There have been several posts regarding a new study [1] (full text):
"Association Between Androgen Deprivation Therapy Use and Diagnosis of Dementia in Men With Prostate Cancer"
The Discussion section ends with:
"While our study suggests an association between ADT and subsequent dementia diagnosis, we were unable to further investigate possible biological mechanisms of this association. It is important to note that dementia may have a latency period of 1 decade or more prior to cognitive manifestations, with some cerebrospinal fluid, serum, and neuroimaging biomarkers present many years before diagnosis. Hence, it is possible that ADT has a modifying or augmenting, rather than de novo, effect on development of dementia." {my emphasis}
Testosterone levels begin to fall in our early 30s. We hardly notice the 1-2% annual drop, but by the time we have reached the PCa years, the loss has been significant.
Many men believe that testosterone [T] drives PCa - the proof being that castration is an effective treatment (for a while - it is not curative). Yet men diagnosed with PCa tend to have lower T than matched controls, & men with the lowest T have the poorest prognosis. And, it appears that PCa is able to lower T [2]:
{post-prostatectomy} "data further suggest that the normal prostate and/or prostate neoplasm could secrete a substance or substances that give negative feedback control to pituitary gonadotropin secretion." [Patrick Walsh, et al, 1998] {T levels increase after radical prostatectomy.}
From the intro. to a 2018 (non-PCa) paper:
"Alzheimer’s disease (AD) is a devastating neurodegenerative disorder showing sex-specific differences in prevalence and genetic risk, making sex hormones and their signaling putative disease modulators (Altmann et al., 2014). The major AD risk factor is age, and sex steroid levels decline with increasing age, precipitously for women with menopause and more gradually for men. While the effects of sex hormones on AD risk have been well-studied in women (Paganini-Hill and Henderson, 1994; Espeland et al., 2004), fewer studies on sex steroids and cognitive function and/or AD risk exist in men."
"Testosterone is the predominant androgen in men and binds to the androgen receptor (AR), regulating expression of multiple genes with diverse biological roles. AR is expressed in many brain regions, including hippocampus (Simerly et al., 1990), a region responsible for learning and memory that is heavily impacted in AD. Previous studies implicate low testosterone levels with cognitive impairment in healthy men, and higher testosterone associates with better performance in cognitive tests (Yaffe et al., 2002). Men diagnosed with mild cognitive impairment (MCI) or AD have lower testosterone levels compared to controls (Hogervorst et al., 2001; Paoletti et al., 2004). Low testosterone levels are also associated with greater risk of AD (Lv et al., 2016), and precede AD diagnosis by 5–10 years (Moffat et al., 2004). Interestingly, brains of cognitively normal men with early AD neuropathology at autopsy have lower testosterone, suggesting lower testosterone may precede onset of clinical AD (Rosario, 2004). Low testosterone levels have also been associated with higher brain amyloid levels in MCI patients (Verdile et al., 2014). Furthermore, the prolonged use of androgen deprivation therapy (ADT) in men with prostate cancer is associated with risk of both cognitive impairment (Gonzalez et al., 2015) and AD (Nead et al., 2015, 2016)."
& another 2018 paper [4]:
"We conducted a prospective longitudinal study of 4069 community-dwelling older men free of dementia aged 71-88 years at baseline. The main objective of the study was to determine if men with low circulating sex hormones were more likely to develop dementia over time. The main biochemical exposures of interest were collected at baseline between 2001 and 2004 and men were assessed for incident dementia via an electronic health records database to the 31 st of December 2013."
"Dementia developed in 499 men over a median of 10.5 years (range 9.4-12.2 years). The risk of developing dementia increased with decreasing total {testosterone} (hazard ratio [HR] 1.14 ...) and calculated free testosterone (HR 1.18 ...) after adjustment for age, baseline cognitive function, depression, body mass, hypertension, cardiovascular disease and total plasma homocysteine. Men in the lowest quartiles of total (adjusted HR 1.39, 95%CI 1.04-1.85) and calculated free testosterone (adjusted HR 1.43 ...) had increased risk of developing dementia compared to those in the highest quartiles."
...
IMO, many men at PCa diagnosis already have an increased risk of dementia. In those men, ADT may act as an accelerant.
...
From the new study [1]:
"Exposure to ADT, compared with no ADT exposure, was associated with a diagnosis of Alzheimer disease (13.1% vs 9.4%; difference, 3.7% ... hazard ratio [HR], 1.14 ...) and dementia (21.6% vs 15.8%; difference, 5.8% ... HR, 1.20 ...)"
I wonder how men with exposure to ADT differ from men with no ADT exposure? It might have been prudent to measure baseline T. Lower T possibly increases the chance of ADT exposure.
The paper only mentions T once:
"There may be a causative relationship between lower testosterone levels and impaired cognitive function, perhaps via impaired neuron growth and axonal regeneration or accumulation of abnormally folded β-amyloid protein."
The lack of interest in baseline T is a fatal flaw IMO. The increased risk of dementia may be overstated.
I know that my testosterone [T] is high on the first 7 days of each BAT month, & I suspect that I am castrate for the last 7 days of the month, but I don't know how fast the transition is.
I have to say, from my experience with 3-month cycle, that the benefits of a big T boost are not immediately apparent. Seemingly, libido requires more than the presence of T. It takes time for those things to kick in. With the monthly BAT cycle, change is rapid, which is the point of the therapy - cells are given little chance to adjust.
Regarding "increased energy or clarity of thought". Perhaps one day I will review my old posts - do a daily count, as a surrogate for energy, & look for posts that seem to show clarity of thought. LOL
When I was on 3 months of high T, I took less time to complete a puzzle in "Absolutely Nasty Kakuro", Level Four:
I recommend the series to anyone fighting ADT brain fog.
What I am finding with BAT, is that the high T phase is too short. I never acquire the speed I once had in the 3-month phases. And it is rare that I complete a puzzle in the hour I spend with my morning coffee.
I did continuous T for about 5 years. I had 6 straight months where the PSA was constant & a long period where the PSADT was >24 months, but there was never a drop. When the PSADT fell to <12 months, I stopped continuous T.
I was thinking about starting BAT, see how that works, then maybe trying continuous Testosterone for a while with Sartor. Though certainly not for 5 years,
I thought the whole reason for trying BAT or straight testosterone for that matter, is to knock things around a bit, and reset the clock so that you can return back to conventional Androgen Deprivation Therapy.
But obviously that is not what you appear to be doing. You are now continuing with BAT. You seem to pleased, or at least accepting of how it is working.
What tips and/or insights do you have for someone who might be starting on the path you have been on (with respect to testosterone and BAT)?
Here is what I believe - partly because of my 15 year experiment. Traditional ADT (i.e. Lupron, etc.) selects for cells that are difficult to manage. Modern ADT (i.e. tratitional ADT + Zytiga, Xtandi, etc.) selects for cells that are even more difficult to treat. Testosterone [T] reinstatement can shock some cells into apoptosis, but the success rate will be lower in men who have had a lot of treatments.
From the start, I did not want to be on ADT for as much as a year, but I knew that shorter periods of castration in the intermittent ADT [IADT] setting did not lead to long ADT 'vacations'. When I finally had to be on ADT, I chose 3 months as my maximum.
I really enjoyed those 3 month vacations with T at ~1,000 ng/dL. But if I had known of BAT, I would have opted for monthly cycles.
When BAT is used at the start of ADT, it has the maximum chance of being effective, It isn't something that I would save for when all else has failed.
Note that BAT is not IADT. It is a form of ADT, where T is given to shock cells back to their original state. It is a way of dealing with the short mean-time-to-failure of traditional ADT (18-24 months).
1. Short periods of castration, lead to shorter periods of castration vacation.
2. You think one month on and one month off is optimal, at least for you.
3. You bipolar androgen therapy (bat) where you use testosterone during the castration vacation is more effective if used early before too many cycles of intermittent adt.
Question: Why exactly do you favor short we cycles of intermittent adt over longer cycles? That seems counter intuitive to me?
It all comes down to not giving PCa cells time to adapt. Adaptation leads to treatment failure.
The T 'vacations' are not really vacations. A single T shot to shock the cells that have had a couple of weeks with virtually no T.
You mention "one month on and one month off". The BAT cycle occurs in a single month. But one month on and one month off is more attractive & might be non-inferior, or even better that BAT.
One month on and one month off might be more prudent than my three months on and three months off.
The key is that the off periods should be with high T.
"When BAT is used at the start of ADT, it has the maximum chance of being effective, It isn't something that I would save for when all else has failed."
Isn't the whole purpose of bat, to use it after adt has failed and the prostate cancer has failed.
If it's purpose is to resensitize prostate cancer to androgen deprivation therapy, what is the benefit to using it early?
So that is a pretty small trial, with only 10 patients. But it appears to confirm the effectiveness of using bat to retrospectively reset castrate resisant prostate cancer.
It was limited to patients who had been on androgen deprivation therapy for at least 12 months. That sort of makes sense.
I assume you have a study that evidences that you can use bat prospectively to prevent castrate resistance from occurring?
I have had a total of 12 years on ADT drugs. And yes I can't answer those Jeopardy questions as fast as I used to. But then I am 73 now. There are times I can't remember names or places without prompting. But what is the alternative?
Anyone know of a Oncologist in Seattle who would prescribe BAT? My husband has been on Lupron for a year, still working but it is really taking a toll on him and his brain, along with his body
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Testosterone injections.
Zytia and testosterone
PSA and Testosterone 
Rise in testosterone 
