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
Objective:To investigate the cognition,application and commendation of menopausal hormone therapy(MHT)among medical institution staff with different professional background.Methods:Female staff aged 40-60 years in 4 t...Objective:To investigate the cognition,application and commendation of menopausal hormone therapy(MHT)among medical institution staff with different professional background.Methods:Female staff aged 40-60 years in 4 tertiary hospitals were randomly selected.The participants'characteristics and the information of cognition,application and recommendation of MHT were collected by questionnaire.Results:A total of 341 people participated in this study,the cognition rate of MHT was 37%and the recommendation rate was 44%.For people with indications of MHT,the utilization rate is 15%,and 84.6%of them have used MHT for less than 3 years.84.6%of those who did not use MHT considered menopause is not a disease and there was no need to use medication.Compared with nurses,doctors know more about MHT(P<0.01),and MHT recommendation rate of doctors was higher than that of nurses(P<0.01).The cognition of MHT were analyzed in menopause group,irregular menstruation group and regular menstruation group,there was no difference was found among these three groups(P>0.05).Conclusion:Strengthening the training of MHT related knowledge in medical institutions,will be helpful to improve the cognition and utilization rate of medical institutions and promote the whole society to study and use MHT.展开更多
Objective To assess the effects of hormone replacement therapy (HRT) on platelet activation in postmenopausal women compared with premenopausal women. Methods The expressions of CD41 and CD62P in fifteen postmenopau...Objective To assess the effects of hormone replacement therapy (HRT) on platelet activation in postmenopausal women compared with premenopausal women. Methods The expressions of CD41 and CD62P in fifteen postmenopausal women before and after HRT were detected using flow cytometry (FCM),with fifteen premenopausal women with a mean age of 47 years as controls.Results The expressions of CD41 and CD62P in postmenopausal women were higher than those in the control group. CD62P(%),CD62P(I) and CD41 were reduced from 36.40±5.9,37.75±5.8,and 470.11±74.0 to 27.97±5.6,26.64±4.9,and 303.23±72.8 after six months of HRT ( P <0.05). Conclusions Platelet activation in postmenopausal women was higher than in premenopausal women and was reduced significantly after six months of HRT. HRT may have a favorable effect on reduction of platelet activity.展开更多
Objective： In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghreli...Objective： In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein（a） （Lp（a））, and plasminogen activator inhibitor type 1 （PAl-l） in postmenopausal women who received oral or transdermal menopausal hormonal therapy （MHT）. Methods： The study involved 76 healthy women： 46 women aged from 44 to 58 years who received oral （26） or transdermal （20） MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp（a）, and PAI-I：Ag were measured by enzyme-linked immunosorbent assay （ELISA）. The concentration of the leptin receptor was measured by enzyme immunometric assay （EIA）. Results： We observed a significantly higher concentration o~ total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAl-1 ：Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAl-1 ：Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions： The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAl-1 ：Ag, which in turn, can lead to a reduction in fibrinolytic activity.展开更多
Background： Menopausal hormone therapy （MHT） has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration ...Background： Menopausal hormone therapy （MHT） has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen （CEE） and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women. Methods： A prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups： Group A received CEE 0.3 mg/micronized progesterone （MP） 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student＇s t-test and analysis of variance. Results： A total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline （all P 〈 0.05）. Among the three groups, only Group C showed significantly increased triglycerides compared with baseline （ 1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P 0.026）. Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups. Conclusions： Among Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.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Objective:To investigate the cognition,application and commendation of menopausal hormone therapy(MHT)among medical institution staff with different professional background.Methods:Female staff aged 40-60 years in 4 tertiary hospitals were randomly selected.The participants'characteristics and the information of cognition,application and recommendation of MHT were collected by questionnaire.Results:A total of 341 people participated in this study,the cognition rate of MHT was 37%and the recommendation rate was 44%.For people with indications of MHT,the utilization rate is 15%,and 84.6%of them have used MHT for less than 3 years.84.6%of those who did not use MHT considered menopause is not a disease and there was no need to use medication.Compared with nurses,doctors know more about MHT(P<0.01),and MHT recommendation rate of doctors was higher than that of nurses(P<0.01).The cognition of MHT were analyzed in menopause group,irregular menstruation group and regular menstruation group,there was no difference was found among these three groups(P>0.05).Conclusion:Strengthening the training of MHT related knowledge in medical institutions,will be helpful to improve the cognition and utilization rate of medical institutions and promote the whole society to study and use MHT.
文摘Objective To assess the effects of hormone replacement therapy (HRT) on platelet activation in postmenopausal women compared with premenopausal women. Methods The expressions of CD41 and CD62P in fifteen postmenopausal women before and after HRT were detected using flow cytometry (FCM),with fifteen premenopausal women with a mean age of 47 years as controls.Results The expressions of CD41 and CD62P in postmenopausal women were higher than those in the control group. CD62P(%),CD62P(I) and CD41 were reduced from 36.40±5.9,37.75±5.8,and 470.11±74.0 to 27.97±5.6,26.64±4.9,and 303.23±72.8 after six months of HRT ( P <0.05). Conclusions Platelet activation in postmenopausal women was higher than in premenopausal women and was reduced significantly after six months of HRT. HRT may have a favorable effect on reduction of platelet activity.
基金Project supported by the Collegium Medicum in Bydgoszcz,Nicolaus Copernicus University in Toruń (No.73/04),Poland
文摘Objective： In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein（a） （Lp（a））, and plasminogen activator inhibitor type 1 （PAl-l） in postmenopausal women who received oral or transdermal menopausal hormonal therapy （MHT）. Methods： The study involved 76 healthy women： 46 women aged from 44 to 58 years who received oral （26） or transdermal （20） MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp（a）, and PAI-I：Ag were measured by enzyme-linked immunosorbent assay （ELISA）. The concentration of the leptin receptor was measured by enzyme immunometric assay （EIA）. Results： We observed a significantly higher concentration o~ total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAl-1 ：Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAl-1 ：Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions： The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAl-1 ：Ag, which in turn, can lead to a reduction in fibrinolytic activity.
文摘Background： Menopausal hormone therapy （MHT） has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen （CEE） and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women. Methods： A prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups： Group A received CEE 0.3 mg/micronized progesterone （MP） 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student＇s t-test and analysis of variance. Results： A total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline （all P 〈 0.05）. Among the three groups, only Group C showed significantly increased triglycerides compared with baseline （ 1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P 0.026）. Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups. Conclusions： Among Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.
