Although estrogen (and testosterone) affect the tissues of the reproductive
system, they also affect other tissues including the brain. The receptors
for sex steroids are more abundant in certain parts of the brain including
the hypothalamus, amygdala, and hippocampus. In females, secretion of
estrogen seems to begin after birth and is maintained at a low level
throughout childhood. With the onset of puberty, the secretion of estrogen
generally increases and undergoes monthly fluctuations. Since the regions
of the brain include those which control emotions and drives, it is
not surprising that the secretion of steroid hormones are implicated
in both normal fluctuations in mood and in mood disorders (affective
disorders). (Ramirez, 2003; Steiner, 2003).Affective disorders are the
most common mental disorders and women are afflicted at twice the rate
as men (with an 8% lifetime risk as opposed to 4% in males). Low concentrations
estrogen have been associated with PMS, postnatal depression, and postmenopausal
depression and estrogen can be used to treat the latter two. Estrogen
decreases are associated with panic, obsessive-compulsive disorder,
anxiety, and postmenopausal depression (Sickel from Steiner, 2000) About
75% women experience some form of PMS and 3-8% of these women suffer
from the more serious emotional and behavioral symptoms of PMDD (premenstrual
dysphoric disorder) (Steiner, 2003; Osterlund, 2001). PMDD affects 5%
of women in reproductive years (Shors, 2003). The late luteal phase
and the early menstrual phase represent the periods in which most hospital
admissions for psychiatric illness occur (Sickel from Steiner, 2000).
An estimated 10% of women experience postpartum depression (Brizendine,
2006). After birth, estrogen levels drop 400 to 1000 times in 48 hours.
Estrogen can be used to treat post-partum depression. . Postpartum depression
more likely in women who are unmarried, experience an unplanned pregnancy,
a problem pregnancy, or have less emotional support during their pregnancy
(Sickel from Steiner, 2000).
A number of studies show that estrogen can relieve depression. Reduction
of serotonin (or the tryptophan it is derived from) increases irritability
and the severity of PMS. Estrogen increases serotonin synthesis, uptake
and receptor number, and functions as an antidepressant . Evidence suggests
that estrogen decreases the expression of 5-HT1A serotonin receptors
and increases the expression of 5-HT2A receptors (Steiner, 2003; Osterlund,
2001; Genazzani, 2002). Estrogen affects synthesis of serotonin through
TH (tryptophan hydrozxylase) and can increase serotonin receptors in
areas of the brain known to affect mood (Shors, 2003). Given that estrogen
can both increase body fat and fight depression, there actually may
have been some observational evidence which gave rise to past sterotypes
linking body size and disposition (Oinonen, 2001). Gonadal hormones
change the transcription rates of serotonin receptors which affects
predisposition to anxiety and depression (Dunn from Steiner, 2000).
GABA is essential for the developing brain where its receptors can
cause depolarization by allowing chloride efflux and can interact with
voltage regulated calcium channels. (As a result, GABA is an excitatory
neurotransmitter in the developing brain and gradually is converted
to an inhibitory neurotransmitter in the mature brain.) GABA influences
patterns of neuronal cell death and synapse formation. Estrogen enhances
the excitatory effects of GABA in brain development, which is the first
mechanism for gender differentiation of the brain to be discovered.
Alterations of GABA circuits can alter maternal and sexual behavior
and change some sexually dimorphic regions of the brain (McCarthy, 2002).
Estrogen is an antioxidant and it offers protection from oxidative stress.
The brain is particularly sensitive to oxidative stress., (Behl, 2001).
In general, estrogen seems to offer some protection from schizophrenia.
Schizophrenia symptoms are milder in women and onset occurs about 4
years later in women than men. Estrogen also seems to decrease susceptibility
to Alzheimer's disease (Osterlund, 2001). Higher levels of estrogen
are correlated with lower incidence and later onset of Alzheimers disease.
Alzheimers risk increases after menopause when estrogen levels drop
and more women than men suffer from age-related Alzheimers (Behl, 2001).
Estrogen treatment decreases the risk of dementia, perhaps by stopping
NMDA-induced neuronal death (Sickel from Steiner, 2000). Estrogen lowers
risk of stroke (Behl, 2001).
Estrogen in mice affects learning (Shors, 2003) and cell proliferation
in the adult mouse hippocampus is increased by estrogen (Behl, 2001).
Estrogen improves some cognitive functions, such as memory, which is
not surprising given that it increases ACh formation in neurons, such
as ACh neurons which project to the hippocampus (Genazzani, 2002). In
mice, astrocytes produce aromatase in lesioned areas of the brain (Behl,
Men who were exposed to DES as fetuses have an increased frequency of
depression (Sickel from Steiner, 2000).
A woman's performance on motor and spatial tasks varies over the course
of the menstrual cycle (Hampson, 1988) and the loss of gonadal hormones
at menopause affects mood, libido, and some aspects of cognition. The
mood and emotional changes also seem to involve changes in the serotoin,
noradrenaline, dopamine, and opiate pathways. (Genazzani, 2002). After
menopause, the rate of depression in females approaches that seen in
men (Shors, 2003). A polymorphism in the estrogen receptor alpha is
associated with variation in some of the characteristics of menopause
such as vaginal dryness and hot flashes (Malacara, 2004).