#lowt #menopause #hormoneimbalances #insomnia
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– Estradiol is predominant prior to menopause
– Estrone is the primary form postmenopausally
– Synthesized by fatty tissue
– Estrogen works synergistically with many biological systems to promote physical, cognitive and affective function
– Estrogens can modulate neuronal excitability, through serotonin, norepinephrine, dopamine, and endorphin regulation
– Estrogen supplementation can decrease both systolic and diastolic blood pressures and reduced norepinephrine levels
Estrogen
– Estrogen modulates mood via the serotonergic system
Estrogen
– Estrogen also regulates glucose metabolism and energy production
– Declines in these processes are characteristic of neurodegenerative diseases
– Estrogens exert neuroprotective actions to maintain cerebrovasculature health including prevention glutamateinduced excitotoxicity and hippocampal shrinkage
– Estrogens exert some antiinflammatory effects
– Naturally occurring higher levels of estrone were associated with poorer cognition, specifically working memory performance
– Estradiol acts in part through nitric oxide (arginine)to increase extracellular dopamine levels.
– Premenopausal females have a better response than males to serotonergic antidepressants, indicating female hormones may improve the efficacy of SSRIs
– Depressed postmenopausal females on supplemental estrogen plus SSRIs showed improved response compared with depressed postmenopausal females without estrogen
– Estrogen alone did not relieve depression
Estrogen and the HPAAxis
– Higher levels of Estradiol produced a stronger HPA axis response during nonthreatening situations and during and after stressors
– Under conditions of anxiety and stress, women attend to threat differently depending on endogenous estradiol levels, being avoidant when estradiol is lower, and vigilant when estradiol is higher
– Estradiol increases the activation of Corticotropin Releasing Hormone and base levels of ACTH
– Chronic stress produces a hyporesponsive HPA axis that is hypersensitive to the modulating effects of estrogen
– Changes in 5HT1A receptor binding in the hippocampus and hypothalamus are restored by estrogen replacement.
Estrogen and the HPAAxis
– Treatment with estradiol could inhibit the negative feedback effects of cortisol increasing cortisol levels
– Estradiol treatment has been shown to increase corticosteroid binding globulin (CBG ) which inactivates cortisol in males
– Low estrogen blunted HPAAxis response (depression)
– High estrogen exacerbated HPAAxis response and sustained higher levels of ACTH – anxiety, inflammation, autoimmune…
Estrogen and Cognition
– HT administered at or around the time of menopause may improve cognition, but HT initiated five years or more after menopause shows no cognitive benefit
– Shorter time between menopause and initiation of HT was associated with larger hippocampal volume
– HT utilizing Estradiol more effectively recalibrates the estradiol/estrone ratio to approximate premenopausal levels.
Testosterone
– Testosterone is essential for maintaining virilization and muscle mass and may also affect libido, mood regulation, bone health and cardiac disease
– Hypogonadal men exhibit a significantly higher prevalence of anxiety disorders and major depressive disorder
– Certain chemotherapies can reduce testosterone and increase anxiety
– testosterone can enhance dopamine and serotonin release in the mesolimbic system
– Testosterone can enhance GABA
– Gonadal dysfunction appears to impair dopamine release but not synthesis (important esp for transgender individuals)
– Gonadal steroids impact HPA axis reactivity differentially.
– Testosterone replacement blunts the CORT and ACTH response to stress.
– Estradiol treatment increases the reactivity of the HPA axis
– To maintain homeostasis, the neuroendocrine system continuously monitors the levels of gonadal steroids using estrogen and androgen receptors in the hypothalamus.
– Dysregulation of either or both of these axes can result in compromised responses to stressful life events.
– Testosterone is suppressed with long term opioid use
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