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.

Depression is very common in reproductive women particularly with premenstrual dysphoric disorder (PMDD), which is a severe form of premenstrual syndrome (PMS). Beta-arrestins were previously implicated in the pathophysiology, diagnosis and treatment for mood disorders. This study examined whether a measurement for beta-arrestin1 levels in peripheral blood mononuclear leukocytes (PBMC), could aid to distinguish between PMDD and PMS. Study participants (n = 25) were non-pregnant women between 18–42 years of age with the symptoms of PMS/PMDD, but not taking any antidepressants/therapy and at the luteal phase of menstruation. The levels of beta-arrestin1 protein in the PBMCs were determined by ELISA using human beta-arrestin1 kit. The beta-arrestin1 levels were compared with the Hamilton Depression Rating Scale scores among these women. The magnitude of the different parameters for Axis 1 mental disorders were significantly higher and beta arrestin1 protein levels in PBMCs were significantly lower in women with PMDD as compared to PMS women. The reduction in beta arrestin1 protein levels was significantly correlated with the severity of depressive symptoms. Beta-arrestin1 measurements in women may potentially serve for biochemical diagnostic purposes for PMDD and might be useful as evidence-based support for questionnaires.

Hydroxyurea (HU), a drug for treating cancers of the blood and the management of sickle cell anemia, induces hypogonadism in males. However, the impact of HU on testicular architecture and function, as well as its effects on the resumption of male fertility following treatment withdrawal, remain poorly understood. We used adult male mice to determine whether HU-induced hypogonadism is reversible. Fertility indices of mice treated with HU daily for ~1 sperm cycle (2 months) were compared with those of their control counterparts. All indices of fertility were significantly reduced among mice treated with HU compared to controls. Interestingly, significant improvements in fertility indices were apparent after a 4-month withdrawal from HU treatment (testis weight: month 1 post-HU withdrawal (M1): HU, 0.09 ± 0.01 vs. control, 0.33 ± 0.03; M4: HU, 0.26 ± 0.03 vs. control, 0.37 ± 0.04 g); sperm motility (M1: HU,12 vs. 59; M4: HU, 45 vs. control, 61%; sperm density (M1: HU, 1.3 ± 0.3 vs. control, 15.7 ± 0.9; M4: HU, 8.1 ± 2.5 vs. control, 16.8 ± 1.9 million). Further, circulating testosterone increased in the 4th month following HU withdrawal and was comparable to that of controls. When a mating experiment was conducted, recovering males sired viable offspring with untreated females albeit at a lower rate than control males (p < 0.05); therefore, qualifying HU as a potential candidate for male contraception.

Previously, we reported that a reduction in β-Arrestin1 protein levels in peripheral blood mononuclear leukocytes (PBMC) significantly correlated with the severity of depression symptoms in women with premenstrual dysphoric disorder (PMDD). This study aimed to determine whether the reduced premenstrual β-Arrestin1 protein levels were associated with changes in the regulator for late luteal phase progesterone secretion. The study participants (n = 25) were non-pregnant women between 18 and 42 years of age not taking any antidepressants or receiving therapy and experiencing the luteal phase of menstruation. ELISA determined the β-Arrestin1 protein in PBMC; testosterone and prolactin levels from the plasma were determined by radioimmunoassay. Reduced levels of β-Arrestin1 protein in women with Hamilton Rating Scale for Depression (HAM-D) scores above 19 were observed alongside significantly higher plasma testosterone and prolactin concentrations. Understanding the mechanism underlying the initiation of PMDD will allow for identification of a key perturbed metabolic enzyme that can serve as a target for drug development to ensure the alleviation of PMDD, which has been suggested earlier as a risk factor for developing major depressive disorders.