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

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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.