Update on TRT experience... as of March 2025

[Don_1213]

Basically pulled from my bio.. that's the easiest place I've found to keep track of things..

12/24 - PSA has been around 0.12 lately, and dropping. Unfortunately - while my testosterone recovered somewhat after coming off of ADT - it has begun dropping again (below 200). After some long discussions with several MD's - all of them seem to think it might be a reasonable thing to try testosterone replacement therapy to try to nudge it back into the "age" normal range for an old guy like me - which is 350-600. This will be done with weekly self-administered injections of Xyosted (horribly expensive, but what isn't - drug plan did pick up most of the cost) and very close PSA and T monitoring (perhaps bi-weekly to start with, then move out to a month for a while if things go well - then see what we decide..) The goal is to restore some strength, improve some of my other comorbidities and perhaps enjoy life just a bit. We'll see what happens.

Life is nothing if not an adventure.

Update 01/01/2025 - Started TRT therapy due to decreasing testosterone levels causing lots of health issues. This might sound a bit risky - but it is a decision of Quantity of Life vs Quality of Life.. maybe. This started out based on my GP's suggestion that I speak with my medical oncologist about the possibility of TRT (Testosterone Replacement Therapy) perhaps helping with the issues I've had for the past several years with my legs and walking. Short version - a combination of peripheral artery disease (PAD) and some nerve impingement between L3 and L4 has caused me difficulty in walking any distance, or even standing stationary for any period of time. I've also experienced symptoms of male hypogonadism - which I'll let you look up - but basically no libido, easily fatigued, loss of muscle mass - bad stuff. My GP thought that TRT might help if I got clearance from my prostate cancer oncologist.

My oncologist (who I've become friends with) and I had a longish talk about QOL vs QOL, and the possible risks involved. The latest thinking on TRT is that (1) it's reasonable for someone with a very low T level to bring the T level back to a normal for your age level (2) it appears that if the cancer isn't currently active - bringing the T back up doesn't increase the chances of recurrence - and it might do just the opposite (3) this should be done with close monitoring - frequent PSA tests (4) patient and MD shouldn't panic if PSA rises to a level "normal" when the patient's T is normal.

After I finished ADT - it took about 6 months but my T finally crossed over into the "normal" range for someone my age (at the time 74) - and it stayed there for around 12 months, then started dropping. It finally dropped to around 180, and my PSA dropped to 0.09. That's when I started TRT...

12/17/24 - 2 weeks into TRT, PSA/T test - PSA remained at 0.09, T climbed to 450

01/28/25 - 6-week PSA/T test - PSA climbed from 0.09 to 0.23, while T climbed from 450 (12/17/25) to 540 (1/28/25) - the climb in PSA trailed the increase in T - which was expected, as was the increase. My PSA had hovered around 0.22 or so for the entire time when I had sort of normal T levels after coming off ADT, so this level isn't the least bit concerning to me.

02/04/25 - about 8 weeks after starting weekly injections, my legs feel better than they have in several years. I can do significantly more at the gym on a stationary bicycle and not have leg cramps at night. My feet finally feel warm. I'm recovering my libido (interest in sex, not that there is much I can do about it), and a feeling of "feeling better" over what I had been experiencing the past few years as my T disappeared.

03/11/25 - Latest 6-week PSA test (~14 weeks total). PSA dropped to 0.21 while T climbed to mid 600's (639)! Great results. My overall health - improving. Fewer other blood tests are out of range now. My legs are better (not perfect - but better), energy is up, mood is up and I get horny sometimes. So far - so good! I'll be talking with my oncologist next week - I'm sure he'll be delighted with the results of our experiment so far!

----------------------------------------------------------------

So that's where I am right now—waiting on a Xyosted delivery. The funny thing, my drug plan approved it (it's out of their formulary..) at a copay of $187/month. While that seems helpful, the pharmacy I'm using has a "direct buy" program - $150/month. Go figure.

03/13/25 - Xyosted arrived. 3-month prescription. Noticeable cost.

-------------------------------------------------------------------

03/21/25 - Phone consult with MO.. my MO is quite happy with how things are going so far. He feels we can move T/PSA testing back to a 2-month schedule, then if it continues as it is - to a 3-month schedule. Sounded OK to me. We had a nice talk about the targeted immunotherapy revolution (he feels it WILL be the cure for cancer) and the excitement in that community with the results to date of several drugs in late stage-3 testing, and his drug which is heading into stage-3. Besides being a great MD to have at my back, I learn something each time we talk. Can't ask for more!

-------------------------------------------------------------------

I'm not suggesting anyone go on TRT, but for men who have the same PCA history as I do.. I thought I'd report on the results - ongoing - and you can decide if that's useful to you.

[PCaWarrior]

Do you know why they picked Xyosted? That's just testosterone enanthate and as far as I can tell they just did some fancy packaging and added an auto-injector so that no generics are availalbe. Reality is that is extremely similar to testosterone cypionate (used by Denmeade for BAT_. You can get about enough cypionate for 2 1/2 months for around $40 with a coupon from goodrx. Cypionate is legal and is the form of T used by most doctors for TRT.

goodrx.com/testosterone-cyp...

This is a short comparison of Xyosted and cypionate. Some factual errors so I wouldn't go by it. A good men's health TRT clinic should know the goods. Most doctors are rather clueless when it comes to the "taboo" testosterone.

goodrx.com/compare/xyosted-...

Oh, and androgens (e.g. T and DHT) cause PSA overexpression. That is (should be?) a well known fact and has been presented in graphical form in clinical trial presentations. I wouldn't be concerned yet by that PSA increase.

I do a type of BAT and without fail my PSA climbs up when my T is high and then comes right back down when my T is low. Maybe 2 -> 0.3. Despite what I wish it's not cancer receding, it's just the expression of PSA.

[Don_1213 in reply to PCaWarrior]

I believe the endocrinologist prescribes it wants to very precisely control the dosage, so we can see what is going on with the T and PSA numbers.

I'm not concerned with the 0.2+/- numbers for PSA. Those are the same numbers that I had when I naturally had testosterone recover on its own. The numbers only dipped below that range when my T started cratering.

The goal of the treatment is to try to get my T to a "normal" level for a healthy adult male, and see where the PSA ends up. One option people have suggested is the gel form where you rub it into your skin daily - to me - that's much more likely to result in the dose not being tightly controlled.

What I found interesting is the lag in PSA numbers vs T level. It seems to be a several-week (or a month) lag for the PSA to change when the T changes. So far T has continued climbing, but it looks (perhaps prematurely) as if PSA has reached a steady-state plateau, which wouldn't be a surprise since it's believed that T above 200 or so has no real effect on PSA numbers (Morgenthailer[?]) refers to that in a few papers of his that I've read.

I looked into the testosterone cypionate that you've suggested - but chances are for now I'll stick with the Xyosted out-of-pocket. The testosterone cypionate requires muscular self-injections. I'm shakey enough that becomes problematical and likely dangerous. The biggest difference - Xyosted is in the self-injector, and it's injected into fat (which I have no difficulty locating or hitting with the injector.

I'm old, What else do I have to spend my money on? I'll probably discuss it with my GP - I have a bet going with him involving a decent sum of money IF I can walk into his examining room on my 80th birthday. Of course, if I win that bet, I also lose, so there is that.. this was his suggestion actually.. he watches out for me (the bet has already paid off IMHO..) We're coming up on the end of the bet. Wonder what it'll take to get me to 90?

It's like Catch22 all over again..

Don

[PCaWarrior in reply to Don_1213]

The IM injections that most guys do with Cypionate is just a historical thing. I've done SubQ but need to inject so much that it becomes a pain - literally.

Cypionate is almost identical to enanthate. I would at least talk to my MO about it. Perhaps he has a good reason. Please let me know what he says. I have to admit that I don't understand why enanthate would be preferred over cypionate. The pharmacokinetics are almost identical. If money isn't an issue and/or the self-injector included with it is worth it for you, I get it. One stop shop.

If you wanted to save, SubQ needles are maybe 20 cents each. And then you need syringes. Another 20 cents or so. I think I pay about $15 for 100 needles and about the same for syringes.

Yeah, the 200 threshold was Morgenthaler.

Several drawbacks to gels: 1 - half life is short so you need to apply at least once a day and should apply twice a day. 2 - After you apply you need to wait and let the area completely dry. Until it dries you can't have anyone touch you. They won't die but it isn't necessarily the best for them - or you since you now have a reduced amount applied to you. 3 - cost, more expensive than cypionate.

And as you mention, the big thing is control. The absorption changes depending on where you apply the gel, how clean the area is, whether you're sweating or not, etc. And to measure the peak values is also difficult. You need to time it pretty well. Orals are even harder. Half-lives as short as 1 or 2 hours. I've never caught the peak.

Androgens are a strange thing. They get stored in the body almost like a stockpile. How and when do they get releaesed? I don't know. You have your injection and your injected T goes into a "depot" in the muscle - abs or butt or wherever. Then the T gets releaesed. Then it has to be converted to DHT to start prodding the cancer. And the cancer isn't going to react instantaneously.

Here is my AI query and response from chatGPT:

"Sounds right. But what are the mechanisms? T traveling into the cells and then much of it converting via 5AR to DHT and then binding to the ARs and then the cell releasing PSA? Others?

Reasoned for a couple of seconds

Your understanding is largely correct. Here's a more detailed breakdown of the mechanisms involved:

Testosterone Increase and Direct Binding:

Once injected, testosterone levels in the blood rise. Testosterone itself can enter prostate cells (both normal and malignant) and bind directly to androgen receptors (ARs). This binding triggers AR activation, which then translocates to the nucleus and modulates gene expression, including upregulation of PSA.

Conversion to Dihydrotestosterone (DHT):

In prostate tissue, the enzyme 5-alpha-reductase converts testosterone to DHT, which has a higher affinity for the androgen receptor. DHT’s more potent activation of the AR further stimulates the transcription of genes involved in prostate cell growth and PSA production.

Additional Pathways:

While the testosterone-to-DHT pathway is key, other factors might play roles in PSA production, such as:

Autocrine and Paracrine Signaling: Prostate cancer cells may produce growth factors that interact with the AR signaling pathway, potentially amplifying the effects of androgen receptor activation.

Receptor Sensitivity and Mutations: In prostate cancer, ARs may become hypersensitive or even mutated, which can lead to an exaggerated response to both testosterone and DHT.

Aromatization to Estradiol: A minor pathway is the conversion of testosterone to estradiol by the aromatase enzyme. Although estradiol primarily acts through estrogen receptors, in some contexts it might indirectly influence prostate cell behavior. However, its direct role in PSA release is less significant compared to the androgen pathway.

In summary, increased testosterone leads to both direct AR stimulation and conversion to the more potent DHT, both of which drive PSA production in prostate cells. Other factors, such as altered receptor sensitivity or additional local signaling mechanisms, can modulate the overall response. Always consult your healthcare provider for personalized information."

I hate it when it "reasons for a couple of seconds" and writes out an elegant answer. Today these chat bots are frequently wrong but in 5 years...?

Here's hoping you get to 90 and beyond. Jack Lalanne lived to 98 and he was vital well into his 90s. In the picture, the little old man was 72.

Jack Lalanne

[Teufelshunde]

Also, you can just get an AutoJect2. I used that way back and is easy.

[Don_1213 in reply to Teufelshunde]

That looks like a marvelous solution.. I'm not afraid of the needle; it's controlling the depth of penetration, which is an issue. AutoJect2 appears to address that issue.

I have one of my "review the results" sessions with my MO this Friday, I have to remember to ask him about Cypionate and AutoJect2.

BTW - Funny thing, I entered "Cypionate " on a DuckDuckGo search bar, and among the results are 3 videos, all entitled "Testosterone Cypionate vs Enanthate" an example is:

youtube.com/watch?v=xygtjRq...(Not working as expected?)

I'll update the thread after I watch these videos..

That link is to a video discussing exactly what we were discussing by a Dr. Robert Stephens, from the UK and the "Men's Health Clinic". He concludes with the statement "there is no difference between enanthate and cypionate when injected intermuscular. There is a difference if injected subcutaneously." The Enanthate instructions are to pinch a fold of skin in the belly area, and inject into that fold of skin (not as easy as it sounds due to the IMHO excessive pressure required to trigger the injector). So the enanthate is subcutaneous.

youtube.com/shorts/De_KfCbW3k4

Same MD talking with another MD, they discuss the absorption and how long between injections - with very little difference between Cypionate and Enanthate, The conclusion was they were basically interchangeable.

My conclusion - I've gotta price Cypionate vs Enanthate. And see if my plan D will cover the Cypionate.

[Don_1213]

Just an update - in checking out the Cypionate vs Enanthate - it turns out that Testosterone Cypionate costs more (not covered by the medical plan - but I haven't tried a pre-auth since I just got one for the Evanthate) than Testosterone Enanthate.

I then explored (because Facebook, which snoops on everything we do on a computer found out I was looking at testosterone put up an ad for) a men's clinic that does testing, prescribing and supply of testosterone (they didn't say what kind) - that was equal in price to the special discount price I'm getting from the pharmacy.

It looks like the self-injector Enanthate may actually be the best deal.. dollar wise. Oh - the clinic was talking about daily microdosing via injection. That's more than I want to get involved in. They felt is maintained a steadier level - but so far I haven't felt and downturn in health about when I'm due for my weekly shot and last weeks shot is 7 days old.