Androgens in the Etiology of Alzheimer's Disease in Aging Men and Possible Therapeutic Interventions

Issue title: Mini-Forum “Mitochondria in Alzheimer Disease”

Guest editors: Xiongwei Zhu

Article type: Research Article

Authors: Fuller, Stephanie J.^{a; b} | Tan, Robert S.^c | Martins, Ralph N.^{a; b; *}

Affiliations: [a] Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia | [b] Sir James McCusker Alzheimer's Disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Hollywood Private Hospital, Nedlands, WA, Australia | [c] University of Texas Medical School & Garden Terrace Alzheimer's Center of Excellence, Houston, TX 77030, USA | Department of Pathology, Case Western Reserve University, Cleveland, OH, USA

Correspondence: [*] Corresponding author: Ralph N. Martins, Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, 100 Joondalup Drive, Joondalup, Western Australia 6027, Australia. Tel.: +61 8 6304 5456; Fax: +61 8 6304 5851; E-mail: r.martins@ecu.edu.au.

Abstract: Animal experiments and cell biology studies have provided evidence that both estrogens and androgens can play a protective role against Alzheimer's disease (AD) related neurodegeneration. Males who become hypogonadal in later life often report problems with their memory. Lower than normal testosterone levels have also been detected in patients prior to the onset of AD, as well as in younger late-onset male AD patients, when compared to appropriate controls. The results of some small clinical trials suggest that testosterone can improve cognitive function in andropause. Although such improvement in cognitive function is subtle, patients on testosterone replacement therapy have reported memory improvements in both declarative and procedural domains. In contrast, there is no clinical evidence to date which suggest that the hormone dihydroepiandrosterone (DHEA) can improve cognitive function. Rises in the levels of the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), have been associated with AD, but the clinical effects of reducing their levels remain to be determined. We hypothesize that androgens, gonadotropin modulators, or perhaps selective androgen receptor modulators may be useful components of therapy aimed at preventing the onset or delaying the progression of AD in male patients.

Keywords: Testosterone, andropause, amyloid-β, Alzheimer's disease, leuprolin, cognition, dehydroepiandrosterone, gonadotropin, androgen receptor

DOI: 10.3233/JAD-2007-12202

Journal: Journal of Alzheimer's Disease, vol. 12, no. 2, pp. 129-142, 2007