Fatigue, weight gain, irritability, sleep issues, and depression are all issues we’ve dealt with either ourselves, or experienced by someone close to us. Many people associate these symptoms with hormone imbalances, but what might not be so obvious is that these symptoms can also be linked to neurotransmitter imbalances. Likewise, the difference in rates of psychiatric disorders between genders suggests that hormones play an important role in conditions commonly associated with nervous system imbalances (Figure 1)1.
Figure 1. This table, published in the Journal of Abnormal Psychology, depicts the incidence of psychiatric disorders between women and men (1).
These interactions demonstrate that the nervous and endocrine systems are intricately coupled, and both are involved in almost every bodily function including cognition, mood, reproduction, sleep, and temperature regulation. The correct balance of neurotransmitters and hormones is critical to preventing symptoms, as well as supporting overall health.
Hormones play an active role in brain function and affect neurotransmitter levels. For example, many women going through menopause experience depression, anxiety, and insomnia, which can also be correlated to neurotransmitter imbalances. The interactions between estrogen and serotonin illustrate this point quite well.
Estradiol supports serotonin levels
Estradiol supports serotonin levels through two different mechanisms (Figure 2). Estradiol increases tryptophan hydroxylase, the rate limiting enzyme in the synthesis of serotonin2. Additionally, estradiol inhibits the enzyme monoamine oxidase (MAO), which degrades monoamine neurotransmitters such as serotonin 3.
Figure 2. Estradiol increases tryptophan hydroxylase which will increase the synthesis of serotonin (2). Estradiol decreases MAO activity, which decreases the rate of monoamine neurotransmitter degradation, leading to increased levels of these neurotransmitters (3).
Estrogen affects serotonin receptor expression
Both estrogen and serotonin receptors coexist in a variety of tissues. Estradiol activation of E2-beta receptors stimulates an increase in serotonin receptor sites (5HT2a). 5HT2a receptors are involved in mood, cognition, and the inhibition of pain2. By increasing the number of serotonin receptors, estradiol up-regulates serotonin activity.
This interaction plays a critical role during menopause, specifically in the incidence of hot flashes. Estrogen and serotonin influence the thermoregulatory set point through the hypothalamus 4. A pre-menopausal woman will have an abundance of estradiol and serotonin in circulation. This also means there will be binding of estrogen receptors and an up regulation of 5-HT2a receptors, leading to a wide thermoregulatory set point.
Figure 3. Estradiol and serotonin have been shown to work together in the hypothalamus to regulate the thermoregulatory set point.
As aging occurs, estrogen levels decline, leading to a decline in serotonin receptors, and potentially serotonin stores. With this decline in serotonin activity, the thermoregulatory set point narrows. This is one mechanism that leads to hot flashes and night sweats in menopausal females (Figure 3).
Additionally, estradiol can act as a central analgesic, and pain sensation is inhibited by the activation of some serotonergic neurons. The up-regulation of the 5HT2a receptors in the brain might play a role in this pain inhibition2.
The interactions between estrogen and serotonin provide evidence that symptoms and conditions typically thought of as exclusively related to hormones can also be influenced by the nervous system. In the next few weeks, we will be covering additional connections between the endocrine and nervous systems, including the interactions between dopamine and testosterone as well as progesterone and GABA. For additional information on the connection between sex hormones and neurotransmitters, see Module 10 of the Reproductive Endocrinology Curriculum (log in required).
Guest author: Megan Geitz is a member of the Clinical Support & Education Department at NeuroScience, Inc. and the resident experts in endocrinology and women’s issues.
1. Eaton, Nicholas R., et al. (2012). An invariant dimensional liability model of gender differences in mental disorder prevalence: evidence from a national sample. Journal of Abnormal Psychology. 121(1):282-289.
2. Rybaczyk, L.A., et al. (2005). An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology. BMC Women’s Health, 5:12.
3. Luine,V.N., et al. (1983). Gonadal hormone regulation of MAO and other enzymes in hypothalamic areas. Neuroendocrinology.36(3):235-241.
4. Berendsen, Hemmie H.G. (1999). The role of serotonin in hot flushes. Maturitas. 36:155-164.