Marder Wendy, Fisseha Senait, Ganser Martha A, Somers Emily C
Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
Clin Med Insights Reprod Health. 2012 Oct 24;2012(6):9-18. doi: 10.4137/CMRH.S10415.
Women with autoimmune diseases such as lupus, scleroderma, and vasculitis receiving cyclophosphamide for severe disease manifestations risk primary ovarian insufficiency(POI) due to gonadotoxicity of this therapy. In addition to loss of reproductive potential, POI is associated with increased risk of morbidity and mortality. Practitioners caring for women requiring gonadotoxic therapies should be familiar with long-term health implications of POI and strategies for ovarian preservation. Accumulating evidence supports the effectiveness of adjunctive gonadotropin releasing hormone analog (GnRH-a) for ovarian protection during gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly and invasive than assisted reproductive technologies used for achievement of future pregnancies, but is not Food and Drug Administration approved for ovarian preservation. This review focuses on POI comorbidities and strategies for mitigation of related sequelae, which can accumulate over decades of hypoesteogenism. These issues are arguably more pronounced for women with chronic autoimmune diseases, in whom superimposed POI further heightens risks of cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is not desired, ovarian protection during gonadotoxic therapy should be a major goal of disease management.
患有狼疮、硬皮病和血管炎等自身免疫性疾病的女性，因严重疾病表现而接受环磷酰胺治疗时，会因该疗法的性腺毒性而面临原发性卵巢功能不全（POI）的风险。除了丧失生殖潜能外，POI还与发病和死亡风险增加有关。照顾需要接受性腺毒性疗法的女性的从业者应熟悉POI的长期健康影响以及卵巢保护策略。越来越多的证据支持辅助性促性腺激素释放激素类似物（GnRH-a）在癌症和自身免疫性疾病人群的性腺毒性治疗期间对卵巢的保护作用。GnRH-a比用于实现未来妊娠的辅助生殖技术成本更低且侵入性更小，但未获得美国食品药品监督管理局批准用于卵巢保护。本综述重点关注POI的合并症以及减轻相关后遗症的策略，这些后遗症可能在数十年的雌激素缺乏状态下累积。对于患有慢性自身免疫性疾病的女性而言，这些问题可能更为突出，因为叠加的POI会进一步增加心血管疾病和骨质疏松症的风险。因此，即使不期望未来怀孕，在性腺毒性治疗期间进行卵巢保护也应是疾病管理的主要目标。
