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Biomedical subjects

Alfred O Mueck

Publications and source records attributed to Alfred O Mueck.

At least 19 recordsLinked to original sources
PubMed2006

The effect of progesterone, testosterone and synthetic progestogens on growth factor- and estradiol-treated human cancerous and benign breast cells.

OBJECTIVE: The effects of progesterone (P), testosterone (T), chlormadinone acetate (CMA), medroxyprogesterone acetate (MPA), norethisterone (NET), levonorgestrel (LNG), dienogest (DNG), gestodene (GSD) and 3-ketodesogestrel (KDG) were investigated in normal human breast epithelial MCF10A cells. In addition, the effects of these steroids were tested in estrogen and progesterone receptor positive HCC1500 human primary breast cancer cells. STUDY DESIGN: MCF10A cells were incubated with each progestogen at 1 microM and 100 nM for 7 days with growth factors epidermal growth factor (EGF), fibroblast growth factor (FGF) and insulin-like growth factor (IGF-I) (GFs, each 1 pM), and HCC1500 cells with GFs and/or estradiol (E2) 100 pM. Cell proliferation rate was measured by ATP-assay and cell death by photometric enzyme immunoassay. Ratios of cell death:proliferation were calculated. RESULTS: MPA and CMA with GFs induced proliferation of MCF10A cells. P, T, NET, LNG, DNG, GSD and KDG had no significant effect. In HCC1500 cells, MPA and CMA with GFs had an inhibitory effect compared to GFs alone. NET, LNG, DNG, GSD, KDG and T enhanced the proliferative effect of GFs. P had no significant effect. No progestogen could further enhance the stimulatory effect of E2 on HCC1500 cells; all but KDG inhibited it. MPA, GSD, T, CMA and NET had an anti-proliferative effect on the mitotic GF and E2 combination. P, LNG, DNG and KDG had no significant effect. CONCLUSIONS: Estrogens and mitogenic growth factors from stromal breast tissue are significant in growth-regulation of breast cells and may alter responses to progestogens. Certain progestogens are able to induce proliferation of or inhibit growth of benign or malignant human breast epithelial cells independently of the effects of growth factors and E2; therefore, choice of progestogen for hormone therapy may be important in terms of influencing possible breast cancer risk.

Breast↗
PubMed2006

Characterization of the stimulatory effect of medroxyprogesterone acetate and chlormadinone acetate on growth factor treated normal human breast epithelial cells.

OBJECTIVE: Evidence is increasing that adding progestogens to hormone replacement therapy may be more harmful than beneficial, however it is debatable whether all progestogens act equally on breast cells. Mitogenic growth factors from stromal breast tissue are important in growth-regulation of breast cells, and may modify responses to progestogens. We investigated the effect of two C-21 derivatives, medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) on growth-factor treated normal breast epithelial cells and tried to explore the underlying mechanisms of proliferation. METHOD: MCF10A (human epithelial, estrogen- and progesterone-receptor negative normal breast cells) were incubated with MPA or CMA at 0.1 and 1 microM for 7 days with the growth factors (GFs) EGF, bFGF and IGF-I at 1pM. The same combinations, as well as growth factors alone, were also incubated with the proliferation inhibitors PD98059 and LY294002 at 1 microM for 4 days. Cell proliferation rate was measured by the ATP-assay. RESULTS: MPA 0.1 and 1 microM, and CMA 1 microM in combination with GFs both significantly increased cell proliferation rate, with MPA having the greatest effect. MPA- and CMA-induced proliferation of GF stimulated cells was blocked by both PD98059 (selective inhibitor of MAP kinases) and LY294002 (phosphatidylinositol 3-kinase inhibitor); GF stimulated cells could not be significantly reduced by any of the inhibitors used. CONCLUSION: MPA and CMA have a stimulatory effect on benign growth factor stimulated MCF10A cells, possibly via activation of MAP kinase and subsequent substrates and activation of PI3-kinase. GF induced proliferation appear to be mediated by pathways other than those investigated here. Growth factors and progestogens therefore have an additive, synergistic effect on cell proliferation, eliciting their effects via different pathways.

Breast↗
PubMed2006

Biochemical markers surrogating on vascular effects of sex steroid hormones.

The main mechanism of possible cardioprotection by estrogens appears to be a direct effect on the vasculature, resulting in an improvement of endothelial function and inhibition of atherogenesis. Numerous observational and experimental studies have demonstrated a positive correlation between estrogens and various biochemical markers surrogating direct vascular effects. In general, most markers are influenced in a similar way by oral and transdermal hormone therapy, although oral therapy may have a faster and more pronounced effect. The main difference between oral and transdermal administration may be confined to markers that are mainly or exclusively produced in the liver. Clinical studies demonstrate that progestogen addition can have an impact on the beneficial estrogen-induced changes of biochemical markers. Concerning the effects of tibolone, inconsistent data have been found. Overall, tibolone-induced beneficial changes on the various biochemical markers appear to be less marked compared with those of hormone therapy. The few data available on the direct effects of androgens on the vascular wall indicate a less favorable action of androgens on biochemical markers than of estrogens. The practical relevance of marker measurements is currently under discussion. Although evidence strongly supports some of these markers as predictors of acute events, it remains to be established whether modifying circulating levels of these markers will influence outcomes.

Androgens↗
PubMed2006

[Hormone replacement therapy for internal risk patients].

Using hormone replacement therapy (HRT), absolute and relative contradictions have to be considered, which are primarily classified according to a "worst case" scenario on the assumption of group effects, in order to satisfy forensic demands. However, in patients with severe complaints it make sense to apply HRT even at increased risk. To minimize the risk, a differentiated choice of the preparation especially in terms of progestin component and application mode is feasible apart from a general dose reduction. For internal risk patients, transdermal estradiol in a patch or gel and neutral progestins like progesterone and dydrogesterone or combination patches for a completely transdermal HRT are to be preferred. In the Women's Health Initiative, a study investigating a population strongly burdened with cardiovascular risks, the most important risks were venous thromboses and strokes, in old age also myocardial infarctions. In this context, the risk groups with diabetes, hypertension and dyslipoproteinemia as well as smokers in general are of particular importance. Other common internal risk groups comprise women with thyroid and hepatobiliary diseases. Rare but prognostically important diseases such as porphyria and lupus erythematosus are considered as relative contraindications. The available data on these risk groups are described and practical recommendations are given.

Administration, Cutaneous↗
PubMed2005

Comparison of possible carcinogenic estradiol metabolites: effects on proliferation, apoptosis and metastasis of human breast cancer cells.

OBJECTIVES: Certain estradiol metabolites may play a pivotal role in breast carcinogenesis. Of special interest are the metabolites 2-hydroxyestradiol (2-OHE2), which can react anti-carcinogenically, and 4-hydroxyestradiol (4-OHE1) and 16a-hydroxyestrone (16-OHE1), which may have procarcinogenic potential. In the present study, we have compared for the first time the effect of these metabolites and their parent substance 17beta-estradiol (E2) on proliferation, apoptosis, apoptosis markers and markers of metastatic property of human breast cancer cells. METHODS: MCF-7 cells (human estrogen-receptor positive metastatic breast cancer cell line) were incubated with the estrogens at concentrations of 0.1-100 nM. Cell proliferation rate was measured by the ATP-assay. Apoptosis was measured by cell death assay and the apoptosis markers cytochrome C, Bcl-2, Fasl and p53 were determined in cell lysates by ELISAs. The markers of metastatic property of the cell line, VEGF and MCP-1 were measured in the cell supernatant by ELISAs. RESULTS: The estrogens E2, 4-OHE2 and 16-OHE1 display a proliferative effect on MCF-7 cells which is accompanied by a down-regulation of apoptosis. Various markers of apoptosis such as Bcl-2, cytochrome C and p53 appear to be involved. No significant effect was found for the metabolite 2-OHE2. VEGF and MCP-1 were up-regulated by E2 and 16-OHE1, whereas 2-OHE2 and 4-OHE2 did not show any effect. CONCLUSIONS: The most potent estrogen regarding proliferation, apoptosis and metastasis of breast cancer cells seems to be estradiol. However, the estradiol metabolites 4-OHE2 and 16-OHE1 elicit similar properties on cell proliferation, apoptosis and metastasis as compared to estradiol but only at higher concentrations. In contrast 2-OHE2 did not show any significant effect on these parameters. Thus, intracellular estradiol metabolism may determine an individual's risk for breast carcinogenesis.

Apoptosis↗
PubMed2005

New evidence regarding hormone replacement therapies is urgently required transdermal postmenopausal hormone therapy differs from oral hormone therapy in risks and benefits.

Controversies about the safety of different postmenopausal hormone therapies (HTs) started 30 years ago and reached a peak in 2003 after the publication of the results from the Women Health Initiative (WHI) trial and the Million Women Study (MWS) [Writing group for the women's health initiative investigations. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002;288:321-33; Million women study collaborators. Breast cancer and hormone-replacement therapy in the million women study. Lancet 2003;362:419-27]. The single HT formulation used in the WHI trial for non hysterectomized women-an association of oral conjugated equine estrogens (CEE-0.625 mg/day) and a synthetic progestin, medroxyprogesterone acetate (MPA-2.5 mg/day)-increases the risks of venous thromboembolism, cardiovascular disease, stroke and breast cancer. The MWS, an observational study, showed an increased breast cancer risk in users of estrogens combined with either medroxyprogesterone acetate (MPA), norethisterone, or norgestrel. It is unclear and questionable to what extent these results might be extrapolated to other HRT regimens, that differ in their doses, compositions and administration routes, and that were not assessed in the WHI trial and the MWS. Significant results were achieved with the publication of the WHI estrogen-only arm study [Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712] in which hormone therapy was reserved to women who had carried out hysterectomy. What emerged from this study will allow us to have some important argument to develop.

Administration, Cutaneous↗
PubMed2005

The effects of progesterone, medroxyprogesterone acetate, and norethisterone on growth factor- and estradiol-treated human cancerous and noncancerous breast cells.

OBJECTIVE: Mitogenic growth factors from stromal breast tissue and estrogens are important in growth regulation of breast cells and may modify different responses dependent on the choice of progestogens. The effects of the acknowledged pharmacologically significantly different progestogens, progesterone, medroxyprogesterone acetate (MPA), and norethisterone, were investigated in breast cells treated with growth factor and/or estradiol, comparing normal and primary cancer cells for the first time. DESIGN: MCF10A (human epithelial, estrogen-receptor-negative and progesterone-receptor-negative normal breast cells) were incubated with progestogens at 1 microM and 100 nM for 7 days and epidermal growth factor, fibroblast growth factor, and insulin-like growth factor at 1 pM. HCC1500 (human estrogen-receptor-positive and progesterone-receptor-positive primary breast cancer cells) were incubated in the same way with growth factors and/or estradiol at 100 pM. Cell proliferation rate was measured by the ATP assay, whereas cell death was measured by photometric enzyme immunoassay. Ratios of cell death to proliferation were calculated from these results. RESULTS: In combination with growth factors, MPA reduced the ratio in favor of a proliferative effect in MCF10A cells, followed by norethisterone. Progesterone had no significant effect on the growth factor response. In HCC1500 cells, MPA with growth factors increased the ratio favoring inhibition, norethisterone had a proliferative effect, and progesterone had no significant effect. In combination with estradiol, MPA increased the ratio to inhibition to the greatest extent, followed by norethisterone and progesterone at 1 muM. In combination with growth factors and estradiol, MPA and norethisterone both showed an inhibitory effect, whereas progesterone had no significant effect. CONCLUSION: Certain progestogens are able to induce the proliferation of benign or malignant human breast cells independently of the effects of growth factors and estradiol. Therefore, the choice of progestogen may be important in terms of influencing a possible breast cancer risk.

Apoptosis↗
PubMed2005

Smoking, estradiol metabolism and hormone replacement therapy.

Many women receiving hormone replacement therapy (HRT) smoke; in the Women's Health Initiative (WHI), one of the largest interventional studies on HRT to date and which recently had to be discontinued, 50% of the 8,500 women on HRT had smoked before or continued to smoke during the study. Remarkably, there is little knowledge about the impact smoking has on the efficacy and side effects of HRT. However, it has been proven that, depending on the type, duration and intensity of nicotine consumption, smoking can reduce or completely cancel the efficacy of orally administered estrogens. Not only does smoking diminish the otherwise well-established beneficial effects of estrogen on hot flashes and urogenital symptoms and its positive effects on lipid metabolism, i.e. by reducing cholesterol, but smoking also specifically reduces estrogen's ability to prevent osteoporosis. The reduction or loss of therapeutic efficacy is mainly caused by dose-dependent elevated hepatic clearance, partially in conjunction with lower estrogen levels, and has been demonstrated only with oral estrogen applications. This failure of therapeutic action should not be compensated for by increasing the dose in smokers as this might result in the production of toxic, even potentially mutagenic estrogen metabolites--compounds recently associated with a higher risk of breast cancer. The favorable effects of estrogens are not lost in smokers when they are applied transdermally. This route enables low dosage and also avoids the formation of unphysiological metabolites by bypassing the liver. Women who continue to smoke despite all warnings should therefore only be treated via the transdermal route. Oral contraceptives, but not HRT, are contraindicated in elderly smokers. However, the principal conclusion of the WHI study was that the lowest dose possible should be chosen, especially in patients with an increased cardiovascular risk, as is the case in smokers.

Administration, Cutaneous↗
PubMed2004

Effect of hormone therapy on BP in normotensive and hypertensive postmenopausal women.

High blood pressure (BP) ranks as the greatest risk factor for cardiovascular disease. The increased cardiovascular risk determined in recent interventional studies has led the health authorities in some countries to re-ignite the discussion about whether hypertension should be listed as a contraindication for hormone replacement therapy (HRT). We reviewed papers published since 1960 and listed in MEDLINE, EMBASE and Biosis, on studies that monitored the course of BP during HRT. We found that both primarily normotensive and hypertensive postmenopausal women actually run only a very low risk of BP increase during HRT, indeed, BP was often lowered. In one of our own studies 1397 hypertensive women with BP diastolic >95 mmHg received transdermal HRT regimens; BP was lowered by an average of 7 mmHg systolic and 9 mmHg diastolic. The results of the more recent 24-h ambulatory BP studies are particularly conclusive. At least 19 such studies have been performed, 13 placebo-controlled and 10 cross-over; 5 found no effect on BP and 14 studies demonstrated BP reductions. BP was lowered by treatment with transdermal estradiol in 11 of 13 studies and by oral estrogen in 4 of 11 studies. The effects were not consistent with regard to systolic or diastolic BP nor to action on day- and night-time BP. It cannot be ruled out that some women with a particular predisposition exhibit an abnormal reaction to the vasoactive effects of HRT, and there is a paucity of long-term data on risk populations, specifically on the progestogenic effects in patients with pre-existing arteriosclerotic lesions. In conclusion, the risk of developing hypertension during HRT is very low, but hormone therapy should always be appropriately indicated and during therapy BP should be checked regularly.

Blood Pressure↗
PubMed2004

Breast cancer risk during HRT: influence of estradiol metabolites on breast cancer and endothelial cell proliferation.

OBJECTIVES: Long-term hormone replacement therapy is associated with an increased breast cancer risk. Evidence is accumulating that estradiol metabolites are involved in carcinogenesis. These metabolites may have proliferating and anti-proliferative properties. We have investigated the effect of 14 metabolites on the proliferation of human breast cancer cells and on the proliferation of human vascular endothelial cells. METHODS: As cell model, human umbilical vein endothelial cells (HUVEC) and the human breast cancer cell line MCF-7 were used. The relationship between dosage and effect was tested over the pharmacological concentration range of 10(-8) to 10(-5) M. RESULTS: In HUVECs, all of 10 A-ring metabolites tested stimulated the growth of the endothelial cells at the lower concentrations. At the highest concentration, some A-ring metabolites caused significant inhibitions. The D-ring metabolites showed no marked effects compared to the A-ring metabolites. In MCF-7 cells also, nearly all A-ring metabolites demonstrated a biphasic reaction behaviour on cell proliferation. For the D-ring metabolites, this biphasic pattern was only found for 16 alpha-hydroxyestrone, but the inhibitory effect of this metabolite was weak. CONCLUSION: These results indicate that certain endogenous estradiol metabolites are able to stimulate breast cancer cell proliferation, and others may be suitable for breast cancer treatment when used in high dosages, since they inhibit cancer cell growth as well as neoangiogensis. This may be of special importance for therapy, since some of these metabolites are virtually devoid of any oestrogenic activity.

Breast Neoplasms↗
PubMed2004

Hormone therapy after endometrial cancer.

Endometrial carcinoma is listed among the absolute contra-indications to hormone therapy. After all the existing opinions so far, hormone therapy after FIGO stage I or II endometrial cancer is still thought of as a possibility, and up to now the continuous combined oestrogen/progestogen replacement therapy would be recommended. However, until today, only observational studies have been put forward. Although no study has established an increased rate of recurrences or mortality, alternatives such as phytopreparations, tibolone, or, in, particular, psychotherapeutic drugs such as venlafaxine should be considered for the relief of climacteric complaints. Progestogen-only therapy also comes particularly into question. Indeed, the wider discussion about the gestagen effects regarding the risks of breast cancer is to be considered. Generally, after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose oestrogen therapy (patches, gels) instead of continuous combined oestrogen/progestogen replacement therapy, and this also is now recommended for patients after endometrial cancer. This is to be noted because of the risk factors for endometrial carcinomas, such as hypertension, obesity, polycystic ovary syndrome, diabetes mellitus, etc. However, each form of hormone therapy should only be exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives.

Contraindications↗
PubMed2004

Hormone therapy after endometrial cancer.

Endometrial carcinoma is one of the absolute contraindications of hormone therapy (HT). After all the existing opinions so far, HT after Stage I or II is still thought of as a possibility and up to now, the continuously combined estrogen (CAS 53-16-7) / progestogen (CAS 57-83-0) replacement therapy (CCEPT) has been recommended. However, only observational studies have been conducted as yet. Although no study established an increased rate of recurrence or mortality, alternatives such as phyto-preparations, tibolone, or particular psychotherapeutic drugs such as venlafaxine should be considered for the relief of climacteric complaints. In particular considered is progestogen-only therapy. However, the currently discussed possible progestogen effects regarding the risk of breast cancer have to be taken into account. Generally after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose estrogen therapy (patches, gels) instead of CCEPT, and this also is now recommended for patients after endometrial cancer. This is important because of the risk factors for endometrial carcinoma, such as hypertension, obesity, polycystic ovary syndrome, diabetes mellitus etc. However, each form of HT should only be exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives.

Clinical Trials as Topic↗
PubMed2004

Estrogens acting as cardiovascular agents: direct vascular actions.

In vitro experiments and in vivo studies indicate that estrogens exert various beneficial effects on the vascular wall. In the present review the recent literature and the results of our own studies on this topic are summarized. By modulating the synthesis of nitric oxide, prostacyclin and endothelin and blocking calcium channels estrogens positively affect the vasotonus. Atherogenesis, which is considered an inflammatory, fibroproliferative process, may be delayed by estrogens via downregulation of inflammatory markers, such as cell adhesion molecules and chemokines. The delay is further supported by the inhibition of smooth muscle cell proliferation and downregulation of angiotensin receptor gene expression as well as by its antioxidative property. In addition, estrogens may stabilize the atherosclerotic plaque by reducing the expression of matrix metalloproteinases. The thrombogenic potency of the ruptured plaque may be reduced also by estrogens via downregulating the synthesis of plasminogen activator inhibitor-1. In addition, own clinical studies suggest that other non-endothelial derived vasoactive surrogate markers, such as serotonin and urodilatin, may be positively influenced by estrogens. Differential effects of progestin addition were observed concerning the direct estrogenic effects on the vasculature. Antagonistic progestin effects have been observed for some markers and may depend on the type of progestin and on its administration mode. Thus, the role of progestin addition remains to be elucidated in further studies.

Animals↗
PubMed2003

Smoking, estradiol metabolism and hormone replacement therapy.

Products for hormone replacement therapy (HRT) in the postmenopause are the second most frequently prescribed drugs in the USA. Among the women receiving this treatment many are smokers. In the Women's Health Initiative (WHI), one of the largest interventional studies on HRT to date and which recently had to be discontinued, 50% of the 8,500 women on HRT had smoked before or continued to smoke during the study. Remarkably, there is little knowledge about the impact smoking has on the efficacy and side effects of HRT. However, it has been proven that, depending on the type, duration and intensity of nicotine consumption, smoking can reduce or completely cancel the efficacy of orally administered estrogens. Not only does smoking diminish the otherwise well-established beneficial effects of estrogen on hot flashes and urogenital symptoms and its positive effects on lipid metabolism, i.e. by reducing cholesterol, but smoking also specifically reduces estrogen's ability to prevent osteoporosis. The reduction or loss of therapeutic efficacy is mainly caused by dose-dependently elevated hepatic clearance, partially in conjunction with lower estrogen levels, and has been demonstrated only with oral estrogen applications. This failure of therapeutic action should not be compensated for by increasing the dose in smokers as this might result in the production of toxic, even potentially mutagenic estrogen metabolites-compounds recently associated with a higher risk of breast cancer. The favorable effects of estrogens are not lost in smokers when they are applied transdermally. This route enables low dosage and also avoids the formation of unphysiological metabolites by bypassing the liver. Women who continue to smoke despite all warnings should therefore only be treated via the transdermal route. Oral contraceptives, but not HRT, are contraindicated in elderly smokers. However, the principal conclusion of the WHI study was that the lowest dose possible should be chosen, especially in patients with an increased cardiovascular risk, as is the case in smokers.

Aged↗
PubMed2003

Effects of oxytocin outside pregnancy.

For a long time, oxytocin was regarded as a pregnancy hormone released by the hypophysis to stimulate labour and milk ejection. In the present survey, data have been collected from the literature to show the spectrum of the hitherto known functions of oxytocin outside pregnancy. It is now known that oxytocin receptors can occur almost ubiquitously in the organism, that oxytocin is also formed outside of the brain and that oxytocin has functions in a number of organs. In the first part of the survey, stimuli that contribute to an increase in oxytocin release are compiled. In the second part, details are given on the individual oxytocin targets. Although the majority of findings are based on the results of animal experiments, there are already a number of studies that indicate similar effects of oxytocin in humans. According to the current state of knowledge, oxytocin appears to be involved in functions in the following organs: male and non-pregnant female reproductive tract, pancreas, cardiovascular system, kidney, brain and breast. There are indications that oxytocin may also have actions in other organs. There continues to be a considerable need for research into oxytocin in order to better understand the physiological and pathophysiological actions and to be able to derive possible therapeutic uses. Further light on the spectrum of functions of oxytocin may be cast by the possibility of the use of oxytocin antagonists.

Animals↗
PubMed2003

Comparison of the effect of progesterone, medroxyprogesterone acetate and norethisterone on the proliferation of human breast cancer cells.

OBJECTIVE: To investigate in vitro the influence of the three most used progestogens in continuous combined HRT on cell proliferation of the human breast cancer cell line MCF-7. STUDY DESIGN: Progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) were investigated in the range of 0.01 nM to 10 microM alone and in combination with 10 nM oestradiol. Cell proliferation was measured after seven days using the ATP-chemosensitivity test. RESULTS: P alone reduced cell proliferation by 20 and 40% at 10(-7) and 10(-5) M. MPA and NET displayed a significant inhibition of cell proliferation between 20 and 25% for MPA and 23 and 41% for NET over the whole concentration range tested. The effect was greatest at 10(-7) M for MPA and at 10(-9) M for NET. In combination with oestradiol, P still significantly reduced cell proliferation, the values being between 12 and 61%. For MPA too an inhibitory effect between 20 and 40% was found, whereas for NET the values were between 23 and 38%. CONCLUSIONS: Our in vitro results indicate that the influence on breast cancer risk using HRT in postmenopausal women may depend on the type of progestogen used as well as on the regimen applied. However, the inhibitory in vitro net effect of the progestogens at clinically relevant dosages is rather minimal and it remains uncertain as to whether progestogens generally may reduce breast cancer risk in long-term treatment. Further clinical trials are urgently required to determine the appropriate choice - if any - of progestogen to complement HRT.

Breast↗
PubMed2003

Hormone therapy after endometrial cancer.

Endometrial carcinoma is often listed in data sheets as an absolute contraindication to hormone replacement therapy. However, observational studies have not shown an increased rate of recurrence or mortality. Thus, it is often used after stage I or II disease. Alternatives such as progestogens, tibolone, raloxifene, venlafaxine and herbal preparations are examined. The use of progestogens is under discussion because of potential adverse effects on the breast. Generally after treatment for endometrial cancer, current preference should be for low-dose oestrogen monotherapy rather than continuous combined therapy with progestogen addition in view of the increased risk of breast cancer and cardiovascular disease found with the latter regimen. It is important to note that risk factors for endometrial cancer such as hypertension, obesity, polycystic ovary syndrome and diabetes mellitus also increase the risk of cardiovascular disease. However, women must be informed about potential risks and the use of alternatives.

Age Distribution↗