We reported previously that reduction in beta-arrestin 1 (β-AR 1) protein levels in peripheral blood mononuclear leukocytes (PBMC) significantly correlated with the severity of depressive symptoms in reproductive women. In this pilot study, we used β-AR 1 protein levels in PBMC as a marker for developing depressive symptoms and the Hamilton Depression Rating Scale (HAM-D) scores to assess potential mood-related side effects of oral contraceptive use for routine birth control among women. We evaluated 29 women in this study. We enrolled the participants in three groups: Estrogen-progestin combination-oral contraceptives (COC, n = 10), progestin-only contraceptives (POC, n = 12), and non-hormonal or no contraceptives (NC, n = 7). We determined the β-AR 1 protein levels in PBMCs by enzyme-linked immunosorbent assay (ELISA). We found that women in the POC group had significantly higher HAM-D scores compared to those in the COC (p < 0.0004) and NC (p < 0.004). The levels of β-AR 1 protein were significantly attenuated in women in the POC group compared to women in the NC group (p = 0.03). Our findings suggest that the use of POC is a potential risk factor for developing depressive symptoms.