The choice of progestogen for HRT in menopausal women: breast cancer risk is a major issue

2018 ◽  
Vol 37 (1) ◽  
Author(s):  
Xiangyan Ruan ◽  
Alfred O. Mueck
Keyword(s):  
Breast Cancer ◽  
Experimental Research ◽  
Observational Studies ◽  
Animal Studies ◽  
Hormone Replacement ◽  
Controlled Study ◽  
Future Research ◽  
Double Blind ◽  
Increased Risk

Abstract Doctors and patients fear the risk of breast cancer when using hormone replacement therapy (HRT). This review focuses on the choice of progestogen for HRT in menopausal. The Women’s Health Initiative (WHI) has been the only large double-blind placebo-controlled study testing the risk of breast cancer (BC) using HRT. No increased risk using estrogen (E)-only was seen, there was a significant decrease in mortality due to BC after the use of HRT which persisted during the recent 18-year follow-up of the WHI. In contrast in the combined arm the risk increased. In about 20 observational studies using mostly medroxyprogesterone acetate (MPA) or estradiol-norethisterone acetate (NETA) an increased BC-risk was observed comparable with the WHI. Only for natural progestogen, progesterone and for dydrogesterone (retro-isomer of progesterone) was no increased risk seen for up to 5–8 years, when compared directly with other progestogens, but for longer treatment an increased risk cannot be excluded. In contrast, the mortality due to BC after use of E-only and combined HRT decreased in about a dozen observational studies, and was very recently confirmed in a Finnish study evaluating 490,000 women using estradiol (E2) plus different progestogens. There have been already more than 70 studies evaluating the risk of BC during HRT, and still there are many open questions. Therefore, this review covers our own and other experimental research which could answer important questions. Experimental research has demonstrated that certain synthetic progestogens, but not progesterone and to some extent also not dydrogesterone, can accelerate the proliferation of breast cancer cells in vitro and in animal studies via special cell membrane components which we recently also detected in patients with BC, and we found differences comparing all available synthetic progestogens. Derived from these mechanisms future research may provide screening for patients at risk and predict the prognosis of possible BC.

Association between hormone replacement therapy and dementia: is it time to forget?

2005 ◽  
Vol 17 (2) ◽  
pp. 155-164 ◽  
Author(s):  
Osvaldo P. Almeida ◽  
Leon Flicker
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Observational Studies ◽  
Animal Studies ◽  
Hormone Replacement ◽  
Health Events ◽  
Increased Risk ◽  
Estrogen Plus Progestin ◽  
History Of

The results of in vitro and animal studies provide a strong rationale for the use of hormone replacement therapy (HRT) to prevent dementia and Alzheimer's disease (AD). In humans, the results of 16 observational studies are consistent with the hypothesis that estrogen use reduces the risk of AD by 10 to 60%. However, women who are prescribed HRT are less likely to have hypertension, diabetes and history of stroke than nonusers. As all of these factors have been associated with increased risk of dementia (including AD), this “prescription bias” may have a significant impact on the results of observational studies. Randomized trials are designed with the aim of avoiding many of the potential biases and confounding (measured or unmeasured) of observational studies. The results of the Women's Health Initiative Memory Study (WHIMS) indicate that HRT (estrogen plus progestin or estrogen alone) increases the risk of dementia (hazard ratio, HR=1.8, 95% CI=1.2–2.6). Taking into account the results of the WHIMS and the adverse health events associated with the use of estrogen plus progestin or estrogen alone, we conclude that HRT cannot be recommended as a safe and effective strategy to prevent dementia.

scholarly journals Probiotics: on-going research on atopic individuals

2002 ◽  
Vol 88 (S1) ◽  
pp. s19-s27 ◽  
Author(s):  
K. Laiho ◽  
U. Hoppu ◽  
A. C. Ouwehand ◽  
S. Salminen ◽  
E. Isolauri
Keyword(s):  
At Risk ◽  
Atopic Eczema ◽  
Atopic Disease ◽  
Interleukin 4 ◽  
Controlled Study ◽  
Future Research ◽  
Gut Microflora ◽  
Double Blind ◽  
Ongoing Research

The challenge for the modern health care system is to fight against the increasing prevalence of atopic disease. The introduction of scientifically composed probiotic functional foods for prophylactic or therapeutic purposes could be one solution. Probiotics are live microbial food supplements or components of bacteria which have beneficial effects on human health. Specific strains have been demonstrated to exert powerful anti-pathogenic, anti-inflammatory and anti-allergic effects. The hygiene hypothesis suggests that atopic disease may arise from a lack of counterbalancing microbial exposure at an early age. The initial compositional development of the gut microflora is considered a key determinant of the development of both the immune responder phenotype and normal gut barrier functions. The regulatory role of probiotics in human allergic disease was first emphasised in the demonstration of a suppressive effect on lymphocyte proliferation and interleukin-4 generationin vitro. Subsequently, a significant improvement in the clinical course of atopic eczema was reported in infants given a probiotic-supplemented diet. The potential of probiotics to reduce the risk of atopic disease has recently been demonstrated in a double-blind, placebo-controlled study: probiotics administered pre- and postnatally for 6 months to at-risk subjects reduced the prevalence of atopic eczema to half of that observed in infants receiving placebo. Ongoing research is directed towards the development of novel techniques to characterise the gut microflora. Future research will clarify the mechanisms to control specific physiological processes in the evolution of atopic disease in at-risk populations or in the management of allergic diseases.

Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris

1985 ◽  
Vol 54 (04) ◽  
pp. 808-812 ◽  
Author(s):  
Ulf Berglund ◽  
Henning von Schenck ◽  
Lars Wallentin
Keyword(s):  
Platelet Aggregation ◽  
Angina Pectoris ◽  
Platelet Function ◽  
Plasma Levels ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Controlled Study ◽  
Double Blind ◽  
Platelet Factor

SummaryThe effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.

Protective Effect of Isothiocyanates from Cruciferous Vegetables on Breast Cancer: Epidemiological and Preclinical Perspectives

2020 ◽  
Vol 20 ◽  
Author(s):  
Suong N.T. Ngo ◽  
Desmond B. Williams
Keyword(s):  
Breast Cancer ◽  
Protective Effect ◽  
Animal Studies ◽  
Cancer Survival ◽  
Breast Cancer Survival ◽  
Human Studies ◽  
In Vitro Studies ◽  
Cochrane Library ◽  
Cruciferous Vegetables

Background: The effect of cruciferous vegetable intake on breast cancer survival is controversial at present. Glucosinolates are the naturally occurring constituents found across the cruciferous vegetables. Isothiocyanates are produced from the hydrolysis of glucosinolates and this reaction is catalysed by the plant-derived enzyme myrosinase. The main isothiocyanates (ITCs) from cruciferous vegetables are sulforaphane, benzyl ITC, and phenethyl ITC, which had been intensively investigated over the last decade for their antibreast cancer effects. Objective: The aim of this article is to systematically review the evidence from all types of studies, which examined the protective effect of cruciferous vegetables and/or their isothiocyanate constituents on breast cancer. Methods: A systematic review was conducted in Pubmed, EMBASE, and the Cochrane Library from inception to 27 April 2020. Peerreviewed studies of all types (in vitro studies, animal studies, and human studies) were selected. Results: The systematic literature search identified 16 human studies, 4 animal studies, and 65 in vitro studies. The effect of cruciferous vegetables and/or their ITCs intake on breast cancer survival was found to be controversial and varied greatly across human studies. Most of these trials were observational studies conducted in specific regions, mainly in the US and China. Substantial evidence from in vitro and animal studies was obtained, which strongly supported the protective effect of sulforaphane and other ITCs against breast cancer. Evidence from in vitro studies showed sulforaphane and other ITCs reduced cancer cell viability and proliferation via multiple mechanisms and pathways. Isothiocyanates inhibited cell cycle, angiogenesis and epithelial mesenchymal transition, as well as induced apoptosis and altered the expression of phase II carcinogen detoxifying enzymes. These are the essential pathways which promote the growth and metastasis of breast cancer. Noticeably, benzyl ITC showed a significant inhibitory effect on breast cancer stem cells, a new dimension of chemoresistance in breast cancer treatment. Sulforaphane and other ITCs displayed anti-breast cancer effects at variable range of concentrations and benzyl isothiocyanate appeared to have a relatively smallest inhibitory concentration IC50. The mechanisms underlying the cancer protective effect of sulforaphane and other ITCs have also been highlighted in this article. Conclusion: Current preclinical evidence strongly supports the role of sulforaphane and other ITCs as potential therapeutic agents for breast cancer, either as adjunct therapy or combined therapy with current anti-breast cancer drugs, with sulforaphane appeared to display the greatest potential.

scholarly journals Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2506
Author(s):  
Mark van Barele ◽  
Bernadette A. M. Heemskerk-Gerritsen ◽  
Yvonne V. Louwers ◽  
Mijntje B. Vastbinder ◽  
John W. M. Martens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Hormone Replacement ◽  
Breast Cancers ◽  
Younger Women ◽  
Alternative Pathways ◽  
Increased Risk ◽  
History Of ◽  
Hormone Sensitive

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.

scholarly journals A double-blind randomized placebo-controlled study of low dose mirtazapine once daily in patients of major depressive disorders on escitalopram

2019 ◽  
Vol 8 (5) ◽  
pp. 1067
Author(s):  
Mallikarjuna Rao I. ◽  
Usha Kiran Prayaga ◽  
Dharma Rao Uppada ◽  
Ramachandra Rao E. ◽  
B. L. Kudagi
Keyword(s):  
Depressive Disorders ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Study ◽  
P Value ◽  
Chi Square ◽  
Double Blind ◽  
Increased Risk ◽  
Significant Difference ◽  
Chi Square Test

Background: The SSRIs being used as 1st line therapy in treatment of depression have delayed therapeutic effect which makes the patient vulnerable to an increased risk of suicide and decreased adherence to the treatment and will prematurely discontinue the therapy. The present study was conducted to evaluate if low dose mirtazapine-escitalopram combination therapy has any add on benefit over monotherapy with escitalopram.Methods: In a single-centered, comparative study involving patients with depression attending the out-patient after screening and exclusion, 60 eligible patients were randomly assigned to receive tablet mirtazapine 7.5 mg plus tablet escitalopram 10 mg intervention or tablet escitalopram 10 mg plus placebo intervention in a double-blind 6-week treatment phase. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline. Participants were evaluated at baseline, 1st, 2nd,4th and 6th week. Results were analyzed using Chi-Square test for adverse effects and independent t-test analysis for efficacy parameter.Results: In the analysis of results at 6th week the numbers of patients achieved remission in mirtazapine group are more with a p-value of 0.018 which is significant and the numbers of responders in mirtazapine group are also more which is statistically significant on chi-square test. There is no significant difference was observed between the two groups with reference to occurrence of adverse effect.Conclusions: Adding low dose mirtazapine has an added benefit in terms of efficacy and getting remission early with more number of responders in the treatment of major depression.

THE RISK OF DEVELOPING GYNECOLOGICAL CANCER IN WOMEN AFTER AN IN VITRO FERTILIZATION PROGRAM

2021 ◽  
pp. 7-13
Author(s):  
Allakhyarov D.Z. ◽  
Petrov Yu.A. ◽  
Palieva N.V.
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
In Vitro Fertilization ◽  
Gynecological Cancer ◽  
The Body ◽  
Fertilization Program ◽  
Vitro Fertilization ◽  
Increased Risk

This article presents reviews of literature sources on the issue of assessing the risk of developing gynecological cancer in women after an in vitro fertilization program. Infertility and infertile marriages have now become quite a big problem of modern medicine. Against the background of the unfavorable demographic situation in the Russian Federation, this problem is becoming quite urgent. The main way to solve this situation is assisted reproductive technologies, among which the most common is in vitro fertilization. The in vitro fertilization program is accompanied by a hormonal ovulation stimulation procedure to obtain a female germ cell capable of fertilization. Against the background of the active use of the in vitro fertilization procedure, many patients had concerns related to the risk of developing gynecological cancer after the IVF procedure, which is due to the use of hormonal drugs to stimulate the ovaries. Also of concern is the fact that certain types of cancer, including ovarian cancer, endometrial cancer and breast cancer, are hormone-dependent. In this regard, multiple large-scale studies were conducted, which showed that the risk of developing gynecological cancer is really increased in patients after the in vitro fertilization program. In particular, breast cancer in women after the in vitro fertilization program is more common by 10%, and in women without a history of pregnancy and over the age of 40, it is more common by 31%. The increased risk may be due to age-related vulnerability to the effects of hormones or higher doses of hormones during the IVF procedure. Ovarian cancer and endometrial cancer are also more common in patients after IVF. According to the research results, it is suggested that it is not the IVF procedure itself that causes the development of cancer, but excessive hormonal load of the body, which leads to the launch of carcinogenesis.

Meta-Analysis

2005 ◽  
Vol 44 (01) ◽  
pp. 127-135 ◽  
Author(s):  
D. Böhning
Keyword(s):  
Breast Cancer ◽  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Mixed Model ◽  
Unobserved Heterogeneity ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Large Trial ◽  
Increased Risk ◽  
The One

Summary Objectives: This contribution provides a unifying concept for meta-analysis integrating the handling of unobserved heterogeneity, study covariates, publication bias and study quality. It is important to consider these issues simultaneously to avoid the occurrence of artifacts, and a method for doing so is suggested here. Methods: The approach is based upon the meta-likelihood in combination with a general linear nonparametric mixed model, which lays the ground for all inferential conclusions suggested here. Results: The concept is illustrated at hand of a meta-analysis investigating the relationship of hormone replacement therapy and breast cancer. The phenomenon of interest has been investigated in many studies for a considerable time and different results were reported. In 1992 a meta-analysis by Sillero-Arenas et al. [1] concluded a small, but significant overall effect of 1.06 on the relative risk scale. Using the meta-likelihood approach it is demonstrated here that this meta-analysis is due to considerable unobserved heterogeneity. Furthermore, it is shown that new methods are available to model this heterogeneity successfully. It is argued further to include available study covariates to explain this heterogeneity in the meta-analysis at hand. Conclusions: The topic of HRT and breast cancer has again very recently become an issue of public debate, when results of a large trial investigating the health effects of hormone replacement therapy were published indicating an increased risk for breast cancer (risk ratio of 1.26). Using an adequate regression model in the previously published meta-analysis an adjusted estimate of effect of 1.14 can be given which is considerably higher than the one published in the meta-analysis of Sillero-Arenas et al. [1]. In summary, it is hoped that the method suggested here contributes further to a good meta-analytic practice in public health and clinical disciplines.

Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study.

1997 ◽  
Vol 15 (3) ◽  
pp. 955-962 ◽  
Author(s):  
P D Delmas ◽  
R Balena ◽  
E Confravreux ◽  
C Hardouin ◽  
P Hardy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Femoral Neck ◽  
White Women ◽  
Treatment Withdrawal ◽  
Controlled Study ◽  
Treatment Needs ◽  
Mineral Density ◽  
Double Blind

PURPOSE To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis. PATIENTS AND METHODS Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment. RESULTS Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities. CONCLUSION Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.

Tamoxifen for the Prevention of Breast Cancer: Psychosocial Impact on Women Participating in Two Randomized Controlled Trials

2001 ◽  
Vol 19 (7) ◽  
pp. 1885-1892 ◽  
Author(s):  
Lesley Fallowfield ◽  
Anne Fleissig ◽  
Rob Edwards ◽  
Andrea West ◽  
Trevor J. Powles ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Group ◽  
Randomized Controlled Trials ◽  
Sexual Functioning ◽  
Self Report ◽  
Controlled Trials ◽  
Double Blind ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Prevention Of Breast Cancer

PURPOSE: The purpose of this study was to evaluate the psychosocial implications of tamoxifen versus placebo in women who are at increased risk of breast cancer. PATIENTS AND METHODS: The 488 women in the psychosocial study were recruited from participants in two placebo-controlled, double-blind, randomized, controlled trials that investigated the efficacy of tamoxifen in the prevention of breast cancer in women who are at high familial risk. During a 5-year period, repeated assessments were made of anxiety, psychological distress, and sexual functioning using standardized questionnaires before treatment at baseline and at 6-month intervals during the trial. RESULTS: Questionnaire completion over 5 years was good, with 71.1% of women returning at least 8 of 10 follow-up assessments. Although scores from individuals showed considerable fluctuation and variation over time, changes in anxiety, mood, and sexual functioning were not associated with treatment group. The number of symptoms reported at 48 months via a self-report cheklist were not associated with treatment group, but vasomotor symptoms were more frequent among tamoxifen-treated women. Symptoms of low energy, breast sensitivity, and visual blurring were reported most frequently in the placebo group. CONCLUSION: In general, these results are comparable to those from the National Surgical Adjuvant Breast and Bowel Project psychosocial study despite differences in study populations, methodology, and instruments. The long-term use of tamoxifen and other selective estrogen response modulators as preventive agents in high-risk groups has been questioned, but we found no evidence of treatment-related side effects that affect women’s psychosocial and sexual functioning.

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