CORRELATION DIFFERENCES BETWEEN SEX AND STRESS HORMONES IN MEN AND WOMEN

The excessive aggression is an actual problem of modern society but the mechanisms of aggressiveness development have not been sufficiently investigated. Women aggression is considered to differ from men one and results obtained on males cannot be extrapolated on females. Sex hormones have a crucial role in the generation of sexually dimorphic aggression circuits during development and their maintenance during adulthood. Hypothalamic pituitary adrenal axis and sympathoadrenal system are major neuroendocrine systems that respond to stress. Stress hormones are involved into behavioral reactions of organism. Gonadal, hypothalamic pituitary adrenal axes, and sympathoadrenal system are tightly interrelated and every of them can influence another one. The purpose of the study was to estimate correlation differences between sex and stress hormones in men and women. Material and methods. Forty healthy young people aged 18 to 22 years with a body mass index of 19-24 (21 women and 19 men) were enrolled in the study. Hormone levels in blood serum were determined by Testosterone, Estradiol, Cortisol ELISA kits (Italy), Epinephrine/Norepinephrine (EPI) ELISA kit (China). Results and discussion. In all phases of the menstrual cycle, the level of cortisol in women was lower than in men, but in the luteal phase these differences were not statistically significant. In all phases of the menstrual cycle, the blood serum norepinephrine content in women was lower than in men, but in the follicular phase these differences were not statistically significant. The level of epinephrine in women during ovulation and luteal phase did not differ from the level of epinephrine in men, but in follicular phase it was significantly lower. Calculations of correlations between individual hormones revealed a significant difference between them in men and women. Positive correlations between testosterone and estradiol and between cortisol and epinephrine; a strong negative correlation between epinephrine and testosterone/ norepinephrine ratio were found in men. Positive correlation between testosterone and cortisol and negative correlation between estradiol and cortisol/testosterone ratio were revealed in women. Conclusion. In women, strong correlations were found between cortisol and sex hormones; in men, strong interrelationship was revealed between cortisol and epinephrine. Both in men and in women (in all phases of the menstrual cycle), high positive correlations between testosterone/norepinephrine and cortisol/norepinephrine ratios were observed.

The excessive aggression is an actual problem of modern society but the mechanisms of aggressiveness development have not been sufficiently investigated. Women aggression is considered to differ from men one and results obtained on males cannot be extrapolated on females. Sex hormones have a crucial role in the generation of sexually dimorphic aggression circuits during development and their maintenance during adulthood. Hypothalamic pituitary adrenal axis and sympathoadrenal system are major neuroendocrine systems that respond to stress. Stress hormones are involved into behavioral reactions of organism. Gonadal, hypothalamic pituitary adrenal axes, and sympathoadrenal system are tightly interrelated and every of them can influence another one.
The purpose of the study was to estimate correlation differences between sex and stress hormones in men and women.
Material and methods. Forty healthy young people aged 18 to 22 years with a body mass index of 19-24 (21 women and 19 men) were enrolled in the study. Hormone levels in blood serum were determined by Testosterone, Estradiol, Cortisol ELISA kits (Italy), Epinephrine/Norepinephrine (EPI) ELISA kit (China).
Results and discussion. In all phases of the menstrual cycle, the level of cortisol in women was lower than in men, but in the luteal phase these differences were not statistically significant. In all phases of the menstrual cycle, the blood serum norepinephrine content in women was lower than in men, but in the follicular phase these differences were not statistically significant. The level of epinephrine in women during ovulation and luteal phase did not differ from the level of epinephrine in men, but in follicular phase it was significantly lower. Calculations of correlations between individual hormones revealed a significant difference between them in men and women. Positive correlations between testosterone and estradiol and between cortisol and epinephrine; a strong negative correlation between epinephrine and testosterone/ norepinephrine ratio were found in men. Positive correlation between testosterone and cortisol and negative correlation between estradiol and cortisol/testosterone ratio were revealed in women.
Conclusion. In women, strong correlations were found between cortisol and sex hormones; in men, strong interrelationship was revealed between cortisol and epinephrine. Both in men and in women (in all phases of the menstrual cycle), high positive correlations between testosterone/norepinephrine and cortisol/norepinephrine ratios were observed.
Research relation to the programs, plans, and department themes. The study was carried in accordance with the research plan of Kharkiv National Medical University "Biochemical mechanisms of dysmetabolic processes development under the influence of chemical factors of the environment", state registration number 0115U000240.
Introduction. The excessive aggression is an actual problem of modern society but the mechanisms of aggressiveness development have not been sufficiently investigated. Women aggression is considered to differ from men one and results obtained on males can not be extrapolated on females [1]. Sex hormones have a crucial role in the generation of sexually dimorphic aggression circuits during development and their maintenance during adulthood [2]. The conversion of testosterone into estrogen in the brain is a key mechanism of many physiological and behavioral processes regulation throughout an animal's life by testosterone [3]. Female fetus is protected from maternal and its own estrogens by alpha-fetoprotein, which binds to estrogens and prevents them from entering to neurons to masculinize them [4]. Hypothalamic pituitary adrenal (HPA) axis and sympathoadrenal system (SAS) are major neuroendocrine systems that respond to stress. Stress hormones are involved into behavioral reactions of organism [5][6]. Gonadal, HPA axes and SAS are tightly interrelated and every of them can influence another ones [7,8].
The purpose of the work was to estimate correlation differences between sex and stress hormones in men and women.
Material and Methods. Forty healthy young people aged 18 to 22 years with a body mass index of 19-24 (21 women and 19 men), students of Kharkiv National Medical University, were enrolled in the study. All procedures and manipulations were carried out in accordance with the ethical standards of the Committee of Ethics and Bioethics of Kharkiv National Medical University and the revised Declaration of Helsinki (2000). All participants signed a written informed consent. All females had the regulatory 28-32-daylong menstrual cycle. They had no surgery and traumas in anamnesis. They have not been taking contraceptives and medicines that may affect their hormonal profile by any way for last 3 months.
In females blood samples were collected 3 times: in follicular, ovulation and luteal phases of menstrual cycle at the same time of day (8.00 -9.00 a.m.). In males blood samples were collected once, at 8.00 -9.00 a.m. Blood serum was prepared and used for hormones level determination. Hormone levels in blood serum were determined by Testosterone, Estradiol, Cortisol ELISA kits (Italy), Epinephrine / Norepinephrine (EPI) ELISA kit (China).
Statistical analysis was performed using nonparametric statistical methods with the help of the Statistica 6.0 software (StatSoft, USA). Mann-Whitney test was used to compare respective parameters in males and females. Wilcoxon test was used to compare parameters in various phases of the cycle. Correlation analysis according to Spearman was used to reveal the relationship between different variables of the same group.
Results and Discussion. Testosterone is considered a male sex hormone, and estradiol is a female sex hormone, but both are present in both men and women, but in different proportions. According to our results, the testosterone/estradiol ratio in men was 144.40 [106.30; 161.19], and in women it ranged from 2.11 [1.58; 3.14] into the follicular phase up to 2.73 [2.00; 4.2] into the luteal phase and was not statistically different depending on the menstrual cycle phase.
In all phases of the menstrual cycle, the cortisol level in women was lower than in men, but in the luteal phase these differences were not statistically significant (in the follicular phase p = 0.044204; during ovulation p = 0.035989) (Fig. 1). Our results are consistent with the literature data on the higher content of both the basal total and free cortisol in the blood serum of men as compared to women [9].
In all phases of the menstrual cycle, the blood serum norepinephrine content in women was lower than in men, but in the follicular phase these differences were not statistically significant (during ovulation p = 0.000984; in the luteal phase p = 0.001345) (Fig. 2). The level of epinephrine in women during ovulation and luteal phase did not differ from the level of epinephrine in men, but in the follicular phase it was significantly lower (p = 0.028733) (Fig. 3). In the literature, there is evidence that not absolute quantity of hormones, but their ratio is important for some their effects. For example, the ratio of testosterone to cortisol is important for the formation of dominance and the development of aggression [10].
In individuals with low cortisol, testosterone correlates positively with dominance, and in individuals with high cortisol, the association between testosterone and dominance is blocked and even acquires the opposite direction [10]. In this regard, we calculated correlation relationships not only between hormones but also their ratios.
Calculations of correlations between individual hormones revealed a significant difference between them in men and women. Thus, positive correlations between testosterone and estradiol (r =+0.50, p=0.028768) and between cortisol and epinephrine (r =+0.86, p=0.000003); a strong negative correlation between epinephrine and testosterone/norepinephrine ratio (r = -0.79, p =0.000048) were found in men.
In women in the follicular phase, strong correlations were found between testosterone and cortisol (r =+0.60, p=0.013626), testosterone/estradiol ratio and cortisol (r =+0.76, p=0.000907), estradiol and cortisol/testosterone ratio (r = -0.66, p=0.007331). Women in the luteal phase were found to have the same correlation relationships as in the follicular phase, except for the association between estradiol and the cortisol/testosterone ratio, namely: between testosterone and cortisol (r =+0.67, p=0.016831), the testosterone/estradiol ratio and cortisol (r =+0.78, p=0.002705). These correlations are consistent with the results of Sharma A.N. et al, according to which it is estradiol, not testosterone, that enhances cortisol-mediated feedback on pulsatory ACTH secretion [11].
During ovulation in women, only the correlation between the testosterone/ norepinephrine and cortisol/norepinephrine ratios was observed (r =+0.75, p=0.000820). It should be noted that the correlation between the above ratios was observed in all groups: in women in all phases of the menstrual cycle (follicular phase -r =+0.92, p=0.000003; luteal phase -r =+0.85, p=0.000807), in men (r =+ 0.63, p=0.003983).
Gonadal hormones have both organizational and activational effects on central nervous system. Organizational effects of testosterone during embryonic development are mainly realized through its conversion into beta-estradiol and predetermine neural pathways (brain masculinization). Organizational effects during puberty play the important role in brain maturation and connections between brain areas. Progesterone and testosterone have diverging effects on the communication between amygdala and prefrontal cortex (van Wingen et al, 2010) [12]. Prefrontal cortex plays a crucial role in neuroendocrine stress responses and emotion regulation and it is characterized by high expression of genes associated with gonadal and HPA axes [7]. In men, cortisol is positively associated with the functional connectivity of amygdala with striatum and frontal regions; in women, it is negative. Stress increases the connectivity between amygdala and striatum (Vogel et al, 2015) and frontal cortex (Veer et al, 2011) in males only [13]. The sex diverging development of brain areas involved into behavioral and stress reactions can explain the differences between sex in the levels and correlations of the above-mentioned hormones.
In animals, testosterone reduces cortisol reactivity to stress, but in men the effect of testosterone depends on stressor type and personality traits of individual. Exogenous testosterone increases cortisol concentration in response to a social-evaluative stressor, especially in men with high dominance trait [14]. The lack of correlations between cortisol and testosterone in men may be due to the heterogeneity of the group relative to dominance. Strong positive correlation between cortisol and epinephrine may be explained by glucocorticoids stimulation of phenylethanolamine-N-methyltransferase activity in a subpopulation of epinephrine-containing chromaffin cells [15]. Conclusion 1. Women had statistically significant and lower serum cortisol and norepinephrine levels than men. 2. In women, strong correlations were found between cortisol and sex hormones. 3. In men, a strong positive correlation between cortisol and epinephrine was revealed maybe due to stimulation of phenylethanolamine-Nmethyltransferase activity by glucocorticoids. 4. Both in men and in women (in all phases of the menstrual cycle), high positive correlation between the testosterone/norepinephrine and cortisol/norepinephrine ratios was observed.
The prospects for further research will concern the study of differences between blood serum levels of thyroid hormones in men and women.