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A BIOLOGICALLY BASED MODEL FOR THE HORMONAL CONTROL OF THE MENSTRUAL CYCLE
Citation:
Harris, L. A., P. M. Schlosser, AND J. F. Selgrade. A BIOLOGICALLY BASED MODEL FOR THE HORMONAL CONTROL OF THE MENSTRUAL CYCLE. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
Recent studies suggest that environmental substances that mimic endogenous estrogens (eg. estradiol) may disrupt the endocrine system. While high-level exposures to estrogenic substances are believed to contribute to such adverse effects as cancer, developmental disorders, and fertility problems, concerns are increasing because low-level exposures occur more frequently for longer periods of time, in our diets (phytoestrogens), in the environment (pesticides), and in hormonal contraceptions and therapies. These exposures might have a profound effect on the menstrual cycle. Therefore, a mathematical model that accurately predicts the blood levels of hormones that control the menstrual cycle would be a useful tool in evaluating the effects of hormonally active substances on the endocrine system. The human menstrual cycle is controlled by the pituitary hormones, luteinizing hormone and follicle-stimulating hormone, and the ovarian hormones, estradiol, progesterone, and inhibin. The model to be presented in this work predicts the time courses of these five hormones as they interact to regulate and maintain the menstrual cycle through positive and negative feedback loops. The model reproduces the time courses of these hormones observed in normally cycling women as reported in the literature. In addition, the model was shown to have two stable periodic solutions for the same parameter set, a large amplitude solution that fits the data for normally cycling women and a small amplitude solution that possesses many similarities to a reproductive disorder referred to as polycystic ovarian syndrome (PCOS). Hormonal treatments for this abnormality were simulated and the normal (large amplitude) cycle that fits the data was successfully recovered from the abnormal (small amplitude) cycle. Finally, simulations of exogenous estrogen exposure show that the normal cycle of the model can be perturbed into the abnormal cycle. Therefore, using this model, an exogenous estrogen input was shown to disrupt the normal menstrual cycle. (This abstract does not reflect EPA policy).