First post. Can’t get E2 under control, starting to worry

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Charliebizz

Well-Known Member
There are some tissues that are carefully regulating their local levels of DHT. Emphasis on SOME. It's silly to think high levels of DHT in serum universally have no effect. Take proviron for example. Look at all the subjective effects proviron has on men, both positive and negative. That's the power of DHT floating around in serum. Does it have effects? You bet it does! Serum DHT is anything but a meaningless number.
I get what your saying but. I had mid range dht on injections. And have sky high dht on cream. Shouldn’t I be getting some sort of “negative” side effect ?
 

FunkOdyssey

Seeker of Wisdom
I get what your saying but. I had mid range dht on injections. And have sky high dht on cream. Shouldn’t I be getting some sort of “negative” side effect ?
Not necessarily, because everyone has individual reactions. You might take proviron and all you get is the increased libido, drive, mood, and confidence. You may not get the acne or whatever else.

I think the nugget of truth in the "serum DHT doesn't matter" position is that most of the tissues where excessive DHT would cause negative side effects are those where levels are being tightly regulated. In other tissues where increased serum DHT can make more of an impact, it has mostly positive effects, such as the brain, muscle, bone, etc.
 

BigTex

Well-Known Member
I think this study supports what @RobRoy was saying in the discussion with the dermatologists via video;


Abstract​

Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels are an important stimulus for androgenic action in target tissues (e.g., prostate). Yet evidence from clinical studies indicates that intracellular concentrations of androgens (particularly in androgen-sensitive tissues) are essentially independent of circulating levels. To assess the clinical significance of modest elevations in serum DHT and the DHT/testosterone (T) ratio observed in response to common T replacement therapy, a comprehensive review of the published literature was performed to identify relevant data. Although the primary focus of this review is about DHT in men, we also provide a brief overview of DHT in women. The available published data are limited by the lack of large, well-controlled studies of long duration that are sufficiently powered to expose subtle safety signals. Nonetheless, the preponderance of available clinical data indicates that modest elevations in circulating levels of DHT in response to androgen therapy should not be of concern in clinical practice. Elevated DHT has not been associated with increased risk of prostate disease (e.g., cancer or benign hyperplasia) nor does it appear to have any systemic effects on cardiovascular disease safety parameters (including increased risk of polycythemia) beyond those commonly observed with available T preparations. Well-controlled, long-term studies of transdermal DHT preparations have failed to identify safety signals unique to markedly elevated circulating DHT concentrations or signals materially different from T.

Circulating levels of DHT in response to testosterone replacement therapy (TRT) do not correlate with those found in androgen sensitive tissue due to homeostatic control of intracellular DHT.
 

FunkOdyssey

Seeker of Wisdom
I think this study supports what @RobRoy was saying in the discussion with the dermatologists via video;


Abstract​

Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels are an important stimulus for androgenic action in target tissues (e.g., prostate). Yet evidence from clinical studies indicates that intracellular concentrations of androgens (particularly in androgen-sensitive tissues) are essentially independent of circulating levels. To assess the clinical significance of modest elevations in serum DHT and the DHT/testosterone (T) ratio observed in response to common T replacement therapy, a comprehensive review of the published literature was performed to identify relevant data. Although the primary focus of this review is about DHT in men, we also provide a brief overview of DHT in women. The available published data are limited by the lack of large, well-controlled studies of long duration that are sufficiently powered to expose subtle safety signals. Nonetheless, the preponderance of available clinical data indicates that modest elevations in circulating levels of DHT in response to androgen therapy should not be of concern in clinical practice. Elevated DHT has not been associated with increased risk of prostate disease (e.g., cancer or benign hyperplasia) nor does it appear to have any systemic effects on cardiovascular disease safety parameters (including increased risk of polycythemia) beyond those commonly observed with available T preparations. Well-controlled, long-term studies of transdermal DHT preparations have failed to identify safety signals unique to markedly elevated circulating DHT concentrations or signals materially different from T.

Circulating levels of DHT in response to testosterone replacement therapy (TRT) do not correlate with those found in androgen sensitive tissue due to homeostatic control of intracellular DHT.
That study does support the safety of elevated serum DHT in general and the lack of an effect in certain tissues. I accept that completely. I just take issue with extrapolating from there to say elevated serum DHT has no effects whatsoever. Again, if this were true, proviron would not exist as a product and it would not do anything when you take it. I've used it personally and I can assure you it has a long list of noticeable effects. I still have hair to this day in a bunch of places that never had hair before.

For a cream-specific example, just consider all the different effects people report with cream vs. injections. People will often report more libido, more assertiveness or aggression, feeling sharper or more stimulated (sometimes excessively to the point of feeling tense or edgy), with better erection quality versus similar T levels on injections. What's going on there? I'd call it elevated serum DHT doing DHT things.
 

Mastodont

Active Member
Hmm, what stance does dr nichols and tot-supra-or-none crowd have on dht since they are cream guys, they advocate getting e2 high for benefits but have they mentioned anything on dht long term, at least Jay and Keith have transparent hairstyles. @Charliebizz are you noticing any hair loss on cream?
 

Nik

Member
I honestly think most of us posting agree much more than we disagree. Understandably it seems that many in our medical profession, most especially these T clinics make it easy on themselves by applying the cookie cutter T fix on every client that walks in their doors. Most likely this is why so many men come here unhappy and looking for answers.

I see quite a few good things on some of the UK sites, like this:

big tex I have seen several of your answers and I see that it is with undecanoate, in my country it is called nebido and it only comes in 4ml ampoules, can I know what the presentation you use is? how to maintain and divide the doses.
 

BigTex

Well-Known Member
big tex I have seen several of your answers and I see that it is with undecanoate, in my country it is called nebido and it only comes in 4ml ampoules, can I know what the presentation you use is? how to maintain and divide the doses.
Ok.....I have used the European Nebido suggested (1000mg/90 d IM) dose and the American Aveed dosing of 750mg (750 mg) injected intramuscularly, followed by 750 mg injected after 4 weeks, then 3 mL (750 mg) injected every 10 weeks thereafter. I took the European dose of 1000mg and did the math coming up with 55mg every 5 days to microdose SUB-Q. It takes about ~14 weeks to peak, after that the dose is very stable. I just went up in the last few weeks to 60mg every 5 days. I don't know of any doctor doing this type of protocol but it is working well with me so far.
 

Nik

Member
Ok... He usado la dosis sugerida de Nebido europeo (1000 mg/90 días IM) y la dosis de Aveed estadounidense de 750 mg (750 mg) inyectada por vía intramuscular, seguida de 750 mg inyectados después de 4 semanas, luego 3 ml (750 mg). ) inyectado cada 10 semanas a partir de entonces. Tomé la dosis europea de 1000 mg e hice los cálculos y obtuve 55 mg cada 5 días para microdosificar SUB-Q. Se necesitan aproximadamente 14 semanas para alcanzar su punto máximo; después, la dosis es muy estable. En las últimas semanas subí a 60 mg cada 5 días. No conozco a ningún médico que haga este tipo de protocolo, pero hasta ahora me está funcionando bien.

Ok.....I have used the European Nebido suggested (1000mg/90 d IM) dose and the American Aveed dosing of 750mg (750 mg) injected intramuscularly, followed by 750 mg injected after 4 weeks, then 3 mL (750 mg) injected every 10 weeks thereafter. I took the European dose of 1000mg and did the math coming up with 55mg every 5 days to microdose SUB-Q. It takes about ~14 weeks to peak, after that the dose is very stable. I just went up in the last few weeks to 60mg every 5 days. I don't know of any doctor doing this type of protocol but it is working well with me so far.
I appreciate your response, now its presentation is in a vial or in an ampoule since to microdose it would be if it is in an ampoule to be able to preserve the rest in some way.
 

Charliebizz

Well-Known Member
Hmm, what stance does dr nichols and tot-supra-or-none crowd have on dht since they are cream guys, they advocate getting e2 high for benefits but have they mentioned anything on dht long term, at least Jay and Keith have transparent hairstyles. @Charliebizz are you noticing any hair loss on cream?
Mine is opposite. I was getting thinner and thinner with my low t. And since trt in general. (First injections now cream) my hair thinning has not progressed whatsoever.
 

BigTex

Well-Known Member
I appreciate your response, now its presentation is in a vial or in an ampoule since to microdose it would be if it is in an ampoule to be able to preserve the rest in some way.
I get mine in a 10ml vial. You could pre-load syringes.
 

Cataceous

Super Moderator
...
How do you know how much enclomiphene and gnrh are not contributing to your total testosterone? Measured with only the blend?
Going by the hypothesis that free testosterone is proportional to the testosterone dose rate, I determined the constant of proportionality when I had relatively unchanging levels on EOD enanthate. With the ability to predict the response to any dose, I found that the use of hCG or ENC/GnRH did not lead to a noticeable increase in serum testosterone. This puts me at the less responsive end of the spectrum, as there are anecdotal reports of significant boosts when adding hCG to TRT.
 

jmbb

Member
Going by the hypothesis that free testosterone is proportional to the testosterone dose rate, I determined the constant of proportionality when I had relatively unchanging levels on EOD enanthate. With the ability to predict the response to any dose, I found that the use of hCG or ENC/GnRH did not lead to a noticeable increase in serum testosterone. This puts me at the less responsive end of the spectrum, as there are anecdotal reports of significant boosts when adding hCG to TRT.
I would imagine it probably has to do with whether one was primary/secondary hypo as well when they started?

When I added in 500iu of HCG twice per week, my trough level on my protocol at the time increased from 950 to 1265, and E2 from 34 to 66 with no other changes. I'm pretty sensitive to it, I can go years without using it and within 2 shots I have a drastic difference in testicular size.
 

RobRoy

Active Member
Hmm, what stance does dr nichols and tot-supra-or-none crowd have on dht since they are cream guys, they advocate getting e2 high for benefits but have they mentioned anything on dht long term, at least Jay and Keith have transparent hairstyles. @Charliebizz are you noticing any hair loss on cream?
There's a new video out on TRT and hormone optimization concerning high DHT levels from testosterone cream
 

RobRoy

Active Member
That study does support the safety of elevated serum DHT in general and the lack of an effect in certain tissues. I accept that completely. I just take issue with extrapolating from there to say elevated serum DHT has no effects whatsoever. Again, if this were true, proviron would not exist as a product and it would not do anything when you take it. I've used it personally and I can assure you it has a long list of noticeable effects. I still have hair to this day in a bunch of places that never had hair before.

For a cream-specific example, just consider all the different effects people report with cream vs. injections. People will often report more libido, more assertiveness or aggression, feeling sharper or more stimulated (sometimes excessively to the point of feeling tense or edgy), with better erection quality versus similar T levels on injections. What's going on there? I'd call it elevated serum DHT doing DHT things.
It's because the cream will raise free testosterone levels better than injections for any given total in the same man. It's the free testosterone cause in the effects not the DHT you're measuring in the serum because that is not reflective of the DHT at the tissue level. Just like measuring estradiol in the serum is no reflection of the estradiol at the tissue level. It's just essentially what is produced peripherally, as well as what has escaped local metabolism. The cream will raise free, testosterone levels and maintain them daily since it is a twice daily application. Most men don't inject daily, so they don't have free testosterone levels that are consistently optimal. It is the free testosterone that enters the tissues where it is converted into DHT or estradiol to exert effects. Not what you measure the serum. So it's the consistent increase in free testosterone levels that causes the effects you're mentioning not the raising of the DHT or estradiol for that matter. If we give DHT to men not on testosterone, and raise their levels 10 times normal it doesn't have any effect on intracellular DHT levels in DHT sensitive tissues. When we do this for two years, it also doesn't have any effect on hair loss, acne, or other skin pathology. What it does do though is significantly inhibit testosterone production, and when you take DHT by itself, you're going to significantly lower your testosterone and estradiol levels. DHT has a negative feedback on testosterone production just like testosterone and estradiol have a negative feedback. I think the real issue here is the relevance of measuring DHT and estradiol in general. Their measurement in the serum has no reflection on tissue levels. When we lower the serum levels of DHT and estradiol we cause harm because we then lower it in the tissues where it is needed and exerts its effects. Proviron is also not bioidentical DHT BTW just like dianabol is not testosterone etc... Can't use a synthetic anabolic steroid and compare it to a bio identical hormone. You've got to understand what's going to be discussed in an upcoming video as well, with regard to androgen receptor, saturation, and enzyme saturation. So we can raise DHT four or five times normal giving a transdermal cream, but let me tell you another reason it has no effect on the tissues, in addition to the fact that the tissues tightly regulate their intracellar DHT levels. The reason is that there are only so many receptors for the DHT to bind to and once those receptors are fully bound with DHT no matter how high you raise DHT it can't exert an effect. You can only raise DHT to a certain point as well, because the five alpha reductase enzyme becomes fully saturated. And DHT sensitive tissues are fully stimulated at a fairly low, testosterone level. So what's your measuring serum is excess that can't exert an effect because they can't bind to a receptor because the receptors are fully saturated. Just like raising testosterone to 10,000 or 30,000 won't have an affect on how someone feels because all the receptors are fully saturated at a much much lower level. Yes you can continue to increase lean muscle mass because androgen receptors are up regulated in skeletal muscle. They are not up regulator in the brain or prostate etc...
 
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RobRoy

Active Member
It's because the cream will raise free testosterone levels better than injections for any given total in the same man. It's the free testosterone cause in the effects not the DHT you're measuring in the serum because that is not reflective of the DHT at the tissue level. Just like measuring estradiol in the serum is no reflection of the estradiol at the tissue level. It's just essentially what is produced peripherally, as well as what has escaped local metabolism. The cream will raise free, testosterone levels and maintain them daily since it is a twice daily application. Most men don't inject daily, so they don't have free testosterone levels that are consistently optimal. It is the free testosterone that enters the tissues where it is converted into DHT or estradiol to exert effects. Not what you measure the serum. So it's the consistent increase in free testosterone levels that causes the effects you're mentioning not the raising of the DHT or estradiol for that matter. If we give DHT to men not on testosterone, and raise their levels 10 times normal it doesn't have any effect on intracellular DHT levels in DHT sensitive tissues. When we do this for two years, it also doesn't have any effect on hair loss, acne, or other skin pathology. What it does do though is significantly inhibit testosterone production, and when you take DHT by itself, you're going to significantly lower your testosterone and estradiol levels. DHT has a negative feedback on testosterone production just like testosterone and estradiol have a negative feedback. I think the real issue here is the relevance of measuring DHT and estradiol in general. Their measurement in the serum has no reflection on tissue levels. When we lower the serum levels of DHT and estradiol we cause harm because we then lower it in the tissues where it is needed and exerts its effects.

Checked it, how about that receptor saturation theory, when unwanted side effects occur on high doses?
 
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RobRoy

Active Member
Checked it, how about that receptor saturation theory, when unwanted side effects occur on high doses?
It's called Androgen receptor sensitivity. Some men can't tolerate a lot and they can make a little bit go long ways and others take a lot to go a little ways. It's as simple as finding the dose that improves the symptoms of the deficiency while avoiding any unwanted side effects. It's not aiming for any specific level and men or so caught up in numbers that they just can't understand that simple fact. If a level of 700 improve symptoms then that's the number and if the level is 1500 to resolve symptoms that's the number. But whatever number it is it has to be balanced against any unwanted side effects. No one should have to add any additional chemical or drug to control side effects no different then we didn't need to take any chemicals or drugs when we were teenagers or in our 20s when we had excellent testosterone levels. And the receptor saturation is not a theory it's proven in the medical literature, and in medical physiology. People just want to ignore physiology, but this receptor saturation is fully understood. The one thing that we haven't found, though is the saturation point in muscle tissue that's why bodybuilders are as big as they are.
 

BigTex

Well-Known Member
I would imagine it probably has to do with whether one was primary/secondary hypo as well when they started?

When I added in 500iu of HCG twice per week, my trough level on my protocol at the time increased from 950 to 1265, and E2 from 34 to 66 with no other changes. I'm pretty sensitive to it, I can go years without using it and within 2 shots I have a drastic difference in testicular size.
I will see how HCG effects me the next time I go test. I have always used 500mg/wk for years but a few months ago just stopped using it. I had a T level in the high 800's with no HCG. Recently I started taking it again. So I will see if it makes any difference. One thing for sure is I don't feel any difference.
 

Charliebizz

Well-Known Member
It's called Androgen receptor sensitivity. Some men can't tolerate a lot and they can make a little bit go long ways and others take a lot to go a little ways. It's as simple as finding the dose that improves the symptoms of the deficiency while avoiding any unwanted side effects. It's not aiming for any specific level and men or so caught up in numbers that they just can't understand that simple fact. If a level of 700 improve symptoms then that's the number and if the level is 1500 to resolve symptoms that's the number. But whatever number it is it has to be balanced against any unwanted side effects. No one should have to add any additional chemical or drug to control side effects no different then we didn't need to take any chemicals or drugs when we were teenagers or in our 20s when we had excellent testosterone levels. And the receptor saturation is not a theory it's proven in the medical literature, and in medical physiology. People just want to ignore physiology, but this receptor saturation is fully understood. The one thing that we haven't found, though is the saturation point in muscle tissue that's why bodybuilders are as big as they are.
I’m a little confused. If they are at full saturation at 700tt. Why would they get side effects going higher then ?
 
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