Increased Serum BDNF Levels in Response to Estrogen and Nitric Oxide Changes in Postmenopausal Women (Effect of Moderate resistance Exercise)

Menopausal is a natural biological process which is happening during cessation termination of woman’s menstruation. In the menopausal duration women are suffering numerous physical and psychological changes that is associated with decreasing oestrogen secretion due to lack of follicular function. In addition physical strength and bone density decline along with weight gain. It has been shown that regular exercise without adverse of medical treatment preserves bone density, and also prevent cardiovascular diseases in menopause women. In addition it improves physical fitness and also life quality along with oestrogen decreasing in menopausal duration and disorders of the nervous system, like losing memory, learning disabilities, decline in brain processing speed are seen. Neurotrophins are growth factors set, that cooperate together in the growing, survival and also function of central and environmental nervous system. One of Neurotrophins is called BDNF which can be play an important role in the nerve activities.  Especially in the hippocampus,   Due to its abundance in the brain and it’s powerful effects on synapses with age that is related today neurological and cognitive analysis of elderly. One of the important factors in the changes of BDNF level in the woman blood is oestrogen (12) . oestrogen is one of major steroid hormones that produced by the women’s ovaries which is made in the brain when needed at presynaptic terminal. In addition the brain can make oestrogen (neurooestrogen) and this does not act as a hormone rather it works in the form of a neutral mediator or neurotransmitter. Due to the important role of oestrogen in the brain, reducing its level in women with age has become a significant problem in women health. Oestrogen levels drop suddenly during menopause and this may play an important role in the nerve function and also age-related neurocognitive diseases such as Alzheimer.  On the other hand fundamental research has shown that nitric-oxide (No) Can affects oestrogen levels by cellular mechanisms and simulation of gonadotropin-releasing hormone secretion and the hypothalamic-pituitary-ovarian pathway. In addition to the benefits of physical fitness exercise can be affective as a non-pharmalogical intervention in menopausal women. Due to the importance of factors affecting oestrogen changes and also nitric-oxide role on the oestrogen secretion chain that can affect the level of BDNF as a neutrophin effective in neuroprotection and reduction of menopausal in women ; according to said before; this research was designed to enquire the eight weeks of moderate intensity resistance training on serum levels of oestrogen, nitric-oxide and BDNF.

In quasi-experimental research, 28 postmenopausal women from Kermanshah city were randomly selected and divided into two groups of resistance training (n = 14) and control (n = 14). Resistance training was performed for eight weeks, three sessions per week at intensity of 45-55% of a maximum repetition. Blood samples were taken in 24 hours before and 48 hours after the intervention in fasting. Data were analyzed using dependent and independent t-tests at the significant level (P < 0.05).

Results of dependent T-test showed that after eight weeks of training intervention, an important increase was observed in serum levels of oestrogen (P <0.001), BDNF (P <0.001) and Nitric-Oxide (P <0.001); however no significant difference was observed in any of the variables (P <0.05), in control group. Also results of independent T-test between the two groups showed there is a significant change in oestrogen (P <0.001), BDNF (P <0.001) and Nitric-Oxide (P <0.001) in the resistance training group compared to the other one.

After eight weeks of training, a significant increase in serum oestrogen levels was observed in the resistance training group. Gonzalo et al.(2019) stated that exercise and changes in the body composition are associated with changes in female hormones and increased estradiol in postmenopausal women (20), which demonstrates the positive role of resistance training on improvement of hormonal condition in postmenopausal women(20). Resistance exercises as a non-pharmacological method, first reduce various menopausal complications (decrease in oestrogen secretion), second reduces oestrogen injection pharmacologically  requirement or treatment implementation that affect oestrogen secretion, which can save on treatment costs and prevent the side effects of oestrogen injection, by considering the 75% increase in serum oestrogen secretion in the training group. At the end of this resistance training, an 18% increase in serum Nitric-Oxide level was observed.  One of the effective communication factors between glands which affect in oestrogen secretion (hypothalamus-pituitary-ovary) is Nitric-Oxide(18), hence resistance training effect on increasing serum oestrogen in postmenopausal women is probably due to the increasing in Nitric-Oxide and stimulate the glandular path to affect oestrogen secretion. On the other hand, oestrogen secretion affects Nitric-Oxide levels.  In this regard, clinical and fundamental research has shown that oestrogen is mediated by an increase in Nitric-Oxide production by the endothelial isoform of Nitric-Oxide synthase (ENOS) due to an increase in ENOS expression and mediated activation levels (21, 22). In addition there was a significant increase in serum BDNF levels, So regarding the increase of BDNF, it can be said that resistance training causes positive changes in the structure and function of neuromuscular junction (NMJ) and hypertrophy of nerve endings (19, 23, 24). According to scientific studies, these changes are due to exercise in NMJ, associated with an increase in Neurotrophins such as BDNF, which is expressed in the nervous system and skeletal muscle (9, 19). Increasing the level of BDNF and its specialized receptor TRKB by exercise causes downstream changes and synaptic plasticity, which has a positive role on neuroprotection (23).  On the other hand, BDNF produced in skeletal muscle by moving backwards can be selectively transported by motor neurons from skeletal muscle and affect the function of nerve cells (9, 19, 23, 25). Considering the role of BDNF in neurogenesis and neurocognitive protection, it can be said that moderate intensity resistance training can play a protective role in reducing neurocognitive complications in postmenopausal women.  In general, the findings of the present study showed that moderate-intensity resistance training is a non-pharmacological method affecting hormonal changes in the form of increased serum oestrogen, which can play a protective role in reducing oestrogen-related complications in older women.  On the other hand, the results showed that resistance training increases BDNF by increasing the level of oestrogen and NO, and considering the protective role of BDNF on the nervous and cognitive system, Because of the protective role of BDNF on the nervous and cognitive system, it can be said that resistance training can prevent neurological-cognitive complications in postmenopausal women by increasing BDNF levels.