Gender differences in subjective stress and neuroendocrine response to a stress task among individuals with opioid dependence: A pilot study

Addict Behav. 2019 May:92:148-154. doi: 10.1016/j.addbeh.2018.12.022. Epub 2019 Jan 5.


Background: Opioid dependence is a significant public health problem in the United States and the number of opioid overdose deaths among women has increased dramatically in comparison to men in the last few years. In this context, understanding the biological mechanisms underlying gender differences in vulnerability to opioid dependence is essential.

Methods: The current pilot study examined gender differences in subjective stress, heart rate (HR), and cortisol/dephydroepiandrosterone (DHEA) response to a laboratory stressor (Trier Social Stress Test; TSST) or a no-stress condition, and drug cue paradigm among men (n = 21) and women (n = 18) with opioid dependence.

Results: Significant group (TSST vs. no stress) differences emerged in self-reported stress [F(1,35) = 23.8, p < .001], HR [F(1,31) = 12.3; p = .001] and cortisol (F1,34 = 5.0; p = .032) response, such that the TSST group was more reactive than the no-stress group. Women reported greater subjective stress [F(1,35) = 6.5, p <= .015] in response to the TSST compared to men. However, men evidenced marginally greater cortisol and DHEA responses to the TSST compared to women [F(1,34) = 2.7; p = .113 and F(1,31) = 3.4; p = .073, respectively].

Conclusions: Although women with opioid dependence reported greater subjective stress when exposed to a laboratory stress paradigm as compared to men, the neuroendocrine response was more robust in men. This pattern was similar to gender findings in men and women with cocaine and tobacco use disorders. The blunted cortisol combined with an increased subjective response among women may be a sign of HPA axis dysregulation which could increase vulnerability to relapse in women.

Keywords: Cortisol; Dephydroepiandrostrone; Gender differences; Heart rate; Opioid dependence; Stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Comorbidity
  • Female
  • Heart Rate / physiology*
  • Humans
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Opioid-Related Disorders / epidemiology*
  • Opioid-Related Disorders / metabolism*
  • Opioid-Related Disorders / physiopathology
  • Pilot Projects
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiopathology
  • Saliva / metabolism
  • Sex Factors
  • Stress, Psychological / epidemiology*
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology


  • Hydrocortisone