SUN-103 - Hormonal Contraceptives and Mood: Assessing the Connection between Synthetic Estrogen, Endogenous Androgens, and Behavior in Female Rats

Mood-related side effects from hormonal contraceptives are one of the most common reasons these contraceptives are discontinued, and yet there is currently no scientific consensus on exactly how these medications influence mood. Given strong evidence that hormonal contraceptives decrease testosterone levels, and that decreased testosterone levels increase depression and anxiety, one possible mechanism for the mood effects of hormonal contraceptives is altered androgen production or function. Using a within subjects design, we conducted an exploratory study in which we dosed 24 female Long-Evans rats with 4 common hormonal birth control regimens in random order: C (vehicle), P (25 μg levonorgestrel), LE (10 μg ethinyl estradiol, 25 μg levonorgestrel) and HE (20 μg ethinyl estradiol, 25 μg levonorgestrel). Each individual was tested for changes to mood under each regimen through a battery of behavioral evaluations: the elevated plus maze as an assessment for anxiety, the social interaction test with a same-sex conspecific for sociality, and the sucrose preference test for anhedonia. Fecal androgen metabolites were measured using an enzyme immunoassay. While a one way within-subjects ANOVA did not find a significant difference in androgen levels, sociality, or anhedonia based on treatment (all ps > .05), we did observe significant differences in anxiety (p = .013) and weight loss (p < .001). Both the HE and LE groups had higher anxiety and more weight loss than the P and C groups. Furthermore, a Pearson’s r test found a significant relationship between fecal androgen metabolites and sociality with a same-sex conspecific in the vehicle group (p = .024), but not in any group receiving levonorgestrel (all ps > .05). These findings suggest some of the mood effects of common birth control regimens may be a result of changes to androgen function, while others may be directly related to estrogens. Given that most research in this field has been unable to draw conclusive results on the side effects of hormonal contraceptives, we advocate for increased communication and collaboration between researchers and medical providers to identify the mechanisms of these side effects, which would improve our understanding of hormonal contraceptives and allow physicians to better counsel patients.

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