(075) Exposing the Unsung Cycle: A Proposed Study to Examine the Connection Between Allopregnanolone and Adverse Mood Effects of Hormonal Contraception

Abstract

Introduction Allopregnanolone is a GABAnergic neurosteroid. Reduced concentration of allopregnanolone in the cerebrospinal fluid (CSF) and serum are closely associated with several neuropsychiatric conditions, including Alzheimer’s disease, anxiety disorders, premenstrual dysphoric disorder, and postpartum depression. Allopregnanolone is a progesterone metabolite predominantly synthesized in women in the ovaries and prior literature shows the menstrual cycle directly affects serum and CSF allopregnanolone concentrations. We hypothesize that allopregnanolone’s biosynthesis is similarly affected by exogenous hormonal contraceptives. In the United States, 65% of reproductive-aged women use hormonal contraceptives and their discontinuation is commonly attributed to adverse changes in mood; yet, little is understood when it comes to what and how specific components of hormonal contraceptives affect mood and how to manage such effects. Objective We aim to review current literature and propose a study to understand the connection between allopregnanolone and the adverse mood effects of hormonal contraceptives in order to improve women’s health. Methods We conducted a semi-systematic literature search, using PubMed Central and other databases, compiling peer-reviewed material using keywords including allopregnanolone AND hormonal contraceptives; combined oral contraceptive; progestin; suppression; levonorgestrel, ethinyl estradiol, medroxyprogesterone. All languages of publication were included where reliable translations were available. Studies were excluded if they did not include serum and/or CSF measurements of allopregnanolone. Results Rodent studies demonstrated that exogenous hormonal contraceptives reduce both the serum and CSF concentration of allopregnanolone. Human studies analyzing only serum allopregnanolone concentrations showed the same results, but no human studies analyzing CSF allopregnanolone concentrations were identified. Only two human studies have examined serum allopregnanolone levels and mood, and no studies have done so in the context of exogenous hormonal contraceptive use. Conclusions While exogenous sex hormones, namely progestins, affect allopregnanolone levels in rodents, their impact on both allopregnanolone levels and mood remains inconclusive and under-researched in humans. We propose a large multi-arm study on humans analyzing CSF and serum allopregnanolone and mood effects following administration of hormonal contraceptives to assess how contraceptives affect allopregnanolone metabolism in connection to adverse mood effects. This research will allow clinicians to better tailor contraceptive selection. Disclosure No