Androgen Function in the Pathophysiology and Treatment of Male Huntington’s Disease Patients

Abstract

Low concentrations of circulating testosterone have been associated with dementia manifesting with advancing age and in neurodegenerative conditions. Huntington's disease (HD) is a dominantly inherited neurodegenerative disease with an invariably fatal outcome. Severe motor symptoms, psychosis and dementia are symptomatic hallmarks of the progression of HD that result from the dysfunction and death of neocortical and basal ganglia neurones. Treatments are directed toward manifest symptoms, although they are largely ineffectual in slowing or preventing disease progression. Emerging data have identified hypothamic pathologies in HD that result in endocrine disturbances. Clinically defined primary or secondary hypogonadism elicit low circulating testosterone concentrations and have been linked to the development of Alzheimer's disease in men. Examining similar neuroendocrine dysfunction in HD including the nature of manifest hypogonadism in male patients could allow an elucidation of the complex pathophysiology of HD and provide an impetus for hitherto untested testosterone replacement therapy.