Pituitary, ovarian and uterine function in dysfunctional uterine bleeding
Fraser, Ian Stewart
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This thesis describes a series of investigations of a rather poorly defined group of menstrual disturbances known as dysfunctional uterine bleeding (DUB). This condition is charact¬ erised by excessively heavy menstrual bleeding and, although commoner at ages 30-50 years, may occur at any time during rep¬ roductive life. The large published literature has been thorough ly reviewed and areas of ignorance highlighted. The investigations described have been devised to elucidate several aspects of pituitary, ovarian and uterine function in women of different ages with ovulatory and anovulatory DUB and compare these with normal women. All have raised questions req¬ uiring future study. The first section describes the use of a combination of isotope dilution techniques and direct sampling of ovarian venous blood and follicular fluid to study the ovar¬ ian blood flow and the ovarian secretion and metabolism of oestra diol and oestrone in women with normal menstrual function or DUB. In normal women 95% of circulating oestradiol was secreted by the developing follicle or corpus luteum. In women with DUB oestro¬ gen metabolism was normal but the dynamics of oestrogen secretion was sometimes disturbed. In some cases multiple follicle growth and inappropriately high oestradiol secretion was observed. In the follicular phase most large follicles were functionally active and contained very high concentrations of oestradiol (>1250 ng/ml). Most adolescents with DUB are anovulatory and a very small proportion develop the more extreme endometrial changes of cys¬ tic glandular hyperplasia (CGH). Follow up of the group of 17 of these adolescents over 10 years revealed a high incidence of long term menstrual and reproductive disturbances. Detailed endocrine assessment over 3 cycles in 4 young women with DUB & CGH,and dynamic testing with oestrogen provocation and gonadotrophin- releasing hormone stimulation in a further 9 young women revealed a failure of positive oestrogen feedback as a cause of the anovulation. All exhibited prolonged follicular activity with, excessive oestradiol secretion. A careful study of perception of menstrual bleeding indi¬ cated that many women perceived their menstrual blood loss to be much heavier than objective measurements demonstrated. Only 38% of women with a convincing clinical history of menorrhagia had a measured blood loss of greater than 80 mis. These women also demonstrated some difficulty in assessing month to month and even day to day changes in blood loss volume. In a differ¬ ent group of 28 women it was found that only 36% of the menstr¬ ual discharge (range 1.6-81.7%) consisted of blood, and the remainder of the fluid is probably an endometrial transudate. This may contribute to difficulties in perception. The final section describes the development and application of two inert gas clearance techniques (with Krypton-85 and Kenon-J.33) for the measurement of endometrial blood flow (EBF) in women. The techniques have been validated by comparison with radioactive-labelled microspheres in sheep. Cyclical fluctua¬ tions in EBF were seen during the menstrual cycle with a pre¬ ovulatory peak, early luteal fall and gradual sustained rise up to the onset of menses. The pattern was similar in ovulatory DUB, while anovulatory women showed variable rates.