The Role of MMPs 1 and 9 and MT-1 MMP in Hormone Replacement Therapy related irregular bleeding

大约40%的澳大利亚女性选择激素替代疗法（HRT）。这种选择通常基于HRT的感知益处，如缓解衰弱的更年期症状（如潮热和出汗），预防脆性骨病（骨质疏松症）和潜在的预防心脏病和记忆丧失（痴呆）。不幸的是，这些女性中的许多人（在英国的一项大型研究中高达三分之二）会出现不规则出血。这不仅不方便，而且引起了人们的担忧，即出血可能是子宫癌等严重疾病的症状。许多HRT使用者随后接受内部检查、测试和手术，以排除癌症作为出血原因。几乎所有病例均未发现其他异常。然而，由于出血问题，许多妇女决定不再继续使用激素替代疗法。人们对使用激素替代疗法的妇女出现不规则出血的原因知之甚少。此外，没有办法预测谁会受到影响，也没有既定的方法来停止或预防出血，除了停止激素替代疗法。这个问题影响所有HRT的准备工作。CI（副教授玛莎·希基）先前的试点研究首次证明，使用激素替代疗法的妇女子宫内膜发生变化，可能导致出血。这些变化与使用避孕药出现突破性出血的年轻女性相似。计划中的项目旨在进一步探索破坏子宫内膜血管并导致出血的重要分子的作用。这增加了开发特定药物来阻止或预防激素替代疗法使用者出血的可能性。这可能会大大提高替代激素疗法的可接受性，从而可能对澳大利亚和全世界妇女的健康产生重大积极影响。

Approximately 40% of women in Australia chose to take Hormone Replacement Therapy (HRT). This choice is usually based upon the perceived benefits of HRT such as the relief of debilitating menopausal symptoms (such as hot flushes and sweats), the prevention of brittle bone disease (osteoporosis) and the potential prevention of heart disease and memory loss (dementia). Unfortunately, many of these women (up to two thirds in a large UK study) then suffer from irregular bleeding. This is not only inconvenient, but raises anxiety that the bleeding may be a symptom of serious illness such as cancer of the womb. Many HRT users then undergo internal examinations, tests and operations to exclude cancer as the cause of the bleeding. In almost all cases no other abnormality is found. However, many women decide not to continue with HRT because of this troublesome bleeding. Very little is understood about the reason why women using HRT have irregular bleeding. Furthermore, there are no ways of predicting who will be affected and no established way to stopping or preventing bleeding apart from discontinuing HRT. This problem affects all HRT preparations. Previous pilot studies by the CI (Associate Professor Martha Hickey) have demonstrated for the first time that there are changes in the lining of the womb in women using HRT which may lead to bleeding. These are similar to changes seen in younger women with breakthrough bleeding using contraceptives. The planned project intends to futher explore the actions of the important molecules which break down the blood vessels of the womb lining (endometrium) and cause bleeding. This raises the possibility that specific agents could be developed to stop or prevent bleeding in HRT users. This is likely to substantially increase the acceptability of HRT and may thus have major positive health implications for women in Australia and worldwide.