Extended Unified Endocrine–Remyelination Hypothesis

This paper proposes a unifying biological framework in which reduced androgen availability—driven by modern hormonal environments—creates a shared vulnerability underlying several neurological and reproductive conditions. The hypothesis integrates emerging evidence across neurology, endocrinology, and reproductive medicine to explain rising prevalence, shifting demographics, and strong sex differences in disorders such as trigeminal neuralgia (TN), cluster headache, SUNCT/SUNA, migraine, adenomyosis, endometriosis, subfertility, PCOS-related dysfunction, and potentially multiple sclerosis (MS). Central to the model is the role of testosterone-dependent remyelination, neuroimmune regulation, and mitochondrial stability, which appear increasingly compromised in women due to long-term exposure to hormonal contraceptives, elevated SHBG, environmental endocrine disruptors, thyroid dysfunction, and menopausal hormonal transitions. These disruptions lower the physiological threshold at which mechanical, inflammatory, or metabolic stress leads to tissue-specific pathology. The hypothesis provides a coherent explanation for several previously disconnected clinical observations, including rising female predominance, earlier ages of onset, anatomical selectivity in TN, hormonal patterns in migraine and TACs, and the increasing incidence of reproductive disorders. It also generates specific, testable predictions and proposes new therapeutic avenues based on restoring androgen-dependent cellular resilience.