绝经激素治疗与骨质疏松症

绝经激素治疗（MHT）是治疗绝经相关的血管舒缩症状和外阴阴道萎缩症状最有效的方法。此外,MHT对绝经后骨质疏松症的预防和治疗均有显著疗效。国际绝经学会及中国绝经学组制定的相关指南已将预防或治疗绝经后骨质疏松症纳入为MHT适应证之一。但雌激素的生理作用广泛,使用时获益和风险并存,故使用MHT预防或治疗绝经后骨质疏松症需注意掌握好适应证及禁忌证。     

绝经激素治疗与绝经相关症状

绝经期是女性生命必经的过程,绝经后由于卵巢功能减退而引起的雌激素缺乏将导致女性出现血管舒缩症状、神经精神症状、泌尿生殖道萎缩等症状以及绝经晚期发生骨质疏松、心血管疾病和老年痴呆等疾病。这些症状和绝经相关的疾病严重影响绝经后女性的生活质量和身心健康,而绝经激素治疗（MHT）是治疗绝经相关症状及预防相关疾病最有效的方法。文章对绝经相关症状作一阐述,并进一步探讨MHT的价值。     

绝经激素治疗与绝经相关症状

绝经期是女性生命必经的过程,绝经后由于卵巢功能减退而引起的雌激素缺乏将导致女性出现血管舒缩症状、神经精神症状、泌尿生殖道萎缩等症状以及绝经晚期发生骨质疏松、心血管疾病和老年痴呆等疾病。这些症状和绝经相关的疾病严重影响绝经后女性的生活质量和身心健康,而绝经激素治疗（MHT）是治疗绝经相关症状及预防相关疾病最有效的方法。文章对绝经相关症状作一阐述,并进一步探讨MHT的价值。     

绝经后激素治疗适应证

伴随绝经过程及绝经后内分泌事件对妇女健康产生的不良影响,出现了一些临床问题需要激素治疗来纠正。激素治疗纠正这些健康问题是效价比最佳的措施。目前激素治疗主要有三大适应证:缓解绝经相关症状、治疗泌尿生殖道萎缩相关疾病、预防和治疗骨质疏松症。     

绝经后骨质疏松症的药物治疗

正绝经后骨质疏松症的治疗药物种类较多,从作用机制来看,分为骨吸收抑制剂、骨形成促进剂和其他类;从适应证来看,分为预防、预防和治疗、治疗用药。但这些抗骨质疏松药物通常不包括钙剂和普通维生素D,后两者被称为骨质疏松症的基础治疗措施。本文将针对目前临床实践中如何应用绝经后骨质疏松症的药物治疗进行阐述。     

绝经激素治疗在妇科恶性肿瘤中的研究进展

妇科三大恶性肿瘤即宫颈癌、子宫内膜癌和卵巢癌发病率逐年上升,并有年轻化趋势。许多患者因治疗妇科肿瘤而发生医源性绝经,迅速出现严重的绝经症状,生活质量下降。绝经激素治疗（menopausal hormone therapy,MHT）能有效控制更年期症状、减轻泌尿生殖道萎缩和预防骨质疏松。研究表明：对宫颈鳞癌、Ⅰ期子宫内膜癌和卵巢上皮性癌行MHT相对安全;不建议对宫颈腺癌、Ⅱ期及以上期别的子宫内膜癌、卵巢颗粒细胞瘤和低级别子宫内膜间质肉瘤行MHT。小剂量MHT在改善绝经症状同时具有较轻不良反应。有关MHT在妇科肿瘤患者中治疗优势的报道日益增多,但仍缺乏大规模研究。临床中应结合具体情况,行个体化MHT。MHT在妇科恶性肿瘤中的应用仍有待探索。     

绝经激素治疗与心血管疾病

绝经增加了绝经后女性患心血管疾病的风险,绝经激素治疗（MHT）不仅能有效缓解更年期血管舒缩等症状,还可以改善心血管疾病发展的中间指标,从而减少围绝经期女性心血管疾病的发生。目前多项临床研究结果表明,对绝经后10年内和60岁以下健康女性在围绝经期开始MHT,心血管疾病发生率和死亡率有所下降。目前缺少MHT能够改善已确诊的心脏疾病的最终证据,不推荐MHT用于心血管疾病的一级预防,也不应用于冠心病的二级预防。     

绝经激素治疗与心血管疾病

绝经增加了绝经后女性患心血管疾病的风险,绝经激素治疗（MHT）不仅能有效缓解更年期血管舒缩等症状,还可以改善心血管疾病发展的中间指标,从而减少围绝经期女性心血管疾病的发生。目前多项临床研究结果表明,对绝经后10年内和60岁以下健康女性在围绝经期开始MHT,心血管疾病发生率和死亡率有所下降。目前缺少MHT能够改善已确诊的心脏疾病的最终证据,不推荐MHT用于心血管疾病的一级预防,也不应用于冠心病的二级预防。     

宫颈癌可否采用绝经激素治疗

宫颈癌是发生于女性生殖系统的恶性肿瘤,从世界范围看,发病率在女性恶性肿瘤中位于第4位。近年来宫颈癌的发病趋于年轻化,在当前的治疗手段下,经治的患者因手术切除卵巢或化疗及放疗损伤卵巢功能而出现人工绝经或提前绝经。绝经后雌激素水平下降引发一系列的问题,如潮热、出汗、烦躁、记忆力减退、骨质疏松、老年痴呆、泌尿生殖道萎缩及心血管疾病等,严重影响患者的生存质量。绝经激素治疗(menopause hormone therapy,MHT)不会诱导宫颈鳞癌及透明细胞癌的发生,也不会增加其复发率,并且可以缓解患者绝经相关症状,提高患者生存质量。而宫颈腺癌类似于子宫内膜癌,可能具有雌激素依赖性,雌激素是其发生的危险因素,针对其绝经期症状需谨慎使用MHT。     

绝经激素治疗与动静脉血栓栓塞性疾病

绝经激素治疗（MHT）是缓解女性更年期症状的重要医疗措施,但MHT也存在一定风险,其中,动静脉血栓栓塞性疾病包括静脉栓塞、肺栓塞、卒中的风险有可能增加。不同种类、不同途径应用MHT对人体的凝血、纤溶系统可产生不同的影响。MHT的治疗剂量、启动时间、持续时间、给药途径、用药方案以及孕激素的种类等所导致的血栓栓塞性疾病的风险不同。合理采用个体化MHT方案,有助于预防或降低动静脉血栓栓塞性疾病的相关风险。     

Menopausale Hormontherapie zur Frakturprävention

Menopausal hormone therapy, bone metabolism and fracture prevention

Based on the currently available data, menopausal hormone therapy (MHT) is an effective tool for preventing postmenopausal acceleration of bone metabolism and osteoporotic fractures. A sufficient calcium, vitamin D and protein dietary intake is a decisive factor for normal bone metabolism and successful fracture prevention and has to precede any hormonal or non-hormonal prevention of fragility fractures.

Therapeutic importance of menopausal hormone therapy

Together with correct nutrition, adequate physical activity and the elimination of factors increasing the risk of falling, MHT occupies an important place in decreasing the fracture incidence in the perimenopause and early postmenopause. In postmenopausal women with increased fracture risk below the age of 60 years or within 10 years after menopause, MHT is one of the first line therapies for prevention and treatment of postmenopausal osteoporosis and fragility fractures. Every MHT should always be individualized. Personal and family history, the results of relevant investigations and the individual needs for fracture prevention have to be considered. In preventing fragility fractures, the benefits of MHT clearly outweigh the risks. As a rule, in the presence of premature ovarian insufficiency MHT should be started without delay and continued at least until the average age of natural menopause.Alternatively, tibolone and selective estrogen receptor modulators can be used depending on the indications, existing climacteric symptoms and the personal risk-benefit profile. In the later postmenopause and in the presence of manifest osteoporosis, a specific treatment with one of the established non-hormonal alternatives should be used.

     

Prävention der postmenopausalen Osteoporose

The international recommendations for pharmacological fracture prevention in postmenopausal osteoporosis have changed in 2013. A distinction must now be made between patients who are still within the “window of opportunity” for estrogen administration and those who have already passed this limit. Following the new international recommendations substances acting through the estrogen receptor are the treatment of first choice for fracture prevention in perimenopausal or early postmenopausal women. For women within the “window of opportunity” the menopausal hormone therapy (MHT) including tibolone is the first choice. For subjects at high risk without vasomotor symptoms, selective estrogen receptor modulators (SERMs) are efficient in the prevention of vertebral fractures, particularly in women with an increased breast cancer risk. Non-hormonal drugs are recommended in the presence of contraindications or rejection of MHT or SERMs; however, the current German S3 guidelines established in 2009 still consider MHT as a therapy of second choice. As before, the new recommendations maintain that MHT should not be started in the later postmenopause beyond the “window of opportunity”. For women in the later postmenopause non-hormonal drugs, such as bisphosphonates (long-term effect on bone), denosumab (effect reversible) should be used. In cases of severe osteoporosis strontium ranelate may be prescribed (not approved in Switzerland). In patients of any age suffering from severe osteoporosis, the analogues of parathormone may be used by specialists. For fracture prevention only substances should be used the efficacy of which has been established by an evidence level of grade A. Not all drugs approved for fracture prevention simultaneously reduce the risks for vertebral, non-vertebral and hip fractures.     

应该重视女性绝经相关骨质疏松症

在绝经早期开始绝经相关激素补充治疗,坚持钙和维生素D的补充,健康的生活方式,是预防骨质疏松症的关键。目前的主要问题是,由于骨质疏松症造成的危害是骨折,而骨折是在骨质已经疏松之后的老年发生,刚刚绝经的妇女往往对此缺乏足够的认识和重视,因此在全国范围内广泛开办更年期门诊,从医务人员入手,进行医生教育、患者教育和人群的医学普及教育是预防骨质疏松的关键。     

激素补充治疗与中老年女性骨质疏松症

骨质疏松症是中老年妇女的常见病。雌激素有明确抑制骨吸收的作用。绝经后由于雌激素的缺乏,导致骨量的快速丢失,使中、老年女性患骨质疏松症的危险大大高于男性。绝经后激素治疗能有效阻止骨丢失,维持骨量,降低骨折危险。特别提倡在60岁以前或绝经10年内开始使用激素治疗。此期间启用激素治疗,除对骨骼的保护作用外,还可以明显缓解绝经症状及降低冠心病风险,获益最多,风险最小。选择绝经激素治疗,是基于生活质量、健康优先原则和个人危险因素而做的个人决策。     

New possibilities for diagnosis and treatment of osteoporosis

Postmenopausal osteoporosis is preventable and treatable. Women need not lose bone mineral density (BMD) after the menopause. Without intervention, all women lose bone after menopause, regardless of the amount of calcium, vitamin D, and exercise they undertake. Postmenopausal women need estrogen replacement, a selective estrogen receptor modulator (SERM), or a bisphosphonate to prevent bone loss. Alendronate, risedronate (bisphosphonates) and raloxifene (SERM) are approved for the prevention of bone loss. The diagnosis of at-risk postmenopausal women can best be accomplished by measuring BMD in all postmenopausal women age 65 years and older regardless of their risk profile and in all postmenopausal women under 65 years with one or more risk factors. Treatment guidelines direct physicians to treat postmenopausal women with T-scores lower than -2.0 SD regardless of their risk profile and postmenopausal women with T-scores lower than -1.5 SD with one or more risk factors. The lower the BMD, the greater the fracture risk, particularly in individuals with increased age, existing fragility fractures, or high bone turnover. The best intervention for a patient should be individually selected, based on careful clinical assessment. Although calcitonin is not approved for prevention, it is approved for treatment. The labeling of estrogens has been modified to state that they may be used to "manage" osteoporosis. The lack of efficacy of calcitonin to prevent bone loss during the first 5 years after menopause, and the lack of prospective fracture reduction data for estrogen, have resulted in these labeling restrictions. Alendronate, risedronate, and raloxifene are currently approved for the treatment of osteoporosis. Both of these compounds have been shown to increase BMD and decrease fracture risk. Monitoring of a patient's response to treatment may be accomplished using serial BMD testing and biomarkers of bone turnover.     

绝经激素治疗与妇科恶性肿瘤

随着人口老龄化,女性绝经后雌激素缺乏所导致的相关疾病越来越受到关注。同时,随着妇科恶性肿瘤发病趋于年轻化,肿瘤治疗导致的医源性绝经进而造成的各种低雌激素相关问题又严重影响患者的生存质量。女性期望在延长生命的同时获得较高的生存质量,绝经激素治疗（MHT）是有效的治疗方案。明确MHT与妇科恶性肿瘤之间关系,选择最佳MHT个体化治疗方案,将成为成功实施MHT的关键。     

绝经激素治疗与妇科恶性肿瘤

随着人口老龄化,女性绝经后雌激素缺乏所导致的相关疾病越来越受到关注。同时,随着妇科恶性肿瘤发病趋于年轻化,肿瘤治疗导致的医源性绝经进而造成的各种低雌激素相关问题又严重影响患者的生存质量。女性期望在延长生命的同时获得较高的生存质量,绝经激素治疗（MHT）是有效的治疗方案。明确MHT与妇科恶性肿瘤之间关系,选择最佳MHT个体化治疗方案,将成为成功实施MHT的关键。     

Variations on hormone replacement therapy: An answer to the ‘one dose fits all’ Women's Health Initiative study

The Women's Health Initiative study worked on the assumption that one dose would fit all asymptomatic postmenopausal women. The investigators therefore often used the wrong dose, of the wrong hormones, on the wrong patients and therefore came to many wrong conclusions. Different combinations of different hormones are necessary for different symptoms and different age groups. Hormone replacement therapy may be commenced in the perimenopausal phase, the early postmenopause, the late postmenopause or after hysterectomy and bilateral salpingo-oophorectomy or a premature menopause. These all require different treatments. Similarly, various indications such as vasomotor symptoms, sexual problems, depression or the treatment/prevention of osteoporosis all need different combinations of estradiol and possibly progestogen and testosterone, according to the specific requirements of the patient.