Testosterone Increases Amygdala Reactivity in Middle-Aged Women to a Young Adulthood Level

Abstract

Testosterone modulates mood and sexual function in women. However, androgen levels decline with age, which may relate to the ageassociated change in sexual functioning and the prevalence of mood and anxiety disorders. These effects of testosterone are potentially mediated by the amygdala. In the present study, we investigated whether the age-related decline in androgen levels is associated with reduced amygdala activity, and whether exogenous testosterone can restore amygdala activity. Healthy young and middle-aged women participated during the early follicular phase of the menstrual cycle, and amygdala responses to biologically salient stimuli were measured with functional magnetic resonance imaging (fMRI). Androgen levels were lower in middle-aged than young women, which was associated with decreased amygdala reactivity. Endogenous testosterone levels correlated positively with amygdala reactivity across the young and middle-aged women. The middle-aged women received a single nasal dose of testosterone in a double-blind, placebocontrolled, crossover manner, which rapidly increased amygdala reactivity to a level comparable to the young women. The enhanced testosterone levels correlated positively with superior frontal cortex responses and negatively with orbitofrontal cortex responses across individuals, which may reflect testosterone-induced changes in amygdala regulation. These results show that testosterone modulates amygdala reactivity in women, and suggest that the age-related decline in androgen levels contribute to the decrease in amygdala reactivity.

Exogenous Testosterone Rapidly Increases Aggressive Behavior in Dominant and Impulsive Men

“…These findings parallel evidence in women in which a single administration of T increases amygdala and hypothalamic reactivity to angry facial expressions (19)(20)(21). Notably, these subcortical brain structures are rich in both androgen and estrogen receptors (22)(23)(24) and play a key role in potentiating reactive aggression in animal models (1,25).…”

“…One hour after drug administration, the phlebotomist drew a second blood draw. Although effects of T on aggressive behavior may be secondary to mood effects, previous studies have failed to document effects of acute T supplementation on subjective mood ratings (18,20), and thus, participants did not complete mood measures after drug administration. Participants then completed a 10-minute session of the Point Subtraction Aggression Paradigm (PSAP; see below), which was used to assay aggressiveness, completed a post-PSAP questionnaire and, then provided a third blood sample.…”

Endogenous testosterone levels are associated with neural activity in men with schizophrenia during facial emotion processing

“…Derntl et al [9] found a significant positive correlation in healthy men between endogenous testosterone and amygdala response to fearful and angry facial expressions, but no correlation with non-threatening expressions such as sadness and happiness. Similar findings have been reported in healthy women whose endogenous testosterone levels correlated positively with amygdala activity during the processing of fearful and angry faces [10]. Stanton et al [11] found that endogenous testosterone levels were negatively correlated with amygdala BOLD activity and positively correlated with ventromedial prefrontal cortex BOLD activity during the processing of angry faces; however, both findings occurred only in healthy males.…”

“…Stanton et al [11] found that endogenous testosterone levels were negatively correlated with amygdala BOLD activity and positively correlated with ventromedial prefrontal cortex BOLD activity during the processing of angry faces; however, both findings occurred only in healthy males. When middle-aged women were given a single dose of testosterone, Van Wingen et al [10] reported positive correlations between exogenous testosterone and activity in the amygdala and superior frontal cortex along with a negative correlation between exogenous testosterone and neural activity in the orbitofrontal cortex and occipital gyrus in response to angry and fearful facial stimuli. Another study reported a significant increase in neural activity in the amygdala and hypothalamus while viewing angry faces after healthy female participants received a .5 ml dose of testosterone [12].…”

Effects of exogenous testosterone and mating context on men's preferences for female facial femininity

“…One structure that appears particularly sensitive to T is the amygdala-a region rich in androgen receptors (Rubinaw & Schmidt, 1996), and which functions to promote vigilance and arousal (Davis & Whalen, 2001). For instance, van Wingen et al (2009) found that among healthy young women, endogenous levels of T were positively associated with amygdala activation, and for middle-aged women-with naturally lower levels of T-an administration of exogenous T rapidly increased amygdala reactivity to a level comparable to other women with naturally higher levels of circulating T. A separate study by Hermans et al (2008) indicated that administration of exogenous T to healthy young women enhanced responsiveness to social threat (as indicated by angry facial expressions) in the amygdala, as well as the hypothalamus and orbitofrontal cortex. This latter finding has been conceptually replicated and extended in males, where Goetz and colleagues (2014) found that a single administration of T to healthy young men rapidly (within 90 minutes) increased amygdala, hypothalamic, and periaqueductal grey reactivity to angry facial expressions.…”