TRT trying to find an answer in a complicated case

[chris_az]

(Undecended left testicle at birth, fused 1st and 2nd ribs at birth, prominent schmols nodes of spine noted at 16, primary Liver cancer at 17 with chemotherapy, primary bladder cancer at 25, osteochronditis of left elbow at 28, osteopenia of spine and thought to be hpogonadotropic hypogonadism at 29.)

I have developed pretty bad gynecomastia on TRT- I never really had much prior- I am due for an operation to remove it next month.


First Hormone pathology prior to TRT

Serum Testosterone only- 11nmol/l this equates to 317ng/dl.

Second pathology following one packet Androgel replacement for four days and androgel removal for four days. The reason for this is quite a complicated story.

LH 0.IU/L
Serum Testosterone 8.9nmol/l, " 257ng/dl

Third pathology off Androgel for 3 weeks

Dynamic tests from baseline after three weeks off TRT showed that LH could be stimulated and showed the Hypothalamus-Pituitary axis was intact.

Serum Testosterone 10.2nmol/l " 294ng/dl


General poor response to one packet of testogel. Increased subsequently to one and a half packets and then finally two the maximum of two packets.

All along I was subjectively very poor.

Pathology tests on two packets of Androgel.

LH 0.1IU/L
Serum Testosterone 29nmol/l " 836ng/dl
E2 129pmol/l, this equates to 37.2pg/ml
SHBG 13nmol/l

Pathology following a change to one packet of Androgel and 0.5mg Arimidex daily.

LH 3.4IU/l
Testosterone 16.3nmol/l
E2 44pmol/l " 12.7pg/ml
SHBG 15nmol/l

Because of continued failure on above treatments various permutations of treatment was tried with little success as detailed below.

one packet of Androgel and 0.25mg arimidex daily. One and a half packets of Androgel and two packets of androgel daily with 0.25mg daily.

Two packets of Androgel and 0.25mg of arimidex every two and three days respectively.

Androgel 5, 7.5 and 10g was then tried in combination with DIM with Indolplex at differing doses ranging from one tablet a day to a quarter a tablet a day with little to no success.

Taking half a dim a day with one and a half packets of Androgel I had the following pathology results;

LH 0.2IU/L
Serum Testosterone 18.2nmol/l " 525ng/dl
Free Testosterone 20.8pg/ml range 8.8-27
DHT 3.62nmol/l range given 0.5-3.7
E2 123pmol/l " 35.5pg/ml
IGF-1 38.48nmol/l range given 23-49
DHEA 6.6UMol/l range given 0.44-13.4
Cortisol 371nmol/l range given <536
SHBG 12nmol/l

I have also been tested for thyroid issues, TSH, Free T4, Free T3 and thyroid antibodies all came back not just normal, but well within the normal ranges.

Most recently I convinced my specialist to trial me on HCG at 500IU once every three days the pathology results for which are;

LH 0.4IU/L
Serum Testosterone 24.3nmol/l " 701ng/dl
E2 142pmol/l " 41pg/ml
SHBG 15nmol/l


The above indicates to me that I probably have hypogonadotropic hypogonadism/secondary hypogonadism.

Despite the fact that HCG worked in increasing my testosterone levels I felt awful- no doubt in due to the E2 level particularly given my low SHBG level which will result in a much higher level of free E2 than is typically seen.

I subsequently was off all treatment for three weeks to obtain a baseline levels.

LH 3.4IU/L
Serum Testosterone 13.2nmol " 381ng/dl
Estradiol 130pmol " 37.5pg/ml

A higher dose of HCG of 1000IU was tried twice a week without success. I tried this because of the consultants recommendation but felt it would fail due to even higher conversion to E2.

It was a failure and subjectively I felt that the symptoms pointed to high E2.

I have in the past tried DHT gel Andractim.

Various doses were tried with little to no success. The thought was that because it is non aromatizable it may work better for me, but it made me feel very tired. Probably because the negative feedback would have reduced testosterone which itself is required for stamina.

Out of interest I have also had genetic tests that showed a typical male phenotype, though I am the carrier for two conditions Hemochromatosis with H63D and antitrypsin deficiency PIMZ.

I do have a history of liver problems having had two thirds of it removed in 1991, however according to liver function tests and CT scans the liver is working fine, though I do wonder if that is also a factor for me given that the liver is responsible for estrogen metabolization.


So no form of TRT has worked for me thus far except Androgel for the first four days that I took it where I felt like I did when I was a teenager.

I will consider all forms of TRT to see what works if it can be prescribed.

I have tried to obtain testosterone I.M, to try that, but due to the prescribing guidelines in the UK, this can only be prescribed via three weekly cycles and I am NOT doing that because it is an exercise in futility.

Before I ever started TRT I felt much better than I ever have on it apart from the magic first four days. Whenever I have tried to come off TRT I have felt much worse even after a month, so it feels like I have reached a point of no return and that the only answer must be found in finding an appropriate treatment regime.

The other reason coming off TRT would seem to be a bad idea is the osteo conditions that I have developed with low T over the years.

P.S

This is an awful lot for anyone to take in let alone sort the wheat from the chaff.

I have an appointment with a geneticist in about six months time, perhaps something will come of that?

All responses are appreciated/thoughts are appreciated irrespective of their nature.

Chris

 

[SPE]

Hmmm...

Doesn't seem to me that your problems are related to T or E. With many of the above protocals and your results in T and E, many men would be happy. I really don't know why you were put on arimidex either as your e2 never got out of range. The HCG dosage you were put on was probably too high, SWALE recommends only 500iu/week when accompanied by T replacement. Other than that, I don't know...

 

[MANWHORE]

Doesn't seem to me that your problems are related to T or E. With many of the above protocals and your results in T and E, many men would be happy. I really don't know why you were put on arimidex either as your e2 never got out of range. The HCG dosage you were put on was probably too high, SWALE recommends only 500iu/week when accompanied by T replacement. Other than that, I don't know...

You read all that? Damn,it's good to have people like you here because even thought i would like to help him my attention span isn't that great. I got to the second paragraph and had to take a sip of beer.

 

[chris_az]

SPE,

As I explained I developed quite bad gynecomastia on TRT, so I believe it very much MUST be associated with my hormonal balance. I am fairly sure of this because I have studied the aetiology of gynecomastia.

It is of note that my SHBG is out of range off the bottom of the normal scale and this will lead to a much higher level of free E2, which like free T maybe crucial.

Also are you saying that 130pmol/l is not high for serum E2?

According to Schering the distributers of Androgel in Europe top of the normal male range for serum E2 should be 75pmol/l.

My case may not be typical- granted, but I am not remotely convinced that my issues are caused by anything other than hormonal factors with a possible liver complication (excess E2 is metabolized by the liver).

Before I took TRT I felt better than I do now and I didn't have gynecomastia. The issues coincide with commencment of TRT, but like I said I have tried coming off TRT and it simply didn't work.

Remember above all the development of significant gynecomastia.

The bloods may not point obviously to excess E2 but the body does and the body does not lie.

On the note of bloods;

I have read papers that state that estrone Sulphate may be a better indicator of estrogen status in the male because of its half life in comparison to E2 and because of the methodology that is employed in many assays where equipement is most often callibrated around female reference values.

Anyway the last point is conjecture.

I thank you for having taken the time to read my post and respond.

I am at a loss as to how I can rectify my problems and instigate a protocol which will work....If I think you are wrong it only means I think we are both at a loss..............

 

[SPE]

Depends on Lab

I've usually seen labs that say e2 should be <54. So, when you wrote "E2 129pmol/l, this equates to 37.2pg/ml", I was thinking it was 37.2, which would be normal. Having gyno isn't always attributed to e2. High progesterone has been known to do the same.

 

[chris_az]

Regarding progesterone, form my understanding and the reading of almost every single gynecomastia paper from the last 20years, progesterone is not mentioned as being a causative factor.

In fact from what I have read if progesterone is low, this can have an adverse effect and lead to estrogen dominence.

That said it is always possible to learn more and you may know something I do not, like I said I have read most of the papers on gynecomastia but not all of them.....I'm only about 98% geek

Like I said SPE thanks for taking the time to look through such a convoluted thread.

My thinking is that because I also have a poor response to Testosterone that this is E2 related.

What I didn't say but should have, was that prior to TRT I always awoke with a morning erection and this now never happens.

That to my mind is an indicator of an E2 issue.


Any/all knowledge that I have points me in a direction as to the cause, but it does not provide me with an answer to my problems or a treatment to rectify them.

Which as you can imagine is frustrating after 2years particularly when I feel ill most of the time.

 

[Random987]

After reading your post, before I got to your Test Cyp restrictions, I was saying to myself, "try test cyp". Is there anyway you can bend the rules by self administering the does? For example, if you can get 300mg of Test Cyp every 3 weeks, can you just give youself 100mg every week? Some people have a better response to test cyp than gels.

 

[SPE]

Free Test

Also, looking at your free test reading it looks to be in the upper 1/2. This is good. I don't think free e2 would necessarily be high if free t is in the middle, do you? Also, below is a study that shows letrozole(an AI, similar to arimidex) given to men DECREASED free E2.



J Clin Endocrinol Metab. 2005 Jul 26; [Epub ahead of print] Related Articles, Links


Comparative Assessment in Young and Elderly Men of the Gonadotropin Response to Aromatase Inhibition.

T'sjoen GG, Giagulli VA, Delva H, Crabbe P, De Bacquer D, Kaufman JM.

Department of Endocrinology, Ghent University Hospital, Belgium (G.T., H.D., P.C., J.M.K.), Department of Public Health, Ghent University, Ghent, Belgium (D.D.B.) and Internal Medicine Sub. Endocrinology Ospedale Putignano-Noci (Bari), Italy (V.A.G.).

1. Context: Aging in men is associated with a decline in serum testosterone (T) levels. 2. Objective: To assess whether decreased T in aging might result from increased estradiol (E2) negative feedback on gonadotropin secretion. 3. Design: Comparative intervention study (2004) 4. Setting: Outpatient Endocrinology Clinic, Ghent University Hospital 5. Participants: Healthy young and elderly men (n = 10 vs. 10) 6. Interventions: placebo and letrozole (2.5 mg/day) 28 days, separated by 2 weeks washout. 7. Main Outcome Measures: Change of serum levels of (Free) E2, LH and FSH, (Free) T, SHBG and gonadotropins response to an i.v. 2.5 microg GnRH bolus. 8. Results: As assessed after 28 days of treatment letrozole lowered E2 by 46% in the young (P = 0.002) and 62% in the elderly men (P < 0.001). In both age groups letrozole, but not placebo, significantly increased LH levels (339 and 323% in the young and the elderly, respectively) and T (146% and 99%, respectively) (P young vs. elderly = NS). Under letrozole, peak LH response to GnRH was 152% and 52% increase from baseline in young and older men, respectively (P = 0.01). 9. Conclusions: Aromatase inhibition markedly increased basal LH and T levels and the LH response to GnRH in both young and elderly men. The observation of similar to greater LH responses in the young compared with the elderly does not support the hypothesis that increased restraining of LH secretion by endogenous estrogens is instrumental in age-related decline of Leydig cell function.

PMID: 16046582 [PubMed - as supplied by publisher]

 

[chris_az]

Hi Random,

Unfortunately if I.M is prescribed it is held and administered by the gp which rules out self admin.

I would consider self admin if this were not the case.

Certainly given my condition I would not consider self admin abuse, however
I would not be comfortable with obtaining it through an illegal source, as I would be too concerned about the possibility of ending up with one bad batch and the potential ramifications of such.

SPE,

Quote
Also, looking at your free test reading it looks to be in the upper 1/2. This is good. I don't think free e2 would necessarily be high if free t is in the middle, do you?
Unquote

I don't know and I don't think any of us know if this can or does happen from a biochemical point of view, so we can only speculate.

However what I do know is that I have been constantly developing gynecomastia and THE number 1 cause and in fact the only underlying cause of this irrespective of the exact nature of the mechanism (drugs, thyroid, liver etc) is a poor androgen to estrogen ratio.

I am utterly convinced that the problems relate to E2 at least until evidence or a more plausable explanation is brought forward.

If my liver is not dealing well with E2, it is possible that a small amount of the hormone could cause problems....but then we are still referring to an E2 issue.

I have tried arimidex and DIM and differing TRT with the protocols above with little success.

The hard questions are where do I go from here?

What is likely to work?


I don't expect anyone to necessarily have or give me the answers, I certainly don't have the answers despite educating myself on these matters for some considerable time and reading the Shippen book, both Carruthers books, thousands of Medline articles and seeing many different endocrinologists.


Complicated eh?

 

[pmgamer18]

First I want to say you sure have been through the shit in you life. How do you get though this.

To me your Dr.'s did not give the gels enough time to work.___Second pathology following one packet Androgel replacement for four days and androgel removal for four days. The reason for this is quite a complicated story.
One needs to stay on it for some time to get the body up to speed. You never gave it any time. When you were on the Two packets how long did you take this. It is a know fact that most men starting on the gels will not make there own T after a short time and start to feel worse then they did before they started on TRT. It takes at least 6 months to a year to get leveled off on T. First you go on it then when you levels come up it takes time for you body to repair the damage that was done from having low T. Your E2 should have been tested first before going on TRT most times if a man is tested doing the right tests. If his test shows him to be low on T and high on E2 if you treat the high E2 the T levels will come up 200 to 300 point on a USA test. And the man would not need to go on TRT. Your Dr. had you on a merry go round here trying a lot of bad things before even testing your E2.

So now that the Dr.'s did it all wrong what can you do now I am not a Dr. and don't know what to tell you.
You seem to have done a good job on the research.

What are you on now.
I have been on TRT for over 21 yrs. and never felt good because my Dr.'s did not know about high E2 in men. Last yr. when I had it tested I was very high now the Gels don't work for me they drive up my E2 and I get sore joints and muscles on them. I am now doing 150 mgs. of Depo T shots every week and doing Hcg 500 IU's 3 times a week this is the best I have ever felt on TRT in the whole 21 yrs. on TRT. As long as I keep Taking the Indolplex/DIM with TMG to keep my E2 in check at 61 I have morning wood every morning I have not had then in over 35 yrs.
Phil
Phil

 

[chris_az]

Hi Phil,

Getting through stuff- no alternative option.

Yes there were many errors made very early on in obtaining a diagnosis and there have also been significant problems in trying to adjust to certain protocols given the restrictions this side of the Atlantic.

Unfortunately the reality is you only start to truly educate yourself because things go wrong, not because of successes.

They say that necessity is the mother of invention, education to it would seem.

I never had to understand chemotherapy or any other procedure that related to the cancers. I felt confident in the medical treatment and knew that there was an enormous level of research and money that went into reaching the conclusions that said my treatment was the best out there.

Not so here, we are on the fringes of medical science, the amount of research is pifflingly small, as is the money that has gone into it. We are 20years behind womens health and I feel as though we the patients are on the cutting edge of medical knowledge along with the few doctors who have any understanding of this condition.

I am a very reluctant researcher- I wished I had not had to do this, but with everyone else seeming to be incompetently managing my health, well I though if anyone was going to mange it incompetently, I might as well play a part No seriously I though I have to try and understand what is going on to a very high laymans level in order to seek out the best people to help me.

Unfortunately the rewards have not been forthcoming.


I was on Testogel for over a year at differing doses so it was given ample time IMHO.


I should also say I get the sore joints as well, quite bad. Interestingly although I have developed osteo conditions as a result of long term low T, I didnt suffer from joint pain too much until I went on TRT.

 

[pmgamer18]

It is to bad you can't try shots every week my joints and muscles are rebuilding as we speak. I was told the same thing now I feel the gels stopped my Testis from making the T that they did and the Gels did not get the to into my joints and muscles so they broke down.
Phil

 

[BigRagu]

all i got to say is DAM.... i'm also had cancer (no chemo or rad or lymphs taken out....)........ but now i know just how lucky i am........ i'm really sorry u had to go through off of that........

as for your treatment i think your doctors never gave it a chance for the gels to work......u should be tested to see how they are working 2 weeks after starting......... if the gels dont work for u then i would go to test shots..... androgel really didn;'t work well for me and was a pain to use so i went to test shots......... WAY better then the androgel and i just get my mom to give them to me................ if your not scared to shoot just do it yourself in the quad............

 

[chris_az]

The problem being is that in the UK we cannot get I.M shots weekly as it is against prescribing guidelines.

If I go and pay for a private doc as opposed to use our health care system (which is crap by the way) the doc will not prescribe for fear of being censored by the GMC- General Medical Council.

The only I.M injections I could get would be Sustan every three weeks- which is a sick joke because it causes E2 problems being an ancient and worthless protocol.

It is really crazy- you know I could probably at a push get them to prescribe 250mg every two weeks, but I couldn't get them to prescribe less testosterone at 100mg weekly, I know because I have tried.

It is absurd, the state/government is sticking its head into businesses that does not darn well concern it to my and other peoples detriment.

 

[HeadDoc]

just like to suggest a slightly different view. With some much of your lliver removed, there may be hormonal isomers and metabolites that are not clearing your system. Take a look at the following site and see if any of the analyses may be of use to you and your doctors.

http://www.pgxlab.com/

 

[ASaxon]

I was under the impression that the liver regenerates itself after partial removal. Live liver donors have half their livers taken out and they grow back to full size within two or three years I believe. Wouldnt that mean that Chris liver has likely grown back to normal size and function?

 

[ASaxon]

Oh, I just reread your post Chris. You have Hemochromatosis so perhaps thats what could contribute to lower liver function if you have it. I assume that you are being treated for that so hopefully that is going well and your liver isnt as much of an issue.

 

[SPE]

Check this site out Chris. Goes over gyno and the hormones involved.

http://www.endotext.org/male/male14/male14.htm

 

[chris_az]

Scott,

I don't have hemochromatosis, but I am a carrier for it. The mutated gene I carry is H63D, the condition is largely caused by c282y. But if I had a child and my wife was also H63D or was C282y then the child would have two copies of rogue genes and would be H63D/H63D or H63D/C282y and would be likely to have the condition which can cause endocrine problems and in fact hypogonadism.

So I happen to just carry the condition, nothing more it would seem.

I also have another liver condition called antitrypsin deficiency, but I have the mild form of the condition being PIMZ phenotype.

These factors are not supposed to have an impact/baring on my condition.

In terms of liver regeneration you are correct to a certain degree.

The liver does regenerate, however it is pie in the sky when doctors talk about full regeneration, it does not happen or at least it does not happen when you take two thirds of it out which includes one lobe via a partial hepatectomy.

My liver is much smaller than your typical liver as explained by the radiographers I have seen over the years that have performed the CT scans.

The only biochemical test of what is going on that I have received is the basic liver function test and I have little faith in liver function tests, because when I had several tumors in my liver one the size of a melon, the liver function tests came back normal. And my girlfriend is a nurse who has worked with the elderly and she has noticed that sometimes patients have died due to liver disease where they too had normal liver function test results.

My liver shows up A-OK on liver function tests and Ok on CT scans- if small.

The problem is here is that the liver is so complex that saying it is fine is easier said than done, after the brain it is the most complicated organ in the human body and performs over five hundred different tasks.

If it performs one like E2 clearance badly who is to notice, is it likely to be picked up on a liver function test?

I doubt it.


Whether the trauma and the fact that only one part of the liver remains (though now enlarged) is causing problems or not is hard for anyone to say. My liver may not be a factor at all.who knows?

The prior problems with the liver may be one more dead end and not the issue...or maybe it is the issue...complications who need them eh?

HeadDoc,

Only just noticed your post, yes this is something I have been thinking about estrogen metabolization and the clearance of hormones.

It is one of the culprits in my 'whodunit and gone knackered up my TRT investigation'.

I'll check out the link.

A lot of the time here I may seem like I am asking for an answer and then kicking up dirt when one is offered. Honestly this is not the case, it is just I have ran the possibles through my mind on so many occasions and applied so much thought and research into what may be going wrong and what maybe the answer, that a lot of issues have been covered and recovered a thousand times.

I really appreciate the time and effort people have taken here I really do!!!!

Maybe something will arise here or in the mind of a doctor one of these days, or perhaps Ill hit upon a piece of information or have a eureka moment sat in the bath or taking a crap.who knows?

I am desperate to feel well, not develop gynecomastia after my op next month, to get a libido back that is non existent and above all to not feel so exhausted all the time.

I am tired of being at a loss and tired of being so ill and the specialists I have seen are tired of my questions, which I loath myself and tired of me.

Specialist often like people who validate their abilities, people who they can treat with success and who by extension show them that they are good at there job. Not people like me who remind them that they are not as knowledgeable or as successful as they would like to think.

It has got to the point with many of the specialist that I see that they think because they have not found an answer, that it must be in my mind.

Quite how gynecomastia, a lack of morning erections and being drenched in sweat (which my girlfriend can attest to) after having sex for about a minute could be psychological as opposed to physiological is beyond me.

Of course it is the cop-out of all cop-outs to blame the patient isnt it.very convenient when you cannot find the answers- to say there are no answers to find.

If only I had the good grace to be a simple case, Im just not playing fair am I?


P.S

With everything so complicated it is easy to ask well is any of this to do with TRT and the hormone problem?

Well I only started to develop the gynecomastia and lose the libido and become badly fatigued after a short period of time after going on TRT so that tell me it is hormone/liver related.

If you read all this I question your sanity

 

[HeadDoc]

Chris AZ , for all that you've suffered your attitude is remarkably positive and optimistic. You've shown no frustration with anyone here who's tried to propose a solution or raise a question. This forum is seeing an increased number of hypogonadal anomalies. It will be of no use to anyone if either the posters or responders critique the deseased instead of the desease. So if you need some cyber space to blow off some steam at the desease, you've found he place. Many of us here do not represent such complicated cases and have been well treated for our problem. We only come back to help the rest along. I guess, in all humility, it is likewize frustrating for us that what has worked for us in not working for everyone. Frankly, my own learning grows with your presentations and others like yourself. Where else could nonmedical persons like ourselves participate in HYPOGONADISM GRAND ROUNDS.