Oxytocin and women's health in midlife

Abstract

Menopause marks the cessation of fertility and the transition to post-reproductive years. Nearly 1 million US women experience menopause annually, but despite the significant impact it has on their physical and mental health, menopause has been insufficiently studied. Oxytocin is a neurohormone that regulates emotionality, social behaviors, and fundamental physiological systems. Localization of oxytocin receptors in the brain, reproductive tissues, bone, and heart support their role in mental health and potentially sleep, along with reproductive and cardiovascular functions. While experimental data linking oxytocin to behavior and physiology in animals are largely consistent, human data are correlative and inconclusive. As women transition into menopause, oxytocin levels decrease while their susceptibility to mood disorders, poor sleep, osteoporosis, and cardiovascular diseases increases. These concurrent changes highlight oxytocin as a potential influence on the health and mood of women along their reproductive life span. Here, we summarize experimental rodent and non-human primate studies that link oxytocin to reproductive aging and metabolic health and highlight the inconclusive findings in studies of women. Most human studies relied on a single oxytocin assessment in plasma or on intranasal oxytocin administration. The pulsatile release and short half-life of plasma oxytocin limit the validity of these methods. We discuss the need for oxytocin assessments in stable bio-samples, such as urine, and to use valid assays for assessment of associations between changing oxytocin levels and well-being across the reproductive life span. This work has the potential to guide therapeutic strategies that will one day alleviate adverse health outcomes for many women.

Keywords: cardiometabolic disease; menopause; mood disorders; reproductive aging; sleep.

Figure:

Central and peripheral release of oxytocin and its function in women’s body. (Created with BioRender.com) 1. Social experiences such interacting with loved ones causes oxytocin (OT) release in the hypothalamus. 2. OT in the brain regulates social behaviors via OT projections from the hypothalamus to emotional, reward and memory-related brain regions such as the amygdala, hippocampus, local projections to the hypothalamus, and nucleus accumbens. 3. Hypothalamic OT neurons project to the posterior pituitary gland and OT is released from the pituitary in a pulsatile manner into the blood. 4. OT circulates in the bloodstream and concentrations fluctuate due to pulsatile release and rapid degradation. 5. OT receptors are metabotropic G-protein coupled receptors (GPCRs). They are found throughout brain tissue, bone systems, the cardiovascular system, and the reproductive tract. 6. Estrogen secretion from the ovaries enhances OT activity via increasing OT and OT receptor expression throughout the brain and other tissue. Aging is accompanied by a decrease in estrogen levels and may lead to compromised OT signaling.