Effects of oral contraceptive pills on mood and magnetic resonance imaging measures of prefrontal cortical thickness

Abstract

Gonadal hormones influence neuronal organization and plasticity. Yet the consequences of altering their concentrations by administering contraceptive agents, which are used by most reproductive-age women in the United States, are unclear. Cross-sectional studies have found both larger and smaller cortical regions alongside a variety of mood alterations in women who use oral contraceptive pills (OCPs) compared to naturally-cycling women. The goal of this study, therefore, was to determine whether there is an effect of OCPs on MRI measures of prefrontal cortical brain structure that may influence regulation of mood. We performed a double-blind, placebo-controlled, randomized crossover study comparing effects of OCPs (0.15 mg levonorgestrel + 0.30 μg ethinyl estradiol) vs placebo (N = 26) on MRI measures of prefrontal cortical thickness and on mood, as indicated by self-report on the Daily Record of Severity of Problems, which also includes one item related to somatic symptoms. MRI measures that reflect cortical thickness were smaller bilaterally in the pars triangularis and in the pars opercularis and frontal pole of the right hemisphere during the OCP arm vs. placebo. Only the effect in the right pars triangularis survived multiple comparisons correction. Right pars triangularis MRI measures of cortical thickness were not related to mood symptoms, but negatively correlated across conditions with severity of somatic symptoms on the DSRP. The somatic symptoms and MRI measures may be independently related to the actions of steroid hormones in OCPs, with OCPs simultaneously inducing both more effects on MRI measures of cortical thickness and somatic symptoms.

Figure 1:

CONSORT diagram describing the overall flow of the study, with the number of excluded participants and reasons for their exclusion at each phase

Figure 2:. OCPs significantly increased BDI scores.

The left panel plots individual scores during the placebo and OCP arms; the right panel depicts the mean (bars) and standard error of the mean (error bars) during each arm of the study.

Figure 3.. OCPs reduce right pars triangularis thickness.

The left panel depicts pars triangularis thickness for each participant during the placebo and OCP arms. The right panel depicts mean (bars) pars triangularis thickness and standard error of the mean (error bars) during each intervention arm.