Pain Outcomes Associated with Exogenous Hormone Therapy in Adults

Chronic pain syndromes are reported to occur approximately 1.5–2 times more frequently in biological females compared to males after puberty. This disparity may be related to differences in endogenous sex hormone levels, hormone receptor activity, or other biological mechanisms. Exogenous hormone therapy (EHT), including testosterone, estrogen, progesterone, and anti-androgen agents, is prescribed in various medical contexts; however, its impact on pain processing and chronic pain outcomes remains poorly understood. Previous research suggests that hormonal exposures may influence the prevalence and severity of chronic pain. Androgen based therapy has been associated with potential reductions in chronic pain, whereas estrogen- and anti-androgen–based therapy may contribute to worsening symptoms. The biological mechanisms underlying these effects are not fully known, but one area of interest is nociplastic pain, a pain mechanism believed to originate from altered central nervous system (CNS) processing, involving amplified or dysregulated nociceptive and sensory signaling. Nociplastic pain is common in conditions such as fibromyalgia, chronic low back pain, and tension-type headaches, which often co-occur as Chronic Overlapping Pain Conditions (COPCs). This study will address a significant knowledge gap by evaluating how specific exogenous hormone regimens influence pain trajectories, nociceptive and sensory processing, and brain function by conducting a prospective observational study with three Aims. Aim 1: Characterize pain trajectories and pain-related symptoms in adults initiating EHT. Aim 2: Evaluate longitudinal changes in CNS pain processing mechanisms using quantitative sensory testing (QST) and neuroimaging in adults initiating EHT. Aim 3: Assess the relationship between EHT, psychological well-being, and pain experience through qualitative interviews. Findings from this research will improve understanding of how exogenous sex hormone exposures influence chronic pain mechanisms and may guide more effective, biologically informed strategies for preventing or reducing pain in patients undergoing hormone therapy.