Photodynamic therapy to the endometrium as a primary treatment modality for menorrhagia
Menorrhagia is a condition which affects a considerable number of women. The traditional treatment is hysterectomy, which has significant morbidity associated with it. Over recent years more minimally invasive techniques have been developed to treat menorrhagia without resorting to hysterectomy. Photodynamic therapy (PDT) is a non-thermal technique which can be used to cause tissue damage. It requires the activation of a photosensitiser with light, which in the presence of oxygen produces cytotoxic oxygen species. 5-aminolaevulinic acid (ALA) is a photosensitising agent which has been used as a pre-cursor for the photoactive protoporphyrin IX (PPIX) in the past to successfully destroy the endometrium in the rat and rabbit model. When the technique has been used in humans, the effect has been unsatisfactory and has not been reproducible. This thesis demonstrates that by the addition of an iron chelator CP94 there is a significantly increased level of PPIX in the endometrium, as measured with fluorescence microscopy after both chemicals are instilled into the uterine cavity of the rabbit. We show that pH has little effect on these data. The optimum time for PDT was shown to be seven hours after instillation. We show a dramatically increased PDT effect when using a combination of ALA and CP94 in the rabbit endometrium. In addition this PDT effect remains at 28 days. These studies showed that it may be possible to improve on the previously reported disappointing clinical results using ALA-PDT by the addition of the iron chelating agent, CP94. We performed preclinical trials of light distribution within the human uterine cavity using different light delivery systems. This showed that an effective light dose could be applied to the irregular shaped endometrial cavity, in order to maximise the PDT effect in humans. The technique is now ready to take into pilot clinical studies.