The Impact of Environment on Hormone Replacement Therapy

Purpose: Women that have undergone long-term menopause exhibit elevated oxidative stress. Prior studies have found equivocal effects of hormone replacement therapy for women in menopause. It has been proposed that hormone replacement therapy is adverse for women 10 years post-menopause. Furthermore, post-menopausal women have a higher risk for Parkinson’s disease than pre-menopausal women. Therefore, we propose that hormone replacement therapy is additive to oxidative stress, resulting in dopaminergic neuronal loss, a hallmark for Parkinson’s disease. Methods: In this study we used dopaminergic 27 cell line that originated from fetal female rats. Cells were exposed to an oxidative stressor, hydrogen peroxide (H2O2), to induce 20% cell death. Following H2O2, cells were treated with either testosterone (100 nM) or 17beta-estradiol (10 nM) to model hormone replacement therapy. Cell viability was assayed using the MTT protocol. Results: H2O2 treatment decreased cell viability approximately 20%. Testosterone treatment further increased H2O2 cell loss by 60%. Although not as potent as testosterone, estradiol did exacerbate H202 induced cell loss by 40%. Neither testosterone nor 17beta-estradiol were damaging to cells in the absence of an oxidative stressor. Conclusions: Depending on the cellular environment, both androgenic and estrogenic steroid hormones can negatively affect neuronal function.