My Ongoing TRT Mystery

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bixt

Well-Known Member
which can mean low gaba

How's your sleep? Fall asleep easy but it's a light unrestful sleep where you wake up feeling like crap?

Ever played around with benzos? (such as diazepam or any other drugs ending in "pam"). If so, how did they make you feel the next day?
 
Defy Medical TRT clinic doctor
How's your sleep? Fall asleep easy but it's a light unrestful sleep where you wake up feeling like crap?

Ever played around with benzos? (such as diazepam or any other drugs ending in "pam"). If so, how did they make you feel the next day?
Benzos make me feel great, able to do chores, have sex, live life without the judge in my head. However, I only take them in dire situations. I sleep well on them and wake up feeling normal, not drugged. However I sometimes get rebound anxiety from them.
 

Keepfit1

Member
Is it possible you might have some anxiety or psychological things going on which may resolve with some kind of therapy, the clue maybe is that you feel better when on benzo or prosaic type drugs, just thinking out loud
 
Is it possible you might have some anxiety or psychological things going on which may resolve with some kind of therapy, the clue maybe is that you feel better when on benzo or prosaic type drugs, just thinking out loud

Oh that is for sure, I have some mild OCD which leads to a near-constant low level anxiety that switches to full anxiety when times get tough. I’m a bit of an odd-bird in regards to most “message board solutions“ where SSRI’s almost completely restore my sexual function for some time and benzos increase productivity and calm. My guess is that they both block the constant judging, questioning, problem solving, fear that my brain likes to do.

I’ve been working with a therapist for a year and am now starting to look into the genetics of things and rebuilding my protocol from the ground up. I’m not ruling out anything from supplements to other hormones like Progesterone and even a psych drug.

I’ve had the best windows of function when I’ve had TRT dialed in on the low side and been on some kind of psychiatric medicine at a low dose. This includes better results than when on hydrocortisone, dhea, thyroid, etc.
 
Too high testosterone can cause anxiety and irritability - upregulates neurotransmitters. They call it "aggression" in the bro-science and think it is something "positive".

Totally agree. I also get a bit concerned with the “symptom resolution” approach and “men’s T levels in the 1940’s were 1700 and they all ate meat and banged their wives and every other woman 4 times a day and then fought in the streets and won two wars!” mindset.

There is research in Trans people that started T and had their SERT lowered significantly from T…this can happen even on the first injection. Which makes me think of all the men who have posted in the past saying they had their first injection and had panic attacks and everyone was telling them, “it’s in your head, take more T and man up”. At least there is now some (albeit new and largely unproven studies) that can support this.
 

Simbarn

Active Member
There is research in Trans people that started T and had their SERT lowered significantly from T…this can happen even on the first injection. Which makes me think of all the men who have posted in the past saying they had their first injection and had panic attacks and everyone was telling them, “it’s in your head, take more T and man up”. At least there is now some (albeit new and largely unproven studies) that can support this.
This is interesting, do you have any links to this research with female to male trans people?
I have arrived at the supposition given my research on the topic that TRT can elevate the activity of our sympathetic nervous system in many men. In effect it may cause an imbalance in the sympathetic and parasympathetic nervous systems, (sympathetic NS dominance) which can lead to to anxiety and erectile/sexual difficulties. The penis has its own delicate balance of these two systems, which can be quite susceptible to changes in sympathetic activity in the penis itself. It may also cause issues with the RAS system up-regulating angiotensin II, which will also negatively influence erectile function.
It could be that the way in which exogenous testosterone is delivered into the body, which differs from the very intricate natural diurnal natural production, causes these issues. It may also be the loss of our gonadotropins (plus other upstream hormones), specifically LH, that contribute to this exacerbation of sympathetic function.

It is very interesting to me that you have found that your sexual function has been markedly improved whilst on a SSRI and testosterone replacement combined. Perhaps this is modulating sympathetic activity to the point whereby erectile function can function more normally again. Your experience with Benzos also mirrors mine, however, these drugs cannot be used long term due to drug tolerance as we all know.

I have spent years researching erectile function specifically, the balance between the sympathetic and parasympathetic activity in the erectile tissues is critical to good erectile function. The mechanisms that keep the penis in a flaccid state 95% of our waking hours are very powerful and have backup systems to ensure the penis stays that way in order to protect it in times of danger. Excess T, even possibly just a small amount may cause significant sexual issues, not to mention psychological issues, either directly or indirectly via the above pathways.

Some men are more sensitive to the upregulation of Norepinephrine in the penis than others. Research is also suggesting that this upregulation may occur due to ageing and may be evident even in middle aged men.

Th reason why PDE5i can significantly help men with the above NE (and Rho-kinase pathway) imbalance in the penis, is because they give the pro-erectile pathways (NO Pathway) more power, thus helping to overcome the excessive inhibitory mechanism in these tissues, restoring some balance, so to speak.
 
This is interesting, do you have any links to this research with female to male trans people?
I have arrived at the supposition given my research on the topic that TRT can elevate the activity of our sympathetic nervous system in many men. In effect it may cause an imbalance in the sympathetic and parasympathetic nervous systems, (sympathetic NS dominance) which can lead to to anxiety and erectile/sexual difficulties. The penis has its own delicate balance of these two systems, which can be quite susceptible to changes in sympathetic activity in the penis itself. It may also cause issues with the RAS system up-regulating angiotensin II, which will also negatively influence erectile function.
It could be that the way in which exogenous testosterone is delivered into the body, which differs from the very intricate natural diurnal natural production, causes these issues. It may also be the loss of our gonadotropins (plus other upstream hormones), specifically LH, that contribute to this exacerbation of sympathetic function.

It is very interesting to me that you have found that your sexual function has been markedly improved whilst on a SSRI and testosterone replacement combined. Perhaps this is modulating sympathetic activity to the point whereby erectile function can function more normally again. Your experience with Benzos also mirrors mine, however, these drugs cannot be used long term due to drug tolerance as we all know.

I have spent years researching erectile function specifically, the balance between the sympathetic and parasympathetic activity in the erectile tissues is critical to good erectile function. The mechanisms that keep the penis in a flaccid state 95% of our waking hours are very powerful and have backup systems to ensure the penis stays that way in order to protect it in times of danger. Excess T, even possibly just a small amount may cause significant sexual issues, not to mention psychological issues, either directly or indirectly via the above pathways.

Some men are more sensitive to the upregulation of Norepinephrine in the penis than others. Research is also suggesting that this upregulation may occur due to ageing and may be evident even in middle aged men.

Th reason why PDE5i can significantly help men with the above NE (and Rho-kinase pathway) imbalance in the penis, is because they give the pro-erectile pathways (NO Pathway) more power, thus helping to overcome the excessive inhibitory mechanism in these tissues, restoring some balance, so to speak.

Here is the study​


Wait, it seems that I am interpreting this wrong. I’ll find the other one.

Results​

One and 4 months of androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus. SERT binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, 4 months of antiandrogen and estrogen treatment in male-to-female transsexuals led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding, indicating a protective effect of estradiol against SERT loss.

I totally agree with everything you’re saying. ANS imbalances and high NE response are totally my situation. There was a great thread years ago on the AllThingsMale form where user chilln documented the use of alpha blockers like doxasosin and Flomax which block NE at the penis and allow erections. They worked for me, but made me so lethargic and blah that it wasn’t worth it.
 
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This is interesting, do you have any links to this research with female to male trans people?
I have arrived at the supposition given my research on the topic that TRT can elevate the activity of our sympathetic nervous system in many men. In effect it may cause an imbalance in the sympathetic and parasympathetic nervous systems, (sympathetic NS dominance) which can lead to to anxiety and erectile/sexual difficulties. The penis has its own delicate balance of these two systems, which can be quite susceptible to changes in sympathetic activity in the penis itself. It may also cause issues with the RAS system up-regulating angiotensin II, which will also negatively influence erectile function.
It could be that the way in which exogenous testosterone is delivered into the body, which differs from the very intricate natural diurnal natural production, causes these issues. It may also be the loss of our gonadotropins (plus other upstream hormones), specifically LH, that contribute to this exacerbation of sympathetic function.

It is very interesting to me that you have found that your sexual function has been markedly improved whilst on a SSRI and testosterone replacement combined. Perhaps this is modulating sympathetic activity to the point whereby erectile function can function more normally again. Your experience with Benzos also mirrors mine, however, these drugs cannot be used long term due to drug tolerance as we all know.

I have spent years researching erectile function specifically, the balance between the sympathetic and parasympathetic activity in the erectile tissues is critical to good erectile function. The mechanisms that keep the penis in a flaccid state 95% of our waking hours are very powerful and have backup systems to ensure the penis stays that way in order to protect it in times of danger. Excess T, even possibly just a small amount may cause significant sexual issues, not to mention psychological issues, either directly or indirectly via the above pathways.

Some men are more sensitive to the upregulation of Norepinephrine in the penis than others. Research is also suggesting that this upregulation may occur due to ageing and may be evident even in middle aged men.

Th reason why PDE5i can significantly help men with the above NE (and Rho-kinase pathway) imbalance in the penis, is because they give the pro-erectile pathways (NO Pathway) more power, thus helping to overcome the excessive inhibitory mechanism in these tissues, restoring some balance, so to speak.
So I was right, just didn’t have my facts straight. This video
at the 10:30 mark talks about how the increase in SERT can further lower already low serotonin levels and lead to panic and increased anxiety in those with certain SERT SNps.
 

Simbarn

Active Member

Here is the study​


Wait, it seems that I am interpreting this wrong. I’ll find the other one.

Results​

One and 4 months of androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus. SERT binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, 4 months of antiandrogen and estrogen treatment in male-to-female transsexuals led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding, indicating a protective effect of estradiol against SERT loss.

I totally agree with everything you’re saying. ANS imbalances and high NE response are totally my situation. There was a great thread years ago on the AllThingsMale form where user chilln documented the use of alpha blockers like doxasosin and Flomax which block NE at the penis and allow erections. They worked for me, but made me so lethargic and blah that it wasn’t worth it.
Thank you very much for this, I will have a good look at both.

I remember Chilln on All Things male. He had some interesting ideas. I have also read a reasonable amount of studies on Alpha1 blockers as I too thought they may help me, given they should block the action of one of the major inhibitory mechanisms in the penis. However there others such as the Rho-kinase pathway, which they won't help.
I tried Alfuzosin, only for a short period however, it didn't seem to help my erections and like you, I felt quite odd on it. Perhaps I should have persisted, as the initial effects of many drugs are not the true intended ones. I chose Alfuzosin as it apparently interferes the least with ejaculatory function.

Did you use the A1 blocker for a long time and which one did you try?
Are you considering reintroducing a low dose of SSRI to your protocol?
I have been seriously considering trying this as I can feel my body is in a state of "fight or flight" much of the time.
I have noticed when I am traveling on holidays, I have used low dose Valium in the past to help me sleep in new places/beds. My sexual function improves noticeably.
This increase in SERT, looks interesting to say the least!
 
Thank you very much for this, I will have a good look at both.

I remember Chilln on All Things male. He had some interesting ideas. I have also read a reasonable amount of studies on Alpha1 blockers as I too thought they may help me, given they should block the action of one of the major inhibitory mechanisms in the penis. However there others such as the Rho-kinase pathway, which they won't help.
I tried Alfuzosin, only for a short period however, it didn't seem to help my erections and like you, I felt quite odd on it. Perhaps I should have persisted, as the initial effects of many drugs are not the true intended ones. I chose Alfuzosin as it apparently interferes the least with ejaculatory function.

Did you use the A1 blocker for a long time and which one did you try?
Are you considering reintroducing a low dose of SSRI to your protocol?
I have been seriously considering trying this as I can feel my body is in a state of "fight or flight" much of the time.
I have noticed when I am traveling on holidays, I have used low dose Valium in the past to help me sleep in new places/beds. My sexual function improves noticeably.
This increase in SERT, looks interesting to say the least!

I sporadically messed with low low dose doxazosin, and it did provide erections when mixed with cialis. I also tried flomax which also worked but created significant retrograde ejaculation. The feeling of doxazosin, even at 0.5mg dosage was like an instant cortisol killer (or at least felt that way). I don’t recall the flomax having any negative body or mind side effects though. Yohimbe (both the herb and the hcl version) are alpha blockers and also granted significant erections, but holy heck the anxiety from the NE release within the body was way too much. It is definitely a weird trip having a panic attack and a raging erection lol.

I am considering 2.5mg Lexapro and will consult a new Dr on Tuesday about it. I’m just like you, on one vacation I took some klonopin to help with the flight and general stress, and once my then gf and I got to our room and got in the hot tub, it was an out of the blue erection. A similar time years ago I took the same benzo, had a few drinks, and we had sex all day, which hadn’t happened to me in years and hasn’t again since.
 

Simbarn

Active Member
I sporadically messed with low low dose doxazosin, and it did provide erections when mixed with cialis. I also tried flomax which also worked but created significant retrograde ejaculation. The feeling of doxazosin, even at 0.5mg dosage was like an instant cortisol killer (or at least felt that way). I don’t recall the flomax having any negative body or mind side effects though. Yohimbe (both the herb and the hcl version) are alpha blockers and also granted significant erections, but holy heck the anxiety from the NE release within the body was way too much. It is definitely a weird trip having a panic attack and a raging erection lol.

I am considering 2.5mg Lexapro and will consult a new Dr on Tuesday about it. I’m just like you, on one vacation I took some klonopin to help with the flight and general stress, and once my then gf and I got to our room and got in the hot tub, it was an out of the blue erection. A similar time years ago I took the same benzo, had a few drinks, and we had sex all day, which hadn’t happened to me in years and hasn’t again since.
Thanks for describing your experience with these blockers. It will help me if I decide to give them another try.
I have read similar accounts in regard to Yohimbine (as its more of an a2 blocker than a1), so have not tried it. It must have been extremely odd given your normal reaction to anxiety and erectile function!

Let me know what happens with your consult with the new doctor and if you do add the Lexapro. 2.5 is certainly a low dose. Why have you chosen this particular SSRI?
I have used Citalopram (older version of Escitalopram) decades ago. I reacted well to it at the time.

My reaction to benzos in regard to sexual function seems to be indicative of a sympathetic dominance issue like you. I also notice generally in the morning when I first wake my erectile/sexual function is much more responsive. After I am up and fully awake, this responsiveness drops markedly.
My research into nocturnal erections and why they occur is relevant here. It is hypothesised that owing to the almost shut down of the locus coeruleus during REM sleep, the inhibitory mechanisms in the penis are significantly suppressed. Erections therefore occur with great ease during these periods of sleep, smooth muscle in the erectile tissues has a much greater tendency to relax and it is thought that just circulating androgen's are sufficient to stimulate this relaxation during REM sleep, confirming the very direct influence testosterone has on nocturnal erections.
When one first wakes the body is still partially in this state.
Do you experience a similar thing in the morning?

Testosterone has a very direct effect with nocturnal erections. When it is low these do appear to lessen in frequency and duration.

The study you have given me was quite fascinating with regard to SERT binding. It does seem to indicate that androgens could influence this significantly as does estrogen.
The webinar on hormones and anxiety has certainly given me more to think about, especially given how I think my body has reacted to exogenous testosterone and symapthetic activity, possibly related to this SERT issue. Since adding recombinant hCG back into my protocol I have noticed definite improvements with my issues and this could be related to how important LH is (as mentioned in the webinar) in the conversion of cholesterol into pregnenolone, as many of us already know here.

I related to what the doctor said on that webinar describing how he began treating guys for low testosterone and how much time he spent learning about female hormones compared to the minor time spent on male hormones in the late 90's. It was not long after this that I began seeing doctors regarding my testosterone issues! They were clueless!
 
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Well this is just odd. I’ve been off and on TRT for almost ten years and about two years ago started to get this “air hunger” feeling where I cant take a deep breath. I figured it was related to TRT but my RBC, Hemocrit, and HGB we’re always within range. I use a CPAP off and on, but even on TRT and no CPAP before, no breathing issues, no Lab signs of blood thickening.

My most recent labs were taken a full five weeks after stopping TRT and now my RBCs are flagged high and my hemocrit and HGB are 0.1 away from flagged as high. These are the highest they have ever been ….even when I had Free and Total T well above range.

This air hunger feeling has gotten worse, not better off TRT. Is it just anxiety?
 

tropicaldaze1950

Active Member
Since I’m seeing my Dr in a week, I have the following questions on what options would be viable for me.

What I know:
1. Clomid did not result in better T, LH and FH did increase, test did not.
2. Cream on body does not absorb, cream on scrotum absorbs too much and DHT goes far to high, also feel too amped up on it.
3. HCG causes anxiety and other complications
4. E2 pre trt is low, like 10 or 11 on sensitive test
5. Shots sometimes work

Untested options:
1. Xyosted
2. Nasal Gel

Would either of the two above be worth a try vs the 30-40mg Cyp IM 2x a week?
T cream on the inner thigh EOD or 2X weekly? Even once every 5 or 7 days? I'm on injections but just brainstorming.
 
T cream on the inner thigh EOD or 2X weekly? Even once every 5 or 7 days? I'm on injections but just brainstorming.
Yes I saw this from Shippen that he had a patient that added scrotal cram who also got too ramped up and once he switched him to inter thigh 1-2x a week it kept dht healthy but in a safe range.
 

GreenMachineX

Well-Known Member
Not yet, been reading a lot of genetic stuff, did my nutrahacker report, and seeing Dr. Rob in a few weeks.

I won the genetic lottery, slow COMT, low MAO-a, low GAD which can mean low gaba/high glutamate, and MTHFR!
I'm slow comt as well, as well as shmt1, mthfs st20, pemt, dhfr, mthsd1 and having a very hard time between getting dialed in on trt and supplements to feel well. What all are you taking for those mutations? Do you have poor sleep also?
 
I'm slow comt as well, as well as shmt1, mthfs st20, pemt, dhfr, mthsd1 and having a very hard time between getting dialed in on trt and supplements to feel well. What all are you taking for those mutations? Do you have poor sleep also?
I’m not sure that field of SNPs is researched far enough to be effective yet. However, I have read that slow comt responds well to HydroxyB12 and also some adaptogens like Ashwagandha. Who really knows though?

I know that my b12 and folate are low and that any Bcomplex makes me super angry within a few minutes. I haven’t messed with folate but typically methyl types of supps make me feel bad. I do think the COMT think has merit because anything that slows COMT (ecgc, green tea, etc) does make me feel truly awful, and this was before learning of my COMT defect. I can recall one time I was in LA and had some special high end green tea and it basically put me down for the day.

The only sources for help with these that I have found are Ben Lynch’s book Dirty Genes and Nutrahacker. Amy Yasko seems to think that everyone needs to start with low dose Lithum OroTate before messing with b12 or folate. Not sure how much merit that has either.

I have yet to mess with the HydroxyB12 but have it here on my counter.

I know to stay away from most stimulants, as I am very sensitive to those.
 

SSHSSA74

Active Member
Hi Everyone,

Looking for some insight into my seemingly complex issues. Been on TRT for 10+ years in all forms, have seen Crisler, Nichols, Defy. Have had windows of feeling great but then issues always creep in.

Background:
1. Took Propecia in college, def caused some issues here and there.
2. Have had Lymes and usually still high levels of active EBV
3. Low vit. D, but supplementing causes high calcium (even with K2) and anxiety
4. Usual issues are anxiety, depression off and on, and E.D.

Past Protocol:
T Cream, Empower 200mg and applied 2 clicks every morning to the scrotum. No hcg or anything else.

Here are my labs, drawn 5 hours after application.

Total Test 1503 (250-1100 ng/dl)
Free Test 396 (35 - 155 pg/ml)
E2 Ultra-sensitive 33

Follow Up Protocol:
50mg Test Cup Mon and Thurs, 12.5mg scrotal cream daily.

Labs:
Total T 1274 ng/dl (High) Range 250-1100
Free T 280.3 pg/nl (High) Range 35-155 pg/ml
DHT 216ng/dl (High) range 12-65
SHBG 26 nmol/l range 10-50
E2 Ultrasenstive 45 (High) range <26

Again on this for the first month or two I felt great, then air hunger, anxiety, worry, feeling overall weird and lost erections again. It is obvious I’m super sensitive to the Scrotal Cream, as my DHT and e2 would stay low even on high doses of just Test Cyp.

Like an idiot I went off everything and now feel like a basket case. I’m thinking of trying 30mg Test Cyp M and Th and 6.25mg of cream on the scrotum. Any insight would be appreciated, thanks!
Try staying on the cream but splitting or lowering your dose.
 
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