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As more women are living longer, there is an increasing need for women to discuss hormone replacement therapy (HRT) with their physicians. This task is complicated by areas of scientific uncertainty and evolving data concerning the risks and benefits of HRT. Benefits of HRT that are supported by strong scientific evidence include relief from menopausal symptoms such as hot flashes, prevention of osteoporosis, cardioprotective effects, relief of urogenital atrophy, and decreased urinary incontinence. Benefits supported by observational evidence include improvement of emotional lability and depression, improved sense of well-being in patients with rheumatoid arthritis, increased dermal and total skin thickness, improved verbal memory skills, and decreased risk of colon cancer. Risks to consider include a possible increase in the incidence of breast cancer and an increase in endometrial cancer in women who have an intact uterus and do not receive a progestin. Women in various risk groups, such as those at risk for coronary artery disease, osteoporosis, or breast cancer, must consider the risk-to-benefit ratio for their own individual circumstances.
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PMID:Current concepts in postmenopausal hormone replacement therapy. 869 Nov 83

Postmenopausal estrogen deficiency may result in a wide variety of physiologic disorders, including vasomotor symptoms, urogenital atrophy, an increase in the risk of coronary heart disease, osteoporotic fractures, and Alzheimer's disease. The growing body of evidence, including much that is newly published, demonstrating that hormone replacement therapy (HRT) can largely prevent or mitigate these sequelae, will be reviewed in this paper. The efficacy of HRT in alleviating vasomotor and urogenital discomfort, the most common symptoms of postmenopausal estrogen deficiency, is well established. Evidence from over 30 epidemiologic studies indicates that estrogen reduces the risk of coronary heart disease (CHD) by 50%. The risk of major CHD has been found to be markedly reduced in women who receive combined estrogen/progestogen therapy compared to nonusers (or estrogen-alone users). Estrogen is recommended as the modality of choice to prevent bone loss: data supporting a positive effect of estrogen on the risk of wrist and vertebral fracture are quite favorable. Similarly, outcomes of recent investigations have demonstrated a positive impact of HRT on both psychological function and the risk of osteoarthritis. In addition, HRT substantially reduces the risk of colon cancer. Moreover, the potential for HRT to delay the progression or reduce the risk for developing Alzheimer's disease is a new area of research that shows promise. Improvements in quality-of-life assessments have also been reported in conjunction with the relief of menopausal symptoms by HRT. Clinicians should be aware of the large amount of new evidence that strengthens the case for wider use of HRT. Based on these new data, physicians may conclude that HRT would benefit the majority of their postmenopausal patients and thus encourage HRT use in the absence of known risk factors.
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PMID:Benefits of hormone replacement therapy--overview and update. 939 82

ERT/HRT is clearly of use in relieving menopausal symptoms such as hot flashes and genitourinary changes. ERT/HRT also clearly reduces the risks of osteoporotic fracture, of cardiovascular events and deaths, and of developing colon cancer. ERT and, perhaps even more, HRT are, however, associated with an increased risk of developing breast cancer. This effect becomes more marked with long-term use (> or = 10 years); ERT/HRT use for more than 10 years is also associated with an increase in deaths from breast cancer. Because the underlying mortality risk for the average woman is, however, much greater from cardiovascular disease (approximately 22%) than from breast cancer (approximately 3.3%), the reduction in risk of cardiovascular death associated with ERT/HRT (from 22% to 15%) much outweighs the increase in risk of death from breast cancer (from 3.3% to 4.1%). Thus, overall, the average woman will gain more year(s) of life than she will lose by taking ERT/HRT. Even for a woman with a high risk of breast cancer and a low risk of cardiovascular disease, there will still be a net, although lower, gain in year(s) of life. Thus, the use of ERT/HRT would seem well worth considering for a well woman at the time of menopause.
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PMID:Estrogen/hormone replacement therapy and the etiology of breast cancer. 992 44

In the decades since hormone replacement therapy (HRT) was introduced, there has never been more controversy surrounding it than at present. Physicians and patients are faced with many questions regarding risk and few definitive answers. This article will discuss the current health benefits associated with hormone replacement, including its beneficial effects on the cardiovascular system, osteoporosis, vasomotor symptoms, colon cancer risk, and Alzheimer's disease. Epidemiologic evidence suggesting an association between HRT, estrogen in particular, and breast cancer will also be discussed. Currently, there is no definitive evidence of a link between HRT and breast cancer risk, particularly with short-term use. Yet, only about 15% of women who would benefit from such therapy actually use it. This is due, in part, to concerns regarding breast cancer risk. For the breast cancer survivor, the current dictum is that estrogen replacement is contraindicated. For these patients and those who choose not to start HRT, the list of adequate, currently available alternatives for the many menopausal symptoms is still insufficient. Because of the known beneficial effects of HRT, its extension to patients with a history of hormone-dependent cancer may be indicated. However, randomized, controlled trials must be performed to assess the potential risks in these patients.
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PMID:Management of menopausal symptoms in the cancer patient. 1054 64

Estrogen used alone (estrogen replacement therapy [ERT]) or with the addition of progesterone (hormone replacement therapy [HRT]) is known to be effective in reducing menopausal symptoms including hot flashes, vaginal dryness and urinary symptoms. It has been traditionally contraindicated, however, in women with a previous diagnosis of breast cancer because of fear that it may increase the risk of recurrence. There are considerable basic scientific data but little methodologically strong observational data and none from randomized studies concerning the use of ERT in women with a prior diagnosis of breast cancer. From our knowledge of the physiology of breast cancer, however, estrogen and/or progestational agents should be used with caution in women with a previous diagnosis of breast cancer. There are currently many alternatives to ERT/HRT in the prevention of menopausal symptoms such as vitamin E, clonidine and selective serotonin reuptake inhibitor antidepressants such as venlafaxine. There are also a variety of other approaches to the prevention of osteoporosis and cardiovascular disease including bisphosphonates, diet, and exercise; and diet, exercise, and statins, respectively. Other suggested beneficial effects of estrogen such as colon cancer prevention can be approached by the use of aspirin or the non-steroidals. Several trials of ERT/HRT used for 2 years versus no therapy in menopausal women with a previous diagnosis of breast cancer are ongoing in Europe and Britain, and should give us stronger data as to the role of HRT in this setting.
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PMID:Hormone replacement in women with a history of breast cancer. 1152 54

Sex steroids are not known to damage DNA directly. They can stimulate or inhibit cell proliferation, and thus can modulate tumor developmental progression. Sex steroid-related tumors in women are represented by breast cancer and endometrial cancer, and a possible relationship exists between sex steroids and both ovarian and colon cancer. Among current ERT users or those who stopped use 1-4 years previously, the relative risk of having breast cancer diagnosed increases by a factor of 1.023 for each year of hormone use. This increase is comparable with the effect on breast cancer of delaying menopause, and seems to be largely limited to lean women. The breast cancers diagnosed during ERT are more likely to contain ER and are less aggressive. Some reports indicate no increase in breast cancer mortality in HRT users. Recent data suggest that an estrogen-progestin regimen may increase breast cancer risk beyond that associated with estrogen alone. However, the effect of progestogens on the breast awaits further clarification. ERT/HRT is generally considered to be contraindicated in breast cancer patients, as no firm data are yet available from randomized clinical trials. Despite the potential risks, ERT/HRT could be considered for breast cancer patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given, particularly in women with ER--(hormone-resistant) cancers. Unopposed estrogen therapy is known to increase endometrial cancer risk, and is appropriate only for hysterectomized women. To negate the excess risk of endometrial hyperstimulation, an adequate progestin dose must be given in a continuous combined regimen or for an appropriate number of days in sequential regimens (10 days or more for some progestogens or 12 days or more for other progestogens). An appropriate combination of estrogen and progestin does not appear to increase, and may even decrease, the risk of endometrial cancer. HRT is generally considered to be contraindicated in endometrial cancer patients. Despite the potential risks, HRT could be considered for patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given. Available data suggest a reduced risk of colorectal adenoma and colon cancer in current users of HRT, but definitive studies are still needed. There is no contraindication to HRT prescription in colon cancer survivors. Consistent epidemiological data describe a decreased incidence of ovarian cancer with oral contraceptive use during the reproductive years. Studies on HRT and risk of epithelial ovarian cancer have produced conflicting results but most data seem to exclude a strong association. While no data contraindicate HRT use in epithelial ovarian cancer survivors, current studies do not allow us to exclude the possibility that estrogens alone could stimulate ovarian cancer growth in a small fraction of patients. Additional studies are required. It is important to consider that not all estrogens and progestins are used with the same dosage, route of administration (oral, transdermal and for estradiol intranasal) and, mostly, different estrogens do not show the same bioavailability and tissue effects. The available data do not allow to discriminate for all these variables and therefore it is inappropriate to consider jointly all forms of hormonal therapy. This issue is considered as an important area for future evaluation and research. The International Menopause Society is in the process of drawing up specific recommendations for further research in the field of HRT and cancer.
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PMID:Controversial issues in climacteric medicine II. Hormone replacement therapy and cancer. International Menopause Society Expert Workshop. 9-12 June 2001, Opera del Duomo, Pisa, Italy. 1158 39

Sex steroids are not known to damage DNA directly. They can stimulate or inhibit cell proliferation, and thus can modulate tumor developmental progression. Sex steroid-related tumors in women are represented by breast cancer and endometrial cancer, and a possible relationship exists between sex steroids and both ovarian and colon cancer. Among current ERT users or those who stopped use 1-4 years previously, the relative risk of having breast cancer diagnosed increases by a factor of 1.023 for each year of hormone use. This increase is comparable with the effect on breast cancer of delaying menopause, and seems to be largely limited to lean women. The breast cancers diagnosed during ERT are more likely to contain ER and are less aggressive. Some reports indicate no increase in breast cancer mortality in HRT users. Recent data suggest that an estrogen-progestin regimen may increase breast cancer risk beyond that associated with estrogen alone. However, the effect of progestogens on the breast awaits further clarification. ERT/HRT is generally considered to be contraindicated in breast cancer patients, as no firm data are yet available from randomized clinical trials. Despite the potential risks, ERT/HRT could be considered for breast cancer patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given, particularly in women with ER-(hormone-resistant) cancers. Unopposed estrogen therapy is known to increase endometrial cancer risk, and is appropriate only for hysterectomized women. To negate the excess risk of endometrial hyperstimulation, an adequate progestin dose must be given in a continuous combined regimen or for an appropriate number of days in sequential regimens (10 days or more for some progestogens or 12 days or more for other progestogens). An appropriate combination of estrogen and progestin does not appear to increase, and may even decrease, the risk of endometrial cancer. HRT is generally considered to be contraindicated in endometrial cancer patients. Despite the potential risks, HRT could be considered for patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given. Available data suggest a reduced risk of colorectal adenoma and colon cancer in current users of HRT, but definitive studies are still needed. There is no contraindication to HRT prescription in colon cancer survivors. Consistent epidemiological data describe a decreased incidence of ovarian cancer with oral contraceptive use during the reproductive years. Studies on HRT and risk of epithelial ovarian cancer have produced conflicting results but most data seem to exclude a strong association. While no data contraindicate HRT use in epithelial ovarian cancer survivors, current studies do not allow us to exclude the possibility that estrogens alone could stimulate ovarian cancer growth in a small fraction of patients. Additional studies are required. It is important to consider that not all estrogens and progestins are used with the same dosage, route of administration (oral, transdermal and for estradiol intranasal) and, mostly, different estrogens do not show the same bioavailability and tissue effects. The available data do not allow to discriminate for all these variables and therefore it is inappropriate to consider jointly all forms of hormonal therapy. This issue is considered as an important area for future evaluation and research. The International Menopause Society is in the process of drawing up specific recommendations for further research in the field of HRT and cancer.
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PMID:Hormone replacement therapy and cancer. 1182 70

The Women's Health Initiative (WHI) is sponsored by the NIH. The study focuses on risk and benefits of strategies that could potentially reduce the incidence of heart disease, breast and colon cancer, and fractures in postmenopausal women. One arm of the study, a double-blind, placebo-controlled trial, looking at the effects of continuous combined estrogen-progestin regimen was stopped prematurely based on health risks which exceeded health benefits. The main reason for this decision was the increase in risk of invasive breast cancer, as well as a slight increase in the rate of myocardial infarction and stroke. In this paper, we inform our colleagues of the detailed results of the study. We comment on its limitation and discuss the new original observations. Finally, we integrate the others to previous world literature data that are confirmed by the WHI study. It is important for the individual prescribing practitioner to issue practical conclusions and therapeutic recommendations. The department of Obstetrics and Gynaecologic of the University of Liege, in agreement with the European Menopause Society and the International Menopause Society, is convinced that there is no alternative to the hormone replacement therapy for menopausal symptoms. We should stick to the traditional indications for hormones, namely vasomotor symptoms and osteoporosis. We should continue to recommend hormones for symptomatic women. One should realize that the risk for breast cancer appears only after several years of use, and the risk for cardiovascular events below age 60 is very small (the age of the patients was 63 at inclusion in the WHI study). We should encourage women to take the necessary measures for routine, periodic breast examinations (both manual, echographic and radiographic). Women who use HRT for more than 5 years should discuss the latest data of the WHI study with their physician, in order to consider their individual benefit-risk equation. Those who feel good on hormones and are fully satisfied with this treatment should learn of possible harm after long-term use. It is important to take into account the importance of quality of life. We should leave to the patient the final decision whether or not to continue the treatment. It is presently impossible to decide whether other estroprogestin associations, other administration routes and other molecules such as estradiol, natural progesterone or other progestins, SERMS and Tibolone could have an impact very different from that of the estroprogestin combination used in the WHI study. It is the duty of every physician to decide, from the complex epidemiological data obtained in the aged women (63-68 years) with a high cardiovascular risk in the WHI study, if it is possible or not in each individual case to recommend the initiation or pursue of an hormone replacement therapy.
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PMID:[Clinical study of the month. Benefit/risk balance of postmenopausal estrogen-progestin treatment in peril in the Women's Health Initiative study: practical attitude of the clinician]. 1240 30

HRT should not be used for prevention of cardiovascular and coronary artery disease. While estrogen plays a role in osteoporosis, the bisphosphonates and raloxifene demonstrate equal or superior efficacy for prevention and treatment, compared with HRT. HRT decreases the risk of colon cancer but increases a woman's chance of developing breast cancer. Short-term use of low-dose HRT remains a valid option for management of menopausal symptoms, especially hot flushes. Pharmacists can help patients interpret the information in the press and guide them in weighing the risks and benefits as they evaluate HRT for use in their own individual situations.
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PMID:MenoPAUSE: taking a second look at the role of HRT. 1462 25

Osteoporosis is one major health condition that contributes to excess morbidity and mortality in women after menopause. In the past, hormone therapy (HT) was prescribed commonly for symptoms of menopause, and there was also evidence that HT protected against osteoporosis. Recently, however, the overall health risks have been reported to exceed benefits, with the beneficial effects seen only in the decreased incidence of hip fractures and colon cancer. The role of HT in menopausal women is unclear at this time, although many women may require it to reduce menopausal symptoms. Osteoporosis may be an area where the benefit of using HT may outweigh the risks in a select group of women. Further, because lower than usual doses of estrogen have been shown to reduce menopausal symptoms and to protect bone, additional research will likely expand physicians' current knowledge of the use of HT in menopausal women. This article reviews the use of low-dose estrogen to promote bone health in postmenopausal women.
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PMID:Bone health and aging: implications for menopause. 1550 43


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