title: Aging of the female reproductive system: a window into brain aging.
abstract: The menopause marks the permanent end of fertility in women. It was once thought that the exhaustion of ovarian follicles was the single, most important explanation for the transition to the menopause. Over the past decade, this perception has gradually changed with the realization that there are multiple pacemakers of reproductive senescence. We will present evidence that lends credence to the hypothesis that the central nervous system is a critical pacemaker of reproductive aging and that changes at this level contribute to the timing of the menopause. Studies demonstrate that an increasing de-synchronization of the temporal order of neuroendocrine signals may contribute to the accelerated rate of follicular loss that occurs during middle age. We suggest that the dampening and destabilization of the precisely orchestrated ultradian, circadian, and infradian neural signals lead to miscommunication between the brain and the pituitary-ovarian axis. This constellation of hypothalamic-pituitary-ovarian events leads to the inexorable decline of regular cyclicity and heralds menopausal transition.
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington 40536, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Wise
authors.forename: M L
authors.initials: ML
authors.lastname: Kashon
authors.forename: K M
authors.initials: KM
authors.lastname: Krajnak
authors.forename: K L
authors.initials: KL
authors.lastname: Rosewell
authors.forename: A
authors.initials: A
authors.lastname: Cai
authors.forename: K
authors.initials: K
authors.lastname: Scarbrough
authors.forename: J P
authors.initials: JP
authors.lastname: Harney
authors.forename: T
authors.initials: T
authors.lastname: McShane
authors.forename: J M
authors.initials: JM
authors.lastname: Lloyd
authors.forename: N G
authors.initials: NG
authors.lastname: Weiland
mesh_terms: D000368:Aged; D000375:Aging; D001921:Brain / Q000502:physiology*; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008593:Menopause; D008875:Middle Aged; D010053:Ovary / Q000502:physiology; D010507:Periodicity; D010902:Pituitary Gland / Q000502:physiology; D012098:Reproduction / Q000502:physiology*
chemical_list: D007986:Luteinizing Hormone