Ankylosing spondylitis (AS) has a striking disease marker, i.e., HLA-B27, indicating the major genetic predisposition; however, expression of disease is also strongly influenced by age- and sex-related factors. Sex steroids studies suggest greater androgenicity in AS than normal control persons. Therapeutic interventions that normalize such sex steroid status have shown clinical improvements in males and females. Muscle histopathology in AS shows frequent changes early in disease consistent with neuropathic and myopathic mechanisms of a noninflammatory nature. Accepting the available, aggregate data, one may infer that sex steroid imbalance in persons susceptible to AS may target axial and proximal muscle tissues, resulting in relative functional hypertonicity. Such phenomenon, developing in preteen and younger adult ages, may contribute to peripheral and axial manifestations of enthesopathy in this disease by complex and currently unknown mechanisms.