439 - Biopsychosocial Impact of Hormone Imbalances
Objectives
- Review the sex hormones and their functions
- Review the impact of sex hormones in the HPA-Axis
- Review causes and consequences of imbalances in
- Estrogen
- Progesterone
- Testosterone
Estrogen
- Multiple forms
- 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 decreased both systolic and diastolic blood pressures and reduced norepinephrine levels
Estrogen
- Estrogen modulates mood via the serotonergic system
- Estrogen also contributes to the
- Downregulation of 5-HT-2 (stimulating) receptors and monoamine oxidase (think MAOIs)
- Downregulation of 5HT1A receptors presynaptically
- Upregulation of postsynaptic serotonin 5-HT1A (calming) receptors
- In one study, 80% of women given estradiol reported significantly decreased mood symptoms after three or six weeks, compared to only 22% of women on placebo
- Similarly, estradiol resulted in improved mood in 68% of peri-menopausal women with depressive disorders, whereas only 20% of women on placebo experienced similar benefit
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 glutamate-induced excitotoxicity and hippocampal shrinkage
- Estrogens exert some anti-inflammatory 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.
The Sex Hormones
- Estrogen
- 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
- Largest clinical trials of HT ever conducted revealed an increased risk of cancer, dementia and cognitive decline with prolonged administration of conjugated equine estrogen (CEE)
Estrogen and the HPA-Axis
- Higher levels of Estradiol produced a stronger HPA axis response during non-threatening 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 5-HT1A receptor binding in the hippocampus and hypothalamus are restored by estrogen replacement.
Estrogen and the HPA-Axis
- 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
- Crosstalk between the hypothalamic–pituitary–gonadal (HPG) and HPA axes could lead to abnormalities of stress responses, and as a result exacerbate peripheral pathologies i.e.:
- Low estrogen --> blunted HPA-Axis response (depression)
- High estrogen - exacerbated HPA-Axis response and sustained higher levels of ACTH - anxiety, inflammation, autoimmune…
Estrogen and Cognition
- Estrogen
- HT administered at or around the time of menopause may i