卵巢功能衰退过程中抑郁和焦虑症状的研究
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摘要
背景
卵巢功能衰退的过程长达二十年左右,是女性一生中重要的阶段。国际上对该阶段的强化关注已有三十年。WHO从上世纪八十年代初起,多次组织专家组讨论该阶段包括命名、分期等多方面问题。发达国家,尤其是美国,从上世纪三十年代开始涉及此过程的研究,约七十年之后,基于一些长期研究的结果,于2001年由专家组提出了关于生殖衰老的STRAW (Stages of Reproductive Aging Workshop)分期系统[1],该系统将女性自青春期至生命终止划分为三大阶段(8个小阶段)。10年之后,基于最新研究的结果,关于生殖衰老分期研究的专题研讨会于2011年在美国提出了更新后的STRAW+10分期系统[2],并于2012年初发表于美国四大杂志。STRAW+10系统将女性自青春期至生命终止仍划分为三大阶段,但由10个小阶段组成：生育期,又分早期(-5期)、峰期(-4期)和晚期(-3b和-3a)；绝经过渡期,又分早期(-2期)和晚期(-1期)；绝经后期,又分绝经后期早期(+l期,再细分为+1a,+2b,+3c期)和绝经后期晚期(+2期)。
然而卵巢功能衰退的速度并非呈线性,当卵巢功能衰退加速时,主要在绝经过渡期和绝经后期早期,伴随内分泌学和生物学上的一系列改变,临床上将可能出现由一系列症状组成的“更年期综合征”,这一系列症状中包括情绪障碍的症状,它们主要表现为抑郁和焦虑。已有研究表明绝经过渡期和绝经后期早期可能是女性抑郁、焦虑症状的一个易感阶段[3]。
关于绝经事件与抑郁的关系,现有研究较多,而且多半是在欧美国家进行,这些研究既包括大样本的社区截面研究,如挪威的HUNT-Ⅱ研究,样本量高达16080[4],也包括长期随访的社区前瞻性队列研究,如随访长达10年的宾夕法尼亚卵巢衰退研究(POAS)[5],随访5年的全美妇女健康研究(SWAN)[6]等。研究总体结果认为绝经过渡期及绝经后期早期确实能使部分女性抑郁的危险性增加。其原因可用以下几个假说来解释：神经生物学假说,多米诺假说和社会心理学假说。神经生物学假说认为与该阶段雌激素的撤退或激素水平的波动有关[7]；多米诺假说认为是与低雌激素相关的血管舒缩症状导致的睡眠紊乱所致[8,9,而并非低雌激素的直接作用：社会心理假说认为与该阶段发生了精神心理和社会学因素的改变有关,如家庭角色的改变、照顾老人等[7,9,10]。关于绝经事件与焦虑的关系,现有研究较少,尤其缺少前瞻性设计的研究。有研究显示焦虑症状在绝经过渡期早期增多,之后减少[11],但另有研究认为焦虑症状与绝经事件没有联系,主要受生活方式、绝经相关症状以及社会心理学因素所影响[12],也有研究推测焦虑症状之所以在绝经过渡期得分较高是受潮热症状的混杂所致[13]。因此在筛查绝经阶段的抑郁焦虑时,多数学者建议选择条目中不包含躯体症状的量表,以减少其它绝经相关症状对抑郁、焦虑的混杂影响。而现有社区研究中对抑郁焦虑调查所采用的工具：流调中心抑郁量表(theCenter for Epidemiologic Studies Depression Scale, CES-D), Zung自评抑郁量表(Self-Rating Depression Scale, SDS)和Zung自评焦虑量表(Self-Rating Anxiety Scale, SAS),以及医院焦虑抑郁量表(Hospital Anxiety and Depression Scale, HADS)[14]等,只要HADS不包含躯体症状,且来自系统总综述[14]和大型人群研究[15]的证据均支持HADS在一般社区人群中应用的可靠性。
国内关于绝经阶段的抑郁、焦虑研究,研究对象主要以门诊病人和社区人群为主,但在研究设计上,均为截面研究,未见前瞻性的研究报道；多数研究对绝经阶段的界定尚未依据国际上达成共识的分期系统,而是简单地冠以围绝经期或更年期的名称,亦或直接以年龄进行界定；在测量工具的选择上主要为SDS和SAS,条目中含有躯体症状,目前不被建议作为绝经阶段女性抑郁焦虑筛查的可靠工具[16]。
本研究是正在进行的“社区妇女卵巢功能衰退过程中健康问题研究”的一部分,先前的研究曾采用加拿大的绝经生活质量问卷对女性的抑郁、焦虑问题进行过分析,结果发现年龄40-60岁的绝经过渡期和绝经后期妇女抑郁、焦虑症状的现患率分别为36.3%和39.4%,计分分析显示绝经过渡期和绝经后期心理症状得分无显著差异[17]；对35-60岁妇女按照STRAW分期系统进行分期,结果显示绝经过渡期早期、绝经过渡期晚期和绝经后期早期心理症状的得分相近,其中绝经过渡期早期显著高于生育期,绝经后期早期显著高于绝经后期晚期[18]。
本研究在此基础上,采用最新的分期系统STRAW+10来描述卵巢功能衰退的过程,选择针对绝经期女性抑郁焦虑筛查特异性较高的医院焦虑抑郁量表进行抑郁、焦虑症状的评估,运用绝经生活质量问卷和生活事件问卷进行其它绝经相关症状和生活事件的调查,旨在描述上述社区研究人群在卵巢功能衰退的过程中抑郁、焦虑症状的表现,并分析其危险因素。
本文分三个部分
第一部分卵巢功能衰退不同阶段抑郁和焦虑症状的流行情况及相关因素
第二部分卵巢功能衰退过程中抑郁和焦虑症状变化与发生情况的1年随访研究
第三部分绝经前女性抑郁焦虑症状的4年随访发生率及影响因素的自身对照研究
第一部分卵巢功能衰退不同阶段抑郁和焦虑症状的流行情况及相关因素
研究目的探讨抑郁和焦虑症状在卵巢功能衰退各阶段的流行情况及相关因素
研究内容
1.比较抑郁和焦虑症状得分与现患率在卵巢功能衰退各阶段的差异。
2.分析血清激素水平、绝经相关症状、生活事件、社会支持、对绝经和衰老的态度、与生殖相关的情绪问题及生活行为等因素与抑郁和焦虑症状的相关性。
研究方法
1.研究设计：横断面研究
2.样本来源：在北京西城区某社区进行的有关社区女性卵巢功能衰退过程中健康问题研究的前瞻性动态队列,选取2011年10月至2012年4月参加该队列研究的妇女为研究对象。
3.研究对象：(1)30-64岁；(2)至少有一侧卵巢和子宫；(3)有近10个月的月经日记或末次月经记录；(4)能理解和阅读中文；(5)自愿参加本研究。但排除近10个月内行激素治疗或口服抗精神类药物、妊娠或哺乳、子宫或卵巢器质性病变以及严重肝肾疾病或癌症者。
4.调查问卷：(1)《妇科内分泌改变及相关健康问题跟踪调查表》(2)医院焦虑抑郁量表；(3)绝经生活质量问卷；(4)社会支持评定量表；(5)压力生活事件量表。
5.检查项目：(1)身高、体重测量：(2)血清FSH和E2检测。
6.统计学方法：建立Epidata3.02数据库,使用SPSS13.0统计软件进行分析。对于两样本或多样本间抑郁、焦虑症状现患率的比较采用χ2检验,两样本抑郁、焦虑得分的比较采用Mann-Whitney U检验,多样本间抑郁、焦虑得分的比较采用Kruskal-Wallis H检验。抑郁、焦虑症状现患率的多因素分析采用Binary logistic回归分析。P<0.05认为有统计学差异。
结果
1.共有330名研究对象纳入分析,平均年龄49.52±7.09岁。其在卵巢功能衰退各阶段的分布为：生育期77人(23.3%),绝经过渡早期(EMT)78人(23.6%),绝经过渡晚期(LMT)65人(19.7%),绝经后早期(EPM)60人(18.2%),绝经后晚期(LPM)50人(15.2%)。
2.该样本抑郁、焦虑症状的现患率分别为20.6%(68人)和7.6%(25人),抑郁合并焦虑的现患率为6.1%(20人)。抑郁症状的现患率在EMT(20人,25.6%)、LMT(14人,21.5%)和EPM(17人,28.3%)显著高于生育期(7人,9.1%)(P<0.05)；焦虑症状的现患率在EMT(10人,12.8%)和EPM(10人,16.7%)显著高于生育期(0人)(P<0.05)。绝经过渡期及以后出现抑郁症状的相对危险度是生育期的3.18倍(P=0.006)。
3.生育期血清FSH水平与抑郁得分显著正相关(r=0.238,P=0.037),抑郁症状者的血清FSH水平显著高于无抑郁症状者[10.95(5.30)IU/L vs7.59(2.75)IU/L,P=0.019],但未发在现卵巢功能衰退的其他阶段抑郁与血清FSH水平的相关性(P>0.05)。
4.在卵巢功能衰退的各个阶段,有抑郁/焦虑症状者的血清E2水平与无抑郁/焦虑症状者的血清E2水平无显著差异(P>0.05)。
5.在卵巢功能衰退的不同阶段与抑郁、焦虑相关的其他绝经症状不同,在EMT,盗汗(P=0.000,OR=18.67)、肌肉和关节疼痛(P=0.042,OR=4.77)和睡眠有问题(P=0.025,OR=6.88)与焦虑症状有关。在LMT,肌肉关节疼痛(P=0.005,OR=5.77)和腰痛(P=0.005,0R=10.68)与抑郁症状有关；在EPM,胃肠胀气或胀痛(P=0.005,OR=6.48)、睡眠有问题(P=0.003,OR=13.91)、体表精神差(P=0.003,OR=7.14)、感到缺乏精力(P=0.005,OR=7.86)以及外貌肤质气色发生变化(P=0.016,OR=4.51)等与抑郁症状有关。
5.多因素logistic回归分析显示,卵巢功能衰退过程中抑郁症状的危险因素包括绝经状态：绝经过渡及绝经后(P=0.032,OR=2.87)、睡眠有问题(P=-0.023,OR=2.09)、自评生活有压力(P=0.009,OR=2.63)等,抑郁症状的保护因素包括：主观支持(P=0.025,0R=0.91)和有意识注意饮食平衡(P=0.000,OR=0.25)等。
6.多因素logistic回归分析显示,卵巢功能衰退过程中焦虑症状的危险因素包括盗汗(P=0.008,OR=4.52)、自评生活有压力(P=0.001,OR=5.73)、家庭成员重病和重伤(P=0.026,OR=5.57)、家庭成员死亡(P=0.018,OR=6.57)以及无工作或退休在家(P<0.05,0R>1)等。
结论与建议
1.在EMT、LMT以及EPM等卵巢功能衰退过程的主要阶段,抑郁症状的现患率平均为25.1%,焦虑症状的现患率平均为10.8%。
2.绝经过渡及绝经能增加抑郁的风险,应加强该阶段女性抑郁的筛查。
3.抑郁、焦虑症状与血清E2水平本身无明显联系,但应进一步关注妇女生育期的抑郁症状与以血清FSH升高为标志的下丘脑-垂体功能改变的关系。
4.睡眠有问题、自评生活有压力是卵巢功能衰退过程中抑郁症状的独立危险因素,主观支持和有意注意饮食平衡是该阶段抑郁症状的独立保护因素。因此应加强该阶段妇女睡眠问题的管理,注重饮食平衡,以及提高主观支持和应对压力的能力。
5.盗汗、自评生活有压力、家庭成员重病或重伤、家庭成员死亡等是卵巢功能衰退过程中焦虑症状的独立危险因素。因此应注重妇女对盗汗等血管舒缩症状的管理,并提供相关措施以提高女性应对压力性生活事件的能力。
第二部分卵巢功能衰退过程中抑郁和焦虑症状变化和发生情况的1年随访研究
研究目的探讨卵巢功能衰退过程中抑郁、焦虑症状的变化、发生情况及影响因素
研究内容
1.比较卵巢功能衰退各阶段转变过程中抑郁、焦虑症状得分和现患率的差异。
2.根据抑郁/焦虑症状在基线和随访间的变化,比较血清E2、FSH和其他绝经症状在基线和随访时的差异。
3.分析基线无抑郁症状/无焦虑症状者随访一年后抑郁/焦虑症状的发生情况。
4.比较随访时新出现抑郁症状者/新出现焦虑症状者与无抑郁症状者/无焦虑症状者在基线以及随访过程中相关指标的差异。
研究方法
1.研究设计历史前瞻性研究
2.研究对象根据纳入第一部分研究的研究对象名单,在社区队列库中选取之前一次随访(1年前)即2010年10月至2011年6月期间参加社区随访、具有完整人口学信息、且在该年度完成医院焦虑抑郁量表和绝经生活质量问卷调查的女性为研究对象。纳入、排除标准同第一部分。以第一部分即2011年10月至2012年4月的截面资料作为随访资料。
3.调查问卷和检查项目同第一部分
4统计学方法
建立Epidata3.02数据库,采用SPSS13.0统计软件进行分析。对于卵巢功能衰退不同阶段转变过程中抑郁、焦虑得分的比较、相关指标在基线和随访间的比较采用Wilcoxon符号秩检验,抑郁、焦虑现患率的比较采用卡方检验。对于有无抑郁或焦虑症状之间基线指标的比较计量资料采用t检验或Mann-WhitneyU检验,计数资料采用卡方检验。抑郁、焦虑症状的多因素分析采用Binary logistic回归分析。P<0.05被认为具有统计学意义。
结果
1.基线共有296人满足入选条件,平均年龄为48.81±7.09岁,平均随访0.97±0.16年。
2.在生育期-EMT组和EPM-EPM组,随访时的抑郁得分显著高于基线(4.59±2.95vs3.09±2.64,P=0.018；5.76±4.27vs3.98±3.92,P=-0.013),随访时的焦虑得分显著高于基线(3.16±2.48vs2.25±1.81,P=-0.028；4.48±4.10vs2.67±3.99,P=0.001)。在生育期-EMT组,随访时的抑郁症状现患率显著高于基线(21.9%vs3.1%,P=0.023)。
3.基线和随访都无抑郁或焦虑症状者,随访时的血清E2显著低于基线(31.78(69.50) pg/ml vs26.95(54.50) pg/ml, P=0.001;30.86(67.40) pg/ml vs26.71(52.40) pg/ml, P=0.001),随访新发抑郁者,随访时的躯体症状得分显著高于基线(2.54±1.28vs2.12±0.98,P=0.002),基线和随访都有抑郁症状者随访时的血清FSH显著高于基线[25.13(51.60) IU/L vs34.13(47.20)IU/L,P=0.046]。
4.258名基线无抑郁症状者,随访1年后新出现抑郁症状的发生率为15.6%(35人),在EMT、LMT和EPM新出现抑郁症状的机率分别为17.2%(10人)、14.6%(7人)和24.4%(11人)。多因素分析显示基线时的抑郁得分(P=0.001,OR=1.39)、体重指数(P=0.031,OR=1.13)、以及随访时躯体症状得分的增高(P=0.001,OR=2.60)是新发抑郁症状的独立危险因素。
5.280名基线无焦虑症状者,随访1年后新出现焦虑症状的发生率为5.4%(15人),在EMT、LMT和EPM新出现焦虑症状的机率分别为9.7%(6人)、3.8%(2人)和7.8%(4人)。多因素分析显示基线时的焦虑得分(P=0.049,OR=1.35)和近1年内出现家庭成员重病/伤或死亡(P=0.003,OR=6.91)是新发焦虑症状的独立危险因素。
结论及建议
1.绝经过渡早期和绝经后早期是新发抑郁、焦虑症状的主要阶段,其中EMT、LMT和EPM等卵巢功能衰退的主要阶段,1年随访抑郁症状的平均发生率为18.5%,焦虑症状的平均发生率为7.3%。
2.血清E2的降低与抑郁症状无明显联系,但是抑郁的存在可能与下丘脑-脑垂体功能的改变有关
3.抑郁得分、体重指数偏高者以及1年内躯体症状得分增高者1年内发生抑郁的风险较高,焦虑得分偏高和近1年内出现负性生活事件者1年内发生焦虑的风险较高。
卵巢功能衰退过程中应加强对绝经过渡早期和绝经后早期女性抑郁、焦虑症状的筛查,对抑郁得分偏高者应引起关注。加强体育锻控制体重、做好对绝经相关躯体症状的管理以及提高女性对压力事件的应对能力对于防治抑郁焦虑症状具有重要意义。控制促性腺激素水平的升高可能对治疗抑郁有效。
第三部分绝经前女性抑郁焦虑症状的4年随访发生率及影响因素的自身对照研究
研究目的分析绝经前女性抑郁、焦虑症状的4年随访发生率,并探讨影响其发生的个体内影响因素。
研究内容
1.比较不同卵巢功能衰退阶段转变下抑郁、焦虑得分随随访年限的变化
2.分析绝经前女性抑郁和焦虑症状的4年随访发生率
3.以自身为对照比较女性发生抑郁症状前后的相关因素
4.以自身为对照比较女性发生焦虑症状前后的相关因素
研究方法
1.研究设计前瞻性队列研究
2.样本来源在北京市西城区某社区进行的有关社区女性卵巢功能衰退过程中健康问题研究的前瞻性动态队列。
3.研究对象(1)年龄30-54岁；(2)20-30岁之间月经规律(21-35天)；(3)至少有一侧卵巢和子宫；(4)在过去10个月内至少有1次自主月经；(5)有至少近6个月的月经日记；(6)HADS-D<8分(抑郁症状研究)或HADS-A<8分(焦虑症状研究)。排除标准：子宫或卵巢器质性病变、目前行激素治疗或口服抗精神类药物、妊娠或哺乳以及患有严重肝肾疾病或癌症等。
4.研究步骤于2007年10至2008年5月在妇泌中心社区队列中选取符合上述条件的健康女性为研究对象。纳入后平均每年随访1次,共随访4次。每年进行抑郁焦虑症状的筛查、绝经相关症状的调查、取血激素测定、身高体重的测量以及回收月经日记等(具体方法详见第一部分)。
5.测量工具(1)《妇科内分泌改变及相关健康问题跟踪调查表》：年龄、文化程度、婚姻状况、家庭平均月收入、初潮年龄、产次等。(2)医院抑郁焦虑量表(3)绝经生活质量问卷(4)月经日记。详见第一部分。
6.统计学分析
建立Epidata3.02数据库,使用SPSS13.0统计软件进行统计分析。通过亡检验(正态资料)或Man-Whitney U检验(偏态资料)进行两样本计量资料的比较；通过矛检验进行分类资料的比较。采用重复测量方差分析比较不同卵巢功能衰退阶段转变下抑郁、焦虑得分随随访年限的变化。采用条件logistic回归模型对抑郁、焦虑症状发生的自身风险进行估计。P<0.05,认为差异有统计学意义。
结果
1.228名基线无抑郁症状的女性随访4年累计新发生抑郁症状51人,占基线人数的22.4%,其中年龄最小者37岁,最大者58岁,平均年龄为48.42±4.47岁,绝经过渡早期占比例较大。
2.随访中新发抑郁症状者在基线时的抑郁得分(4.12±2.08vs2.62±2.14,P=0.000)和躯体症状得分(2.08±0.89vs1.77±0.73,P=-0.003)均显著高于无抑郁症状者。
3.条件logistic回归分析显示,血清FSH水平的增加(P=0.008,OR=1.10)、血管舒缩症状(P=0.033,OR=3.54)和躯体症状得分的增加(P=0.032,OR=5.90)是女性自身发生抑郁症状的危险因素。
4.271名基线无焦虑症状的女性随访4年累计新发生焦虑症状29人,占基线人数的10.7%,其中年龄最小者39岁,最大者54岁,平均年龄为47.81±3.82岁,绝经过渡早期占比例较大。
5.随访中新发焦虑症状者基线时的焦虑得分(3.45±2.34vs2.03±1.87,P=0.002)、抑郁得分(6.14±3.38vs3.72±3.03,P=0.000)、体重指数(25.85±3.34kg/m2vs24.42±3.10kg/m2,P=0.021)以及躯体症状得分(2.39±1.06vs1.85±0.79kg/m2,P=0.001)均显著高于无焦虑症状者。
6.条件1ogistic回归分析显示,躯体症状得分的增加是女性自身出现焦虑症状的危险因素(P=0.007,0R=35.56)。
7.重复测量分析显示卵巢功能衰退阶段的转变和随访年限对抑郁(F=3.486,P=0.018；F=25.413,P=0.000)、焦虑得分(F=5.307,P=0.003；F=3.257,P=0.023)均有显著影响,MT-MT和MT-EPM组的抑郁(P=0.002,0.043)、焦虑得分(P=0.003,0.034)均显著高于4年随访持续位于生育期组；第4年随访的抑郁、焦虑得分显著高于基线(P=0.000)。
结论及建议
1.绝经前女性随访4年抑郁、焦虑症状的累积发生率分别为22.4%,10.7%。绝经过渡早期是新发抑郁、焦虑抑郁焦虑症状的易感阶段。
2.绝经相关的躯体症状和血管舒缩症状,以及以血清FSH水平升高为标志的脑垂体-卵巢轴功能的改变是女性自身新发抑郁症状的独立危险因素。其中躯体症状还是女性自身新发焦虑症状的危险因素。
3.绝经过渡期及向绝经后转变能增加抑郁、焦虑得分。
围绝经期女性应加强对其自身躯体症状和血管舒缩症状的管理,注重对自身抑郁、焦虑症状的筛查。而在临床诊疗方案中针对脑垂体-卵巢轴功能改变的干预可能对女性自身抑郁的防治有效。
Background
Ovary aging strides across female's decades of life, therefore, it has important meaning for women. Three stages and10substages are divided during women's life from puberty and the end of life according to the criteria of the Stages of Reproductive Aging Workshop+10. Among them, menopausal transition and early postmenopause are more important stages which were characterized by not only the fluctuation of hormone level, but also the physical, psychological and social changes. Therefore, both menopausal transition and early postmenopause are presumed to be vulnerable period of depression and anxiety. However, the direct reason of depression and anxiety during menopausal stages has been controversial for many years. Therefore, there is lack of clear guidelines for doctors to execute the best diagnosis and therapy plan for depression and anxiety in climacteric clinic.
For the association of depression with menopausal transition, a lot of studies were conducted including both the cross-section study with large samples and prospecitive cohort study with long follow-up year. Most of these studies were located in European or the United States. The main results support the negative effect of menopausal transition on depression, although most women do not suffer from depression in this period. The neurobiological theory posits that the hypoestrogenic state or the fluctuation of hormone levle derives the onset or worsening of pre-existing mood symptoms in perimenopausal women at risk of depression. The domina theory attributes the occurrence of depression to sleep disturbance which is caused by vasomotor symptoms correlated with decreased estrogen levels. In contrast, the psychological theory focused on the psychosocial factors, such as the burden of caring for aging patients or the changes of family roles. For anxiety, less study is conducted to explore its association with menopausal transition, especially for the longitudinal study. Some study showed that anxiety symptoms increased in early menopausal transition, then decreased. While the other studies attribute anxiety during menopausal transition to life style, menopause related symptoms and psychosocial factors or the confounding of hot flashes, rather than menopausal stages. Therefore, measurements without physical symptoms in items were suggested to be used for the screening of depression and anxiety in order to avoid the confounding of other menopause related symptoms. But among the measurements used currently, only the Hospital Anxiety and Depresison Scale(HADS) does not including physical symptoms in items.
In contrast, in China, it is lack of studies which were the longitudinal study design and used standard staging system to divide ovary aging process. Besides, measuremens in most study were limited to the scales of SDS and SAS which were not suggested to be the right measures to screen depression and anxiety of menopausal women because of the physical symptoms items.
Our study is part of the "health related problem study in community women during ovary aging process". Studies were once conducted to compare the psychosocial symptoms among different stages of ovary aging. The result showed that women in early menopausal transiton and early postmenopause were more likely to have higher scores of psychosocial symptoms.
Based on our previous study, the aim of this dissertation was to investigate and compare the prevalence of depression and anxiety among different stages of the ovary aging process and to explore the possible influencing factors, by using of the new revised STRAW+10system, main measurements such as Hospital Anxiety and Depression Scale (HADS) with higher specificity for the screening of anxiety and depression in menopausal women, Menopause-specific Quality of Life Questionnaire(MENQOL) for the investigatin of menopausal related symptoms and Life Events Scale(LES) for the measure of stress life events..
This dissertation contains three sections:
Section I The prevalence and related factors of depression and anxiety symptoms during diferent stages of ovary aging process
Section II Changes and new-onset incidence of depression and anxiety symptoms during ovary aging process in one year follow-up
SectionⅢ Self-control study of incidence of depression and anxiety in4years'follow-up and influencing factors for premenopausal women
Section I The prevalence and related factors of depression and anxiety symptoms during different stages of ovary aging process
Objective To analyze the prevalence and related factors of depression and anxiety symptoms in different stages of ovary aging process.
Specific aims
1. To compare the differences of depression or anxiety scores and prevalence among different stages of ovary aging
2. To explore the association of depression and anxiety symptoms with serum hormone level, menopausal symptoms, life events, social support, the attitude to menopause or aging, reproductive events related mood problems, and life behavior, respectively.
Methods
1. Study design:cross-sectional study
2. Sample source:A prospective cohort study about health problem during ovary aging which was conducted in one community in west district in Beijing since2005. Women who were followed up or recruited between October in2011and April in2012were regarded as the participants of this study.
4. Participants:Voluntary women aged30to64years old, with intact uterus and at least one ovary, having last10months'menstrual cycle diary or the record of final menstruation, with the ability of understanding the content of questionnaire were recruited from the ovary aging study cohort. But those women who got hormone therapy or took antipsychotic medicine, or got pregnant or lactation during the past10months, had uterus or ovarian organic disease, severe liver or kidney disease or cancer, were excluded.
5. Measurements:The changes of gynecological endocrinology and related health problem follow-up questionnaire, Hospital Anxiety and Depression Scale, Menopause-specific Quality of Life Questionnaire, Social Support Scale and Life Events Scale.
6. Examination:weight and height measureand serum FSH and E2level assay
7. Statistical analysis:All data were entered into database Epidata3.02and were analyzed by SPSS13.0. χ2test was use to compare the differences of depression or anxiety prevalence。Mann-Whitney U test and Kruskal-Wallis H test were use to compare the differences of depression or anxiety scores in different groups. Binary logistic regression model was used to explore the possible factors of depression or anxiety.
Results
1. A total of330women were included the final analysis with an average age of49.52±7.09years.77women (23.3%)were in reproductive stage,78women(23.6%) were in early menopausal transition(EMT),65women(19.7%) were in late menopausal transition(LMT),60women(18.2%)were in early postmenopause(EPM) and50(15.2%) women were in late postmenopause(15.2%).
2. The prevalence of depression and anxiety were20.6%(65women) and7.6%(25women)respectively, and the combination prevalence of both symptoms was6.1%(20women). The prevalence of depression in EMT(20women,25.6%), LMT(14women,21.5%) and EPM(17women,28.3%) were higher than reproductive stage(7women,9.1%), and the prevalence of anxiety in EMT(10women,12.8%) and EPM(10women16.7%) were higher than reproductive stage (0)(P<0.05). Women who were in menopausal transition or postmenopause had the risk of3.18times to suffer from depression than premenopausal women.
3. In reproductive stage, serum FSH level was positively correlated with depression score (r=0.238,P=0.037), and the FSH level was higher in those women who were depressive [10.95(5.30) IU/Lvs7.59(2.75) IU/L, P=0.019]. But no significant correlation was found between serum FSH level and depression or anxiety in any other stages of ovary aging process(P>0.05).
4. There was no significant difference of E2level between women with depression or anxiety and women without it(P>0.05).
5. Depression and anxiety symptoms were correlated with different menopausal symptoms in different stages of ovary aging. In EMT, night sweat (P=0.000,OR=18.67), muscle and joint pain(P=0.042,OR=4.77)and sleep problem(P=0.025,OR=6.88) were correlated with anxiety. In LMT, muscle and joint pain(P=0.005, OR=5.77) and waist pain(P=0.005,OR=10.68)were correlated with depression. In EPM, bloating or swelling to ache(P=0.005,OR=6.48),sleep problem(P=0.003,OR=13.91), bad body spirit(P=0.003,OR=7.14), tiredness(P=0.005,OR=7.86) and the appearance or skin changes(P=0.016,OR=4.51) were correlated with depression.
5. Logistic regression model showed that the risk factors of depression for women during the ovary aging process included menopausal transition and postmenopause(P=0.032), sleep problem(P=0.023, OR=2.09) and life stress(P=0.009, OR=2.63), while the protective factors of depression included subjective social support (P=0.025, OR=0.91)and attention to a balanced diet (P=0.000, OR=0.25)
6. Logistic regression model showed that the risk factors of anxiety for women during the ovary aging process included night sweat(P=0.008,OR=4.52), life stress(P=0.001,OR=5.73), the occurrence of severe disease or seriously injured for family members(P=0.026,OR=5.57), the death of family members (P=0.018,OR=6.57), and unemployment or retired (P<0.05,OR>1).
Conclusions
1. During the main stages of ovary aging process including EMT, LMT and EPM, the average prevalence of depression symptoms was25.1%and anxiety symptoms was10.8%.
2. Menopausal transition and postmenopasue can increase the risk of depression symptoms.
3. There was no any correlation between serum E2level and depression or anxiety. More attention should be paid on the associatin of depression symptoms in reproductive stage with the function of hypothalamus and pituitary.
4. Menopausal transition and postmenopause, sleep problem, life stress can increase the risk of depression, while subjective support and attention to a diet balance were protective factors of depression.
5. Night sweat, life stress and negative life events from family members can increase the risk of anxiety.
Section II The changes and new-onset incidence of depression and anxiety symptoms during ovary aging process in one year follow-up syudy
Objective:To analyze the changes and incidence of depression and anxiety during ovary aging process, and to explore the possible influencing factors.
Specific aims
1. To compare the difference of depression and anxiety score or prevalence during different transition stages of ovary aging process.
2. To compare the difference of variables between baseline and follow-up grouped by the changes pattern of depression and anxiety symptoms.
3. To analyze the incidence of new-onset of depression and anxiety in one year follow-up.
4. To compare the baseline characteristics or some variables'changes during the follow-up between women with depression or anxiety and women without the symptom.
Methods
1. Study design:Retrospective cohort study
2. Participants:Among annually assessment of the ovary aging study cohort, those who were assessed between October in2010and June in2011, with completed demographic information, HADS AND MENQOL investigation data and included in section I study were selected to offer the baseline data. The data from section I study were used as the follow-up one.
3. Questionnaire and examination:the same with section I except Social Support Scale and Life Events Scale
4. Statistical analysis
All data were entered into database Epidata3.02and were analyzed by SPSS13.0. The Wilcoxon test was used to compare the changes of depression or anxiey score and other variables between baseline and follow-up among different changes stages of ovary aging process, x2test or Mann-Whitney U test/Kruskal-Wallis H test was used to compare the baseline characteristics between women with symptoms and asymptomatic women. Binary logistic regression model was used for multiple factors analysis of depression or anxiety
Results
1. A total of296participants were included at baseline, with an average age of48.81±7.09year and an average follow-up time of0.97±0.16year.
2. During the transition stages from reproductive stage to EMT, and from EPM to EPM, the scores of depression at follow-up was significantly higher than baseline(4.59±2.95 vs3.09±2.64, P=0.018;5.76±4.27vs3.98±3.92,P=0.013), the scores of anxiety at follow-up was significantly higher than baseline(3.16±2.48vs2.25±1.81, P=0.028;4.48±4.10vs2.67±3.99,P=0.001), and so did the prevalence of depression during the transition from reproductive stage to EMT(21.9%vs3.1%,P=0.023).
3. For women without depression or anxiety symptoms at both baseline and follow up, serum E2level at follow-up was significantly lower than baseline(31.78(69.50)pg/ml vs26.95(54.50)pg/ml,P=0.001;30.86(67.40) pg/ml vs26.71(52.40)pg/ml,P=0.001); For women with new onset depression at follow-up, the score of physical symptoms was significantly higher than baseline(2.54±1.28vs2.12±0.98, P=0.002); For women with depression both at baseline and follow-up, the serum FSH level was higher at follow-up[25.13(51.60)IU/L vs34.13(47.20)IU/L,P=0.046]
4. The incidence of new-onset depression was15.6%(35women)after one year follow-up for258women without depression at baseline, with the incidience in EMT, LMT and EPM were17.2%(lOwomen),14.6%(7women), and24.4%(11women), respectively. Multiple factors analysis showed that baseline depression score(P=0.001,OR=1.39), BMI(P=0.031,OR=1.13) and the increase of physical symptoms score(P=0.001,OR=2.60) were independent risk factors of new onset of depression.
5. The incidence of anxiety was5.4%(15women) after one year follow-up for280women without anxiety at baseline, with the incidence in EMT, LMT and EPM were9.7%(6women),3.8%(2women) and7.8(4women), respectively. Multiple factors analysis showed that the higher anxiety symptom score at baseline(P=0.049,OR=1.35) and the occurrence of severe disease/seriously injured/death for family members in the last year (P=0.006, OR=6.91)were independent risk factors of anxiety.
Conclusions
1. The vulnerable stages of new onset of depression and anxiety were EMT and EPM. During the main stages of ovary aging process including EMT, LMT and EPM, the average new onset incidence of depression symptoms in one year follow-up was18.5%and anxiety symptoms was7.3%.
2. The risk of depression was higher for those women who had higher level of depression score and BMI, and the increase of physical symptoms score. While the risk of anxiety was higher for those women who experienced negative life events in the last year and and the higher level of anxiety score.
3. The decrease of serum E2was not correlated with depression, but the depression might be related to the function changes of hypothalamus and pituitary.
SectionⅢ Self-control study of incidence of depression and anxiety in4years' follow-up and its influencing factors for premenopasual women
Objective To investigate the incidence of depression and anxiety in4years'follow-up in premenopausal women and to explore within-women influencing factor.
Specific aims
1. To compare the differences of depression and anxiety scores among different follow-up year grouped by the different transition stages of ovary aging.
2. To calculate the incidence of depression and anxiety in4year's follow-up.
3. To compare the risk factors within women before and after the occurrence of depression.
4. To compare the risk factors within women before and after the occurrence of anxiety
Methods
1. Study design:Prospective cohort study
1. Sample resource:Ovary aging study cohort in Gynecological endocrinology and women health center in PUMCH
3. Participants:women without depression(HADS-D<8)or anxiety (HADS-A<8), aged30-54years, having regular menstrual cycle during the age of20to30years, having intact uterus and at least one ovary, with at least one independent menstruation in the past10months and at least6months'menstrual diary were recruited. The exclusion criteria were the same with Section I.
4. Study procedure:The baseline data were collected between October in2007and May in2008. Then annually assessment was conducted for4times. Each assessment included the screening of depression and anxiety symptoms, investigation of menopausal symptoms, serum hormonal assay and height and weight measure. And so does the menstrual diary recycling.
5. Measurements:The changes of gynecological endocrinology and related health problem follow-up questionnaire, HADS, MENQOL, and menstruation diary card.
6. Statistical analysis
All data were entered into database Epidata3.02and were analyzed by SPSS13.0. χ2test or Mann-Whitney U test/Kruskal-Wallis H test was used to compare the baseline characteristics between women with symptoms and asymptomatic women. Repeated measure was used to analyse the changes of ovary aging stages and follow-up year on the scores of depression and anxiety. Conditional logistic regression model was used to estimate the within women risk of depression and anxiety symptoms.
Results
1. For228women without depression symptoms at baseline, with an average age of48.42±4.47year, the incidence of new onset of depression in4years' follow-up was22.4%.39.2%depression women were in EMT which was higher than other stages.
2. The scores of depression(4.12±2.08vs2.62±2.14,P=0.000) and physical symptoms(2.08±0.89vs1.77±0.73.P=0.000) at baseline in women with depression symptoms at follow-up were higher than women without depression.
3. Conditional logistic regression analysis showed that, the increase of serum FSH level(P=0.008,OR=1.10), vasomotor symptoms(P=0.008,OR=1.10) and physical symptoms(P=0.008,OR=1.10) were within-women risk factors of depression.
4. For271women without anxiety symptoms at baseline, with an average age of47.81±3.82year, the incidence of new onset of anxiety in4years' follow-up was10.7%.51.7%women were in EMT which was higer than other stages.
5. The scores of anxiety(3.45±2.34vs2.03±1.87,P=0.000), depression(6.14±3.38vs3.72±3.03,P=0.000), BMI(25.85±3.34kg/m2vs24.42±3.10kg/m2, P=0.021) and physical symptoms(2.39±1.06vs1.85±0.79kg/m2,P=0.001) at baseline for women with anxiety symptoms at follow-up were higher than women without anxiety.
6. Conditional logistic regression analysis showed that, the increase of physical symptoms(P=0.007, OR=35.56) were within-women risk factors of anxiety.
7. Repeated meausure showed that the scores of both depression(F=3.486, P=0.018;F=25.413,P=0.000) and anxiety(F=5.307,P=0.003;F=3.257,P=0.023)were influenced by the changes of ovary aging and the follow-up year.The scores of depression and anxiety were significantly higher in MT-MT(P=0.002,0.043)and MT-EPM(P=0.003,0.034)than in reproductive stages, and were significantly higher in the fourth follow-up year than baseline(P=0.000).
Conclusions
1. The new onset incidence of depression and anxiety for premenopausal women were22.4%and10.7%, respectively. EMT was the vulnerable stages for women to suffer from depression and anxiety.
2. Menopausal symptoms such as physical symptoms and vasomotor symptoms, and the changes of pituitary-ovarian axis characterized by the increase of FSH were independent within-women risk factors of depression. And the physical symptoms were also the within-women risk factors of anxiety.
3. Stay in MT and transition to EMP could increase the scores of depression and anxiety.
卵巢功能衰退的过程长达二十年左右,是女性一生中重要的阶段。国际上对该阶段的强化关注已有三十年。WHO从上世纪八十年代初起,多次组织专家组讨论该阶段包括命名、分期等多方面问题。发达国家,尤其是美国,从上世纪三十年代开始涉及此过程的研究,约七十年之后,基于一些长期研究的结果,于2001年由专家组提出了关于生殖衰老的STRAW (Stages of Reproductive Aging Workshop)分期系统[1],该系统将女性自青春期至生命终止划分为三大阶段(8个小阶段)。10年之后,基于最新研究的结果,关于生殖衰老分期研究的专题研讨会于2011年在美国提出了更新后的STRAW+10分期系统[2],并于2012年初发表于美国四大杂志。STRAW+10系统将女性自青春期至生命终止仍划分为三大阶段,但由10个小阶段组成：生育期,又分早期(-5期)、峰期(-4期)和晚期(-3b和-3a)；绝经过渡期,又分早期(-2期)和晚期(-1期)；绝经后期,又分绝经后期早期(+l期,再细分为+1a,+2b,+3c期)和绝经后期晚期(+2期)。
然而卵巢功能衰退的速度并非呈线性,当卵巢功能衰退加速时,主要在绝经过渡期和绝经后期早期,伴随内分泌学和生物学上的一系列改变,临床上将可能出现由一系列症状组成的“更年期综合征”,这一系列症状中包括情绪障碍的症状,它们主要表现为抑郁和焦虑。已有研究表明绝经过渡期和绝经后期早期可能是女性抑郁、焦虑症状的一个易感阶段[3]。
关于绝经事件与抑郁的关系,现有研究较多,而且多半是在欧美国家进行,这些研究既包括大样本的社区截面研究,如挪威的HUNT-Ⅱ研究,样本量高达16080[4],也包括长期随访的社区前瞻性队列研究,如随访长达10年的宾夕法尼亚卵巢衰退研究(POAS)[5],随访5年的全美妇女健康研究(SWAN)[6]等。研究总体结果认为绝经过渡期及绝经后期早期确实能使部分女性抑郁的危险性增加。其原因可用以下几个假说来解释：神经生物学假说,多米诺假说和社会心理学假说。神经生物学假说认为与该阶段雌激素的撤退或激素水平的波动有关[7]；多米诺假说认为是与低雌激素相关的血管舒缩症状导致的睡眠紊乱所致[8,9,而并非低雌激素的直接作用：社会心理假说认为与该阶段发生了精神心理和社会学因素的改变有关,如家庭角色的改变、照顾老人等[7,9,10]。关于绝经事件与焦虑的关系,现有研究较少,尤其缺少前瞻性设计的研究。有研究显示焦虑症状在绝经过渡期早期增多,之后减少[11],但另有研究认为焦虑症状与绝经事件没有联系,主要受生活方式、绝经相关症状以及社会心理学因素所影响[12],也有研究推测焦虑症状之所以在绝经过渡期得分较高是受潮热症状的混杂所致[13]。因此在筛查绝经阶段的抑郁焦虑时,多数学者建议选择条目中不包含躯体症状的量表,以减少其它绝经相关症状对抑郁、焦虑的混杂影响。而现有社区研究中对抑郁焦虑调查所采用的工具：流调中心抑郁量表(theCenter for Epidemiologic Studies Depression Scale, CES-D), Zung自评抑郁量表(Self-Rating Depression Scale, SDS)和Zung自评焦虑量表(Self-Rating Anxiety Scale, SAS),以及医院焦虑抑郁量表(Hospital Anxiety and Depression Scale, HADS)[14]等,只要HADS不包含躯体症状,且来自系统总综述[14]和大型人群研究[15]的证据均支持HADS在一般社区人群中应用的可靠性。
国内关于绝经阶段的抑郁、焦虑研究,研究对象主要以门诊病人和社区人群为主,但在研究设计上,均为截面研究,未见前瞻性的研究报道；多数研究对绝经阶段的界定尚未依据国际上达成共识的分期系统,而是简单地冠以围绝经期或更年期的名称,亦或直接以年龄进行界定；在测量工具的选择上主要为SDS和SAS,条目中含有躯体症状,目前不被建议作为绝经阶段女性抑郁焦虑筛查的可靠工具[16]。
本研究是正在进行的“社区妇女卵巢功能衰退过程中健康问题研究”的一部分,先前的研究曾采用加拿大的绝经生活质量问卷对女性的抑郁、焦虑问题进行过分析,结果发现年龄40-60岁的绝经过渡期和绝经后期妇女抑郁、焦虑症状的现患率分别为36.3%和39.4%,计分分析显示绝经过渡期和绝经后期心理症状得分无显著差异[17]；对35-60岁妇女按照STRAW分期系统进行分期,结果显示绝经过渡期早期、绝经过渡期晚期和绝经后期早期心理症状的得分相近,其中绝经过渡期早期显著高于生育期,绝经后期早期显著高于绝经后期晚期[18]。
本研究在此基础上,采用最新的分期系统STRAW+10来描述卵巢功能衰退的过程,选择针对绝经期女性抑郁焦虑筛查特异性较高的医院焦虑抑郁量表进行抑郁、焦虑症状的评估,运用绝经生活质量问卷和生活事件问卷进行其它绝经相关症状和生活事件的调查,旨在描述上述社区研究人群在卵巢功能衰退的过程中抑郁、焦虑症状的表现,并分析其危险因素。
本文分三个部分
第一部分卵巢功能衰退不同阶段抑郁和焦虑症状的流行情况及相关因素
第二部分卵巢功能衰退过程中抑郁和焦虑症状变化与发生情况的1年随访研究
第三部分绝经前女性抑郁焦虑症状的4年随访发生率及影响因素的自身对照研究
第一部分卵巢功能衰退不同阶段抑郁和焦虑症状的流行情况及相关因素
研究目的探讨抑郁和焦虑症状在卵巢功能衰退各阶段的流行情况及相关因素
研究内容
1.比较抑郁和焦虑症状得分与现患率在卵巢功能衰退各阶段的差异。
2.分析血清激素水平、绝经相关症状、生活事件、社会支持、对绝经和衰老的态度、与生殖相关的情绪问题及生活行为等因素与抑郁和焦虑症状的相关性。
研究方法
1.研究设计：横断面研究
2.样本来源：在北京西城区某社区进行的有关社区女性卵巢功能衰退过程中健康问题研究的前瞻性动态队列,选取2011年10月至2012年4月参加该队列研究的妇女为研究对象。
3.研究对象：(1)30-64岁；(2)至少有一侧卵巢和子宫；(3)有近10个月的月经日记或末次月经记录；(4)能理解和阅读中文；(5)自愿参加本研究。但排除近10个月内行激素治疗或口服抗精神类药物、妊娠或哺乳、子宫或卵巢器质性病变以及严重肝肾疾病或癌症者。
4.调查问卷：(1)《妇科内分泌改变及相关健康问题跟踪调查表》(2)医院焦虑抑郁量表；(3)绝经生活质量问卷；(4)社会支持评定量表；(5)压力生活事件量表。
5.检查项目：(1)身高、体重测量：(2)血清FSH和E2检测。
6.统计学方法：建立Epidata3.02数据库,使用SPSS13.0统计软件进行分析。对于两样本或多样本间抑郁、焦虑症状现患率的比较采用χ2检验,两样本抑郁、焦虑得分的比较采用Mann-Whitney U检验,多样本间抑郁、焦虑得分的比较采用Kruskal-Wallis H检验。抑郁、焦虑症状现患率的多因素分析采用Binary logistic回归分析。P<0.05认为有统计学差异。
结果
1.共有330名研究对象纳入分析,平均年龄49.52±7.09岁。其在卵巢功能衰退各阶段的分布为：生育期77人(23.3%),绝经过渡早期(EMT)78人(23.6%),绝经过渡晚期(LMT)65人(19.7%),绝经后早期(EPM)60人(18.2%),绝经后晚期(LPM)50人(15.2%)。
2.该样本抑郁、焦虑症状的现患率分别为20.6%(68人)和7.6%(25人),抑郁合并焦虑的现患率为6.1%(20人)。抑郁症状的现患率在EMT(20人,25.6%)、LMT(14人,21.5%)和EPM(17人,28.3%)显著高于生育期(7人,9.1%)(P<0.05)；焦虑症状的现患率在EMT(10人,12.8%)和EPM(10人,16.7%)显著高于生育期(0人)(P<0.05)。绝经过渡期及以后出现抑郁症状的相对危险度是生育期的3.18倍(P=0.006)。
3.生育期血清FSH水平与抑郁得分显著正相关(r=0.238,P=0.037),抑郁症状者的血清FSH水平显著高于无抑郁症状者[10.95(5.30)IU/L vs7.59(2.75)IU/L,P=0.019],但未发在现卵巢功能衰退的其他阶段抑郁与血清FSH水平的相关性(P>0.05)。
4.在卵巢功能衰退的各个阶段,有抑郁/焦虑症状者的血清E2水平与无抑郁/焦虑症状者的血清E2水平无显著差异(P>0.05)。
5.在卵巢功能衰退的不同阶段与抑郁、焦虑相关的其他绝经症状不同,在EMT,盗汗(P=0.000,OR=18.67)、肌肉和关节疼痛(P=0.042,OR=4.77)和睡眠有问题(P=0.025,OR=6.88)与焦虑症状有关。在LMT,肌肉关节疼痛(P=0.005,OR=5.77)和腰痛(P=0.005,0R=10.68)与抑郁症状有关；在EPM,胃肠胀气或胀痛(P=0.005,OR=6.48)、睡眠有问题(P=0.003,OR=13.91)、体表精神差(P=0.003,OR=7.14)、感到缺乏精力(P=0.005,OR=7.86)以及外貌肤质气色发生变化(P=0.016,OR=4.51)等与抑郁症状有关。
5.多因素logistic回归分析显示,卵巢功能衰退过程中抑郁症状的危险因素包括绝经状态：绝经过渡及绝经后(P=0.032,OR=2.87)、睡眠有问题(P=-0.023,OR=2.09)、自评生活有压力(P=0.009,OR=2.63)等,抑郁症状的保护因素包括：主观支持(P=0.025,0R=0.91)和有意识注意饮食平衡(P=0.000,OR=0.25)等。
6.多因素logistic回归分析显示,卵巢功能衰退过程中焦虑症状的危险因素包括盗汗(P=0.008,OR=4.52)、自评生活有压力(P=0.001,OR=5.73)、家庭成员重病和重伤(P=0.026,OR=5.57)、家庭成员死亡(P=0.018,OR=6.57)以及无工作或退休在家(P<0.05,0R>1)等。
结论与建议
1.在EMT、LMT以及EPM等卵巢功能衰退过程的主要阶段,抑郁症状的现患率平均为25.1%,焦虑症状的现患率平均为10.8%。
2.绝经过渡及绝经能增加抑郁的风险,应加强该阶段女性抑郁的筛查。
3.抑郁、焦虑症状与血清E2水平本身无明显联系,但应进一步关注妇女生育期的抑郁症状与以血清FSH升高为标志的下丘脑-垂体功能改变的关系。
4.睡眠有问题、自评生活有压力是卵巢功能衰退过程中抑郁症状的独立危险因素,主观支持和有意注意饮食平衡是该阶段抑郁症状的独立保护因素。因此应加强该阶段妇女睡眠问题的管理,注重饮食平衡,以及提高主观支持和应对压力的能力。
5.盗汗、自评生活有压力、家庭成员重病或重伤、家庭成员死亡等是卵巢功能衰退过程中焦虑症状的独立危险因素。因此应注重妇女对盗汗等血管舒缩症状的管理,并提供相关措施以提高女性应对压力性生活事件的能力。
第二部分卵巢功能衰退过程中抑郁和焦虑症状变化和发生情况的1年随访研究
研究目的探讨卵巢功能衰退过程中抑郁、焦虑症状的变化、发生情况及影响因素
研究内容
1.比较卵巢功能衰退各阶段转变过程中抑郁、焦虑症状得分和现患率的差异。
2.根据抑郁/焦虑症状在基线和随访间的变化,比较血清E2、FSH和其他绝经症状在基线和随访时的差异。
3.分析基线无抑郁症状/无焦虑症状者随访一年后抑郁/焦虑症状的发生情况。
4.比较随访时新出现抑郁症状者/新出现焦虑症状者与无抑郁症状者/无焦虑症状者在基线以及随访过程中相关指标的差异。
研究方法
1.研究设计历史前瞻性研究
2.研究对象根据纳入第一部分研究的研究对象名单,在社区队列库中选取之前一次随访(1年前)即2010年10月至2011年6月期间参加社区随访、具有完整人口学信息、且在该年度完成医院焦虑抑郁量表和绝经生活质量问卷调查的女性为研究对象。纳入、排除标准同第一部分。以第一部分即2011年10月至2012年4月的截面资料作为随访资料。
3.调查问卷和检查项目同第一部分
4统计学方法
建立Epidata3.02数据库,采用SPSS13.0统计软件进行分析。对于卵巢功能衰退不同阶段转变过程中抑郁、焦虑得分的比较、相关指标在基线和随访间的比较采用Wilcoxon符号秩检验,抑郁、焦虑现患率的比较采用卡方检验。对于有无抑郁或焦虑症状之间基线指标的比较计量资料采用t检验或Mann-WhitneyU检验,计数资料采用卡方检验。抑郁、焦虑症状的多因素分析采用Binary logistic回归分析。P<0.05被认为具有统计学意义。
结果
1.基线共有296人满足入选条件,平均年龄为48.81±7.09岁,平均随访0.97±0.16年。
2.在生育期-EMT组和EPM-EPM组,随访时的抑郁得分显著高于基线(4.59±2.95vs3.09±2.64,P=0.018；5.76±4.27vs3.98±3.92,P=-0.013),随访时的焦虑得分显著高于基线(3.16±2.48vs2.25±1.81,P=-0.028；4.48±4.10vs2.67±3.99,P=0.001)。在生育期-EMT组,随访时的抑郁症状现患率显著高于基线(21.9%vs3.1%,P=0.023)。
3.基线和随访都无抑郁或焦虑症状者,随访时的血清E2显著低于基线(31.78(69.50) pg/ml vs26.95(54.50) pg/ml, P=0.001;30.86(67.40) pg/ml vs26.71(52.40) pg/ml, P=0.001),随访新发抑郁者,随访时的躯体症状得分显著高于基线(2.54±1.28vs2.12±0.98,P=0.002),基线和随访都有抑郁症状者随访时的血清FSH显著高于基线[25.13(51.60) IU/L vs34.13(47.20)IU/L,P=0.046]。
4.258名基线无抑郁症状者,随访1年后新出现抑郁症状的发生率为15.6%(35人),在EMT、LMT和EPM新出现抑郁症状的机率分别为17.2%(10人)、14.6%(7人)和24.4%(11人)。多因素分析显示基线时的抑郁得分(P=0.001,OR=1.39)、体重指数(P=0.031,OR=1.13)、以及随访时躯体症状得分的增高(P=0.001,OR=2.60)是新发抑郁症状的独立危险因素。
5.280名基线无焦虑症状者,随访1年后新出现焦虑症状的发生率为5.4%(15人),在EMT、LMT和EPM新出现焦虑症状的机率分别为9.7%(6人)、3.8%(2人)和7.8%(4人)。多因素分析显示基线时的焦虑得分(P=0.049,OR=1.35)和近1年内出现家庭成员重病/伤或死亡(P=0.003,OR=6.91)是新发焦虑症状的独立危险因素。
结论及建议
1.绝经过渡早期和绝经后早期是新发抑郁、焦虑症状的主要阶段,其中EMT、LMT和EPM等卵巢功能衰退的主要阶段,1年随访抑郁症状的平均发生率为18.5%,焦虑症状的平均发生率为7.3%。
2.血清E2的降低与抑郁症状无明显联系,但是抑郁的存在可能与下丘脑-脑垂体功能的改变有关
3.抑郁得分、体重指数偏高者以及1年内躯体症状得分增高者1年内发生抑郁的风险较高,焦虑得分偏高和近1年内出现负性生活事件者1年内发生焦虑的风险较高。
卵巢功能衰退过程中应加强对绝经过渡早期和绝经后早期女性抑郁、焦虑症状的筛查,对抑郁得分偏高者应引起关注。加强体育锻控制体重、做好对绝经相关躯体症状的管理以及提高女性对压力事件的应对能力对于防治抑郁焦虑症状具有重要意义。控制促性腺激素水平的升高可能对治疗抑郁有效。
第三部分绝经前女性抑郁焦虑症状的4年随访发生率及影响因素的自身对照研究
研究目的分析绝经前女性抑郁、焦虑症状的4年随访发生率,并探讨影响其发生的个体内影响因素。
研究内容
1.比较不同卵巢功能衰退阶段转变下抑郁、焦虑得分随随访年限的变化
2.分析绝经前女性抑郁和焦虑症状的4年随访发生率
3.以自身为对照比较女性发生抑郁症状前后的相关因素
4.以自身为对照比较女性发生焦虑症状前后的相关因素
研究方法
1.研究设计前瞻性队列研究
2.样本来源在北京市西城区某社区进行的有关社区女性卵巢功能衰退过程中健康问题研究的前瞻性动态队列。
3.研究对象(1)年龄30-54岁；(2)20-30岁之间月经规律(21-35天)；(3)至少有一侧卵巢和子宫；(4)在过去10个月内至少有1次自主月经；(5)有至少近6个月的月经日记；(6)HADS-D<8分(抑郁症状研究)或HADS-A<8分(焦虑症状研究)。排除标准：子宫或卵巢器质性病变、目前行激素治疗或口服抗精神类药物、妊娠或哺乳以及患有严重肝肾疾病或癌症等。
4.研究步骤于2007年10至2008年5月在妇泌中心社区队列中选取符合上述条件的健康女性为研究对象。纳入后平均每年随访1次,共随访4次。每年进行抑郁焦虑症状的筛查、绝经相关症状的调查、取血激素测定、身高体重的测量以及回收月经日记等(具体方法详见第一部分)。
5.测量工具(1)《妇科内分泌改变及相关健康问题跟踪调查表》：年龄、文化程度、婚姻状况、家庭平均月收入、初潮年龄、产次等。(2)医院抑郁焦虑量表(3)绝经生活质量问卷(4)月经日记。详见第一部分。
6.统计学分析
建立Epidata3.02数据库,使用SPSS13.0统计软件进行统计分析。通过亡检验(正态资料)或Man-Whitney U检验(偏态资料)进行两样本计量资料的比较；通过矛检验进行分类资料的比较。采用重复测量方差分析比较不同卵巢功能衰退阶段转变下抑郁、焦虑得分随随访年限的变化。采用条件logistic回归模型对抑郁、焦虑症状发生的自身风险进行估计。P<0.05,认为差异有统计学意义。
结果
1.228名基线无抑郁症状的女性随访4年累计新发生抑郁症状51人,占基线人数的22.4%,其中年龄最小者37岁,最大者58岁,平均年龄为48.42±4.47岁,绝经过渡早期占比例较大。
2.随访中新发抑郁症状者在基线时的抑郁得分(4.12±2.08vs2.62±2.14,P=0.000)和躯体症状得分(2.08±0.89vs1.77±0.73,P=-0.003)均显著高于无抑郁症状者。
3.条件logistic回归分析显示,血清FSH水平的增加(P=0.008,OR=1.10)、血管舒缩症状(P=0.033,OR=3.54)和躯体症状得分的增加(P=0.032,OR=5.90)是女性自身发生抑郁症状的危险因素。
4.271名基线无焦虑症状的女性随访4年累计新发生焦虑症状29人,占基线人数的10.7%,其中年龄最小者39岁,最大者54岁,平均年龄为47.81±3.82岁,绝经过渡早期占比例较大。
5.随访中新发焦虑症状者基线时的焦虑得分(3.45±2.34vs2.03±1.87,P=0.002)、抑郁得分(6.14±3.38vs3.72±3.03,P=0.000)、体重指数(25.85±3.34kg/m2vs24.42±3.10kg/m2,P=0.021)以及躯体症状得分(2.39±1.06vs1.85±0.79kg/m2,P=0.001)均显著高于无焦虑症状者。
6.条件1ogistic回归分析显示,躯体症状得分的增加是女性自身出现焦虑症状的危险因素(P=0.007,0R=35.56)。
7.重复测量分析显示卵巢功能衰退阶段的转变和随访年限对抑郁(F=3.486,P=0.018；F=25.413,P=0.000)、焦虑得分(F=5.307,P=0.003；F=3.257,P=0.023)均有显著影响,MT-MT和MT-EPM组的抑郁(P=0.002,0.043)、焦虑得分(P=0.003,0.034)均显著高于4年随访持续位于生育期组；第4年随访的抑郁、焦虑得分显著高于基线(P=0.000)。
结论及建议
1.绝经前女性随访4年抑郁、焦虑症状的累积发生率分别为22.4%,10.7%。绝经过渡早期是新发抑郁、焦虑抑郁焦虑症状的易感阶段。
2.绝经相关的躯体症状和血管舒缩症状,以及以血清FSH水平升高为标志的脑垂体-卵巢轴功能的改变是女性自身新发抑郁症状的独立危险因素。其中躯体症状还是女性自身新发焦虑症状的危险因素。
3.绝经过渡期及向绝经后转变能增加抑郁、焦虑得分。
围绝经期女性应加强对其自身躯体症状和血管舒缩症状的管理,注重对自身抑郁、焦虑症状的筛查。而在临床诊疗方案中针对脑垂体-卵巢轴功能改变的干预可能对女性自身抑郁的防治有效。
Background
Ovary aging strides across female's decades of life, therefore, it has important meaning for women. Three stages and10substages are divided during women's life from puberty and the end of life according to the criteria of the Stages of Reproductive Aging Workshop+10. Among them, menopausal transition and early postmenopause are more important stages which were characterized by not only the fluctuation of hormone level, but also the physical, psychological and social changes. Therefore, both menopausal transition and early postmenopause are presumed to be vulnerable period of depression and anxiety. However, the direct reason of depression and anxiety during menopausal stages has been controversial for many years. Therefore, there is lack of clear guidelines for doctors to execute the best diagnosis and therapy plan for depression and anxiety in climacteric clinic.
For the association of depression with menopausal transition, a lot of studies were conducted including both the cross-section study with large samples and prospecitive cohort study with long follow-up year. Most of these studies were located in European or the United States. The main results support the negative effect of menopausal transition on depression, although most women do not suffer from depression in this period. The neurobiological theory posits that the hypoestrogenic state or the fluctuation of hormone levle derives the onset or worsening of pre-existing mood symptoms in perimenopausal women at risk of depression. The domina theory attributes the occurrence of depression to sleep disturbance which is caused by vasomotor symptoms correlated with decreased estrogen levels. In contrast, the psychological theory focused on the psychosocial factors, such as the burden of caring for aging patients or the changes of family roles. For anxiety, less study is conducted to explore its association with menopausal transition, especially for the longitudinal study. Some study showed that anxiety symptoms increased in early menopausal transition, then decreased. While the other studies attribute anxiety during menopausal transition to life style, menopause related symptoms and psychosocial factors or the confounding of hot flashes, rather than menopausal stages. Therefore, measurements without physical symptoms in items were suggested to be used for the screening of depression and anxiety in order to avoid the confounding of other menopause related symptoms. But among the measurements used currently, only the Hospital Anxiety and Depresison Scale(HADS) does not including physical symptoms in items.
In contrast, in China, it is lack of studies which were the longitudinal study design and used standard staging system to divide ovary aging process. Besides, measuremens in most study were limited to the scales of SDS and SAS which were not suggested to be the right measures to screen depression and anxiety of menopausal women because of the physical symptoms items.
Our study is part of the "health related problem study in community women during ovary aging process". Studies were once conducted to compare the psychosocial symptoms among different stages of ovary aging. The result showed that women in early menopausal transiton and early postmenopause were more likely to have higher scores of psychosocial symptoms.
Based on our previous study, the aim of this dissertation was to investigate and compare the prevalence of depression and anxiety among different stages of the ovary aging process and to explore the possible influencing factors, by using of the new revised STRAW+10system, main measurements such as Hospital Anxiety and Depression Scale (HADS) with higher specificity for the screening of anxiety and depression in menopausal women, Menopause-specific Quality of Life Questionnaire(MENQOL) for the investigatin of menopausal related symptoms and Life Events Scale(LES) for the measure of stress life events..
This dissertation contains three sections:
Section I The prevalence and related factors of depression and anxiety symptoms during diferent stages of ovary aging process
Section II Changes and new-onset incidence of depression and anxiety symptoms during ovary aging process in one year follow-up
SectionⅢ Self-control study of incidence of depression and anxiety in4years'follow-up and influencing factors for premenopausal women
Section I The prevalence and related factors of depression and anxiety symptoms during different stages of ovary aging process
Objective To analyze the prevalence and related factors of depression and anxiety symptoms in different stages of ovary aging process.
Specific aims
1. To compare the differences of depression or anxiety scores and prevalence among different stages of ovary aging
2. To explore the association of depression and anxiety symptoms with serum hormone level, menopausal symptoms, life events, social support, the attitude to menopause or aging, reproductive events related mood problems, and life behavior, respectively.
Methods
1. Study design:cross-sectional study
2. Sample source:A prospective cohort study about health problem during ovary aging which was conducted in one community in west district in Beijing since2005. Women who were followed up or recruited between October in2011and April in2012were regarded as the participants of this study.
4. Participants:Voluntary women aged30to64years old, with intact uterus and at least one ovary, having last10months'menstrual cycle diary or the record of final menstruation, with the ability of understanding the content of questionnaire were recruited from the ovary aging study cohort. But those women who got hormone therapy or took antipsychotic medicine, or got pregnant or lactation during the past10months, had uterus or ovarian organic disease, severe liver or kidney disease or cancer, were excluded.
5. Measurements:The changes of gynecological endocrinology and related health problem follow-up questionnaire, Hospital Anxiety and Depression Scale, Menopause-specific Quality of Life Questionnaire, Social Support Scale and Life Events Scale.
6. Examination:weight and height measureand serum FSH and E2level assay
7. Statistical analysis:All data were entered into database Epidata3.02and were analyzed by SPSS13.0. χ2test was use to compare the differences of depression or anxiety prevalence。Mann-Whitney U test and Kruskal-Wallis H test were use to compare the differences of depression or anxiety scores in different groups. Binary logistic regression model was used to explore the possible factors of depression or anxiety.
Results
1. A total of330women were included the final analysis with an average age of49.52±7.09years.77women (23.3%)were in reproductive stage,78women(23.6%) were in early menopausal transition(EMT),65women(19.7%) were in late menopausal transition(LMT),60women(18.2%)were in early postmenopause(EPM) and50(15.2%) women were in late postmenopause(15.2%).
2. The prevalence of depression and anxiety were20.6%(65women) and7.6%(25women)respectively, and the combination prevalence of both symptoms was6.1%(20women). The prevalence of depression in EMT(20women,25.6%), LMT(14women,21.5%) and EPM(17women,28.3%) were higher than reproductive stage(7women,9.1%), and the prevalence of anxiety in EMT(10women,12.8%) and EPM(10women16.7%) were higher than reproductive stage (0)(P<0.05). Women who were in menopausal transition or postmenopause had the risk of3.18times to suffer from depression than premenopausal women.
3. In reproductive stage, serum FSH level was positively correlated with depression score (r=0.238,P=0.037), and the FSH level was higher in those women who were depressive [10.95(5.30) IU/Lvs7.59(2.75) IU/L, P=0.019]. But no significant correlation was found between serum FSH level and depression or anxiety in any other stages of ovary aging process(P>0.05).
4. There was no significant difference of E2level between women with depression or anxiety and women without it(P>0.05).
5. Depression and anxiety symptoms were correlated with different menopausal symptoms in different stages of ovary aging. In EMT, night sweat (P=0.000,OR=18.67), muscle and joint pain(P=0.042,OR=4.77)and sleep problem(P=0.025,OR=6.88) were correlated with anxiety. In LMT, muscle and joint pain(P=0.005, OR=5.77) and waist pain(P=0.005,OR=10.68)were correlated with depression. In EPM, bloating or swelling to ache(P=0.005,OR=6.48),sleep problem(P=0.003,OR=13.91), bad body spirit(P=0.003,OR=7.14), tiredness(P=0.005,OR=7.86) and the appearance or skin changes(P=0.016,OR=4.51) were correlated with depression.
5. Logistic regression model showed that the risk factors of depression for women during the ovary aging process included menopausal transition and postmenopause(P=0.032), sleep problem(P=0.023, OR=2.09) and life stress(P=0.009, OR=2.63), while the protective factors of depression included subjective social support (P=0.025, OR=0.91)and attention to a balanced diet (P=0.000, OR=0.25)
6. Logistic regression model showed that the risk factors of anxiety for women during the ovary aging process included night sweat(P=0.008,OR=4.52), life stress(P=0.001,OR=5.73), the occurrence of severe disease or seriously injured for family members(P=0.026,OR=5.57), the death of family members (P=0.018,OR=6.57), and unemployment or retired (P<0.05,OR>1).
Conclusions
1. During the main stages of ovary aging process including EMT, LMT and EPM, the average prevalence of depression symptoms was25.1%and anxiety symptoms was10.8%.
2. Menopausal transition and postmenopasue can increase the risk of depression symptoms.
3. There was no any correlation between serum E2level and depression or anxiety. More attention should be paid on the associatin of depression symptoms in reproductive stage with the function of hypothalamus and pituitary.
4. Menopausal transition and postmenopause, sleep problem, life stress can increase the risk of depression, while subjective support and attention to a diet balance were protective factors of depression.
5. Night sweat, life stress and negative life events from family members can increase the risk of anxiety.
Section II The changes and new-onset incidence of depression and anxiety symptoms during ovary aging process in one year follow-up syudy
Objective:To analyze the changes and incidence of depression and anxiety during ovary aging process, and to explore the possible influencing factors.
Specific aims
1. To compare the difference of depression and anxiety score or prevalence during different transition stages of ovary aging process.
2. To compare the difference of variables between baseline and follow-up grouped by the changes pattern of depression and anxiety symptoms.
3. To analyze the incidence of new-onset of depression and anxiety in one year follow-up.
4. To compare the baseline characteristics or some variables'changes during the follow-up between women with depression or anxiety and women without the symptom.
Methods
1. Study design:Retrospective cohort study
2. Participants:Among annually assessment of the ovary aging study cohort, those who were assessed between October in2010and June in2011, with completed demographic information, HADS AND MENQOL investigation data and included in section I study were selected to offer the baseline data. The data from section I study were used as the follow-up one.
3. Questionnaire and examination:the same with section I except Social Support Scale and Life Events Scale
4. Statistical analysis
All data were entered into database Epidata3.02and were analyzed by SPSS13.0. The Wilcoxon test was used to compare the changes of depression or anxiey score and other variables between baseline and follow-up among different changes stages of ovary aging process, x2test or Mann-Whitney U test/Kruskal-Wallis H test was used to compare the baseline characteristics between women with symptoms and asymptomatic women. Binary logistic regression model was used for multiple factors analysis of depression or anxiety
Results
1. A total of296participants were included at baseline, with an average age of48.81±7.09year and an average follow-up time of0.97±0.16year.
2. During the transition stages from reproductive stage to EMT, and from EPM to EPM, the scores of depression at follow-up was significantly higher than baseline(4.59±2.95 vs3.09±2.64, P=0.018;5.76±4.27vs3.98±3.92,P=0.013), the scores of anxiety at follow-up was significantly higher than baseline(3.16±2.48vs2.25±1.81, P=0.028;4.48±4.10vs2.67±3.99,P=0.001), and so did the prevalence of depression during the transition from reproductive stage to EMT(21.9%vs3.1%,P=0.023).
3. For women without depression or anxiety symptoms at both baseline and follow up, serum E2level at follow-up was significantly lower than baseline(31.78(69.50)pg/ml vs26.95(54.50)pg/ml,P=0.001;30.86(67.40) pg/ml vs26.71(52.40)pg/ml,P=0.001); For women with new onset depression at follow-up, the score of physical symptoms was significantly higher than baseline(2.54±1.28vs2.12±0.98, P=0.002); For women with depression both at baseline and follow-up, the serum FSH level was higher at follow-up[25.13(51.60)IU/L vs34.13(47.20)IU/L,P=0.046]
4. The incidence of new-onset depression was15.6%(35women)after one year follow-up for258women without depression at baseline, with the incidience in EMT, LMT and EPM were17.2%(lOwomen),14.6%(7women), and24.4%(11women), respectively. Multiple factors analysis showed that baseline depression score(P=0.001,OR=1.39), BMI(P=0.031,OR=1.13) and the increase of physical symptoms score(P=0.001,OR=2.60) were independent risk factors of new onset of depression.
5. The incidence of anxiety was5.4%(15women) after one year follow-up for280women without anxiety at baseline, with the incidence in EMT, LMT and EPM were9.7%(6women),3.8%(2women) and7.8(4women), respectively. Multiple factors analysis showed that the higher anxiety symptom score at baseline(P=0.049,OR=1.35) and the occurrence of severe disease/seriously injured/death for family members in the last year (P=0.006, OR=6.91)were independent risk factors of anxiety.
Conclusions
1. The vulnerable stages of new onset of depression and anxiety were EMT and EPM. During the main stages of ovary aging process including EMT, LMT and EPM, the average new onset incidence of depression symptoms in one year follow-up was18.5%and anxiety symptoms was7.3%.
2. The risk of depression was higher for those women who had higher level of depression score and BMI, and the increase of physical symptoms score. While the risk of anxiety was higher for those women who experienced negative life events in the last year and and the higher level of anxiety score.
3. The decrease of serum E2was not correlated with depression, but the depression might be related to the function changes of hypothalamus and pituitary.
SectionⅢ Self-control study of incidence of depression and anxiety in4years' follow-up and its influencing factors for premenopasual women
Objective To investigate the incidence of depression and anxiety in4years'follow-up in premenopausal women and to explore within-women influencing factor.
Specific aims
1. To compare the differences of depression and anxiety scores among different follow-up year grouped by the different transition stages of ovary aging.
2. To calculate the incidence of depression and anxiety in4year's follow-up.
3. To compare the risk factors within women before and after the occurrence of depression.
4. To compare the risk factors within women before and after the occurrence of anxiety
Methods
1. Study design:Prospective cohort study
1. Sample resource:Ovary aging study cohort in Gynecological endocrinology and women health center in PUMCH
3. Participants:women without depression(HADS-D<8)or anxiety (HADS-A<8), aged30-54years, having regular menstrual cycle during the age of20to30years, having intact uterus and at least one ovary, with at least one independent menstruation in the past10months and at least6months'menstrual diary were recruited. The exclusion criteria were the same with Section I.
4. Study procedure:The baseline data were collected between October in2007and May in2008. Then annually assessment was conducted for4times. Each assessment included the screening of depression and anxiety symptoms, investigation of menopausal symptoms, serum hormonal assay and height and weight measure. And so does the menstrual diary recycling.
5. Measurements:The changes of gynecological endocrinology and related health problem follow-up questionnaire, HADS, MENQOL, and menstruation diary card.
6. Statistical analysis
All data were entered into database Epidata3.02and were analyzed by SPSS13.0. χ2test or Mann-Whitney U test/Kruskal-Wallis H test was used to compare the baseline characteristics between women with symptoms and asymptomatic women. Repeated measure was used to analyse the changes of ovary aging stages and follow-up year on the scores of depression and anxiety. Conditional logistic regression model was used to estimate the within women risk of depression and anxiety symptoms.
Results
1. For228women without depression symptoms at baseline, with an average age of48.42±4.47year, the incidence of new onset of depression in4years' follow-up was22.4%.39.2%depression women were in EMT which was higher than other stages.
2. The scores of depression(4.12±2.08vs2.62±2.14,P=0.000) and physical symptoms(2.08±0.89vs1.77±0.73.P=0.000) at baseline in women with depression symptoms at follow-up were higher than women without depression.
3. Conditional logistic regression analysis showed that, the increase of serum FSH level(P=0.008,OR=1.10), vasomotor symptoms(P=0.008,OR=1.10) and physical symptoms(P=0.008,OR=1.10) were within-women risk factors of depression.
4. For271women without anxiety symptoms at baseline, with an average age of47.81±3.82year, the incidence of new onset of anxiety in4years' follow-up was10.7%.51.7%women were in EMT which was higer than other stages.
5. The scores of anxiety(3.45±2.34vs2.03±1.87,P=0.000), depression(6.14±3.38vs3.72±3.03,P=0.000), BMI(25.85±3.34kg/m2vs24.42±3.10kg/m2, P=0.021) and physical symptoms(2.39±1.06vs1.85±0.79kg/m2,P=0.001) at baseline for women with anxiety symptoms at follow-up were higher than women without anxiety.
6. Conditional logistic regression analysis showed that, the increase of physical symptoms(P=0.007, OR=35.56) were within-women risk factors of anxiety.
7. Repeated meausure showed that the scores of both depression(F=3.486, P=0.018;F=25.413,P=0.000) and anxiety(F=5.307,P=0.003;F=3.257,P=0.023)were influenced by the changes of ovary aging and the follow-up year.The scores of depression and anxiety were significantly higher in MT-MT(P=0.002,0.043)and MT-EPM(P=0.003,0.034)than in reproductive stages, and were significantly higher in the fourth follow-up year than baseline(P=0.000).
Conclusions
1. The new onset incidence of depression and anxiety for premenopausal women were22.4%and10.7%, respectively. EMT was the vulnerable stages for women to suffer from depression and anxiety.
2. Menopausal symptoms such as physical symptoms and vasomotor symptoms, and the changes of pituitary-ovarian axis characterized by the increase of FSH were independent within-women risk factors of depression. And the physical symptoms were also the within-women risk factors of anxiety.
3. Stay in MT and transition to EMP could increase the scores of depression and anxiety.
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