Androgen deprivation therapy (ADT, also called hormone therapy) is a strategy of biochemically controlling prostate cancer (PCa) by depriving it of testosterone. It is used in cases where
- Radiation or ablation is planned and the doctor needs to “shrink” the prostate gland to increase the effectiveness of the treatment
- PCa had already escaped the gland prior to treatment (advanced PCa)
- Primary treatment failed (recurrence)
- PCa has spread and is growing in the bones or other organs (metastatic PCa)
There are two approaches to ADT: 1) chemical castration which reduces the amount of testosterone produced by the testicles, and 2) antiandrogen therapy which blocks the ability of the body to use testosterone.
I have already written about a 2015 study that suggested a link between ADT and reduced mental function. On top of the sexual, emotional and health-related side effects of ADT, that study set off alarm bells in the PCa community because it added to the very small body of evidence that hormone therapy could impair cognition, possibly leading to dementia and Alzheimer’s disease. The relatively few earlier studies were based on small populations, raising the issue of reliability of the data.
A new study by Khosrow-Khavar et al. (2017)[i] may help ease those fears. What sets it apart from the relatively few earlier studies with small populations is the large cohort: 30,903 men (mean age 70.7 years) diagnosed with nonmetastatic PCa between April 1, 1988 and April 30, 2015. All cases were observed until April 30, 2016. Some of the patients used ADT of one type or another during the observational period, during which a total of 799 patients were diagnosed with Alzheimer’s disease or other forms of dementia.
When the authors analyzed the raw numbers, there was no greater risk of dementia for those who were on ADT than for those who were not. This was true regardless of how long they used ADT, or what type. The incidence of dementia was comparable to that in a non-PCa population. Thus, the results of this observational study are reassuring. It remains to be seen whether future research will confirm the authors’ work.
However, ADT has other serious side effects. The American Cancer Society lists the following possible side effects of chemical castration:
- Reduced or absent sexual desire
- Erectile dysfunction (impotence)
- Shrinkage of testicles and penis
- Hot flashes, which may get better or go away with time
- Breast tenderness and growth of breast tissue
- Osteoporosis (bone thinning), which can lead to broken bones
- Anemia (low red blood cell counts)
- Decreased mental sharpness [My note: not the same as dementia]
- Loss of muscle mass
- Weight gain
- Increased cholesterol levels
Some research has suggested that the risk of high blood pressure, diabetes, strokes, heart attacks, and even death from heart disease is higher in men treated with hormone therapy, although not all studies have found this.[ii] It should be pointed out that using antiandrogen therapy without chemical castration may produce fewer sexual side effects.
ADT is not curative. Eventually, the cancer will become resistant to the drugs (this is called hormone refractory prostate cancer). When this happens, immunotherapy may offer some promise before chemotherapy is prescribed. However, multiparametric MRI can play a useful role in identifying the location and extent of prostate cancer activity, which in turn can help determine a) which treatment strategy to use and b) how well it’s working. For instance, in cases of radiation recurrence signaled by a rising PSA, mpMRI of the prostate and pelvic area can detect whether a recurrent tumor is still localized. If so, the patient may qualify for a potentially curative ablation treatment as an alternative to ADT.
Most important, when it comes to PCa, the best scenario is early detection when the greatest range of treatments – including Active Surveillance and focal treatment like Focal Laser Ablation – is available. Our Center supports routine PSA screening, and the use of 3T mpMRI before biopsy if PSA is suspicious. We offer the most advantageous detection and diagnostic protocol: 3T mpMRI, in-bore MRI guided targeted biopsy, and genomic testing. Prostate cancer is a highly treatable and curable disease. While we join in the hope that dementia risk is now off the list of ADT side effects, we know that it’s possible to avoid hormone therapy by nipping PCa in the bud long before it reaches that point.
[i] Khosrow-Khavar F, Rej S, Yin H, Aprikian A, Azoulay L. Androgen Deprivation Therapy and the Risk of Dementia in Patients With Prostate Cancer. J Clin Oncol. 2017 Jan 10;35(2):201-207.