Low SHBG, scrotal T cream increased DHT, drove E2 to <2

[davidrn]

My SHBG has run in the 12-15 range with pretty much any TRT changes I have made. My protocol last month was T Cyp (SQ) 24mg x3/wk, HCG 200 iu 3x wk, DHEA 25 mg 3 x wk, Pregnenolone 50mg 3 x wk, and T Cream to scrotum each night, a very small dose. Seemed to work, and a set of labs found DHT was aprox 100. (At that set of labs SHBG was 14). Unfortunately, even though I felt it was working at first, my E2 (high sensitivity) was at <2. Did the E2 go down because of the higher DHT offsetting T to E2 conversion? Or is it related to E2 and its relationship to SHBG?
I dropped the cream, and my e2 returned this week to 22.

 

[Cataceous]

DHT is supposed to have some aromatase-inhibiting activity, but I wouldn't have expected such a dramatic result at near-physiological levels. I'm equally inclined to suspect the accuracy of the estradiol test. Those sensitive tests are completely wrong on occasion.

 

[davidrn]

DHT is supposed to have some aromatase-inhibiting activity, but I wouldn't have expected such a dramatic result at near-physiological levels. I'm equally inclined to suspect the accuracy of the estradiol test. Those sensitive tests are completely wrong on occasion.

Agree, I would be suspect of the result, but, I had two labs with those low E2 levels. My first was 5, and I wasn't sure about accuracy, and I didn't feel different, so waited. I retested a month later and I believe it was accurate when it came out <2, after no protocol changes, and two low E2's in a row. I am only assuming the DHT and E2 are related. With the T Cyp I am taking in 3 x week injections, at 72mg/wk, I am only around 400 TT. However adding in the small dab of T Cream (QD) to the scrotum, my peak was 1100, and trough around 850. So, the T cream was contributing (I believe) a fair amount of my TT (and FT levels). My FT is always supraphysiological related to my low SHBG. My goal is to have my TT around 500-650, this (I believe) would keep the FT within a reasonable level.
,

 

[Cataceous]

Interesting. That seems like a large increase in testosterone from a "small dab" of cream. But if scrotal absorption is as high as 60% then I guess it wouldn't take much. I have also had a mysterious crash of estradiol verified by several tests. I never did figure out exactly why it happened.

 

[davidrn]

Thanks for your response, do you think increasing DHT (R/T Test Cream to scrotum) was the only factor at work? Or did you have any other issues that changed when your E2 dropped? I am unsure at what is in play here, my issues are the low SHBG, and the cream raising my TT and DHT. E2 has to have something to stick to, right? so, if my SHBG is low, wouldn't my free E2 also be low? Anyone else have a theory?

 

[Cataceous]

With respect to SHBG, it's the opposite: low SHBG means higher free estradiol. In addition, it means free estradiol is higher relative to free testosterone than in those with normal SHBG. It's been hypothesized that this is one of the reasons why guys with low SHBG have more problems.

My period of low estradiol coincided with SHBG dropping from ~30 nMol/L to single digits. I assume the drop in estradiol caused the drop in SHBG, instead of the other way around. The drop also coincided with my temporarily stopping use of hCG and trialing a SARM. I'd already lowered my dose of anastrozole to 0.14 mg per week and stopped it altogether after getting the first low result for estradiol. So there were quite a few things going on, but none should really have led to undetectable estradiol.

 

[Omi7276]

With respect to SHBG, it's the opposite: low SHBG means higher free estradiol. In addition, it means free estradiol is higher relative to free testosterone than in those with normal SHBG. It's been hypothesized that this is one of the reasons why guys with low SHBG have more problems.

My period of low estradiol coincided with SHBG dropping from ~30 nMol/L to single digits. I assume the drop in estradiol caused the drop in SHBG, instead of the other way around. The drop also coincided with my temporarily stopping use of hCG and trialing a SARM. I'd already lowered my dose of anastrozole to 0.14 mg per week and stopped it altogether after getting the first low result for estradiol. So there were quite a few things going on, but none should really have led to undetectable estradiol.

Doesn't DHT also lower SHBG .

 

[Cataceous]

Doesn't DHT also lower SHBG .

DHT is an androgen, and androgens tend to reduce SHBG.

With respect to SHBG, it's the opposite: low SHBG means higher free estradiol. ...

What I should have said is that low SHBG means higher free estradiol when total estradiol is constant. However, this is not a realistic scenario. It's better to model the creation rate of estradiol as constant. This has the same implication as it does for testosterone, in that the free hormone levels stay constant while total levels vary with SHBG.

 

[Vince]

My SHBG has run in the 12-15 range with pretty much any TRT changes I have made. My protocol last month was T Cyp (SQ) 24mg x3/wk, HCG 200 iu 3x wk, DHEA 25 mg 3 x wk, Pregnenolone 50mg 3 x wk, and T Cream to scrotum each night, a very small dose. Seemed to work, and a set of labs found DHT was aprox 100. (At that set of labs SHBG was 14). Unfortunately, even though I felt it was working at first, my E2 (high sensitivity) was at <2. Did the E2 go down because of the higher DHT offsetting T to E2 conversion? Or is it related to E2 and its relationship to SHBG?
I dropped the cream, and my e2 returned this week to 22.

I would think by your labs You're taking something to lower your estrogen levels. Are you taking any type of AI?

 

[Cataceous]

So would you necessarily recommend AI for low SHBG subjects ( as my estrogen ECLIA is high ; can't get Ultra sensitive as it's not available in my country) .
Also , why do you think low SHBG people benefit from testosterone cream ? Likke is it less suppressive on SHBG or has slow mean clearance value ?

I've come to prefer using ECLIA for testing estradiol due to its better reliability. However, this shouldn't be done unless you're pretty confident you won't see much cross-reactivity. If you can measure C-reactive protein and if it is low then you can probably trust an immunoassay estradiol test.

I wouldn't automatically recommend an AI for low SHBG subjects. It's true that if estradiol is high then that implies an above-normal free level as well. But I'd also want to know about the ratio of estradiol to testosterone. A normal ratio makes elevated estradiol less problematic. Are there any symptoms that could be linked to it, such as excessive emotionalism or rising prolactin?

If low SHBG people are indeed benefitting from topical testosterone then perhaps it has to do with more reasonable dosing compared to injections. This does mean less suppression of SHBG, but there may be other factors related to the reduced hormonal buffering with low SHBG.

 

[davidrn]

I would think by your labs You're taking something to lower your estrogen levels. Are you taking any type of AI?

I have to believe that the <2 E2 was a lab error, it came up at the next lab test with very little changes. I did dilute my scrotal cream from 50mg/ml to 25mg/ml , that brought my FR/TT both within range . (My MD writes an Rx for 200mg cream, then I dilute it 400%, do this mostly for cost savings) I do take DIM three days a week, unclear how much an effect this has on my E2. I didn't think just taking scrotal T cream was enough, but libido is all I am concerned about, and that's working.

 

[RickB]

With respect to SHBG, it's the opposite: low SHBG means higher free estradiol. In addition, it means free estradiol is higher relative to free testosterone than in those with normal SHBG. It's been hypothesized that this is one of the reasons why guys with low SHBG have more problems.

My period of low estradiol coincided with SHBG dropping from ~30 nMol/L to single digits. I assume the drop in estradiol caused the drop in SHBG, instead of the other way around. The drop also coincided with my temporarily stopping use of hCG and trialing a SARM. I'd already lowered my dose of anastrozole to 0.14 mg per week and stopped it altogether after getting the first low result for estradiol. So there were quite a few things going on, but none should really have led to undetectable estradiol.

I've come across a number of posts lately where you mention free E2 in relation to low SHBG. So I guess the inverse must be true?

Are high-SHBG guys' total E2 levels misleading exactly like their total T levels are, since large amounts of both their T and E2 are being bound to SHBG?

So, in general, wouldn't it be better for everyone to test free E2 in addition to E2?

 

[davidrn]

I did get one free E2 test a few years ago, because of my low SHBG, the results were WNL, but there are no real optimal levels listed anywhere, so I don't know what we can do with the actual results. I lost my account last week, and I got a new account, thought I would move the question over here.
Currently I am 66 years old, 145lbs, 5'7",have an auto immune disease: RA and use Humira. My current protocol is:

T Cream (200 mg diluted with Lubriderm to 25 mg) I apply this daily to scrotum ( I started using it straight from the compounding quik tube, but diluted it to bring my T levels down. Costs for 200 or 25 mg are the same, so I use a 200mg and dilute it 300% with Lubriderm, my Urologist thought that was a good (fiscal) idea.
DHEA 25 mg 3x wk
DIM 200 mg 3x wk
Pregnenolone 100mg 3 x wk
Progesterone cream (aprox 25mg dose ) applied to scrotum

Here are last weeks labs (thanks for the discount Nelson)
TT 529 (post T Cream 8 hours)
FT 122
E2 33
DHT 192 (12-65)
DHEA 234 (20 -217 for my age)
SHBG 15 (22-77, dropped last 2 were 17 and 19)
Prolactin 9.4 (2 -18)

I am feeling well, but libido still has room for improvement, I am unsure of which labs I should work to change. My E2 was slightly higher, but my SHBG is also very low, should I increase my DIM to daily? I have not used an AI in a few years. I have started to take DIM daily, might be just enough? Is the DHT level too high? I read levels (using scrotal T cream) in the thousand + range, so assume I am only slightly elevated? Any other thoughts would be appreciated.

 

[RickB]

I did get one free E2 test a few years ago, because of my low SHBG, the results were WNL, but there are no real optimal levels listed anywhere, so I don't know what we can do with the actual results.

@Cataceous should probably know a preferred range since he is a proponent of this test.

 

[Systemlord]

TT 529 (post T Cream 8 hours)

You're supposed to test creams at 4 hours.

 

[davidrn]

You're supposed to test creams at 4 hours.

As my coffee mug say's, I am not retired, I am a professional grampy. So, I was planning on visiting the grandson for a couple weeks, I had time in the AM before leaving to get labs, and I woke up at 1am,applied the T cream and got tested at 0830. ( he lives in a non testing state) I have a decent amount of TT and FT results from the past 6 months, all with the current protocol. I usually test for peak, and maybe once a year I do a trough. My biggest concern is the DHT level, I know many guys go over a thousand, so, is 192 an optimal level? Or will there be side effects that I might have from this level? Also, is there an optimal prolactin level? I am sort of smack in the middle of the range, is this OK?

 

[Systemlord]

Also, is there an optimal prolactin level? I am sort of smack in the middle of the range, is this OK?

It's different for everyone as with any other hormone. Genetics allow certain people to tolerate high levels without issues while others are more sensitive. Men with higher end progesterone levels on TRT typically require higher testosterone levels to feel dialed in.

 

[Cataceous]

I've come across a number of posts lately where you mention free E2 in relation to low SHBG. So I guess the inverse must be true?

Are high-SHBG guys' total E2 levels misleading exactly like their total T levels are, since large amounts of both their T and E2 are being bound to SHBG?

So, in general, wouldn't it be better for everyone to test free E2 in addition to E2?

Indeed, I think the situation with other hormones is the same as it likely is with testosterone: the production or dose rate directly drives the free levels, with total levels dependent on the free levels and the amounts of the binding proteins. So, yes, I expect high SHBG inflates total estradiol, which could lead to misinterpreting lab results. Ideally we should be considering free estradiol, either measured or calculated or both, and especially when SHBG is low or high.

@Cataceous should probably know a preferred range since he is a proponent of this test.

There's probably not harmonization yet, so you must use the range of the particular test. At least some of the tests seemed to correspond pretty well to results calculated via the Multi-Ligand method. In these cases a generous normal range is something like 0.2-1.5 pg/mL.