A lifelong model for the female reproductive cycle with an antimüllerian hormone treatment to delay menopause

A system of 16 non-linear, delay differential equations with 66 parameters is developed to model hormonal regulation of the menstrual cycle of a woman from age 20 to 51. This mechanistic model predicts changes in follicle numbers and reproductive hormones that naturally occur over that time span. In particular, the model illustrates the decline in the pool of primordial follicles from age 20 to menopause as reported in the biological literature. Also, model simulations exhibit a decrease in antimüllerian hormone (AMH) and inhibin B and an increase in FSH with age corresponding to the experimental data. Model simulations using the administration of exogenous AMH show that the transfer of non-growing primordial follicles to the active state can be slowed enough to provide more follicles for development later in life and to cause a delay in the onset of menopause as measured by the number of primordial follicles remaining in the ovaries. Other effects of AMH agonists and antagonists are investigated in the setting of this model.

► Hormonal control of the menstrual cycle is modeled from age 20 to menopause.
► The model predicts changes in follicle numbers and reproductive hormones due to aging.
► Hormonal treatments are tested which may delay menopause.
► The effects of AMH agonists and antagonists are investigated using model simulations.
► An ad hoc procedure is presented to estimate model parameters.