Brainstem and spinal cord dysfunction from androgen deprivation

[MateoBeach]

This morning I had my 2nd decompression surgery of my left L-2 spinal nerve root in 2 months. I had disabling pain progressing since last Summer rendering me unable to walk due to pain on most days. One day after the first surgery the pain actually got worse due to "hypoxia re-perfusion injury", and it never got better. It turns out that my hypogonadism (low testosterone syndrome) from ADT contributed to this in at least two ways. First is that I had lost so much muscle that I did not have good strength stabilization of my spine. Low T also contributed towards bone weakening from demineralization. Now it turns out that the regulatory (autonomic) functions in the spine are regulated and maintained by androgen receptors. ( See article below.)This probably contributed to my profoundly strong and prolonged reperfusion response. (Decreased blood flow from vascular spasm and resulting ROS damage and sequelae.)

For this repeat surgery I had a 400 mg injection of testosterone cypionate two days ago. I will go very gently for the first two weeks, and then hit my exercise program with progressive intensity to recover my normal strength. BTW I feel so much better on testosterone. Not just libido, but mentation is sharper and clear, moods positive, all systems "Go!".

Also reporting on the results of the "second half" of my personal test of the effects of testosterone on my PC. Recall that after a 6 week trial of injectable T (400mg T-cyp q 2 weeks)my PSA rose only modestly: from 0.080 to 0.180. The second half was to determine if my PSA would continue to rise even after, off the cycle. Last week, 4+ weeks off the testosterone, my PSA had come down to 0.123. This suggests that, for now at least, my PC does not respond adversely to cycled T therapy. So I will continue to use it intermittently in cycles to control my severe hypogonadism.

Androgen Receptors in Spinal Cord and Brainstem

onlinelibrary.wiley.com/doi...

Sex hormones, including androgens and estrogens, play an important role in autonomic, reproductive and sexual behavior. The areas that are important in these behaviors lie within the spinal cord and brainstem. Relevant dysfunctional behavior in patients with altered androgen availability or androgen receptor sensitivity might be explained by the distribution of androgens and their receptors in the central nervous system. We hypothesize that autonomic dysfunction is correlated with the androgen sensitivity of spinal cord and brainstem areas responsible for autonomic functions. In this study, androgen receptor immunoreactive (AR‐IR) nuclei in the spinal cord and brainstem were studied using the androgen receptor antibody PG21 in four uncastrated young adult male cats. A dense distribution of AR‐IR nuclei was detected in the superior layers of the dorsal horn, including lamina I. Intensely stained nuclei, but less densely distributed, were found in lamina X and preganglionic sympathetic and parasympathetic cells of the intermediolateral cell column. Areas in the caudal brainstem showing a high density of AR‐IR nuclei included the area postrema, the dorsal motor vagus nucleus and the retrotrapezoid nucleus. More cranially, the central linear nucleus in the pons contained a dense distribution of AR‐IR nuclei. The mesencephalic periaqueductal gray (PAG) showed a dense distribution of AR‐IR nuclei apart from the most central part of the PAG directly adjacent to the ependymal lining. Other areas in the mesencephalon with a dense distribution of AR‐IR nuclei were the dorsal raphe nucleus, the retrorubral nucleus, the substantia nigra and the ventral tegmental area of Tsai. It is concluded that AR‐IR nuclei are located in specific areas of the central nervous system that are involved in the control of sensory function and autonomic behavior. Furthermore, damage of these AR‐IR areas might explain related dysfunction in humans.

Yes I know it's cats. but it shows some of the wider distribution and functions of AR in mammals. Meow.

[Hidden]

From one hypogonadism to another. I feel your pain . This is why I feel that my skeleton is creaking . Not just this joint or that , everyone of them . I saw you . You looked great .. I’m sorry that youre going thru these bone issues.. when you describe how good the T feels .. I dream of that day . A return of cognition muscle strength and stamina. That would be a dream come true . I will ask my new doc next visit .. You are right on this point .. Great explanation .Us guys going through it , feel it everyday . Good luck moving forward. 🌵

[CSHobie in reply to Hidden]

Oh boy, I dream of T, more than anything else.

[Hidden in reply to CSHobie]

Don’t know if I’ll ever see it again? A pipe dream for now. Peace CSHobie✌️

[CSHobie]

Mateo, has your pain level increased since you received the T shots?

I have been told that people such as myself, with pain, can never get T injections due to the fear that pain will increase.

This Hypogonadism is just as bad as the disease.

[MateoBeach in reply to CSHobie]

I don’t have any painful bone mets. So there was no pain during the trial. Just a very pain from my spinal nerve compression that was not cancer related but degenerative. Feel I am healing more “ normally” with this 2nd surgery. Just local inflammation at surgery site. Leg pain is gone for now. 👍🏼😊

[Hidden in reply to MateoBeach]

Oh yah! Good bye leg pain 🤙🏽

[Hidden in reply to CSHobie]

😩

[LearnAll]

Mateobeach, sorry to hear about bone weakening due to ADT. In first 9 months , when I was on Lupron+Zytiga, my bone density dipped low because my Total T reached 1.5 ng/dlAfter stopping this regimen and being only on Bicalutamide, bone density increased again as T came up to 455 ng/dl. Some residual muscle weakness and bone weakness still persist but overall it is much better.

For men, T is truly elixir of life. I saw the profound good change when T came back. Hoping Bicalutamide works longer time. So far so good. Wish you strong bones again.

[MateoBeach in reply to LearnAll]

Thank you. Hoping for a very long run for you with bicalutamide. Curious if occasional cycle of T might restore response to it?

[LearnAll in reply to MateoBeach]

That is my hypothesis and that,s why I take short breaks and let PSA rise up to 3.0 and then, restart until PSA drops again close to 0.5. The goal is not just killing cancer cells but also preserve our bones and muscles at the same time.

Mateobeach, I have not been able to find the answer to the following question:

"In a man whose prostate is fully intact and general health is very good, what level of PSA can be assumed as coming from normal, prostate cells which are still there?"

We know ideal PSA in men without prostate should be less than 0.1 or zero BUT what about men who has prostate gland fully present.

Does any one have answer to this question..I can't find a clear answer anywhere.

[MateoBeach in reply to LearnAll]

That will make monitoring by PSA more difficult, especially when the contribution from cancer burden is low. For a normal (average) sized non-inflamed prostate the contribution of PSA may be up to 4.0 I do not know how much ADT suppresses non-cancerous PSA production. I think one would have to use peak and trough values to make some estimate. Or correlate a PSMA scan for total burden and SUV max values and assume the contributions may be proportionate. But I am just speculating. Many variables. Would assume anything above 5 is from cancer.

[LearnAll in reply to MateoBeach]

Heavy ADT can totally block ALL PSA production...from normal as well as cancerous cells in many me, In my case, PSA went below 0.2 which means almost total lockdown..no business open. After stopping heavy ADT and being only on Bicalutamide, some PSA shops started opening up.. and PSA started creeping up from 0.2 to 0.9 in last 8 months. I follow other 12 biomarkers and all are normal indicating lack of significant cancerous cells . My prostate size based on Ultrasound reading is 27 c.c. (ml) so up to PSA of 2.7 can be considered to be coming out from normal epithelial cells of prostate after ADT total lockdown was lifted.

[toml77]

Have you ever been treated with Zometta?

[MateoBeach in reply to toml77]

I’ve been on Prolia for several years. And I use estradiol patches when on ADT. So my bones are actually pretty good. My spine problem is from a life of hard activities and accumulated degeneration of discs and arthritic changes. The spinal nerve issue is a nerve problem. That is why the testosterone activity in maintaining brain, spine and nerve function as indicated in that article (for example) is important beyond the bone mineralization effects.

[Hidden in reply to MateoBeach]

Yes , I remember “ a mogul skier” . T is key to be a healthy male..

[Spyder54 in reply to toml77]

Just posted this: cancernetwork.com/view/zole...

[MateoBeach in reply to Spyder54]

Yes I have been taking celecoxib (400 mg/day) since the start of my PC in 2007. Now with Prolia which should pair as well with it as Zometa, maybe better

[j-o-h-n]

Geez if my T comes back.... I'll have to do all that heavy lifting that my wife does now... I think I'm better off the way I am....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 04/27/2021 7:53 PM DST

[Spyder54]

I was worried about “spinal collapse”. Only 7 mos in to ADT, but, Thought hope not. I just visited a sports medicine Doc this past Tuesday for S.I. Joint (sacro-illiac) joint steroidal injection. Heavier yardwork than normal, and I was on my back flat for 2 days. This inject is done with ultrasound. As he rolled the ultrasound guide over my lower spine, lumbar region he said “you have other issues going on. I too was an addicted skier with 6 seasons of 100+ days on the mountain running gates, and carving bumps 30,000 vertical before lunch. We play hard, and pay for it later (now at 67). Wouldn't do it differently. It almost sounds like alternating T, almost like a modified “BAT” may be in all of our futures? ADT is such an ugly process. I like how you guys above have clearly written this. Searching for solutions.