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围绝经期综合征激素替代治疗致溢乳1例

2019-04-27 王敬唯 岳红萍 姚伟林 实用妇科内分泌杂志

周某某,女,48岁,中等偏瘦体型,因“月经紊乱半年,停经70+天伴潮热、睡眠差”2014年10月来我院门诊就诊,患者平素月经规律,初潮年龄14岁,经期3~5天,周期28~30天,月经来潮前无乳房胀痛等相关病史。近半年来出现月经紊乱,经期为5~7天,周期1~3月不等,患者偶有潮热、盗汗等症状,近期睡眠差,患者自测尿HCG阴性,来我院门诊检查治疗,患者近期精神可,睡眠稍差,二便正常,体重无明显变化。

病例资料

周某某,女,48岁,中等偏瘦体型,因“月经紊乱半年,停经70+天伴潮热、睡眠差”2014年10月来我院门诊就诊,患者平素月经规律,初潮年龄14岁,经期3~5天,周期28~30天,月经来潮前无乳房胀痛等相关病史。近半年来出现月经紊乱,经期为5~7天,周期1~3月不等,患者偶有潮热、盗汗等症状,近期睡眠差,患者自测尿HCG阴性,来我院门诊检查治疗,患者近期精神可,睡眠稍差,二便正常,体重无明显变化。

既往史:甲状腺功能减退10+年,予“优甲乐”治疗,曾因“腰痛2+月”,在我院骨科诊断为右侧股骨头缺血坏死(Ⅲ级),双侧髋关节退行性改变,予维生素D3肌注治疗,否认糖尿病高血压、冠心病等慢性病史,否认手术史、外伤史、输血史等。生育史:1-0-0-1(足月顺产一胎),家族史:父母均体健,无家族遗传史。

查体:生命体征平稳,心肺查体未见明显异常,双乳表皮完好,无红肿、无破溃,触诊无压痛,未扪及包块,余查体未见明显异常。患者来我院门诊后行妇科超声、女性激素、血HCG、甲功双乳房B超、心电图等相关检查,妇产超声示:宫内膜厚约0.5cm,未见明显异常;女性激素示:雌二醇:5.01pg/ml、FSH:41.64mIU/L;血HCG阴性;甲功:未见明显异常;空腹血糖:4.8mmol/L;乳腺超声示:双侧乳腺囊肿。考虑患者上述情况后诊断:围绝经期。

与患者沟通后患者有维持月经的意愿,故予以克龄蒙(戊酸雌二醇/醋酸环丙孕酮)口服,改善上述症状。患者服用1周期后,症状好转,患者要求继续上述方案治疗。考虑患者有乳腺囊肿,故建议患者服药期间定期复查乳腺超声或钼靶,2015年12月复查乳腺钼靶结果示:(1)双侧乳腺增生症,建议定期复查。(2)双侧腋区副乳腺(Picture1)。考虑患者情况,告知患者乳腺良性疾病为HRT慎用指征,与患者沟通后,患者要求继续予HRT治疗,告知患者定期监测乳腺情况。2016年4月患者无明显诱因出现溢乳,患者因“双侧乳汁分泌”半月,到我院门诊检查治疗,患者诉溢出乳汁为淡黄色液体,无异味,乳房无胀痛、无其他特殊不适,门诊乳房查体:双乳未触及包块,乳头无皴裂、无破溃,挤压乳头见谈黄色液体流出,无异味。逐步完善血清泌乳素、头颅MRI、乳腺超声和钼靶等相关检查。血清泌乳素结果示:PRL:13.7ng/ml;

颅MRI:未见明显异常。复查乳腺超结果提示:双侧乳腺小叶增生。追问患者病史,患者近期除服用克龄蒙及优甲乐外未服用其他药物,患者生活平静,未行剧烈运动,睡眠及大小二便正常,考虑患者情况嘱患者继续服用克龄蒙,继续观察。3月后患者复诊,仍有乳汁分泌,查乳腺钼靶示:双侧乳腺增生。考虑患者情况嘱患者暂停服用克龄蒙观察。患者停药1月后,患者溢乳症状减轻,之后3月内逐渐消失。定期随访患者乳腺情况,患者无溢乳出现,2017年3月患者复查乳腺钼靶示:双侧乳腺增生症(Picture2),建议复查。2017年5月复查妇科超声示:子宫内膜厚0.3cm,未见明显异常。2017年6月30日复查乳腺超声示:双侧乳腺多发囊性结节。2018年5月,她再次重复乳房钼靶扫描示轻度增生的小叶(Picture3)。随访患者情况,至截稿时患者无潮热、盗汗、失眠等更年期症状,患者一般情况好,无不适。






讨论

围绝经期是女性一生中一个非常重要的时期,激素补充治疗(hormonereplacementtherapy,HRT),可以有效缓解绝经相关症状,在治疗窗口期(绝经10年内,60岁以下)开始启动HRT治疗,会对骨骼、血管和神经系统带来长期的保护作用,是一种有效缓解女性围绝经期症状的方法,近年来已较广泛应用于该类女性的治疗。

在HRT的治疗中方法很多,如单纯雌激素,单纯孕激素,雌孕激素序贯用药、雌孕激素联合连续用药及雌激素局部用药等多种方法。其中,雌孕激素序贯用药,适用于有完整子宫、围绝经期或绝经后期希望有月经样出血的妇女。克龄蒙是最早的激素替代疗法的复方制剂,采用序贯配方,前11天为2mg的戊酸雌二醇,后10天含2mg的戊酸雌二醇和1mg的醋酸环丙孕酮,然后是7天的用药间隙期。醋酸环丙孕酮是一种高效孕激素,能起到良好的内膜转化作用,保护子宫内膜,由于它是孕酮的衍生物,因而对乳腺也有保护作用。克龄蒙是序贯而非连续联合配方,除缓解围绝经期症状外,还可以提供规律的月经周期。本病例中,围绝经期女性,48岁,月经紊乱,有潮热、盗汗等症状、腰椎退行性改变予维生素D3治疗病史,且其有意愿有月经来潮,正适合应用克龄蒙。对于有溢乳症状的女性,应想到的原因可能有:妊娠、乳腺疾病、高泌乳素血症等,该病人行了血液HCG、乳腺超声等检查,未提示妊娠、乳腺疾病等相关病症,故想到是否有高泌乳素血症。催乳素(prolactin,PRL)是垂体前叶分泌的一种多肽蛋白激素,具有促进乳汁分泌的作用。根据2011年内分泌学会HPRL临床诊疗指南,单次检测血清泌乳素高于25μg/L即可诊断高泌乳素血症。

根据相关文献的学习可知,高泌乳素的原因有如下几个方面:(1)生理性因素:精神因素、运动、进食、睡眠、性交、乳头刺激、应激(手术、低血糖心肌梗死、晕厥、外伤)等可引起泌乳素暂时性升高;(2)药物性因素:雌激素、西米替丁、利血平、抗癫痫药物、阿片等,其中雌激素及避孕药:作用于垂体泌乳素细胞,促进泌乳素合成与释放;(3)病理性因素①垂体疾病,②下丘脑及垂体柄疾病,③原发或继发性甲状腺功能减退,④肝、肾功能不全,⑤多囊卵巢综合征:文献报道有6%~20%的多囊卵巢综合征患者伴有泌乳素水平升高,可能是由于继发性雌激素刺激泌乳素细胞合成致泌乳素分泌增多,⑥异位泌乳素分泌增多:如支气管源肿瘤、肾上腺样瘤。⑦腹壁外伤:如手术或带状疱疹慢性刺激,⑧肢端肥大症:50%的生长激素腺瘤可以伴有HPRL。

综合考虑,患者既往有甲低病史,促甲状腺激素释放激素、促甲状腺激素升高致泌乳素升高,但患者一直定期检测甲功,在我院内分泌科就诊予“优甲乐”调整甲功,甲功在服用克龄蒙前、中、后均控制在正常范围内,故该患者溢乳症状,不考虑该因素引起。患者在HRT治疗期间,无相关引起泌乳素增高的生理因素影响,无其他药物服用史,颅脑MRI未见明显异常,平素月经正常,妇科超声未见明显异常。曾有文献报道过胰岛素抵抗和高胰岛素血症可以促进垂体细胞分泌泌乳素,但患者查空腹血糖在正常范围内,中等偏瘦体型,虽未行胰岛素相关抗体检查,但考虑该患者的溢乳与该因素的相关性较小,综上所述,不考虑其他病理因素引起该患者溢乳。患者在排除其他因素的情况下,停用克龄蒙一段时间后,溢乳症状逐渐消失,故考虑该患者溢乳可能与克龄蒙的服用相关,曾有文献报道过雌激素及避孕药:作用于垂体泌乳素细胞,促进泌乳素合成与释放,在平时临床工作中,这种情况较罕见,起初并未考虑该因素引起的溢乳,但通过患者的基本情况,病史及相关检查证实该患者的溢乳为克龄蒙HRT相关。

克龄蒙引起的溢乳在临床上是非常罕见的,希望本次的病例分享可以给不明原因溢乳的病人提供参考,也希望大家HRT治疗时遵循HRT治疗的适应症及禁忌症,在给予围绝经及绝经期妇女关爱的同时,注意药物副作用可能出现的情况,出现问题时严格筛查,必要时及时停药,防止严重问题的出现。

原始出处:

王敬唯,岳红萍,姚伟林,罗芳,李寅,端娅,张松.围绝经期综合征激素替代治疗致溢乳1例[J].实用妇科内分泌杂志(电子版),2019(04):163-164.

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    2019-04-29 海豹
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