Loss of Ovarian Hormones and Accelerated Somatic and Mental Aging

Abstract

Bilateral oophorectomy in premenopausal women is a unique condition causing the abrupt and premature loss of ovarian hormones, primarily estrogen. Bilateral oophorectomy causes an alteration of several fundamental aging processes at the cellular, tissue, organ, and system levels, leading to multimorbidity, frailty, and reduced survival. However, many questions remain unanswered.

Independent Roles of Estrogen Deficiency and Cellular Senescence in the Pathogenesis of Osteoporosis: Evidence in Young Adult Mice and Older Humans

“…In addition, it is possible that in contrast to our findings in young adult mice, sex steroid deficiency may result in senescent cell accumulation in middle‐aged mice, which should be tested in future studies. Interestingly, it appears that long‐term estrogen deficiency in women who had ovariectomies as young adults can experience accelerated development of aging phenotypes once these women are much older . Thus, it remains at least formally possible that estrogen deficiency over decades could turn out to be associated with an increase in senescent cell accumulation, a speculation that warrants further investigation.…”

“…Interestingly, it appears that long-term estrogen deficiency in women who had ovariectomies as young adults can experience accelerated development of aging phenotypes once these women are much older. (24) Thus, it remains at least formally possible that estrogen deficiency over decades could turn out to be associated with an increase in senescent cell accumulation, a speculation that warrants further investigation. Finally, it will be interesting in future studies to establish whether accelerated cellular aging occurs with sex steroid deficiency as it relates to other hallmarks of skeletal aging, (8) including genomic instability (eg, impaired DNA repair) and mitochondrial dysfunction (eg, oxidative stress).…”

“…Support for a potential interaction between sex steroid deficiency and cellular senescence comes from evidence suggesting that premature ovarian dysfunction causes accelerated decline in physical and cognitive functions . Indeed, bilateral oophorectomy in animals and humans causes premature loss of ovarian hormones, predominantly estrogen, and leads to multimorbidity, frailty, and the accelerated functional decline of several tissues, including bone . However, the question of which specific underlying mechanism(s) drives accelerated aging in response to sex steroid deficiency remains largely unanswered.…”

“…(22,23) Indeed, bilateral oophorectomy in animals and humans causes premature loss of ovarian hormones, predominantly estrogen, and leads to multimorbidity, frailty, and the accelerated functional decline of several tissues, including bone. (24) However, the question of which specific underlying mechanism(s) drives accelerated aging in response to sex steroid deficiency remains largely unanswered. Because as in other tissues, the skeletal aging process is driven by fundamental nonadaptive mechanisms that are interconnected, linked, and overlap, (8) we focused our primary analyses on cellular senescence biomarkers and the SASP in young adult mice that had undergone gonadectomy to avoid the confounding effects of other fundamental aging mechanisms that exist in the context of older age.…”

Risk factors of neurovascular ageing in women

“…Longitudinal data from defined cohorts of women will help to identify mechanisms by which changes in the hormonal milieu contribute to cerebrovascular ageing, brain structure and ultimately cognition. This review summarises the phenotypes of three cohorts of women identified through the medical records‐linkage system of the Rochester Epidemiology Project (REP) and the Mayo Clinic Specialized Center of Research Excellence (SCORE) on Sex Differences: (i) menopausal women with histories of normotensive or hypertensive pregnancies; (ii) women who had bilateral oophorectomy ≤45 years of age; and (iii) women who experienced natural menopause and used menopausal hormone treatments for 4 years . Cardiovascular risk factors, cardiovascular structure, cerebrovascular reactivity, brain structure and cognition were examined in each of these cohorts.…”