What is the role of hormones on the function and development of the brain?

Hormones and the Brain: Theory and Practice, by Dr, Sarah L. Berga

Key Points

Highlights:

• The effects of hormones on the function and development of the CNS vary greatly. However, recent studies have shown that estrogens confer a neuroprotective effect on the brain and thus on cognition and behavior while progestogens counteract the effects of estrogen. 

Importance:

• Understanding the role of essential hormones in brain functions and their interplay will allow researchers and physicians to treat neuropsychiatric effects of specific hormone therapies and postmenopause-associated cognitive decline.

Key Points: 

• Hormones affect cellular growth, and senescence (apoptosis, gene silencing) and that more significant exposure to estrogens have been associated with neuroprotective mechanisms that decrease the risk of neurodegenerative diseases such as vascular dementia and Alzheimer's disease.

• Cortisol (increased in stress) has been shown to highjacks the cellular machinery needed for estrogen action. Thus, chronic stress may inhibit the affirmative action of estrogens in the brain and therefore may affect cognition.

• The risk and benefit of any hormonal therapy should include a consideration of the impact of the hormone on current and future brain health.

Lay Summary

Dr. Sarah L. Berga, Professor, and Chair of Obstetrics and Gynecology Wake Forest School of Medicine aim to talk about the effects of sex hormones such as estrogens and progestins on brain health with an emphasis on the neuroprotective characteristics of estrogens. Throughout her presentation, results from many different studies are explained to highlight that estrogen affects many functions of the brain and that stress and progestins have been found to counteract the neuroprotective functions of estrogens.

Dr. Berga begins the discussion by considering the effects of menopause on the cognitive health of women. During menopause, studies have found that postmenopausal women experience “soft symptoms” such as difficulty with word finding, irritability, and reduce libido. Additionally, decreases in estrogen put women at higher risk of neurodegenerative disorders such as dementia and general cognitive decline. However, Dr. Berga notes that not all estrogens are the same and may have varying effects depending on each person. This is reflected by the fact that women experience menopause in different ways with varying symptoms.

Generally, hormones have an effect on cellular growth and senescence (apoptosis, gene silencing) and that greater exposure to estrogen has been associated with increased telomere length. Neurotransmitter systems in neurons are also affected by sex steroids and thus have an impact on mood, cognition, learning and memory, attention, and arousal. In some cases, these effects become translated to changes in behaviors. Hydroxyprogesterone, known to be one of the more potent progestogens, decreases female sexual initiation in one study on monkeys.

Thyroid hormones such as thyroxine influence cerebral blood flow and brain metabolism. Multiple brain regions have to be affected in order for behavioral changes to be observed. Hormone users have been seen to have a preservation of frontal and parietal cortical metabolism while estradiol users experienced a three standard deviation better chance of verbal performance compared to Premarin (conjugated estrogen medication) users.

Many studies have also found that estrogens aid in memory formation and neuronal health. Without estradiol, there is a loss of synapses in the prefrontal cortex according to studies on rhesus monkeys. This accurately reflects some of the cognitive behavioral changes seen in some postmenopausal women. Letrozole which is an aromatase inhibitor reduced the number of synapses in the hippocampus of female mice. The hippocampus is a region that is involved in memory formation and short-term storage. Women receiving hormone therapy with conjugated estrogen observed an improvement in oral reading and short-term verbal memory. Progestogens generally antagonize the positive cognitive effects of estrogen.