Total T over 550 reduces risk of cardiovascular events - is TRT warranted?

[Marco N Cognito]

So, what if your average TT is 500? Is TRT automatically warranted?

http://defymedical.com/resources/bl...-dl-reduced-the-risk-of-cardiovascular-events

 

[Jasen Bruce]

Im no physician but in my experience I would have your Testosterone Free and Total tested more than once, especially if you are that close to 500ng. Having multiple tests over a few weeks (3-4 tests) and taking an average might be more accurate than a single test. This will also show fluctuation in your levels over a short period of time. There also may be some benefit in trying an "HP axis" stimulation protocol to see if you can produce more T endogenously prior to starting TRT.

 

[Marco N Cognito]

Im no physician but in my experience I would have your Testosterone Free and Total tested more than once, especially if you are that close to 500ng. Having multiple tests over a few weeks (3-4 tests) and taking an average might be more accurate than a single test. This will also show fluctuation in your levels over a short period of time. There also may be some benefit in trying an "HP axis" stimulation protocol to see if you can produce more T endogenously prior to starting TRT.

Yes, that level is the average over the last couple years. Already have tried every herb and supp under the sun to raise endo T for last few years. FT is really low, as it is being bound by SHBG (which is because of long-term T3-only thyroid med). Tried everything for that. No change. Also, E2 is almost non-existent. What's stopping me from doing TRT? My biggest fear: had a couple of blood clots last year.

 

[Jasen Bruce]

Marco- Your fear is valid, as you know TRT can increase H&H however this can be monitored with due diligence if the need arises that you require TRT.

I am sure you have addressed this in other posts but the big question is "how do you feel?" You are literally right at the fence line so treatment might be based on A) Your symptomology B) Risk to benefit of raising your T a few hundred points.

This is where the good Docs like Crisler, Saya, or MCclain come in.

 

[Marco N Cognito]

Marco- Your fear is valid, as you know TRT can increase H&H however this can be monitored with due diligence if the need arises that you require TRT.

I am sure you have addressed this in other posts but the big question is "how do you feel?" You are literally right at the fence line so treatment might be based on A) Your symptomology B) Risk to benefit of raising your T a few hundred points.

This is where the good Docs like Crisler, Saya, or MCclain come in.

In addition to H&H, the risk is in raising E2 which is also a major trigger for thrombotic events. Again, yes, diligence and super-frequent monitoring.

My libido is good, but as my doc says, that's the last thing to go. I've had a scrip for it for months and my vial sitting on my desk staring at me. Obviously, the doc is much more confident than I am. The ultimate decision when to take the plunge rests with me. While there are a ton of issues that he and I both feel confident would resolve over time, the risks are still a concern. Definitely not a slam dunk like the guy with <500 TT.

 

[JSayaMD]

Yes, that level is the average over the last couple years. Already have tried every herb and supp under the sun to raise endo T for last few years. FT is really low, as it is being bound by SHBG (which is because of long-term T3-only thyroid med). Tried everything for that. No change. Also, E2 is almost non-existent. What's stopping me from doing TRT? My biggest fear: had a couple of blood clots last year.

Marco,

Hopefully your physician did a coagulopathy work-up on you (or referred you to a hematologist that did) following your blood clot episodes BEFORE giving you that script for testosterone.

Testosterone replacement, in some unfortunate men, can lead to the discovery of an underlying coagulopathy (like Factor V Leiden) after the fact...ie: after they develop a blood clot. This is not very common, but common enough to be worrisome especially with your history of clotting.

Dr Saya

 

[Marco N Cognito]

Marco,

Hopefully your physician did a coagulopathy work-up on you (or referred you to a hematologist that did) following your blood clot episodes BEFORE giving you that script for testosterone.

Testosterone replacement, in some unfortunate men, can lead to the discovery of an underlying coagulopathy (like Factor V Leiden) after the fact...ie: after they develop a blood clot. This is not very common, but common enough to be worrisome especially with your history of clotting.

Dr Saya

Thanks for chiming in, Dr. Saya.

We have run every coagulation test known and even some esoteric thrombosis panels (Labcorp and Esoterix). Am +/+ (homozygous carrier) for MTHFR C677T which can cause clots if homocysteine is elevated, but my HCY is consistently normal (average: 7.5) as I've addressed it with methylfolate, methylB12, etc.

I am also +/- (heterozygous carrier)for the PAI-1 gene which puts me at intermediate risk for thrombosis, but the hemo does not think this is clinically significant. We also ruled out all other genetic causes (am negative for FVL, protein C, S, APS, etc.) however, my FVIII, d-dimer and other acute phase reactors have remained elevated. Again, the hemo did not think these were clinically significant (which means to me, he doesn't know). I am now thinking there is an immune component (e.g. chronic infection) that is causing the hypercoagulable state. as I have some past exposure to pathogens that my immune system may not have resolved (low normal WBC/NK cells). My Lp(a) and CRP are also elevated. I have read that elevated Lp(a) can put one at risk for clotting s well. TRT helps bring Lp(a) and inflammation down.

So, at this point, we don't know have a cause.

In my research, the only documented risk factors with respect to clots lie in the management (or mismanagement) of E2 and prevention of polycythemia.

Some recent studies:
http://www.ncbi.nlm.nih.gov/pubmed/23925401
http://cat.sagepub.com/content/early...85154.abstract
"In 60 men on testosterone, 20 (33%) had high estradiol (E2 >42.6 pg/mL). When exogenous testosterone is aromatized to E2, and E2-induced thrombophilia is superimposed on thrombophilia-hypofibrinolysis, thrombosis occurs."

We all know that management of E2 and polycythemia is mandatory while on TRT, but how much of other factors could play into this equation???

These studies show that androgen deficiency can be a cause of low fibrinolysis and other elevated blood factors:
http://www.ncbi.nlm.nih.gov/pubmed/8844628
http://www.ncbi.nlm.nih.gov/pubmed/18591887

I am clearly deficient in free T and E2 and need treatment. Knowing this history is one of the major reasons I've been holding off with TRT. I would hate to go back on a thinner like coumadin just so I can do TRT. At this point, I actually need T to aromatize to E2.

Bottom line: Since T has both pro- and anti-thrombotic effects, my sense is that for those of us that have hypercoagulation issues, extreme vigilance need be implemented in the monitoring of E2, CBC, and follow-up blood factors.

When it comes to HRT, I have found hemos to be a waste of time. They automatically relegate it as a contraindication and know zip about it.

By the way, do you/Defy have access to injectable methylfolate (L-5-MTHF)?

 

[JSayaMD]

Marco,

You seem to be a very bright guy, also well-informed on the topic, which puts you way ahead of the game (and some - or all - of the medical providers you may have encountered thus far). As you mentioned, careful E and H/H management crucial for every patient, CRITICAL for you.

The acute phase reactants and your inflammation/chronic infection theory is worth investigating. Occult/chronic infections, abscesses, etc certainly could contribute. Common occult infection sites should be investigated (abdominal, DENTAL - often overlooked but very important and common source of chronic infection/inflammation - not to mention bacterial seeding of the blood --> bacterial seeding of the entire body!).

I will have Jasen get in touch with our pharmacies to look into the injectable methylfolate.

Dr Saya

 

[Marco N Cognito]

Marco,

You seem to be a very bright guy, also well-informed on the topic, which puts you way ahead of the game (and some - or all - of the medical providers you may have encountered thus far). As you mentioned, careful E and H/H management crucial for every patient, CRITICAL for you.

The acute phase reactants and your inflammation/chronic infection theory is worth investigating. Occult/chronic infections, abscesses, etc certainly could contribute. Common occult infection sites should be investigated (abdominal, DENTAL - often overlooked but very important and common source of chronic infection/inflammation - not to mention bacterial seeding of the blood --> bacterial seeding of the entire body!).

I will have Jasen get in touch with our pharmacies to look into the injectable methylfolate.

Dr Saya

The most well-known infections are borreliosis (Lyme), Mycoplasma, Chlamydia, and the herpes family virus (EBV, CMV, HHV-6). All the Lyme tests I've done show no sign of infection, but it is almost impossible to know for sure if you're infected unless you present symptoms (which I don't as far as I can tell). I show past (IgG) antibodies to all the herpes viruses, but again, no symptoms that I can tell, but it's possible if the titer is high enough, may support a dx of a chronic active infection. This battle goes back many years (I was on heparin for several months about 12 years ago) and I was never able to resolve whether I had an infection or not, yet the immune, inflammatory, and now, coagulation, indicators are ever present. I am digging deeper now. I have already looked into SIBO for gut issues and I am negative (take tons of probiotics).

Do you know what lab tests are available for bacterial infections caused from dental abscesses?

Thanks for looking into the methylfolate. My local compounding pharmacy tells me it's not available as it's too unstable to make into a sterile injectable.

 

[Jasen Bruce]

Marco- I looked into the methyl-folate injectable with the two main pharmacy suppliers, McKesson and PCCA. Neither provide any raw material for methyl-folate so it cannot be compounded into an injectable. Right now it appears that it is only available as an OTC 1mg capsule through PCCA. It is very cheap. There is also a high dosed 7.5mg Rx tablet available but it is very expensive. The cost for the pharmacy (not counting mark up) is over $100 for 90 tablets!

Pharmacies can compound injectable Folic Acid 5mg/ml X 10ml inexpensively.

 

[Marco N Cognito]

Marco- I looked into the methyl-folate injectable with the two main pharmacy suppliers, McKesson and PCCA. Neither provide any raw material for methyl-folate so it cannot be compounded into an injectable. Right now it appears that it is only available as an OTC 1mg capsule through PCCA. It is very cheap. There is also a high dosed 7.5mg Rx tablet available but it is very expensive. The cost for the pharmacy (not counting mark up) is over $100 for 90 tablets!

Pharmacies can compound injectable Folic Acid 5mg/ml X 10ml inexpensively.

Thanks for the heads up on the injectable. I figured this was the case. Since I cannot metabolize regular folic acid due to the methylation defect, methylfolate is the only option. I have been getting mine from various OTC mfgers.

 

[JSayaMD]

The most well-known infections are borreliosis (Lyme), Mycoplasma, Chlamydia, and the herpes family virus (EBV, CMV, HHV-6). All the Lyme tests I've done show no sign of infection, but it is almost impossible to know for sure if you're infected unless you present symptoms (which I don't as far as I can tell). I show past (IgG) antibodies to all the herpes viruses, but again, no symptoms that I can tell, but it's possible if the titer is high enough, may support a dx of a chronic active infection. This battle goes back many years (I was on heparin for several months about 12 years ago) and I was never able to resolve whether I had an infection or not, yet the immune, inflammatory, and now, coagulation, indicators are ever present. I am digging deeper now. I have already looked into SIBO for gut issues and I am negative (take tons of probiotics).

Do you know what lab tests are available for bacterial infections caused from dental abscesses?

Thanks for looking into the methylfolate. My local compounding pharmacy tells me it's not available as it's too unstable to make into a sterile injectable.

The definitive test to see if a dental infection/abscess is seeding your system with harmful bacteria would be a blood culture. However, a single blood culture cannot necessarily rule out infection, so often (in the hospital at least) 2 or 3 drawn at different times provides a fairly conclusive answer. If something is being seeded into your blood (from anywhere), it should grow in one of those cultures (however there is also a fairly high false positive rate due to contamination, so IF positive - a repeat confirmatory culture would probably be in store, while starting the appropriate antibiotics in the meantime of course, if indicated).

Another key part of the dental work-up is a thorough dental exam including imaging (x-rays) if not done recently.

Dr Saya

 

[Marco N Cognito]

The definitive test to see if a dental infection/abscess is seeding your system with harmful bacteria would be a blood culture. However, a single blood culture cannot necessarily rule out infection, so often (in the hospital at least) 2 or 3 drawn at different times provides a fairly conclusive answer. If something is being seeded into your blood (from anywhere), it should grow in one of those cultures (however there is also a fairly high false positive rate due to contamination, so IF positive - a repeat confirmatory culture would probably be in store, while starting the appropriate antibiotics in the meantime of course, if indicated).

Another key part of the dental work-up is a thorough dental exam including imaging (x-rays) if not done recently.

Dr Saya

Everyday, I am adding to the shopping list of possible causes to my clotting issues. The good news is that I learn more every day. The bad news is that it remains untreated until I have the confidence to move forward. In addition to the possibility of chronic infection, I have mild sleep apnea which I have yet to treat as well - and, as well know, can cause or exacerbate many of these issues, including thrombosis. Just in the last day, I have found an even more likely and dangerous culprit: elevated Lp(a) and BNP, both markers for CHD. My Lp(a) was up from 30 which is mildly elevated to over 100 in a matter of mos.

What's more is that I have discovered (again, thanks to 23andme) that I have an inherited susceptibility to CHD:
http://www.ncbi.nlm.nih.gov/pubmed/22508051

I have the G allele to this SNP (homozygous +/+).

Unfortunately, neither diet nor exercise has been found to lower Lp(a) levels. Not even statins can lower. High-dose vitamin C, niacin and fish oil, lysine, proline, and believe or not, TRT, are some of the only treatments to reduce Lp(a). So now, maybe the tables have turned and T may actually be an ally I need not fear. It is still a risk and I won't know until I try it:
http://www.healthcentral.com/cholesterol/c/42538/76023/lipoprotein/

Yes, Lp(a) could be the cause of my clots:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596719/
http://lpi.oregonstate.edu/fw12/lipoprotein.html

Likely that I will need to go on a hypotensive (BP med) and anticoagulant (blood thinner). The risk of an MI or TIA is too great. I have a scrip for HCTZ which is a diuretic that lowers BP, however I think it screws with aldosterone/renin which is already low. As I also have a mutationrenin-angiotensin-system, I may be better off with an ACE inhibitor: http://www.ncbi.nlm.nih.gov/pubmed/18347611?dopt=Abstract

I am thinking of having a modified Lipo-C injectable compounded with added proline, lysine, and ascorbic acid. hose three compound when mixed in a certain ratio, have been shown in research (Linus Pauling) to lower Lp(a). A sc route would be far more effective than oral, IMO.

Thoughts?