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