Nelson Vergel
Founder, ExcelMale.com
The higher the T dose, the lower the SHBG. Guys with low SHBG are trying to avoid high T peaks that may further decrease their SHBG. That is why they inject daily using very small doses. Like microdosing.
One of the problems with low SHBG may be the ratio of free estradiol (fE2) to free testosterone (fT). Without TRT, the normal HPTA uses free estradiol as its primary regulator. With a fixed free estradiol, the lower the SHBG the lower the free testosterone. This means low SHBG provides a built-in propensity towards hypogonadism.
So the symptomatic low-SHBG guy goes on TRT. What happens? Now the exogenous testosterone is directly controlling free testosterone. With a fixed free testosterone, the lower the SHBG the higher the free estradiol. What this means in practice is that the low-SHBG guy starts with a higher fE2/FT ratio than in normal guys, and increasing testosterone via large, infrequent injections pushes the ratio even higher.
If we posit that there is a tolerable normal range for the fE2/fT ratio then it's clearly safer for the low-SHBG guy to avoid large peaks in his serum testosterone and estradiol. This is accomplished with smaller and more frequent injections.
Here are some numbers calculated using the multi-ligand model:
In this thought experiment there are two guys on TRT who are identical except for SHBG. They are on the same E5D doses of testosterone cypionate. In the last line of the table the peak fE2/fT ratio of the guy with normal SHBG is chosen as the reference point. The normal guy is operating in a range of 93-100%. The low-SHBG guy starts out at 106% and then climbs to 111%. Suppose symptoms occur at over 109%. In this case daily injections would probably help. But if symptoms occur at a lower figure, such as 107%, then a dose reduction would also be necessary, and this would risk sending free testosterone too low, which might cause other symptoms. It's easy to see why TRT can be a struggle for guys with low SHBG.
Edit: The premise of free estradiol increasing relative to free testosterone at low SHBG is based on an assumption of total estradiol being driven directly by free testosterone. But it seems more likely that free estradiol follows free testosterone, making total estradiol the dependent variable. In other words, neither free estradiol nor free testosterone changes much when SHBG is reduced in isolation. It's still plausible that lower SHBG leads to reduced androgenic activity relative to estrogenic activity—without a dependence on the free hormone levels.
So the symptomatic low-SHBG guy goes on TRT. What happens? Now the exogenous testosterone is directly controlling free testosterone. With a fixed free testosterone, the lower the SHBG the higher the free estradiol. What this means in practice is that the low-SHBG guy starts with a higher fE2/FT ratio than in normal guys, and increasing testosterone via large, infrequent injections pushes the ratio even higher.
If we posit that there is a tolerable normal range for the fE2/fT ratio then it's clearly safer for the low-SHBG guy to avoid large peaks in his serum testosterone and estradiol. This is accomplished with smaller and more frequent injections.
Here are some numbers calculated using the multi-ligand model:
In this thought experiment there are two guys on TRT who are identical except for SHBG. They are on the same E5D doses of testosterone cypionate. In the last line of the table the peak fE2/fT ratio of the guy with normal SHBG is chosen as the reference point. The normal guy is operating in a range of 93-100%. The low-SHBG guy starts out at 106% and then climbs to 111%. Suppose symptoms occur at over 109%. In this case daily injections would probably help. But if symptoms occur at a lower figure, such as 107%, then a dose reduction would also be necessary, and this would risk sending free testosterone too low, which might cause other symptoms. It's easy to see why TRT can be a struggle for guys with low SHBG.
Edit: The premise of free estradiol increasing relative to free testosterone at low SHBG is based on an assumption of total estradiol being driven directly by free testosterone. But it seems more likely that free estradiol follows free testosterone, making total estradiol the dependent variable. In other words, neither free estradiol nor free testosterone changes much when SHBG is reduced in isolation. It's still plausible that lower SHBG leads to reduced androgenic activity relative to estrogenic activity—without a dependence on the free hormone levels.
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Thank you for the explanation. I've been trying to figure out why TRT does me more harm than good for 7 years, and that's exactly what it is. When I started my shbg was < 30. With TRT it went to 1 digit and I developed lipomastia, accumulation of subcutaneous fat, I became more anxious and very fatigued, in addition to increased insulin and blood glucose. I mean, it just hurt me.
By reducing the dose to 100mg/week and splitting it, I felt some improvement. When I went to the carnivore diet I improved more.
But I still feel a lot of fatigue.
Given that nandrolone does not have major impacts on shbg, could it be beneficial for this group of patients to add small doses of deca?
I've added a note to that post explaining that it may be using a flawed assumption. Nonetheless, low SHBG may be problematic, even if the reasons why are more complicated than a shift in the balance of free hormones. If low SHBG decreases androgenic activity relative to estrogenic activity then it is possible that nandrolone could push things in the right direction in some tissues. However, if the idea has merit then it would seem to make more sense to use a non-aromatizing steroid that has an androgenic/anabolic ratio closer to that of testosterone. DHT?
Taking low SHBG to the extreme, there's this interesting case study in which male and female siblings had undetectable SHBG, and yet "... reported only mild symptoms, which could, however, not be directly related to the SHBG deficiency. Surprisingly, the absence of SHBG and the low sex hormone concentrations did not interfere with male gonadal differentiation or pubertal development and reproductive function of the gonads in both the male and the female."
The male still had some issues: "Despite normal free T levels, the patient had multiple signs that could be related to a decreased T availability: low libido, decreased spontaneous morning erections, fatigue, muscular weakness, decreased shaving frequency (once per 4 d), inability to concentrate, sleep disturbance, and depressed mood."
Very interesting. Thank you again for sharing your knowledge.
So would the decrease in androgenic activity promote a type of estrogenic dominance in peripheral tissues?
As it has been 7 years of trying with trt, in that time I have carried out some experiments. In search of some kind of resolution of hypogonadism and reduction of side effects I tested:
- deca only: strong reduction of anxiety and noticeable improvement in well-being, mood, irritability and post-workout recovery. Strong reduction in libido, but the erection only got worse after 3 months. The difficulties in losing weight remained, even on a hypocaloric diet. However, I had not yet tested keto or carnivore. I tested using pregnenolone and dhea in order to increase e2, but I didn't get good results and ended up returning to traditional TRT.
- Masteron only: as in Brazil we have difficulty obtaining pure dht, I did a test using only Masteron, as it is a derivative with fewer side effects compared to stano. Libido held for some time, but I got really anxious. My shbg has decreased a lot.
In an attempt to lose weight, I cycled with oxandrolone, stano and masteron, individually, using base test. With stano I had my biggest body change, with a huge increase in muscle mass, and a wider back. I suspect that I was dht deficient during my teens, as I always had very little body hair, a fairly thin beard, and wide hips compared to my shoulders. This relationship improved after using stano, but I could not decrease subcutaneous fat and I had a lot of anxiety and fatigue.
- I test 125mg/week divided into 2 or 3 applications: it was the best experience in 7 years. At first the doctor gave me Nebido, then Sustanon and then Cypionate. I currently do with enanthate. The symptoms decreased with the smaller and fractional dose, I managed to lose 8kg, I don't feel anxiety and the libido is normal (with higher doses my e2 reached 150, I thought about sex 25 hours a day, it caused me sexual compulsion, lipomastia and a lot of subcutaneous fat in the belly, even training and on a hypo diet).
I'm going to try a small dose of deca to see if I can overcome the fatigue issue. I intend to use 125mg of deca and keep the 125mg of enanthate.
Is there any benefit to the SHBG issue of using propionate in small, frequent doses in place of enanthate?
So would the decrease in androgenic activity promote a type of estrogenic dominance in peripheral tissues?
As it has been 7 years of trying with trt, in that time I have carried out some experiments. In search of some kind of resolution of hypogonadism and reduction of side effects I tested:
- deca only: strong reduction of anxiety and noticeable improvement in well-being, mood, irritability and post-workout recovery. Strong reduction in libido, but the erection only got worse after 3 months. The difficulties in losing weight remained, even on a hypocaloric diet. However, I had not yet tested keto or carnivore. I tested using pregnenolone and dhea in order to increase e2, but I didn't get good results and ended up returning to traditional TRT.
- Masteron only: as in Brazil we have difficulty obtaining pure dht, I did a test using only Masteron, as it is a derivative with fewer side effects compared to stano. Libido held for some time, but I got really anxious. My shbg has decreased a lot.
In an attempt to lose weight, I cycled with oxandrolone, stano and masteron, individually, using base test. With stano I had my biggest body change, with a huge increase in muscle mass, and a wider back. I suspect that I was dht deficient during my teens, as I always had very little body hair, a fairly thin beard, and wide hips compared to my shoulders. This relationship improved after using stano, but I could not decrease subcutaneous fat and I had a lot of anxiety and fatigue.
- I test 125mg/week divided into 2 or 3 applications: it was the best experience in 7 years. At first the doctor gave me Nebido, then Sustanon and then Cypionate. I currently do with enanthate. The symptoms decreased with the smaller and fractional dose, I managed to lose 8kg, I don't feel anxiety and the libido is normal (with higher doses my e2 reached 150, I thought about sex 25 hours a day, it caused me sexual compulsion, lipomastia and a lot of subcutaneous fat in the belly, even training and on a hypo diet).
I'm going to try a small dose of deca to see if I can overcome the fatigue issue. I intend to use 125mg of deca and keep the 125mg of enanthate.
Is there any benefit to the SHBG issue of using propionate in small, frequent doses in place of enanthate?
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Just to put my question about using propionate in place of larger esters in context. I have an mthfr mutation and I've been researching for a few years about the relationship of this mutation with other altered genes like Comt and Maoa. According to studies by Dr Ben Lynch, when these genes are slow they cause problems in the elimination of dopamine, serotonin and estrogen. I've had some symptoms of serotonin syndrome using marijuana and pictures similar to psychosis using Ritalin or even caffeine in high doses. I have only mthfr test but symptoms of Slow Comt and Slow Maoa.
Several articles claim that estrogen increases serotonin. My hypothesis is that by slowly metabolizing testosterone and estrogen, those who have slow comt/maoa will have worse well being with higher doses of testosterone/e2.
Fast metabolizers, Fast Comt/Maoa, are the ones who benefit the most from high doses of testosterone/estrogen. These are the ones who feel a clear decrease in anxiety and depression when starting TRT.
Thinking about this slowness in metabolizing estrogen and since propionate has a short half-life, would there be any hypothetical benefit in these cases?
Several articles claim that estrogen increases serotonin. My hypothesis is that by slowly metabolizing testosterone and estrogen, those who have slow comt/maoa will have worse well being with higher doses of testosterone/e2.
Fast metabolizers, Fast Comt/Maoa, are the ones who benefit the most from high doses of testosterone/estrogen. These are the ones who feel a clear decrease in anxiety and depression when starting TRT.
Thinking about this slowness in metabolizing estrogen and since propionate has a short half-life, would there be any hypothetical benefit in these cases?
It seems like a reasonable hypothesis.
Maybe, although the anecdotal evidence is rather indirect. Lower fluid retention has been reported with propionate versus longer esters. The assumption is that there's less estrogenic activity, but androgens also have a direct role in fluid balance.
Ditto here. You might spring for a free estrogen test to see if it is reflective of slower metabolism. I would also look at calculated results. Even simpler, though less reliable: a total hormone ratio, E2/T, that is over 0.6% may also hint at a higher rate of aromatization and/or slower E2 clearance.
It's amazing how much more knowledge you have of hormonal physiology than 100% of the doctors I've seen in the last 7 years.
I have a spreadsheet with dozens of exams I've taken over that time, I started the spreadsheet to try to find out why I always felt so bad with TRT. I didn't do exams in the tests with nandrolone, masteron and clomid because I was already tired of so many exams. Clomid would be very interesting because it increases shbg, but I couldn't keep it for more than 1 month at low doses, it made me very irritable.
I added E2/T and pretty much the whole time I was above 0.6 as you predicted. Always with very high free testosterone and low shbg.
As you yourself stated earlier, it is really very complex to replace testosterone in men with low shbg.
To date, I have only seen one doctor (Brazilian Paulo Muzy, who is a bodybuilder) say that patients with SHBG < 30 before starting TRT tend to get worse with replacement.
Something I haven't tried yet is HCG as a replacement, which apparently can be interesting as it increases shbg. What do you think of HCG only?
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Pnw0031
Member
Can you explain how low shbg makes trt very complex? Struggling with low shbg atm
Systemlord
Member
I'm getting better the longer I'm on TRT, and my SHBG more than doubled. A type 2 diabetic is the one exception where SHBG will increase on TRT.
Shbg is a testosterone binding protein. When you have low shbg, too much free testosterone circulates through your body. Too much of a good thing can be bad...
Testosterone and Estradiol go together, if the free test "overflows" the estradiol also tends to be higher and cause symptoms of estrogenic predominance.
So the big problem for men with low shbg on TRT is that the replacement decreases shbg even more, causing even more problems such as: insulin resistance, difficulties in losing weight, worsening libido, increased anxiety, gynecomastia/lipomastia, etc.
I'm glad it's going well. Can you share which ester, amount and frequency of your TRT?
I recently spent 3 months without testosterone replacement and used a month of low dose clomid. Only when I take the testosterone can I lose weight.
My weight decreased by 8kg on a carnivore diet and training little, since without replacement the post-workout recovery is terrible.
I started using it again 2 weeks ago, I applied 50mg on Monday, 75mg on Thursday, this second plus 50mg. I have difficulty in greater fractionation because it is enanthate, 250ml/ml.
But even with this fractionation and moderate doses, I had strong side effects this week. My weight went up 2kg in water retention and I entered a hypomania/anxiety and insomnia frame even stronger than normal. Last night I managed to sleep after 800mg of phosphatidylserine.
I'm going to test 25mg 2 or 3x a week. Apparently I won't be able to go beyond 75mg.
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Pnw0031
Member
A bit of a late reply but do you have any advice to raise shbg?
Systemlord
Member
A halving of SHBG won’t change Free T much at all. SHBG has less impact on Free T than most people believe.
Systemlord
Member
Jatenzo @ 237 mg twice daily. Jatenzo uses testosterone undecanate and another formula to absorb in the small intestine via fats.
This dosage puts my Total T around 900-1000 ng/dL at 2 hours and as low as 300 ng/dL 12 hours later. I feel the same at 2 hours as I do at 12 hours.
Downvote for complete misinformation.
Play some numbers in the Vermulean or TruT calculator and see the results when one halves SHBH. Certainly not “won’t change free T much at all”. Quite the contrary in fact.
You must have missed the discussions on this. You are assuming total testosterone is fixed. It's not. You should think of it as the dependent variable. Instead, free testosterone is relatively fixed, set by either the HPTA or the testosterone dose in TRT. If SHBG changes in isolation then total testosterone changes accordingly. A simple way to visualize the concept is to view SHBG as a reservoir for testosterone. The bigger the reservoir, the more total testosterone that can be held. In contrast, free testosterone is more akin to a flow rate, like the water entering the reservoir at one end and leaving at the other. A sponge analogy can also be used. More technical detail in this post.
Those discussions are your hypothesis yes, and I do believe the body will regulate to achieve a certain FT - but I’m adding the caveat that this is true only when natural with a functioning HPTA. Think of an aeroplane on autopilot.
Once you throw in exogenous test > than perhaps 50-70mg a week, however, the body has no control over the FT achieved by the dose. The very fact of the matter is that the FT is now higher than the set point and so the body tries to bring it down. By reducing LH all the way to 0. That’s it. There is no magical way the body can control the release from the depo, the time to cleave the ester etc in order to achieve some above set point FT. The body does not know how much you have injected, the size and strength of the depot.
You are in manual control of this aeroplane. The dosage injected is one input variable, the SHBG is a constant and the FT is the function output.
Still don’t believe me? The best way to test this is to alter the constant in the above equation - alter the SHBG. Use Danazol or Stanazolol to drop the SHBG. And the function output (free test) will increase, by measurement or by formula. Then throw in some clomid, watch SHBG rise, along with a reduction in FT.
Once you throw in exogenous test > than perhaps 50-70mg a week, however, the body has no control over the FT achieved by the dose. The very fact of the matter is that the FT is now higher than the set point and so the body tries to bring it down. By reducing LH all the way to 0. That’s it. There is no magical way the body can control the release from the depo, the time to cleave the ester etc in order to achieve some above set point FT. The body does not know how much you have injected, the size and strength of the depot.
You are in manual control of this aeroplane. The dosage injected is one input variable, the SHBG is a constant and the FT is the function output.
Still don’t believe me? The best way to test this is to alter the constant in the above equation - alter the SHBG. Use Danazol or Stanazolol to drop the SHBG. And the function output (free test) will increase, by measurement or by formula. Then throw in some clomid, watch SHBG rise, along with a reduction in FT.
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