International Journal of Human Research and Social Science Studies

Neurodivergent women with chronic musculoskeletal syndromes experience disproportionate premenopausal symptom burdens that are poorly characterized in extant clinical paradigms and practice. The compounded interplay of estrogen fluctuations in premenopause with sensory–executive differences and baseline nociception from joint or connective-tissue pathology yields intensified pain, mood dysregulation, and functional decline. Evidence indicates estrogen modulates nociception, neuroinflammation, bone remodeling, and monoaminergic signaling; premenopausal variability magnifies pain, affective lability, and cognitive drift—effects accentuated in autism and ADHD. Coexisting hypermobility, fibromyalgia, or connective-tissue disorders compromise joint integrity and proprioception, increasing susceptibility to estrogen-dependent changes in bone microarchitecture and tendon homeostasis. This article advances an integrative neuroendocrine–musculoskeletal framework that balances neurodivergent conditions and musculoskeletal diagnoses equally while focusing explicitly on premenopause. Methodologically, it synthesizes convergent findings from endocrinology, pain science, and neuropsychiatry to delineate mechanisms—estrogen withdrawal, dopamine dysregulation, neuroimmune priming, and gut–brain signaling—relevant to this intersection. The analysis differentiates oral versus transdermal hormone therapies, emphasizes bioidentical, liver-sparing regimens, and appraises nonhormonal agents (e.g., SSRIs/SNRIs, gabapentinoids) alongside lifestyle interventions that elevate BDNF and attenuate inflammation. Special attention addresses risk modifiers salient to neurodivergent women: progesterone sensitivity, estradiol-mediated alcohol reward potentiation, executive dysfunction affecting adherence, and sensory hyperreactivity to foreign-body contraceptives. The proposed care model operationalizes neuroinclusive practice through structured monitoring, shared decision-making, and cross-disciplinary coordination, offering a decision matrix for individualized, route-specific hormone strategies and adjuncts. Anchored in premenopausal physiology, this approach aims to mitigate pain and psychiatric morbidity, preserve bone and functional capacity, and set a research agenda to close equity gaps in women’s neuroendocrine health.

Premenopause, Neurodivergence, Musculoskeletal syndromes, Transdermal hormone therapy, Neuroinflammation

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