Do oral contraceptives modulate the effects of stress induction on one-session exposure efficacy and generalization in women?

Abstract

Rationale: The administration of glucocorticoids (GC) as an adjunct to exposure represents a promising strategy to improve one-session exposure outcome in anxiety disorders. It remains to be determined whether similar effects can be induced with the use of acute stress. Furthermore, the possible modulation of exposure effects by hormonal factors (e.g., use of oral contraceptives (OCs)) was not explored so far.

Objectives: We investigated whether acute stress prior to one-session exposure for spider fear affects its efficacy in women using oral contraceptives (OC) relative to free-cycling (FC) women. In addition, effects of stress on generalization of exposure therapy effects towards untreated stimuli were examined.

Methods: Women with fears of spiders and cockroaches were randomly assigned to a Stress (n = 24) or No-Stress (n = 24) condition prior to one-session exposure. Of these 48 participants, 19 women used OC (n = 9 in the Stress, and n = 10 in the No-Stress group). All FC women had a regular menstrual cycle and were tested only in the follicular phase of their menstrual cycle. Pre-exposure stress induction was realized with the socially evaluated cold-pressor test. Exposure-induced changes towards treated and untreated fear stimuli were tested with behavioral approach tests for spiders and cockroaches and subjective fear and self-report measures.

Results: Acute stress did not influence exposure-induced reduction in fear and avoidance of the treated stimuli (spiders). Similarly, stress had no effect on the generalization of exposure-therapy effects towards untreated stimuli (cockroaches). Exposure-induced reduction in subjective fear and self-report measures for treated stimuli was less evident in women using OC specifically after pre-exposure stress. Women using OC had higher levels of subjective fear and scored higher in self-report measures at post-treatment (24 h after exposure) and follow-up (4 weeks after exposure).

Conclusions: OC intake may represent an important confounding factor in augmentation studies using stress or GC.

Keywords: Anxiety disorders; Cortisol; Glucocorticoids; Oral contraceptives; Single-session exposure; Spider fear; Stress.

Fig. 1

Outline of the experimental design and main outcome measures. At the beginning of the experiment the participants underwent two BATs (spider and cockroach), and thereafter, presented with spider and cockroach-related questionnaires (Pre-SECPT treatment stage). Thereafter, the participants underwent the SECPT either under the stress condition with hands submerged in cold water or under the no-stress condition with hands submerged in warm water. Twenty-five minutes after the SECPT, all participants received a short psychoeducation and in-vivo guided spider exposure. After a delay of 24 h, the spider BAT was repeated and both the spider and the cockroach fear-related questionnaires were presented (Post-treatment phase). Long-term effects of exposure were evaluated four weeks later (Follow-up phase). At follow-up, both spider and cockroach BATs were repeated and spider and the cockroach fear-related questionnaires were presented. Abbreviations: BAT: Behavioral avoidance test, SECPT: Socially evaluated cold-pressor test

Fig. 2

Monitoring of salivary cortisol concentrations of the Stress and No-Stress groups. Each data point represents mean and SEM salivary cortisol concentrations that have been measured during 7 sampling points on experimental day 1, two sampling points on day 2 and another two sampling points on experimental day 3 (see Table 1 for details)

Fig. 3

Subjective fear at the initial approach distance. A-B. Subjective fear ratings (SUDS) during the spider-BAT during pre-exposure, post-exposure, and follow-up measurements of the Stress and No-Stress groups. C.-D. Subjective fear ratings during the cockroach-BAT during pre-exposure, and follow-up measurements of the Stress and No-Stress groups. Bars represent mean and SEM of the SUDS scores. Abbreviations: FC: Free-cycling, OC: Oral contraceptive, SUDS: Subjective units of distress Scale

Fig. 4

Spider and cockroach-related questionnaires. Pre-, post-exposure and follow-up assessment of spider- and cockroach-related questionnaires of the Stress and No-Stress groups. A.-F. Bars represent mean and SEM of the fear of spiders, spider beliefs and spider phobia scores, respectively. G.-J. Bars represent mean and SEM of the fear of cockroach, and cockroach beliefs scores, respectively. Abbreviations: FC: Free-cycling, OC: Oral contraceptive, FSQ: Fear of spiders questionnaire, SBQ: Spider beliefs questionnaire, SPQ: Spider phobia questionnaire, FCQ: Fear of cockroaches questionnaire, CBQ: Cockroach beliefs questionnaire. *: p < 0.05; T-test for independent samples