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Older men with low testosterone may have gonadotroph autoantibodies
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Specific antibodies against gonadotrophs are found in a subset of older men with age-related low testosterone levels; however, whether the antibodies are pathogenic and contributory to age-related declines in testosterone remains unknown, according to data from a proof-of-concept study.
Shehzad Basaria, MD, associate professor at Harvard Medical School, and colleagues evaluated 182 men grouped by age: those aged at least 65 years with age-related low testosterone level (cases; n = 100); young, healthy eugonadal men aged 18 to 50 years (young controls; n = 50); and older, healthy eugonadal men (older controls; mean age, 66 years; n = 32). Researchers sought to determine the prevalence of antibodies to gonadotrophs in older men with age-related low testosterone compared with young and older controls.
Pituitary antibodies were found in 8% of cases compared with 42% of younger controls and 9% of older controls; however, the granular positivity pattern (most specific for pituitary autoimmunity) was observed only in cases (4%; P = .001). Researchers used double indirect immunofluorescence to confirm that the antibodies were directed specifically against the gonadotrophs.
“We report the presence of specific antigonadotroph antibodies in a subset of older men with low serum testosterone levels associated with aging,” the researchers wrote. “The findings of this proof-of-concept study offer a novel mechanism that might contribute to age-related decline in testosterone levels.” – by Amber Cox
Disclosure: Basaria reports receiving a research grant from AbbVie Pharmaceuticals and previously consulting for Eli Lilly and Takeda.
Perspective
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Gary Wittert, MBBch, MD, FRACP, FRCP
Although there is considerable literature describing low serum testosterone levels associated with inappropriately low luteinizing hormone (LH) levels with increasing age in men, it is now recognized that this is primarily due to obesity and the related burden of chronic disease, use of certain medications, depression, discontinuation of smoking and the presence of otherwise undetected pituitary or hypothalamic pathologies rather than ageing per se (Shi Z, et al. J Clin Endocrinol Metab. 2013;doi:10.1210/jc.2012-3842. Camacho EM., et al. Eur J Endocrinol. 2013;doi:10.1530/EJE-12-0890).
This manuscript by Ricciuti and colleagues describes the presence of antibodies directed to pituitary gonadotrophs in 4% of men over the age of 65 years with low testosterone and inappropriate LH. No such antibodies were found in 50 younger men or 32 older men being observed after prostatectomy for organ-confined prostate cancer without low testosterone. Accordingly this may represent another mechanism responsible for low testosterone in a small proportion of older men.
Pituitary antibodies are well documented to occur and to result in impaired hormone production. Aging is associated with an increase in autoimmunity and inflammation (Castle SC. Clin Infect Dis. 2000;31:578-585), possibly due to the effect of accumulated epigenetic changes (Grolleau-Julius A, et al. Clin Rev Allergy Immunol. 2010;39:42-50). Nevertheless, the presence of antibodies does not imply pathogenicity; there are too few men in the elderly controls to be sure that antibodies do not occur. Further investigation is required to progress the intriguing observation made, for example, establishing the functional consequences of the gonadotrophs antibodies by dynamic testing using clomiphene citrate, and evaluation of these antibodies in large and longitudinally followed cohorts of men.
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