Executive function is influenced by oestrogen- in the brain the area associated to executive functions, memory and attention is the prefrontal cortex (Pettit, 2013). As during the female lifespan the levels of oestrogen changes, and the executive functions experiences some issues when these levels are low, for example after childbirth and around menopause (Craig et al., 2008). Although the low levels of oestrogen after childbirth and lactation are temporary, after the menopause these levels do not increase naturally.
As the world population experience longer life span, some diseases are estimated to increase with age. One of the most common type of dementia is Alzheimer’s disease, which mostly occur in later life (Lephart & Hedges, 2003). Alzheimer’s disease affects the working memory, attention planning and other executive functions; it is a progressive disease and it is considered by deteriorating cognitive deficits, affective disturbances, delusion, and on the later stages, it also start motor and sensory problems (Lephart & Hedges, 2003). Most of the patients with Alzheimer’s disease showed episodic memory loss, semantic memory loss and depressed mood (Ka & Birkha, 2000). In the brain of an Alzheimer’s patient, the episodic memory loss is related to severe pathological changes within hippocampal and parahippocampal structures of the medial temporal lobes (Hyman et al., 1984 as cited in Ka & Birkha, 2000) and to a deficiency in the neurotransmitter acetylcholine (Coyle et al., 1983 as cited in Ka & Birkha, 2000). In 1975, a pioneer study in rats found that oestrogen upregulates the activity of choline acetyltransferase in the rats brain (Luine, Khylchevskaya, & McEwen, 1975). After ten years, another study confirmed that the activity of choline acetyltransferase in the medial aspect of the horizontal diagonal band nucleus, the frontal cortex, and cornu ammonis 1 (CA1) of the dorsal hippocampus were increased after the administration of oestrogens (Luine, 1985). Furthermore, the human nucleus basalis of meynert (a telencephalic structure that provides most of the acetylcholine to the cerebral cortex) in Alzheimer’s disease has been noticed the upregulation of oestrogen receptors (Behl, 2002). Thus, many studies suggest the use of oestrogens as a treatment of Alzheimer’s disease, as in fact, oestrogens increases the activity of acetylcholine, promotes the growth of neurons and their connections, enhances blood flow in the brain and seems to constrain the toxic effect of ?-amyloid (“Alzheimer’s disease: recent progress and prospects–Part II.,” 2001). However, the prominent reason in the treatment of Alzheimer’s disease with oestrogens is the low rate of Alzheimer’s disease in women who after menopause had used the hormone replacement therapy (“Alzheimer’s disease: recent progress and prospects–Part II.,” 2001). Despite of this fact, some studies showed that the use of oestrogen replacement therapy (ORT) had no improvement of the cognition and no halts the degeneration of women with Alzheimer’s disease (Larkin, 2000). Because of the changes of oestrogens during the women lifespan, some studies suggest that there is a critical time related to start the hormonal replacement therapy to have an effect in Alzheimer’s disease (Brinton, 2004; Ka & Birkha, 2000; Pettit, 2013). Thus, oestrogen changes is not only affects women with Alzheimer’s disease, but also the executive functions in all women during their lifespan.
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Oestrogen is commonly known as female sex hormone, and there are three types of oestrogen, the 17?-oestradiol, oestrone and oestriol (Darlington, 2002). There are two other types of sex hormones, the male sex hormone – testosterone, and the pregnancy hormone – progesterone. The release of these hormones are controlled by the hypothalamus through the secretion of gonadotropin-releasing hormone which acts on the anterior pituitary gland to stimulate the release of the follicle-stimulating hormone and luteinising hormone (Darlington, 2002). During the female lifespan the levels of oestrogens change, such as menstrual cycle, pregnancy and menopause (Pettit, 2013). The menstrual cycle occurs during puberty and last until menopause, except during pregnancy. The ovulation occurs when there is a peak in the release of luteinising hormone, this hormone regulates the secretion of oestrogen, which in conjunction with the follicle-stimulating hormone control the development of the follicle (Darlington, 2002). The oestrogen levels reaches the peak during ovulation phase (mid cycle) and the bottom during the menstrual phase (bleeding), during menstrual cycle (Pettit, 2013). In the pregnancy the levels of oestrogens also gradually change, they reach a peak by the third trimester of the pregnancy, and this peak will be the highest level of oestrogen in the female lifespan. On the other hand, the lowest level of oestrogen in a female lifespan will be the menopause, when the levels of oestrogens decline both in the brain and in the body (Melton, 2000 as cited in Pettit, 2013). The differentiation of the female physiology is this cyclic rise and fall of hormones levels (Darlington, 2002).
Furthermore, oestrogen is not only responsible for reproductive functions, it has a role on the peripheral and central nervous systems, and it also affects the development, growth, differentiation, maturation and function of several tissues in the body (Behl, 2002).
Some studies had investigated the differences between men and women and concluded that most of the differences in the brain mechanism and structure is related to oestrogens; the structural, cellular, and molecular differences in the brain is called true dimorphisms (Gillies & McArthur, 2010). The main areas of the brain that are affect by these differences are the hippocampus, amygdala and cortex, which are responsible for the memory and cognition (Kelly et al., 1999; Baron-Cohen et al., 2005 as cited in Gillies & McArthur, 2010). Additionally, oestrogen receptors are also found in astrocytes and other types of glial cell; in the hypothalamus, the amygdala, the preoptic area, and the forebrain are the highest levels of oestrogen receptors expression; and the oestrogen receptors density is greater in the hypothalamus than in extra hypothalamic regions, for instance the hippocampus and the cerebral cortex (Behl, 2002).
To investigate how the fluctuations of oestrogen affect both the neuropsychological and neurophysiological parameters, and to visualise changes during the menstrual cycle, a study has use a functional magnetic resonance imaging (fMRI) to image cortical activation patterns associated with cognitive and motor activation. The results showed that in both neuropsychological tasks blood oestrogen level had a profound effect on the size but not on the lateralisation or the localisation of cortical activation patterns; moreover a noticeable increase in perfusion in cortical areas involved in both cognitive tasks was noticed during the oestrogen peak in the female brain (Dietrich et al., 2001). Another study also investigate the oestrogen fluctuations during the menstrual phase, the results suggested that when the oestrogen are in their peak, some regions show enhanced activation; one of these regions was the cortical region, which is has a connection with auditory and linguistic functions, which mean that additional functional networks are recruited (Schoning et al., 2007). Craig and collegues (2008) stated that women in specific times of their lives, (for instance childbirth, and around menopause), commonly complain of memory problems, which are related with oestrogen changes; their results showed that a biological justification for previous reports might be the higher oestrogen levels, which is associated with improvement of verbal memory performance during the normal menstrual cycle.
Therefore, the main problem of the oestrogen changes is the menopause, where the oestrogens levels drastically fall. Evidence from a study showed an executive dysfunction in a women at menopause without hormonal replacement therapy, the results also suggested that the interruption of cognitive processes is promoted by the frontal lobes rather than the hippocampus; additionally, oestrogen improves the execution of working memory tasks and the prefrontal cortex is essential for intact working memory (Keenan, Ezzat, Ginsburg, & Moore, 2001). A longitudinal study showed significant differences in regional cerebral blood flow during the memory tasks between women on ORT and women without, also women on ORT had better performance on neuropsychological tests of figural and verbal memory (Resnick, Maki, Golski, Kraut, & Zonderman, 1998). Hence many studies had showed the improvement of executive functions, memory and attention on the ORT for women in menopause, however there is a crucial timing to start the ORT, the critical period hypothesis. The oestrogen need to be taken when neurological health is still intact to have positive effects, before or at the time of menopause, otherwise if the replacement start after menopause, it can have harmful effects (Rettberg, Yao, & Brinton, 2014).
In conclusion, oestrogen is very important to the best functioning of the female brain. Executive functions, memory and attention are especially related to the levels of oestrogen. During the female lifespan the levels of oestrogens naturally change, reaching the peak on the third trimester of pregnancy and the lowest levels at menopause. Many studies showed the importance of the oestrogen replacement therapy, not only to alleviate the menopause symptoms but especially on the improvement of cognition. However there is the critical period hypothesis, which suggest that the time to start the ORT is before or at the time of the menopause to have the beneficial effect of it. Although there is a relation between low oestrogen levels and Alzheimer’s disease, evidences showed that the use of OTR in Alzheimer’s patients had no improvement. Finally, oestrogens and time are together, and the crucial timing to start the OTR can modify a life, the importance of future researches in this area is to provide a better future for women and maybe decrease the numbers of Alzheimer’s patients.
