Computer Simulation of the Human Pituitary-Ovarian Cycle: Studies of Follicular Phase Estradiol Infusions and the Midcycle Peak

A mathematical model of the hormonal changes during the pituitary-ovarian cycle has been developed based on the previous model of Bogumil et al. Our model incorporates the following distinctive features: 1) discontinuous pulsatile secretion of luteinizing hormone (LH), with regulation of its production rate dependent on both the size and frequency of pulsations; 2) the midcycle LH surge (and FSH surge) are triggered by a significant fall of serum estradiol (E2) after E2 has been maintained at a high level for a critical period of time; 3) the magnitude of the LH and FSH surges depends on the dose and duration of E2 in the antecedent follicular phase; 4) the sensitivity of the pituitary to E2 feedback changes during the follicular phase, i.e., low E2 during the early follicular phase provides a stimulus for increased LH release in the mid-follicular phase; 5) effects of LH and FSH on the ovary are manifested only after an arbitrary delay; 6) LH is metabolized in a two compartment rather than a single compartment system. The model displays an ideal or “limit” cycle similar to that of the Bogumil model, with some notable exceptions: 1) the midcycle FSH and LH peaks are coincident; 2) the midcycle FSH peak reaches values higher than those observed in the early follicular phase; 3) LH values do not fall progressively during the follicular phase; 4) the model responds appropriately to simulated infusion of estradiol for 36 h commencing on day 2 or day 8 of the follicular phase, consistent with recent physiological studies. These studies indicate that the Bogumil-Vande Wiele model is a suitable basis for further analysis of the control mechanisms of the menstrual cycle.