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Delayed secondary sexual development
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Delayed secondary sexual development

I am a 29 year old Caucasian male living in the UK. I am also a family physician, but given my relative lack of expertise in this particular area I wanted to post this problem to get the opinions of others including physicians.

For as long as I can recall, I have been bothered about the rate of my secondary development. This has had a fairly profound effect on me psychologically and, in all honestly, I'm not sure why I waited until now to ask about this.

My mother was not a late bloomer, my father may well have been given what he has said before (but he is not particularly forthcoming about these matters). I know that he certainly had developed normally by the time he was my age.

I probably got my first downy blonde pubic hair when I was about 14. By the time I left high-school, (17) I had only a very fine downy hair on my upper lip, and virtually no detectable axillary hair. I did not have hairy legs or arms. My height was average until mid-highschool; I then became a bit below average and have ended up at 5ft 8.5 inches. I suspect this is probably within the range to be expected from my father who is 5ft 10-ish and mother who is 5ft 3.5inches. My genital development, I believe, is probably normal too.

Througout University I hardly had to shave. I guess to make me feel more grown up, I tended to shave every few days with just a dry razor (not particularly good for my skin!) even though I could have gotten away without shaving. Even now, I really struggle to grow anything resembling a sideburn and the main concentration of my facial hair is on my upper lip and chin, with a very small sparse amount of it (both dark brown, similar to my pubic hair, and blonde) on my cheeks. This actually makes it sound much more than it truly is:- it is hardly visible except on close inspection. In the past 6 months I have developed a small amount (but definitely more than I had) of downy hair on my chest which starts blonde and some of which has become a little darker over time. Again, this is only visible on very close inspection.

I have become so bothered with my appearance that it was a real factor in my developing depression over the past few years. It has had a fair impact on my life with me avoiding dating/going to pool/beach/gym etc, and generally feeling inferior to other guys in my peer group who are developed. A number of people - strangers and less immediate family - have blurted out how young I look. My depression fortunately is much improved and is now stable over the past 12 months, but my physical development issues are still present.

I eventually decided the time had come to see my own family doctor and get some bloods done. The following are the results (bear in mind these are UK units/reference ranges in brackets):-

Renal function – normal

Liver function –
Alkaline phosphatase 126 IU/L (30-120)
Bilirubin – normal
AST – 74 IU/L (5-42)
ALT – 217 IU/L (5-60)

Cholesterol (total) 5.8 mmol/L (3.1-5.2)

Thyroid function – normal

Sex hormone profile -
FSH – 2.1 U/L (0.7 – 11.1)
LH – 2.6 U/L (1.3 – 70)
Prolactin – 220 microU/L (60 – 360)
Progesterone <2 (3 – 7)
Estradiol 218 pmol/L (0 – 206)
Testosterone 29.8 nmol/L (10 – 36)
SHBG 35.0 nmol/L (6 – 45)
Free Androgen Index 85.1% (36 – 156)

I have already had my liver function looked at, and given I don’t drink alcohol, it has been put down as hepatic steatosis. I am a little over-weight, but not obese, and my gastroenterologist thinks this is the reason for my deranged Liver function. My liver ultrasound was normal.

I am wondering if the raised estradiol levels could have any effect on delaying/counteracting my sexual development. I know it is marginal. Are the estradiol levels coming from my body fat; I can hardly believe this as there are plenty of males my age who are heavier and have still developed normally.

My family doctor has simply said the results were fine … end of story. I on the other hand think that I’d still like an answer to this problem. It gets extremely frustrating seeing others 10 or more years my junior who are more physically developed.

Does anyone have any experience of this, or wish to offer opinions on what I should do next/ how to take this further (given the fact that any secondary referrals have to go through my family doctor here in the UK). Am I over-reacting?

Cheers, in anticipation.
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43 Comments
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Hi,

I consulted my husband (MD from El Salvador) and he thinks you should have a MRI or CT scan performed for a possible tumor. As well as a kareotype test.
Also, perhaps when you were young you were exposed to a lot of X-Rays/Chemo or you suffer cryptorchidism?
He does not think you are overreacting and you should test yourself further to find out why the delay is there.

Hopet this helps.
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Thanks for your reply.

No, I wasn't exposed to any particular radiation/chemotherapy or other agents I can imagine would result in hypogonadism etc. Didn't suffer cryptorchidism either.

I also don't have any other particular symptoms of pituitary tumour. No visual disturbance, no anosmia.

Thanks for not thinking I'm over-reacting. The frustration lies in the fact that I've obviously gone into puberty etc but I feel it's never-ending!!
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Still keen to hear more opinions ...
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Any more thoughts?
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I can help you WDW, but i would first like to ask if you are a GP yourself? Where about are you based if you don't  mind me asking? For months now i have been getting illtreated by the UK NHS for adrenal fatigue, hypothyroidism and primary hypogonadism. I am very well versed in all of the above hormonal problems and know how to treat these conditions but i cannot gain acccess to blood testing labs in the UK due to ill-service by the NHS and falsely informed GP's.

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megazoide, any success with your treatment ? what symptoms did you experience in particular? what improvements have occured already? sorry about too many questions but would be much appreciated if you could answer them!
Thanks.
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Am a GP in Scotland. I am frustrated because my own GP doesn't perceive any problem with me. I don't know enough about this myself and have only limited people I can ask without feeling I'm telling colleagues my whole life story!

What's your story megazoid?
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WDW, If you don't mind me asking - where about in Scotland are you based (Your GP Practice)? I am from Scotland myself. If you would like to take this private, please look for me on "meso forums" (type this into google) and you will find me under the same name as here. I recieve a high percentage of emails and messages asking for advice and help, but i will keep a look out for your message. I am looking to change GP Practice and feel i could work better with someone like yourself who is both sharing similar conditions and willing to take an open-minded approuch and not blunder everything into being a mental health condition.

At present i am unable to get any form of treatment from the NHS including blood test's, so i was forced to self-medicate while working with an outstanding Dr in the states. So far, so good. To really optimize and get myself back to normal i need access to blood work so i can find the correct dosages for me. This isn't possible at present.

I developed low testosterone, adrenal fatigue and hypothyroidism from a testicular injury that occurred (development of large variococele). This lead to a rapid down fall in all hormones (testosterone, estridol, DHT and thyroid hormoens) and a stressful situation for my adrenals to deal with. Which eventually lead to low cortisol, elevated DHEA, low testosterone, low thyroid hormone and low estridol.
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Here is a breakdown (and opinion) on your situation:

If possible i would prefer to take this private or even better, speak on the phone. This isn't something that's easy to give comprehensive feedback on.

Being overweight put's you at greater risk of developing of female fat distribution. It can also lead to symptoms of hypothyroidism occuring due to down regulation of active thyroid hormone. For example Increased abdominal fat leads to higher levels of E2 which can directly effect the liver due to the increased aromitization that occurs when testosterone is converted. E2 (Estridol) is the female hormone. The more weight you carry the higher the levels of estridol (generally speaking). High E2 can lower DHT. DHT is the male hormone responsible for muscle gain/definition, hair distribution and secondary sexual development. It also has various roles on the brain which i am not going to go into here (would take too long to explain).

Looking over your results your testosterone is high yet your LH is low, a normal LH is 3.9+. The pituitary cannot tell the difference between estridol or testosterone, so if estridol is high, the pituitary gland is capable of down regulating and releasing less testicular stimulation hormone (LH). Most healthy men have a normal LH pulse that averages 3.9. LH is released every 15 minutes on average.

Another element of of this feedback loop is that elevated estridol counter-acting the effects of thyroid hormone. Estridol and thyroid hormone (T3) both fight for the same cell receptors and thus high estridol can over-power thyroid hormone and down regulate it's effects which stressess the body (which seeks an equilibrium) and can lead to weight gain. This is why high estridol leads to fat development, gynocostia and so fourth (feminzation).


Your results reflect this:

Cholesterol (total) 5.8 mmol/L (3.1-5.2) - Cholesterol is the 'building' block of all hormones, this values looks normal. Men that go on testosterone replacement theropy can develop very low cholesterol which is just as dangerous as high. Can you tell me more about your diet and weight distribution?

Thyroid function – normal: This isn't enough information. There is no such thing as normal, just standard deviation of a specific lab's patients. You need to test the following:

TSH
TRH
Total T3/T4
Free T3/T4

Thyroid releases T4, in the presence of liver problems, conversation between T4 to T3 may be disrupted. I would recommend the above tests be down to elevate the ratio of free T3/4.

Sex hormone profile -
FSH – 2.1 U/L (0.7 – 11.1) - This value is fine.Sperm production is normal.
LH – 2.6 U/L (1.3 – 70) - This should really be about 3.9, but this isn't abnormally low either.
Prolactin – 220 microU/L (60 – 360) - Seem's a little high, though prolactin can be elevated due to it's increase directly after sex (it down regulates testosterone). Vit B6 supplementation is useful here.

Progesterone <2 (3 – 7) - This seem's low. It would be wise to run a 4x Saliva test to elevalate adrenal function and check production of DHEA, progesterone, Cortisol, etc.

Estradiol 218 pmol/L (0 – 206) - This seem's very high. Estridol can lower DHT which can lead to feminzation occuring and reduction of male characteristics (hair growth, muscle development, etc), high estridol can also stress the adrenal glands over time which produce DHEA/Progesterone and cortisol. Cortisol is essential to the body as  it carrys the hormones to there destination (among other tasks). Various methods can be used to low estridol but i feel it's important to find out why it's so high in the first place.

Testosterone 29.8 nmol/L (10 – 36) - This reading is very high, which is a good sign.


SHBG 35.0 nmol/L (6 – 45) - This reading is normal. This suggests your body can 'cope' with a higher level of estridol, however this may cause down regulation of free testosterone and DHT.
Free Androgen Index 85.1% (36 – 156) - This isn't an accurate test, but it dosen't look too bad.

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Megazoid, thanks for your opinion, and the long reply (!). I am not based with one specific practice. I locum. I'm sorry that you aren't getting the access to bloods that you would like. That must be very frustrating. Unfortunately, apart from the fact that I do not have a specific practice, I think it would be unethical of me to say exactly in what locality I practice as it could well be construed as touting for business, though I appreciate you aren't meaning to put me in such a position.

My gut reaction is that I probably have some form of Constitutional delay, but frankly it is quite frustrating. I guess my development is progressing (have noticed this in the past few months) but it is quite slow.

(By the way, my TFTs  - I had the full results - show I'm euthyroid). And most of my excess body weight is centripetally distributed.. unfortunately ;-)
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Can you please post your full thyroid labs and i will take a closer inspection. Was your Free T3 at the top 1/3 of the range? If you're tsh was above 2.0, then sub-clinical hypothyrodism is possible. A perfect TSH is somewhere between 0.6 -> 1.0. Anything higher must be investigated for adrenal problems.

If your free t3 is at the bottom of the range, you will have a hard time shifting weight with the high estridol reading you have.

What would you recommend in my situation for getting blood work done on the NHS?
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Suggest you either ask GP for referral to endocrinologist, or if you don't feel you have a great relationship with your GP, suggest trying another GP either in the same Practice or a different one. You can use Choose and Book to choose which hospital/consultant within a certain locality to which you'd like referred i.e. doesn't have to be the absolute nearest hospital to you.
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Think I should just wait for a few months and see how things progress? I think people may think I'm over-reacting because things are developing but just at a slow slow pace.
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What confirmed you being euthyroid? I am assuming with your normal thyroid panel you also got Reverse T3 tested that confirmed this? I have read about this condition were there is apparently enough T3 but the actual tissue levels are low because T4 doesn't convert properly into T3

I want to get this and the 24 hour T3/T4 urine test because my TSH history this year is all over the place. It seems to be hypothyroidism and low adrenal reserve like Mega. The thing is I also have a 29 total testosterone level so I am wondering how everything will find "balance" with treatment. I am also paying out for full bloodwork. I failed an acth stim (increase of 12%) and had an "abnormal" tsh from the endo clinic along with saliva so have a decent understanding about my condition

I can say from personal experience now if you have messed up adrenals Isocort is a godsend; it is almost a euphoric feeling to be supplimenting what isn't getting produced. I felt the difference after day one. You also need cortisol for your thyroid hormones to get into your cells properly

The whole thing with E2 is a can of worms. It seems these feminizing hormones including Progesterone get out of control when there is any imbalance in the male body

Do you take Thyroxine or Armour? I would imagine you need direct T3 also with this condition with conversion/tissue uptake problems etc
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Have asked an Endocrinologist, and they think it is not necessary to check T3 but are more concerned with checking dihydrotestosterone.  I don't take any replacement hormones.
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I don't know why they are concerned about checking DHT with that total testosterone level you have. Its not like you are wanting to inhibit an essential sex hormone through medication or anything and you can't suppliment it.

The fact you have thyroid illness and don't know how long this has been manifesting may explain a lot about your high Estradiol and development issues. E2 competes with thyroid for cell receptor cites and like Mega pointed out - the pituitary can't tell the difference between this and bioavailable "free" testosterone.

When Cortisol is not being produced adequately the building materials are often used for other hormones on a divergent pathway. Looks like this may also be contributing to E2 - UK Endocrinologists would never talk to you like this because they don't check healthy adrenal function

This is your entire being effected with thyroid, it is more than a butterfly in the throat. Have you checked your basal body temperature upon awakening with a thermometer under your tongue?  If your temperature falls below 97.8F this is not good. I don't know with Euthyroid if you can run on a average-normal temp. Optimal is 98.6F  

With Euthyroid doesn't your body make too much RT3 at the expense of T3? And this isn't worth testing?

I would imagine being a GP yourself that you could arrange the 24 hour urine and Reverse T3 test if you wanted it. When I know something is wrong with me I want all the right tests doing

www.redappleclinic.co.uk - 24 hour saliva adrenal, thyroid and insulin panel. These post to Diagnos Techs in the states. I would be VERY intrigued to see your results
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Um, euthyroid means a normal thyroid function - neither hypo or hyper-thyroid. I don't have thyroid disease. And they recommended checking DHT to make sure I don't have a 5-alpha reductase deficiency.
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I apologise it seems sick euthyroid I was banging on about - I would still get the right tests done for thyroid function. A blood test can be meaningless as thyroid uk etc have proved

http://en.wikipedia.org/wiki/Euthyroid

The state of having normal thyroid gland function. Found in 40-70% of hospitalised elderly patients. Due to chronic/severe illness or surgery, there is a marked decrease in the liver conversion of T4 to T3. This is because of the reduced activity of Type 1 deiodinase. The condition is characterised by a low plasma T3 despite a normally functioning thyroid.

Examples of a nonfunctioning thyroid gland may be hypothyroidism or hyperthyroidism as opposed to euthyroidism, a functioning thyroid.

http://en.wikipedia.org/wiki/Euthyroid_sick_syndrome

Euthyroid sick syndrome is a thyroid hormone disorder where the levels of T3 and/or T4 are at unusual levels, but the thyroid gland does not appear to be dysfunctional.

Ill patients may have normal to low TSH depending on the spectrum of illness. Total T4 and T3 levels may be altered by binding protein abnormalities, and medications. Reverse T3 are generally increased signifying inhibition of normal Type 1 enzyme or reduced clearance of reverse T3. Measurement of free T4 and/or free T3 levels will be normal.
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Yeah, cheers, I have seen sick euthyroid. You can have some who is sick euthyroid who has abnormal results but clinically they aren't hypo/hyper. Just because of temporary concurrent illness.
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Dr Peatfield says if all tests are abnormal but the patient seems fine with sick euthyroid - that infact the patient does sooner or later become ill and will need treatment

What is more commonly seen is that all tests are normal but the patient is obviously ill. This may be called Euthyroid Hypometabolism. This is why I mentioned getting RT3 tested in my previous post because T4 doesn't convert properly into T3 and the tissue levels are infact low. This situation can occur with growth hormone deficiency, nutritional failures and low adrenal function

There is also Thyroid Hormone Resistance...

It is also intriguing how in the states any tsh over 2 is considered suspicious for primary hypothyroidism while here they just drop you anywhere in the range and most labs aren't very sensitive anyway. I am near 4 usually but have been more than double this in the Endocrine clinic with normal "frees" that my body can't use - of course I have to tell my GP all this and the only way to really get things done is go private

I find it interesting when Mega felt normal his tsh was 0.6 and is now 2.5 and I have had this reading once also. Again it is a terrible test in general
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hi everyone i was gonna post my own question about this same subject matter but i seen this post and im in the same situation. of course im a teenager. but iv been having trouble developing myself. im 16 and still have no body hair and my penis and testes are not fully grown. anyone know what could be wrong with me. what causes puberty to happen. hormones right. hey bud goodluck with your problem.
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Hi there

At 16 I wouldn't worry yourself about hormones just yet, you sound like a late developer and this is the case for many; especially being male. I know it isn't easy with peer pressure etc but you will probably have a raging sex life in the next year or so onwards when that testosterone spikes with everything else  

Take care mate
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i agree with the prevous poster that your E2 is out competing your testosterone. An aromatase inhibitor would not be out of the question for improved devlopment.
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An aromatase inhibitor? I don't think I've come across them.... any names offhand?
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Oops, googled it and realised I knew them by a different name!
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Please keep us updated on your progress with this; we are all going through hard times. I have HC and Armour at the ready just getting a sex hormone profile in blood although I know I have high total T. I know things will be off with other hormones but you want to see everything that is wrong with you first, its only right.

are you going to use Arimidex?
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Just to update you all, I have an appointment with an endocrinologist (finally!). I suspect I may still not get anywhere, but here's keeping my fingers crossed. Another little side-issue was that my ferritin was low for some reason; haven't quite worked out why that should be given I have a normal diet. I'm not clinically anaemic fortunately.
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As predicted, I didn't get anywhere with my appointment. Was told I probably have androgen receptor gene mutation. No trial of any treatment whatsoever. Great. Geez, have almost thought of buying testosterone off internet just for a trial, but since I have been told this may melt my liver due to my deranged liver function tests, I had better not. When does emotional distress become a big enough problem for someone to realise they have to  try something, even if it fails??
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My last testosterone is 9.3nmol/L (range 8.6 - 56). Now I don't know where I stand.
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My last testosterone is 9.3nmol/L (range 8.6 - 56). Now I don't know where I stand.
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"When does emotional distress become a big enough problem for someone to realise they have to  try something, even if it fails?? "

My problem is different to yours but I know exactly how you feel about just taking a gamble and hpoing for the best.  

Don't know anything about hormones but hopefully someone here will be able to give you some guidance.

Best of luck bud.
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Your liver funtion tests must be causing problems. Have you had a full MOT in bloodscreening tests for Coeliacs, lymes, systemic candida infection and the like? It must be frustrating not knowing what is causing that. Much of T4 and other hormones get converted in the liver as you will know so it could be worth looking into further investigation of whats causing them results

I know I mentioned this before but shbg looks elevated that can be the result of T4 not being converted and used effectively by the body that could again be attribued to your poor liver function. I don't know what to think on that score without knowing your thyroid results and if you have more than one tsh and free t4 result? With your LFT I think getting the active hormone free t3 tested could give a good account of things. They generally don't test for this to save the NHS money. Sad but true

What is happening with sex hormones now is anyones guess on your latest update but at least now you have a log of results to keep track of. I would keep an eye on the next main sex hormone Prolactin with such a contrast of results. Just because you aren't getting headaches or visual disturbances doesn't mean there may not be some sort of pituitary disorder going on.

I would get IGF-1 (Insulin-like growth factor) tested aswell

Suppliment some iron pills to get your Ferritin up and Zinc to control E2. I would check your B12 also for your next bloodwork
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Cheers guys, I am becoming a DIY doctor I have to say! I have organised to check GH, IGF-1, Coeliac screen, Ferritin, LFTs and thyroid autoantibodies on my next bloods (next week). Also I'm going to put in a semen sample to check fertility. My oestradiol is now normal (83). I am trying to reduce my weight (it's not absolutely horrendous) and remain basically teetotal. Am now somewhat concerned that because my last bloods were done in England (I went for a second opinion there) that the ones I next have will be done in the original lab that said my testosterone was normal. I know, I know, it sounds crazy, but it is going through my head that the results will be normal ... again. I would actually prefer it remains low-normal. How many times do they need to repeat these bloods to determine some treatment is merited!????
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My condition almost same as yours .
I'm 29 years old software professional , 60Kilograms,  BP,BIOCHEMISTRY, HAEMATOLOGY etc normal. I don't have secondary sexual characteristics developed.
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Sorry about the lab confusion, I know how horrible this is for people. It must be hard for you being a family physician dealing with such issues and your job also but now know firsthand how some of your patients feel solely depending on chemical testing

Some labs use different ranges and the last one that checked you is a huge range of "normal" compared to the first and it could simply be a laboratory error that you are at the lower end of the range they are using. It is clear you need testing again with that result.

http://nptech.co.uk/bloodtests.html - This is another option to see a very good snapshot of things. I think they will check Reverse t3 aswell if you contact them if not iwdl.net certainly will

Hope you get to the bottom of all this
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I would hope it wasn't simply lab error as I paid a small fortune for those bloods privately! But I am getting them retested. Just wish something would get done.
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I've asked for salivary and blood testing kits from the lab mentioned previously, and am awaiting these. My latest T was high and I just don't have any faith in the current tests. I am so frustrated by everything that if I feel apathetic to everything. I am so fed up with everything. So so so fed up with everything.
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Im sorry about to hear your frustrations man. i know little about the subject but have you considered being tested for Androgen Insensitivity Syndrome? Mild Androgen Insensitivity Syndrome (MAIS) to be more specific. i know 1 clinic that does that but its not cheap.. you probably have heard about it being a gp
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No I haven't heard of a particular clinic... could you enlighten me... I'd really appreciate it. I can't explain just how down I am about the whole subject. You'd think that (wrong as it may be) I would be more likely to get somewhere with diagnosis and treatment being a GP but it's just not happening, and the Consultants are just as patronising to me as they seem to be to all the other patients. Please let me know what clinic you are talking about Legend07. Cheers, man.
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have a look here man http://www.****.htm
its the 11th post. its a proper clinic.. but they charge £1500 for that test !
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Could you send me any references you have about the following statements you made in a forum post on Sep 19, 2007:

"Estridol and thyroid hormone (T3) both fight for the same cell receptors and thus high estridol can over-power thyroid hormone and down regulate it's effects which stressess the body (which seeks an equilibrium) and can lead to weight gain."
- and -
"high estridol can also stress the adrenal glands over time which produce DHEA/Progesterone and cortisol"

My Thyroid testing shows that my TSH is about at 15% of the "Normal" range, my FT4 is about + 8% from my TSH, (I've heard it should be within 20%), but my FT3 is +50% from my FT4 levels (also should be within 20%).  I have an ACTH Stim test and a 24-hour Cortisol Saliva test showing I have low cortisol levels, so that may explain the downregulation of the TSH level.  I also thought that low cortisol levels were blocking the T3 from binding and was causing the FT3 to be elevated because it wasn't being used quickly enough, but now based on your statements I'm thinking it might be something else.

As part of the 24-hour Cortisol Saliva test, they tested Estradiol (E2), Progesterone, and Testosterone (T), (aside from showing my low and "flattened" daily cortisol rhythm).  I know Saliva testing of these hormones may be off compared to blood work, but I assume that the patterns should be somewhat the same.  My E2 was 3 times higher than the top of the reference range (at 450% of range), and my T was low at -35% of the Normal range.  

I had blood work done a few weeks later. It showed my Total T (7%) and LH (0.3%) were low with an “undetectable” FSH, however it showed my IGF-1 (107%) high.  (Doc didn't check E2 for some reason...)  I also have labs from the baseline of my ACTH Stim test showing my Pregnenolone is low (-1% of range), and my DHEA(S) is high (135% of range). My morning ACTH (144%) was high, by my morning cortisol was only at 26% of range.

I think I've already found reference that states that E2 can have a negative feedback of the hypothalamus-pituitary-gonadal axis at the hypothalamus, (thus seriously inhibiting T production through my low LH and FSH), and that excess E2 can raise the GHRH level and thus probably the IGF-1.

If you can provide me with reference that state the effect of E2 on the binding of T3 and the effect of high E2 on the adrenals, then I think I have figured out exactly how my body is screwed up, and at least a place to start to adjust/treat.

I don't think I present any physical clinical symptoms of high E2 levels, (there are plenty of healthy 32-yr-old males who are 5'10" high and weigh 185 lb...), so I've got to really sell this to the Doc through logic and references. Any material that you could provide would be highly appreciated, and the more "reliable" the source the better.
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Update:

Well, six months down the line I have now lost 22lb and continue to go to the gym doing mainly cardiovascular stuff to get my fitness up. My secondary sexual characteristics are a little better than they were just six months ago. I notice a little smattering more of hair on my chest/tummy and face; not much but a little difference. Still not apparent unless looking hard. I still can't fill out side-burns. I am a little more confident in myself because of the weight loss but still have a long way to go. I still think it excessive to have to wait until 30 before I start feeling I am on a par with a 20-yr old maturity-wise.
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