Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Clin Chem. 2014 Jan;60(1):68-77. doi: 10.1373/clinchem.2013.202556.
Menopausal hormone therapy (HT) continues to have a clinical role in symptom management, but identifying women for whom benefits will outweigh the risks remains a challenge. Although hormone therapy (HT) is the most effective strategy for ameliorating vasomotor and other symptoms, randomized clinical trials show an unfavorable balance of benefits and risks for many women. However, closer examination of data from these trials suggests that it may be possible to classify women as better or worse candidates for HT by using individual risk stratification.
Data from 2 landmark trials-the Women's Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS)-suggest an important role for clinical characteristics, serum biomarkers, genomic markers, and gene-environment interactions in developing a personalized approach to the prediction of risk for cardiovascular disease (CVD) events for women while on HT. The available data suggest several characteristics of women who are optimal candidates for HT use: younger age (<60 years), recent onset of menopause (<10 years), favorable lipid profile (LDL cholesterol <130 mg/dL or LDL/HDL cholesterol ratio <2.5), absence of metabolic syndrome, and absence of factor V Leiden genotype. The identification of other characteristics is an area of active investigation. In addition, women at high risk for venous thromboembolism should avoid systemic HT or choose a transdermal rather than oral delivery route.
Personalized medicine-i.e., the use of the specific biological profile of an individual to guide the choice of treatment-is highly relevant for clinical decision-making regarding HT and offers promise for improved treatment efficacy and safety.
绝经激素治疗(HT)在症状管理方面仍然具有临床作用,但确定哪些女性的获益将超过风险仍然是一个挑战。尽管激素治疗(HT)是改善血管舒缩和其他症状的最有效策略,但随机临床试验显示,许多女性的获益与风险之间存在不利平衡。然而,对这些试验数据的更仔细检查表明,通过使用个体风险分层,可能有可能将女性分类为更好或更差的 HT 候选者。
两项具有里程碑意义的试验——妇女健康倡议(WHI)和心脏和雌激素/孕激素替代研究(HERS)的数据表明,临床特征、血清生物标志物、基因组标志物和基因-环境相互作用在为接受 HT 的女性预测心血管疾病(CVD)事件风险方面具有重要作用。可用数据表明了一些适合接受 HT 的女性的特征:年龄较轻(<60 岁)、绝经时间较短(<10 年)、良好的血脂谱(LDL 胆固醇<130mg/dL 或 LDL/HDL 胆固醇比值<2.5)、无代谢综合征和无因子 V 莱顿基因型。其他特征的识别是一个活跃的研究领域。此外,有静脉血栓栓塞风险的女性应避免全身 HT 或选择透皮而非口服给药途径。
个性化医学——即使用个体的特定生物学特征来指导治疗选择——对于 HT 的临床决策具有高度相关性,并为提高治疗效果和安全性提供了希望。