Prostate
What does hormone therapy for prostate cancer do to the rest of the body?
Androgen deprivation is still the commonest drug treatment for prostate cancer in Korea. Two years of it measurably changes bone, and a national cohort found a signal in the brain.
By Andrew Cho
Reporter
- Published
- Reading time
- 5 minutes
Answer
Androgen deprivation therapy affects far more than the prostate: in a two-year study of 115 men starting it, bone mineral density fell significantly at every measured site in those not given zoledronic acid — by 3.0 to 5.0 percent — and bone microarchitecture and strength at the wrist and ankle declined even in those who were, while a Korean national cohort of 10,168 propensity-matched pairs found a higher risk of Alzheimer's disease (adjusted hazard ratio 1.39, 95% CI 1.21 to 1.59) though not of overall dementia, vascular dementia or Parkinson's disease.
Key takeaways
- Androgen deprivation therapy remained the most common pharmacological treatment for prostate cancer in Korea across 2011 to 2021, although its share declined as androgen receptor-targeting agents came into use.
- In a two-year study of 115 men starting androgen deprivation, bone mineral density fell significantly at every measured site among the 72 not given zoledronic acid, with mean decreases from 3.0 percent at the leg to 5.0 percent at the femoral neck.
- Among the 43 men given zoledronic acid, central bone density was largely preserved, but bone area, volumetric density, microarchitecture and strength still declined significantly at the wrist and ankle.
- The largest changes at the distal radius were in cortical area (10.1 percent decline without zoledronic acid, 6.5 percent with) and failure load (11.6 percent and 10.2 percent).
- In a Korean national cohort of 10,168 propensity-matched pairs, androgen deprivation was associated with a higher risk of Alzheimer's disease (adjusted hazard ratio 1.39, 95% CI 1.21 to 1.59).
- The same cohort found no increased risk of overall dementia, vascular dementia or Parkinson's disease.
- The mean age of Korean prostate cancer patients in 2021 was 73.07 years, with more than 80 percent aged 65 or older — the age at which bone loss and cognitive risk already matter.
Androgen deprivation works by removing testosterone, and testosterone does a great deal besides feeding prostate cancer. The treatment is effective and often necessary. What is less consistently explained is what else changes, and over what timescale.
What happens to bone
A two-year observational study followed 115 men from the start of androgen deprivation, measuring bone density by DXA at the spine, hip, femoral neck, whole body, arms and legs, and bone microarchitecture and strength at the wrist and ankle by high-resolution peripheral quantitative CT. Forty-three received zoledronic acid from the outset under national guidelines; seventy-two did not.
| Measure | No zoledronic acid | With zoledronic acid |
|---|---|---|
| Cortical area | −10.1% | −6.5% |
| Total volumetric BMD | −8.8% | −5.5% |
| Failure load | −11.6% | −10.2% |
In the men without zoledronic acid, areal bone density fell significantly at every site measured, from 3.0 percent at the left leg to 5.0 percent at the femoral neck. In those given it, spine and hip density held — but the wrist and ankle measurements declined significantly in both groups.
The signal in the Korean brain data
A real-world nationwide Korean cohort matched 10,168 pairs of men on propensity score and compared those who received androgen deprivation with those who did not.
HR 1.39
The specificity of that result is the part worth holding onto. Alzheimer's disease was raised; overall dementia, vascular dementia and Parkinson's disease were not. A finding confined to one diagnosis within a family of related ones is harder to explain by general confounding than a uniform rise across all of them would be — but it is also the kind of pattern that sometimes reflects how diagnoses are coded rather than what happened to patients.
Who this applies to in Korea
A nationwide study of every Korean patient treated for prostate cancer between 2011 and 2021 found prevalence rising from 220 to 532 per 100,000 adult men, an increase of 170.45 percent. The mean age in 2021 was 73.07 years, with more than 80 percent aged 65 or older, and diabetes, pulmonary disease and mild liver disease were common alongside.
That is the population receiving androgen deprivation: men in their seventies who are already losing bone and already at background risk of cognitive decline. The treatment effects described here land on top of that, not instead of it.
None of this is an argument against hormone therapy, which is prescribed because prostate cancer is the more immediate problem. It is an argument for the two questions that follow from it: whether bone protection has been discussed and started, and whether bone is being monitored anywhere other than the hip.
Sources
- 1
van Oostwaard MM, Bevers MSAM, Driessen JHM, Wyers CE, van den Bergh JP
Central and peripheral areal BMD, bone microarchitecture, and strength after initiation of androgen deprivation therapy in men with prostate cancer: a two-year follow-up studyFrontiers in Endocrinology 2026;17:1862001
doi:10.3389/fendo.2026.1862001 · PMID:42662144
https://doi.org/10.3389/fendo.2026.1862001 - 2
Jeon HL, Choo E, Jeong SH, Yun J, Jeong CW, Lee H
Risk of Alzheimer's disease and Parkinson's disease following androgen deprivation therapy in a real world nationwide cohortScientific Reports 2025;15(1):23490
doi:10.1038/s41598-025-08279-6 · PMID:40603530
https://doi.org/10.1038/s41598-025-08279-6 - 3
Jung J, Kang H, Choo E, Kang HY, Jeong CW, Jeon HL, Lee H
Prostate cancer in Korea: nationwide trends in prevalence and medication use during 2011-2021Cancer Epidemiology 2026;101:102987
doi:10.1016/j.canep.2026.102987 · PMID:41547116
https://doi.org/10.1016/j.canep.2026.102987
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