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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effectiveness of estrogen therapy for alleviating severe depressions was investigated in a double blind study in which large doses of estrogen were administered to 15 premenopausal and 8 postmenopausal women and placebos were administered to 12 premenopausal and 5 postmenopausal women. The estrogens and placebos were administered over a three month period, and the women were blind rated each week by psychologists and psychiatrists using Hamilton rating scales for depression. There was a significant decline in the depression scores for the group treated with estrogens when compared to the placebo treated group. Considerable variation in the degree of improvement for the women in the estrogen treated group was observed. These variations were not related to age or to menstrual status but were significantly related to depression duration. Women with shorter histories of depression were more likely to show improvement than women with longer illness durations. Efforts were also made to understand the physiological mechanisms through which estrogen treatment contributed toward reducing depression. Previous studies revealed that decreased availability of norepinephrine at the central adrenegic receptor sites in the brain was related to the manifestation of depression while increased availability of norepinephrine at these sites was ralated to a manifestation of elation. Increased availability of norepinephrine has been shown to be related to an inhibition of monoamine oxidase activity (MAO), and estrogen, in turn, has been demonstrated to inhibit MAO activity. During the 3 month study period, 2 blood samples were obtained from the women every week and analyzed for MAO activity. All patients had elevated levels of plasma MAO activity prior to treatment. In estrogen treated patients, MAO levels declined significantly; MAO levels unexplicably increased for the placebo treated group. Reduced MAO activity was not, however, significantly correlated with lower depression ratings. In determining the risk/benefit ratio of estrogen therapy both the risk of developing endometrial cancer and the risks of life long disability and suicide stemming from severe depression should be considered. Tables show 1) mean depression ratings and average MAO activity levels before and after treatment for the estrogen and placebo treated groups and 2) degree of change in depression ratings before and after treatment for both groups of women.
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PMID:Estrogen therapy for severe persistent depressions in women. 21 2

This paper reports the preliminary results of a cohort study of 4544 British women receiving hormone replacement therapy (HRT). These women were recruited at 21 specialist menopause clinics around Britain. Up to the end of June 1983, the mean duration of HRT use per woman was 67 months of which, on average, 43% was 'opposed' use. In general, however, both the amount of progestogen given and the number of days per cycle for which it was given was less than would have been the case if the women had been receiving modern opposed therapy. The major focus of the study was to monitor mortality and cancer incidence in the cohort. The mortality results were broadly reassuring: overall mortality was significantly lower than expected on the basis of national rates (relative risk 0.58) and mortality ratios were below unity for all specific causes of death examined apart from cancer of the ovary (relative risk 1.43, 95% confidence limits 0.62-2.82) and suicide or suspected suicide (relative risk 2.53, 95% confidence limits 1.26-4.54). The most likely explanation for the latter finding is selection bias--thus at least 7 of the 11 women who died from suicide or suspected suicide had a psychiatric history before receiving HRT. The cancer incidence results were less reassuring, although they should be interpreted with some caution because cancer registry rates were used for comparative purposes. With this proviso, endometrial cancer risk was significantly elevated (relative risk 2.84, 95% confidence limits 1.46-4.96); many of the women concerned had taken therapy which was predominantly or entirely opposed although only one woman had received an opposed regimen which would now be considered adequately protective to the endometrium. Breast cancer incidence was also significantly increased (relative risk 1.59, 95% confidence limits 1.18-2.10); detailed analysis suggested that the use of unopposed ethinyl-oestradiol in particular might have undesirable effects on the breast.
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PMID:Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy. 362 Apr 11

Clinical researchers prospectively followed 166,755 female nurses, 30-55 years old, between 1976 and June 1, 1988, to compare the mortality risk of women who had ever used oral contraceptives (OCs) with those who had never used OCs. Most of the women did not use OCs after 1976, indicating that, if they had used OCs, they were likely to be the high-dose OCs. During the 20 years, 2879 women had died. The causes of death included cancer (1456), cardiovascular conditions (568), suicide (114), other traumatic causes (151), and other causes (590). The age-adjusted relative risk of total mortality for women who had ever used OCs was 0.99. When the researchers also controlled for body mass index and cigarette smoking, the relative risk for ever users was 0.93. Whey they controlled for all of the above and follow-up interval, parity, age at menarche, age at 1st birth, and menopause, they observed that ever use had an increased relative risk of breast cancer mortality (1.09) and a reduced risk for mortality from ovarian and endometrial cancer (0.34 and 0.81, respectively). The reduced risk for ovarian cancer continued after cessation of use (relative risk = 0.79). The apparent increased risk for breast cancer was mostly limited to current users (relative risk = 1.63). When the researchers controlled for age, body mass index, and cigarette smoking, they noted that women who had used OCs for at least 10 years had a somewhat increased relative risk of mortality (1.06). An elevated cardiovascular mortality risk (1.54) among these women was largely offset by the reduced cancer mortality risk (0.84). There was no overall trend in risk with increasing duration of past use of OCs for total mortality or mortality related to cardiovascular disease or cancer. The research indicates that OC use is safe.
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PMID:Oral contraceptive use and mortality during 12 years of follow-up: the Nurses' Health Study. 815 42

To assess the risks and benefits of menopausal hormone replacement therapy, we followed a 23,346-member, population-based cohort of Swedish women who were prescribed menopausal estrogens for an average of 8.6 years for mortality. Compared with the general population, the standardized mortality ratio for all-cause mortality in this cohort was 0.77 (95% confidence limits = 0.73, 0.81). Deaths in each of the 12 major categories of causes of death except for injuries occurred 12% to 86% less frequently than expected. We examined in detail four specific causes of death according to the type of hormone prescribed, namely weak estrogens (primarily estriol), more potent estrogens (primarily estradiol and conjugated estrogens) in combination with a progestin, and more potent estrogens without a progestin. Mortality from endometrial cancer was not related to the prescription of weak estrogens or an estrogen-progestin combination, but mortality was 40% higher in women prescribed more potent estrogens without a progestin. Women prescribed weak estrogens, more potent estrogens, and the combined estrogen-progestin regimen were at reduced risk of death from ischemic heart disease (standardized mortality ratios of 0.7, 0.6, and 0.4, respectively). The more potent estrogens and the estrogen-progestin combination were associated with a marked reduction in risk of intracerebral hemorrhage (standardize mortality ratios of 0.4 and 0.6, respectively) and "other" cerebrovascular disease, but not other types of stroke. The concern that use of progestins would lead to psychic disorders related to suicide received no support from our results. Breast cancer results are described elsewhere. These data provide little evidence of an adverse effect of the combined estrogen-progestin regimen as compared with estrogens alone on mortality. They do indicate, however, that both selection factors and biology may contribute to the almost across-the-board-reduction in mortality associated with hormone replacement therapy.
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PMID:Cause-specific mortality in women receiving hormone replacement therapy. 911 97

This article describes the origins and evolution of "antiestrogenic" medicines for the treatment and prevention of breast cancer. Developing drugs that target the estrogen receptor (ER) either directly (tamoxifen) or indirectly (aromatase inhibitors) has improved the prognosis of breast cancer and significantly advanced healthcare. The development of the principles for treatment and the success of the concept, in practice, has become a model for molecular medicine and presaged the current testing of numerous targeted therapies for all forms of cancer. The translational research with tamoxifen to target the ER with the appropriate duration (5 years) of adjuvant therapy has contributed to the falling national death rates from breast cancer. Additionally, exploration of the endocrine pharmacology of tamoxifen and related nonsteroidal antiestrogen (e.g. keoxifene now known as raloxifene) resulted in the laboratory recognition of selective ER modulation and the translation of the concept to use raloxifene for the prevention of osteoporosis and breast cancer. However, the extensive evaluation of tamoxifen treatment revealed small but significant side effects such as endometrial cancer, blood clots and the development of acquired resistance. The solution was to develop drugs that targeted the aromatase enzyme specifically to prevent the conversion of androstenedione to estrone and subsequently estradiol. The successful translational research with the suicide inhibitor 4-hydroxyandrostenedione (known as formestane) pioneered the development of a range of oral aromatase inhibitors that are either suicide inhibitors (exemestane) or competitive inhibitors (letrozole and anastrozole) of the aromatase enzyme. Treatment with aromatase inhibitors is proving effective and is associated with reduction in the incidence of endometrial cancer and blood clots when compared with tamoxifen and there is also limited cross resistance so treatment can be sequential. Current clinical trials are addressing the value of aromatase inhibitors as chemopreventive agents for postmenopausal women.
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PMID:Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer. 1716 90