The menopause and aging, a comparative perspective

• The STRAW criteria for the menopause correspond to some rodent aging changes.
• Ovarian cell loss begins prenatally in all mammals.
• Hypothalamic impairments in aging rodents are robust, but sporadic in perimenopausal women.
• In aging rodents, hypothalamic impairments are associated with chronic unopposed estrogens.

The neuroendocrinology of menopause is reviewed from a comparative perspective, with emphasis on laboratory rodent models. These changes are compared by the 2011 STRAW criteria (Stages of Reproductive Aging Workshop). Ovarian cell loss begins prenatally in all mammals studied, with exponential depletion of primary follicles and oocytes in association with loss of fecundity by midlife. Rodents and humans also share progressively increasing irregularity in ovulatory cycles and increasing fetal aneuploidy as oocyte depletion become imminent. Hypothalamic impairments of the estrogen-induced surge of pituitary gonadotrophins (luteinizing hormone, LH; follicle stimulating hormone, FSH) are prominent in middle-aged rodents, but sporadic in peri-menopausal women. In aging rodents, hypothalamic impairments of the LH surge have been experimentally associated with prolonged phases of sustained estradiol (E2) and very low progesterone (P4) (‘unopposed estradiol’). Although peri-menopausal women also show hyper-estrogenic cycles, there is no indication for irreversible hypothalamic desensitization by E2. Ongoing cognitive assessments in clinical trials of estrogen therapy with and without P4 or other progestins may further inform about possible persisting effects of unopposed estrogens.This article is part of a Special Issue entitled ‘Menopause’.