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第十五届中国神经精神药理学学术会议

作者：楼忠泽 Laboratory of Behavioral Neuroscience Ningbo Addiction Research and Treatment CenterSchool of MedicineNingbo University

OBJECTIVE To investigate the effect of estrogen replacement therapy on novel-object recognition and extinction of conditioned fear memory in ovariectomized(OVX ) rats. METHODS Sixty sexually mature(> 90 d) female SD rats weighing 250 - 350 g were used as *** rats were randomly divided into 7 groups as follows:OVX with low dose of estrogen replacement(OVX +LD,0.1 mg·kg,n =9),medium dose(OVX + MD,0.3 mg·kg,n =9) and high dose(OVX + HD,0.9 mg·kg,n=9),estrogen replacement with medium dose at 2 weeks after OVX(MD + 2W,n = 9) and 4 weeks after OVX(MD +4W,n = 8),OVX group(n = 8) and Sham group(SH,n = 8 ).One week after arrival,all rats underwent surgery,and after at least 1 week of recovery from surgery,rats were allowed to *** to the different dose and time schedules,each group was administrated estrogen or vehicle via subcutaneous injection on the dorsal side of the *** maintenance one month after ovariectomized surgery,then,the Novel-object recognition and extinction of conditioned fear memory were *** The rats after OVX showed accessdependent impairments on novel-object recognition and the estrogen replacement therapy can reversal this phenomenon,but not the HD ***,the effect is associated with the time schedules of estrogen,the earlier the *** extinction of conditioned fear memory,the OVX rats produced significantly less freezing by fear context than that of SH rats,after chronic administration with estrogen one month exhibited the enhanced acquisition of context fear,except HD *** replacement therapy also increased the speed of extinction of conditioned fear *** These results indicate that estrogen may have an effect on the central nervous system,and it plays an important role for improving emotional learning and memory during deprive of sex hormone.

关键词： estrogen replacement therapy ovariectomized cognitive function

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The effect of estrogen replacement therapy on novel-object recognition and extinction of conditioned fear memory in ovariectomized rats

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中国药理学与毒理学杂志 2012年第3期 434-434页

作者：楼忠泽 Laboratory of Behavioral Neuroscience Ningbo Addiction Research and Treatment CenterSchool of MedicineNingbo University

OBJECTIVE To investigate the effect of estrogen replacement therapy on novel-object recognition and extinction of conditioned fear memory in ovariectomized(OVX) *** Sixty sexually mature(>90 d) female SD rats weighing 250-350 g were used as *** rats were randomly divided into 7 groups as follows: OVX with low dose of estrogen replacement(OVX+LD,0.1 mg·kg-1,n=9),medium dose(OVX+MD,0.3 mg·kg-1,n=9) and high dose(OVX+HD,0.9 mg·kg-1,n=9),estrogen replacement with medium dose at 2 weeks after OVX(MD+2W,n=9) and 4 weeks after OVX(MD+4W,n=8),OVX group(n=8) and Sham group(SH,n=8).One week after arrival,all rats underwent surgery,and after at least 1 week of recovery from surgery,rats were allowed to *** to the different dose and time schedules,each group was administrated estrogen or vehicle via subcutaneous injection on the dorsal side of the *** maintenance one month after ovariectomized surgery,then,the Novel-object recognition and extinction of conditioned fear memory were *** The rats after OVX showed access-dependent impairments on novel-object recognition and the estrogen replacement therapy can reversal this phenomenon,but not the HD ***,the effect is associated with the time schedules of estrogen,the earlier the *** extinction of conditioned fear memory,the OVX rats produced significantly less freezing by fear context than that of SH rats,after chronic administration with estrogen one month exhibited the enhanced acquisition of context fear,except HD *** replacement therapy also increased the speed of extinction of conditioned fear *** These results indicate that estrogen may have an effect on the central nervous system,and it plays an important role for improving emotional learning and memory during deprive of sex hormone.

关键词： estrogen replacement therapy ovariectomized cognitive function

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Menopausal depression:comparison of hormone replacement therapy and hormone replacement therapy plus fluoxetine

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Chinese Medical Journal 2004年第2期17卷 189-194页

作者：刘平何方方白文佩郁琦史蔚吴宜勇贺丹军肖计划郑晔廖秦平 Lilly Research Laboratories Eli Lilly Shanghai Representative. Office Shanghai 200001 China Peking Union Medical College Hospital Beijing 100730 China The First Affiliate Hospital Peking University Beijing 100034 China Lilly Research Laboratories Eli Lilly Shanghai Representative. Office. Shanghai 200001 China Beijing Hospital Beijing 100730 China People' s Hospital of Jiangsu Province Nanjing 210029 China Huaqiao Hospital Jinan University Guangzhou 510630

BACKGROUND: To compare the efficacy and safety of hormone replacement therapy (HRT) combined with fluoxetine, with HRT alone, in post-menopausal women suffering from depression. METHODS: A randomized, open-label, parallel trial was applied. HRT was administered to all patients for 2 cycles, with 14 days of estrogen therapy and 14 days of estrogen plus progesterone. Patients who were randomly assigned to the HRT plus fluoxetine group were given fluoxetine in combination with HRT. Hamilton Depression Rating Scale (HAMD), Kupperman Menopausal Index (KMI), and Clinical Global Impressions scale were used to measure the efficacy. RESULTS: One hundred and twenty-three post-menopausal patients with depression were enrolled in the study. Among them, 120 had at least one post-treatment visit and entered into the statistical analysis. The mean total HAMD scores were significantly lower, and the percentages of HAMD score reductions were higher in the HRT plus fluoxetine Group compared with the HRT Group, after at least 3 weeks of treatment, with an average difference of 5 points at the endpoint. The Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores were significantly different in the 2 groups, in favor of the combination therapy. The mean total KMI was significantly lower in the Combination Group compared with the HRT Group, after at least 6 weeks of treatment, with an average 4.5-point difference between the groups. No statistically significant differences were found in most of the adverse events reported in the Combination Group compared with the HRT group, with the exception of 3 symptoms, i.e., dry mouth, loss of appetite, and abdominal distention. They were mild to moderate in severity. Two patients in the HRT group, but none in the combination group, dropped out due to adverse events. CONCLUSION: HRT plus fluoxetine therapy was effective in the treatment of menopausal depression with a satisfactory safety profile.

关键词： estrogen replacement therapy Menopause Adult Comparative Study Depressive Disorder Female Fluoxetine Humans Middle Aged Research Support, Non-U.S. Gov't Treatment Outcome

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Effects of Transdermal estrogen therapy on Expressions of estrogen Receptors and T-lymphocyte Apoptosis in Surgically Menopausal Women

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Cellular & Molecular Immunology 2009年第4期6卷 277-283页

作者： Jing Zhang Xing Chen Shaofen Zhang Guangyan Zhou Xian Xia Liming Lu Department of Gynecology Obstetrics and Gynecology Hospital FudanUniversity Shanghai 200011 China Shanghai Institute of Immunology Shanghai Jiaotong University Shanghai200025 China Department of Gynecology Obstetrics and Gynecology Hospital Fudan University 419 Fangxie Road Shanghai 200011China

Studies have demonstrated estrogen replacement therapy can improve the life quality of surgically menopausal women. However, the mechanisms in this process remain poorly defined. Here we show the effect of transdermal estrogen therapy on expressions of estrogen receptors and T-lymphocyte apoptosis in surgically postmenopausal women. Fifteen surgically menopausal women, 15 naturally menopausal women and 15 young women were chosen in our studies. Peripheral vein blood was collected and serum E2 and FSH levels were assessed using ACCESS. T-lymphocyte apoptosis and the expressions of Fas, FasL and ER subtypes α and β were determined. The serum E2 levels of surgically menopausal woman were significantly higher, and the ＂Improved Kupperman Index＂ and the scores of ＂Menopause Specific Quality of Life Questionnaire＂ in surgically menopausal women were significantly low after ERT. The rates of T-lymphocyte apoptosis and FasL expression in surgically menopausal women were decreased after ERT, but the difference was not significant. The expressions of ERa and ERβ in two menopausal groups were significantly lower than those of the young group. They were both significantly up-regulated after 3 months of ERT. Transdermal ERT could significantly upregulate the serum E2 level, could improve menopausal symptoms and life quality of surgically menopausal women and upregulate ERa and ERβ expressions on T lymphocytes, especially ERp. Thus, the low dose of transdermal ERT may have a protective effect on menopausal women＇s immune function and aging.

关键词： estrogen replacement therapy surgical menopause estrogen receptor T-lymphocyte apoptosis

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Percutaneous estrogen in prevention of early postmenopausal bone loss in Chinese women

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Chinese Medical Journal 2002年第12期115卷 1790-1795页

作者：孙爱军林守清余卫秦明伟陈凤领张颖魏扬 Bruno de Lignieres 北京协和医院妇产科北京100730 北京铁路医院北京100038 NeckerHospital

OBJECTIVE: To identify the optimal dosage of 17beta-estradiol gel + oral progestin for preventing bone loss in postmenopausal Chinese women. METHODS: A 3-year open label, randomized, prospective clinical trial was conducted. Sixty healthy women who had been postmenopausal for 1 to 5 years were recruited and divided into following 4 groups: group 1, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus micronized progesterone (MP) 100 mg/d; group 2, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d; group 3, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus micronized progesterone (MP) 100 mg/d; and group 4, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d. estrogen and progestin were given continuously for 25 days per month. Bone mineral density (BMD) was measured using quantitative computed tomography (QCT) for trabecular bone of L2-5 and dual energy X-ray absorptiometry (DEXA) for L2-4 and hip 5 times during the trial at baseline and at the 6-, 12-, 18-, 24- and 36-month visits. RESULTS: Fifty-nine patients (98.3%, 59/60) stayed in the study for 1 year, 56 patients (93.3%, 56/60) for 2 years, and 51 (85%, 51/50) for 3 years. On average, menopausal symptoms were relieved by 80% after 6 months of treatment. By the 24th month, the mean increase in BMD ranged from 4.3% to 7.5% in trabecular bone; and by the 36th month, it ranged from 4.2% to 6.2% in L2-4 and 1.61% to 3.77% in the neck. There were significant difference after treatment (P 0.05) was found in improvement of symptoms, levels of bone markers or BMD. CONCLUSION: A daily dose of estradiol gel, either 0.75 mg or 1.5 mg, is effective in preventing early postmenopausal bone loss and relieving menopausal symptoms. After 3-year treatment, spinal BMD could increase steadily, so does hip BMD, especially in the first 2 years.

关键词： Administration, Cutaneous Adult Bone Density Estradiol estrogen replacement therapy Female Fractures, Bone Humans Medroxyprogesterone 17-Acetate Middle Aged Osteoporosis, Postmenopausal

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生命过程的医学化

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科学技术哲学 2018年第7期 117-127页

作者：唐文佩张大庆

20世纪30年代，随着内分泌学的发展，医学界对于绝经期症状的解释发生了急剧的变化，绝经从一个易于患病的生命阶段，到被定义为一种激素缺乏性疾病，需要补充雌激素加以治疗。在制药商和医学界的宣传下，雌激素替代疗法不仅成为妇女们... 详细信息

20世纪30年代，随着内分泌学的发展，医学界对于绝经期症状的解释发生了急剧的变化，绝经从一个易于患病的生命阶段，到被定义为一种激素缺乏性疾病，需要补充雌激素加以治疗。在制药商和医学界的宣传下，雌激素替代疗法不仅成为妇女们热议的话题，更成为其为之奔走争取的权利。直到20世纪70年代中期，雌激素致癌风波兴起，人们才开始反思激素治疗绝经的利弊得失。本文回顾了绝经医学化的演变过程，认为其在给予女性医疗帮助的同时，也将社会、文化、生理因素综合作用下的不适症状简约为个体的生理性改变，固化了女性身体机能较弱的刻板印象，有可能将女性置于更大的健康风险之中。

关键词：绝经医学化雌激素替代疗法激素替代疗法 menopause medicalization estrogen replacement therapy hormone replacement therapy

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皮下脂肪组织中SCD1基因甲基化与绝经年龄相关性研究（英文）

皮下脂肪组织中SCD1基因甲基化与绝经年龄相关性研究（英文）

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2019浙江省妇产科医师大会及妇产科学学术年会

作者：卢莎 Zhifen Zhang 杭州市妇产科医院 Department of Obstetrics and Gynecology Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital) Department of Gastroenterology Hangzhou Third People’s Hospital Department of Obstetrics and Gynecology the Affiliated Hangzhou Hospital of Nanjing Medical University Laboratory of Gene Diagnosis the Affiliated Hangzhou Hospital of Nanjing Medical University Department of Obstetrics and Gynecology the Second People’s Hospital of Tonglu

Objective :This study was designed to investigate associations between menopausal age and the DNA methylation levels of stearoyl-coenzyme A desaturase 1(SCD1,selected by the Illumina Infinium Human Methylation 450 BeadChip) and explore the changes in mRNA levels of SCD1 and DNMTs in response to estrogen replacement therapy(ERT).Methods :In the human experiment,we performed subcutaneous adipose tissue DNA extraction on 85 menopausal *** of SCD1 was measured by MethyLight *** the rat experiment,we established models of menopause(OVE group) and ERT(OVE+E2 group).The mRNA levels of SCD1,DNMT1,DNMT3A and DNMT3B were *** :The results showed that DNA methylation of SCD1 was inversely correlated with menopausal age(r = 0.370,P < 0.001).In the rat study,the mRNA levels of SCD1 decreased(P < 0.001) and that of DNMT3A(P < 0.001) and DNMT3B(P < 0.001) increased after *** :Methylation levels of SCD1 were significantly associated with menopausal ***3A and DNMT3B may be involved in the methylation of SCD1.

关键词： DNA methylation SCD1 menopausal age estrogen replacement therapy DNMTs mRNA

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Protective and super-imposing effects of Estradiol , Breviscapini, Lumbrokinase In focal cerebral ischemic-reperfusion injury on rats

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中国临床神经科学 2000年第Z1期8卷 69-页

作者： Shang huiFang Luo ZuMing Department of Neurology the First Affilliated Hospital of West China University of Medical Sciences Chengdu 610041 P.R.China Department of Neurology the First Affilliated Hospital of West China University of Medical Sciences Chengdu 610041 P.R.China

Baekgrouad: Postmenopausal estrogen replacement therapy is always associated with a decrease in risk of stroke incidence and mortality. The breviscapini and lumbrokinase can protect brain from ischemic injury..Experiments in animal models suggest estradiol can protect brain from ischemic injury. But we know little about the mechanism of brain protection role of estradiol. Espectically we don't know if estrodiol plus other brain protective drugs such as breviscapini and lumbrokinase have superimposing protection. Objective: To study protective function and its mechanism of estradio breviscapini and lumbrokinase after cerebral ischemic reperfusion tn overiectimiaed rat. Methods: We made the local ischemic repenfusion model with thread emgolism of right middle cerebral artery (MCA) of young female SD rars which werc bilaterally ovariectomized two weeks ago were used. These rats were randomized into sham-operated group, control group, estrodiol group, brevisacapini group, 10 SD rats each group. We admistrated each group with reseponsed treatment when rats were subjected to half an hour of MCAO. MCA were oecluded 2 hours and followed by 70 hours of reperfusion. Sham-poerated group were exposed cervical common artery and weren't occluded MCA. The rats were killed at 72 hours. The observed patameters each group listed: 1) The neurological deficit scores were made after MCAO 2 hours and bcforc killed. 2) Each group excluded sham operaated group were caculaled cerebral infarct volume ratio and edema volume with stereological microscoppe. 3) The level of Nitrc oxide (NO) in serum were determined with nitrate redutase method. 4) The level of Interlukin-I (IL-1) and tumor necrosis factot (TNF) were determined by biological activity method. 5) Ultrastructure of neuron were observed with electron microscope. All the rcsults from different groups were compared with each other. The drugs identified effictive in formcr study plus estradiot wcre admistratcd to rats to obscrvcd ifthey

关键词： estrogen replacement therapy middle cerebral artery neurological deficit infarct volume ratio electron microscope cerebral infarction protective effects brain protection animal models

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