Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast c...Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated.The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy,with an elevated risk of breast cancer.The evidence currently available from randomized trials and observational studies is based on data from different populations,drug formulations,and routes of administration.Even though the risks of MHT and breast cancer have received a great deal of attention,information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed.Furthermore,the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied.Therefore,this review aimed to describe the biological effects of estrogen,progesterone,and their metabolites on the proliferation of breast cancer cells,based on relevant basic research and clinical trials,to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.展开更多
Menopausal hormone therapy(MHT)is used to treat menopausal complaints including the genitourinary syndrome of menopause,to prevent osteoporosis,and to treat bleeding problems.Since these can be the indications also in...Menopausal hormone therapy(MHT)is used to treat menopausal complaints including the genitourinary syndrome of menopause,to prevent osteoporosis,and to treat bleeding problems.Since these can be the indications also in young women,especially with POI(premature ovarian insufficiency)or with surgical menopause(bilateral oophorectomy),also the old term"Hormone Replacement Therapy(HRT)”is still used.The effective component is the estrogen component without relevant difference in the efficacy of the various MHT-preparations.Additional preventive benefits are reduction of cardiovascular disease(including prevention of diabetes mellitus and metabolic syndrome),reduction of colon cancer,and perhaps also Alzheimer's disease,if started within a Kwindow of opportunity",i.e.in perimenopause or within 6-10 years after menopause.Primary indication for progestogen addition is to avoid the development of estrogen-dependent endometrial cancer,i.e.addition not recommended in hysterectomized women.Two main schedules,sequential-or continuous-combined estrogen/progestogen regimens,are used for treatment of bleeding problems.For this and for optimizing menstrual regulation detailed recommendations are given including proposed dosages for the available different progestogens if added to oral or transdermal estradiol in different estrogen dosages.The WHI-study demonstrated the main risks using MHT within a“worst-case scenario",i.e.start of MHT in old women with high risk for breast cancer and cardiovascular diseases,whereby only^conjugated equine estro-gens”and^medroxprogesterone acetate”have been tested.One main result was that the progestogen component is decisive for the risk of breast cancer,which according to own experimental research and observational studies may be reduced using the physiological progesterone or its isomer dydrogesterone.In addition we propose to push forward research for screening patients with increased breast cancer risk like we have done in the past decade demonstrating that certain membrane-bound receptors in breast cancer tissue or blood can increase this risk.To reduce the risk of venous thromboembolism and stroke,transdermal estradiol(gels,patches,)should be used,in free combination with progesterone or dydrogesterone as"golden standard"in patients with increased risk.To increase the compliance in our patients without special risks we mostly use the available fix-combinations of estradiol/dydrogesterone getting strong efficacy,good menstrual regulation or amenorrhea,respectively,but also other combinations may be indicated to take advantage of for example androgenic or antiandrogenic progestogens.展开更多
Although a wide range of studies have addressed the relationship between estrogen receptor(ER) expression and prognosis in non-small cell lung cancer(NSCLC), that relationship remains controversial. This is in large p...Although a wide range of studies have addressed the relationship between estrogen receptor(ER) expression and prognosis in non-small cell lung cancer(NSCLC), that relationship remains controversial. This is in large part because there is no consensus on the rate of ER expression in NSCLC or on the intracellular distribution of ER expression. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. For example, it is supposed from previous studies that ERs in the cytoplasm and nucleus have different relationships to prognosis than ERs in the cytoplasm. Moreover, ER signaling in NSCLC is known to be affected by aromatase, progesterone receptor and epidermal growth factor receptor mutation. However, there has been little functional analysis these mutants and subtypes. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.展开更多
The relevance of postmenopausal hormone therapy(HT)for breast cancer risk has been long debated,although it is one of the most important barriers for women to accept HT.Various opinions have been reported from recent ...The relevance of postmenopausal hormone therapy(HT)for breast cancer risk has been long debated,although it is one of the most important barriers for women to accept HT.Various opinions have been reported from recent randomized clinical trials and epidemiological studies.These unanswered questions include:whether HT has a positive impact on breast cancer;whether risks of therapy with unopposed estrogen and combined estrogenprogestin are different;and whether different types and routes of estrogen and progestogens,as well as the duration and cessation of HT use,have different impacts on this disorder.Recently,there has been some good news such as the following:the currently available data do not provide sufficient evidence to prove a causal relationship between postmenopausal HT and breast cancer;breast cancer in postmenopausal women using HT usually has better prognosis than that of nonusers.In conclusion,HT is still the most effective method of relieving climacteric symptoms for many postmenopausal women.However,a possible risk of breast cancer associated with long-term HT usage should not be ignored.With respect to prevention of breast cancer,regular evaluation of individual breast cancer susceptibility and close follow-up through mammography and/or breast sonography are necessary strategies for the safety of HT use.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China(Grant Nos.61673024 and 81971348)the Clinical Medicine Plus X-Young Scholar Project,Peking University,and the Fundamental Research Funds for the Central University(Grant No.PKU2018LCXQ001).
文摘Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated.The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy,with an elevated risk of breast cancer.The evidence currently available from randomized trials and observational studies is based on data from different populations,drug formulations,and routes of administration.Even though the risks of MHT and breast cancer have received a great deal of attention,information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed.Furthermore,the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied.Therefore,this review aimed to describe the biological effects of estrogen,progesterone,and their metabolites on the proliferation of breast cancer cells,based on relevant basic research and clinical trials,to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.
基金supported by National Natural Science Foundation of China(No.81671411)Beijing Municipal Administration of Hospitals’Ascent Plan of China(No.DFL20181401).
文摘Menopausal hormone therapy(MHT)is used to treat menopausal complaints including the genitourinary syndrome of menopause,to prevent osteoporosis,and to treat bleeding problems.Since these can be the indications also in young women,especially with POI(premature ovarian insufficiency)or with surgical menopause(bilateral oophorectomy),also the old term"Hormone Replacement Therapy(HRT)”is still used.The effective component is the estrogen component without relevant difference in the efficacy of the various MHT-preparations.Additional preventive benefits are reduction of cardiovascular disease(including prevention of diabetes mellitus and metabolic syndrome),reduction of colon cancer,and perhaps also Alzheimer's disease,if started within a Kwindow of opportunity",i.e.in perimenopause or within 6-10 years after menopause.Primary indication for progestogen addition is to avoid the development of estrogen-dependent endometrial cancer,i.e.addition not recommended in hysterectomized women.Two main schedules,sequential-or continuous-combined estrogen/progestogen regimens,are used for treatment of bleeding problems.For this and for optimizing menstrual regulation detailed recommendations are given including proposed dosages for the available different progestogens if added to oral or transdermal estradiol in different estrogen dosages.The WHI-study demonstrated the main risks using MHT within a“worst-case scenario",i.e.start of MHT in old women with high risk for breast cancer and cardiovascular diseases,whereby only^conjugated equine estro-gens”and^medroxprogesterone acetate”have been tested.One main result was that the progestogen component is decisive for the risk of breast cancer,which according to own experimental research and observational studies may be reduced using the physiological progesterone or its isomer dydrogesterone.In addition we propose to push forward research for screening patients with increased breast cancer risk like we have done in the past decade demonstrating that certain membrane-bound receptors in breast cancer tissue or blood can increase this risk.To reduce the risk of venous thromboembolism and stroke,transdermal estradiol(gels,patches,)should be used,in free combination with progesterone or dydrogesterone as"golden standard"in patients with increased risk.To increase the compliance in our patients without special risks we mostly use the available fix-combinations of estradiol/dydrogesterone getting strong efficacy,good menstrual regulation or amenorrhea,respectively,but also other combinations may be indicated to take advantage of for example androgenic or antiandrogenic progestogens.
文摘Although a wide range of studies have addressed the relationship between estrogen receptor(ER) expression and prognosis in non-small cell lung cancer(NSCLC), that relationship remains controversial. This is in large part because there is no consensus on the rate of ER expression in NSCLC or on the intracellular distribution of ER expression. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. For example, it is supposed from previous studies that ERs in the cytoplasm and nucleus have different relationships to prognosis than ERs in the cytoplasm. Moreover, ER signaling in NSCLC is known to be affected by aromatase, progesterone receptor and epidermal growth factor receptor mutation. However, there has been little functional analysis these mutants and subtypes. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.
文摘The relevance of postmenopausal hormone therapy(HT)for breast cancer risk has been long debated,although it is one of the most important barriers for women to accept HT.Various opinions have been reported from recent randomized clinical trials and epidemiological studies.These unanswered questions include:whether HT has a positive impact on breast cancer;whether risks of therapy with unopposed estrogen and combined estrogenprogestin are different;and whether different types and routes of estrogen and progestogens,as well as the duration and cessation of HT use,have different impacts on this disorder.Recently,there has been some good news such as the following:the currently available data do not provide sufficient evidence to prove a causal relationship between postmenopausal HT and breast cancer;breast cancer in postmenopausal women using HT usually has better prognosis than that of nonusers.In conclusion,HT is still the most effective method of relieving climacteric symptoms for many postmenopausal women.However,a possible risk of breast cancer associated with long-term HT usage should not be ignored.With respect to prevention of breast cancer,regular evaluation of individual breast cancer susceptibility and close follow-up through mammography and/or breast sonography are necessary strategies for the safety of HT use.
