Aspects on menstrual physiology, pathology and medical treatment of menorrhagia

Sammanfattning: Menstruation is the monthly process by which the endometrium in fertile women is discarded if no pregnancy occurs. The physiology and pathology of menstruation has been extensively studied; still several steps are not fully understood. Menorrhagia, heavy regular menstrual bleeding, is a gynaecological symptom of disease. It is only a symptom of an underlying disease and not an illness in itself. Nevertheless menorrhagia, sometimes without adequate preceding evaluation, has been the reason of surgical interventions such as endometrial ablation or hysterectomy. The aims of this work was to study menstrual physiology in order to find a link between the progesterone withdrawal before menses and the vasoconstriction in endometrial coiled arteries during menses. Furthermore general and local causes of menorrhagia were studied and two medical treatments of menorrhagia were evaluated. The results support a chain of events linking progesterone withdrawal to upregulation of the thrombin receptor, leading to an increased thrombin response and a release of endothelin, in turn leading to constriction in the coiled arteries. This chain of events fits well into existing theories on inflammation and tissue degradation in the endometrium at the time of menstruation. The results also show that there is a high probability of revealing an earlier undiagnosed von Willebrands Disease when properly examining a woman with menorrhagia. In addition to this other causes of increased bleeding often found are platelet dysfunction disorders. Furthermore there was a significant correlation between the amount of menstrual blood loss and the fibrinolytic activity in the menstrual fluid both for women who bleed normally and for women with menorrhagia. Evaluation of medical treatment showed that menstrual blood loss was significantly reduced with up to 41 % during treatment with a new antifibrinolytic drug, an ester prodrug of tranexamic acid. Treatment with desmopressin nasal inhalation and the commercially available form of tranexamic acid also reduced menstrual blood loss with up to 33%. A reduction in menstrual blood loss of 30% during two days was achieved with only desmopressin treatment. In summary, a crucial link in the physiological events regulating onset, duration and cessation of normal menstrual bleeding is presented. Two important facts on the aetiology of menorrhagia have been established. First that undiagnosed bleeding disorders are found to be a common reason for menorrhagia and second that there is a high correlation between the menstrual blood loss and the local fibrinolytic activity in menstrual fluid. And finally two alternative medical treatments for menorrhagia were evaluated. Taken together, these results provide an improved understanding of menstrual physiology and pathology. This may lead to a better evaluation of the symptom menorrhagia as well as a better treatment of the underlying causes, thus reducing the frequency of unnecessary surgical interventions.