The Influence of Menstrual Cycle and Androstadienone on Female Stress Reactions: An fMRI Study

Abstract

Communicating threats and stress via biological signaling is common in animals. In humans, androstadienone (ANDR), a synthetic male steroid, is a socially relevant chemosignal exhibited to increase positive mood and cortisol levels specifically in (periovulatory) females in positively arousing contexts. In a negative context, we expected that such effects of ANDR could amplify social evaluative threat depending on the stress sensitivity, which differs between menstrual cycle phases. Therefore, this fMRI study aimed to examine psychosocial stress reactions on behavioral, hormonal and neural levels in 31 naturally cycling females, between 15 early follicular (EF) and 16 mid-luteal (ML) females tested with ANDR and placebo treatment in a repeated-measures design. Regardless of odor stimulation, psychosocial stress (i.e., mental arithmetic task with social evaluative threat) led to elevated negative mood and anxiety in all females. A negative association of social threat related amygdala activation and competence ratings appeared in ML-females, indicating enhanced threat processing by ANDR, particularly in ML-females who felt less competent early in the stress experience. Further, ML-females showed reduced performance and stronger stress-related hippocampus activation compared to EF-females under ANDR. Hippocampal activation in ML-females also correlated positively with post-stress subjective stress. Contrarily, such patterns were not observed in EF-females or under placebo in either group. Strikingly, unlike passive emotional processing, ANDR in a stressful context decreased cortisol concentration in all females. This points to a more complex interaction of ovarian/gonadal hormones in social threat processing and stress reactivity. Our findings suggest that ANDR enhanced initial evaluation of self-related social threat in ML-females. Female stress reactions are related to stress sensitivity through enhanced awareness and processing of social cues in a stressful context, with menstrual cycle phase being a critical factor.

The human body odor compound androstadienone leads to anger-dependent effects in an emotional Stroop but not dot-probe task using human faces

“…Based on similar procedures performed in our group [34, 35], a 250μM solution of AND (purity of AND ≥ 99%; Steraloids Inc., Newport, RI, USA) was prepared, diluted in propylene glycol and masked with 1% musk oil (Sigma–Aldrich, Deisendorf, Germany; please refer to S4 Text for the exact chemical composition of the musk oil used). This concentration close to detection threshold [36] has been shown to increase autonomic arousal in women [37].…”

Neurobiological mechanisms underlying sex-related differences in stress-related disorders: Effects of neuroactive steroids on the hippocampus

“…Data regarding sex differences in hippocampal activation during psychosocial stressors are however limited and inconsistent. While some studies report higher activation in men ( Kogler et al, 2017 ; Seo et al, 2011 ), others report higher activation in women ( Kogler et al, 2015 ; Abercrombie et al, 2011 ), particularly women during their luteal cycle phase ( Chung et al, 2016 ; Chung et al, 2016 ). Furthermore, in women stronger hippocampal activation was related to increased subjective stress ratings ( Kogler et al, 2015 ; Chung et al, 2016 ).…”

Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia

“…Our female subjects participated in the study during their luteal phase. As previous studies showed that amygdala activation in response to psychological stressor depends on menstrual cycles (Chung et al, 2016) and that cortisol responses to social stress are comparable between females in a luteal phase and males (Kirschbaum et al, 1999), we investigated on female participants only in their luteal phase. However, no conclusion regarding the neural responses is drawn from the current study.…”