33) at a 240 mg/day dose. In pts with previous therapy including TAM, MPA and other antitumor agents, the rate was 18.2% (2/11) at a 120 mg/day dose. Side effects such as elevation of GOT, GPT and serum Ca level, decrease of hemoglobin, anorexia, nausea/vomiting, fatigue, dizziness and hot flush were observed. These side effects were moderate in grade and reversible. Dose dependency of side effects was not clearly observed in grade and incidence. From these results, NK 622 is expected to be a safe drug with efficacy in first line therapy at a dose of 40 mg/day and in second or third line therapy at a dose of 120 mg/day.
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PMID:[Phase II study of NK 622 (toremifene citrate) in advanced breast cancer, a multicentral cooperative dose finding study]. 842 89

Most clinicians advise women to continue using contraception for 12 months after menstruation has ceased. Some recommend that women less than 45 years old continue contraception for 2 years after menstruation has ceased. A fertility specialist says that women can stop taking nonhormonal methods after 6 months of amenorrhea if women experience hot flushes. If there are no classic menopausal symptoms, however, they should wait for 12 months before stopping contraception use. Hormonal methods may mask menopausal signs. If a woman has no contraindications, she can use them safely until age 50, however. Women should still use contraception after menopause because irregular ovulation may occur. In older women, the most useful measure of ovarian history is perhaps a good menstrual history rather than a high level of follicle stimulating hormone. A woman needs to consider her age, health status, menstrual history, sexuality, risk of sexually transmitted diseases, past contraception use, lifestyle, obstetric history, and attitude toward abortion when choosing a contraceptive method during the perimenopausal years. Options may include male or female sterilization, combined oral contraceptives, the progestogen-only pill, Depo-Provera, IUD, female barrier methods (diaphragm, cervical cap, contraceptive sponge, and female condom), condoms, spermicides, and postcoital contraception. Assuming the mucus signs can be reliably determined, natural family planning is an alternative for some older women. Depending on coitus interruptus can be stressful for older women because it is not easy to distinguish between a possible pregnancy and an irregular menses.
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PMID:Contraception in the perimenopause. 1228 72

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

Oestrogen therapy is the gold standard treatment for hot flushes/night sweats, but it and oestrogen/progestin are not suitable for all women. MPA (medroxyprogesterone acetate) reduces hot flushes, but its effectiveness compared with oestrogen is unknown. In the present study, oral oestrogen [CEE (conjugated equine oestrogen)] and MPA were compared for their effects on hot flushes in a planned analysis of a secondary outcome for a 1-year randomized double-blind parallel group controlled trial in an urban academic medical centre. Participants were healthy menstruating women prior to hysterectomy/ovariectomy for benign disease. A total of 41 women {age, 45 (5) years [value is mean (S.D.)]} were enrolled; 38 women were included in this analysis of daily identical capsules containing CEE (0.6 mg/day) or MPA (10 mg/day). Demographic variables did not differ at baseline. Daily data provided the number of night and day flushes compared by group. The vasomotor symptom day-to-day intensity change was assessed by therapy assignment. Hot flushes/night sweats were well controlled in both groups, one occurred on average every third day and every fourth night. Mean/day daytime occurrences were 0.363 and 0.187 with CEE and MPA respectively, but were not significantly different (P=0.156). Night sweats also did not differ significantly (P=0.766). Therapies were statistically equivalent (within one event/24 h) in the control of vasomotor symptoms. Day-to-day hot flush intensity decreased with MPA and tended to remain stable with CEE (P<0.001). In conclusion, this analysis demonstrates that MPA and CEE are equivalent and effective in the control of the number of hot flushes/night sweats immediately following premenopausal ovariectomy.
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PMID:Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy. 1741 85

Excessive menstrual bleeding reflects aberrant angiogenesis, generally due to submucosal myomas and endometrial polyps, although it is also frequently observed with long-term progestin-only contraception, impaired haemostasis and hormonal disorders. Surgery (hysterectomy, endometrial ablation) is used too frequently. Uterine artery embolisation is also an option for myomas. Medical treatments include combined oral contraception, progestins and levonorgestrel-releasing Intrauterine System. Gonadotropin-releasing hormone agonists provide significant improvements in bleeding for myomas, but also decrease estrogen secretion (e.g. hot flushes, decreased bone mass). Progestins, although used widely, remain poorly effective as they promote myoma cell growth. Recently, Selective Progesterone Receptor Modulators (SPRMs) have been shown to induce amenorrhea whilst maintaining endogenous estrogen secretion. Phase II studies have also demonstrated decreased fibroid size in SPRM-treated women. Although the mechanism of amenorrhea observed after SPRM treatment is still poorly understood, they may control uterine bleeding via a direct effect on endometrial blood vessels. Suppression of bleeding in women with uterine fibroids receiving SPRMs is associated with moderate reductions in uterine artery blood flow, without major changes in angiogenic factors and extracellular matrix composition; a clear difference to modifications observed with progestins. These data suggest major progress in the treatment of excessive menstrual bleeding.
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PMID:Current and future medical treatments for menometrorrhagia during the premenopause. 2218 55


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