Research increasingly suggests that ADT may confer some risk of cognitive decline. However, we don’t know whether ADT’s impact on cognitive function varies with the treatment used to suppress testosterone.
To explore this issue, researchers from Taiwan analyzed the medical records of over 17,000 men diagnosed with prostate cancer. About 75% of the men were on ADT, while the remaining 25% were not. ADT medications included luteinizing hormone-releasing hormone agonists (LHRH agonists; e.g., Zoladex), anti-androgens (e.g., Casodex), or combination therapy with an LHRH agonist and an anti-androgen. A few patients had a bilateral orchiectomy.
Results: Cognitive decline was diagnosed ~ 3x more often in the men on ADT compared to the controls (i.e., 794 cased for men on ADT versus 271 for men not on ADT). Furthermore, the incidence of cognitive decline differed according to the ADT medication used. Antiandrogens were associated with the highest incidence of cognitive decline (18.5 cases per 1,000 person-years), followed by combined therapy (13 cases per 1,000 person-years), bilateral orchiectomy (11 cases per 1,000 person-years), LHRH agonists (8 cases per 1,000 person-years), and Non-ADT users (7 cases per 1,000 person-years).
When compared to the non-ADT group, men in the antiandrogen group and the combined therapy group had significantly greater risk of overall cognitive decline and also Parkinson’s disease. Those in the antiandrogen group had significantly greater risk of dementia. No significant relationship was found between the duration of ADT exposure and the risk of cognitive decline.
The mechanisms underlying these observed effects remain unclear. It is also not known whether the same results would be seen in a non-Chinese population.
Researchers hypothesize that complex hormonal feedback systems between the body and the brain may ultimately lead to neurodegeneration and cognitive decline. However, the mechanisms are poorly understood and further research is needed.
To read the study, see:
https://www.sciencedirect.com/science/article/pii/S1877782119301675?via%3Dihub
Hong, J.H., Huang, C.Y., Chang, C.H., Muo, C.H., Jaw, F.S., Lu, Y.C., & Chung, C.J. (2020). Different androgen deprivation therapies might have a differential impact on cognition – An analysis from a population-based study using time-dependent exposure model. Cancer Epidemiology. Advance Online Publication. doi: 10.1016/j.canep.2019.101657