High estrogens / SHBG

#21
Docs never understand my thyroid numbers. I'm a clinician myself (non-MD category), and I look at things from the "functional" perspective, so when they say things look fine or that NDT is required to bring things in line, I always question their reasoning.

Back in the early days, I tried .5 grain of NDT on and off, and every time it made me feel worse. It wasn't until I put 2 and 2 together and realized that I had more than enough T4 and that NDT (with its typical 4:1 ratio T4:T3) was overloading the balance.

What does the body do when there is too much T4? It converts it to RT3. And too much RT3 leads to clogged T3 receptors, so even if free T3 looks good, the body feels hypothyroid. The way my labs look are like this:

Free T4: 1.67 ng/dL (0.82-1.77)
Free T3: 3.8 pg/mL (2.0-4.4)
TSH: 3.1 uIU/mL (0.45-4.5)
RT3: 25.2 ng/dL (9.2-24.1)

See what I mean? A good clinician will ask why RT3 is high. Most docs don't even test for it. The most common reason -- high cortisol is slowing down the conversion of T4 > T3 and RT3 is pooling.

The only situation where you want to take straight T3 (without T4) is when this is happening. It's literally the only approach that will clear out that excess RT3. If free T4 is trending with a TSH above 1, then NDT is useful. Be careful, though, if free T4 looks good (as in my case).

It's not a long term strategy if the original cortisol problem isn't fixed. In my case, cortisol was tending to go high because of estrogen. Higher estrogen results in higher reactivity to antigens (think allergies). Allergic reactions tend to raise cortisol. On my labs, eosinophils are always high.... They have finally been coming down because T is going up. As a matter of fact, this allergy season (after starting T therapy), I had no allergic symptoms. None. There is a reason women suffer more from asthma than men, especially during their cycle.

Estrogen effects in allergy and asthma

I have some good news to report, actually --- I think I've found a solution for my high SHBG and lack of response from testosterone. I had a flash of insight last night -- and it occurred to me that by raising testosterone, it's triggered a biofeedback look in the steroid hormone chain to slow down Pregnenolone / DHEA production --- they simply aren't needed when exogenous supply has increased. Then I remembered that my Progesterone has been low on previous labs. Just as an experiment last night, I rubbed a topical solution of Pregnenolone / DHEA onto my forearms (5mg / 5mg) and literally within a couple of hours, I felt completely different. The weak erections immediately disappeared.

So I need to dig a little more in this area. I might try just straight Progesterone and DHEA together, since they would synergistically bring down cortisol -- and that's ultimately what's interfering with both thyroid and testosterone.

It makes you think ... how many men out there have optimal hormone levels but aren't getting the benefits because cortisol is too high? I think it should be mandatory for guys to do a 4-point salivary test before fooling around with other options, especially those that "overtrain". Everyone knows that too much training is catabolic, primarily through excess cortisol.

Bit by bit, this will all become clearer.

If you are curious about the T3 drops I have been using, a lot of the "peptide shops" sell it. You can also do some hunting around the Ray Peat forum, as that crowd seems to be very pro-thyroid (a more is better mentality). But again, don't touch straight T3 if your T4 is going low. You can benefit from NDT instead.
Sounds like you’re very knowledgeable about the thyroid. I’ve been doing a ton of research on the thyroid lately, and it scares me that the level of knowledge you have is more than some endocrinologist with a medical degree. Why they aren’t being taught to test for RT3, I have no idea. But you’re spot on. Straight T3 is what you personally need. Clearly you have enough T4, it’s just converting into RT3. So any exogenous T4 is obviously a bad idea. How some doctors still don’t understand this is beyond me. So in your case, straight T3 is the answer, along with the cofactors iodine and selenium.

So since you’re pretty knowledgeable about the thyroid, I have a quick question. Here are my labs, what do you think is going on. I have average morning temps of 96.1, extreme brain fog, and a bunch of other hypothyroid symptoms. My guess is that my free T3 isn’t getting into the cells, and is pooling in my blood. So my questions are, what do you think is going on, and do you think NDT would help me? I’m thinking a trial of NDT would be the best option, but just curious if you had any insight. Thanks.

T3 total - 83 (76-181)
T4 total - 5.6 (4.5-10.5)
Free T3 - 3.7 (2.3-4.2)
Free t4 - 0.9 (0.8-1.8)
Rt3 - 11 (8-25)
TSH - 0.73 (0.4-4.5)
Thyroglobulin antibodies - (<1)
Thyroid peroxidase antibodies -(1) Range - (<9)

And you’re spot on with guys not paying enough attention to cortisol and DHEA. I see guys on here all the time with low DHEA, that don’t think it’s that important to treat. But it’s literally just as important as testosterone. Plus, like you said, DHEA and cortisol oppose each other. So low DHEA can give you a good idea on where your cortisol sits. I personally have the opposite. Low cortisol and DHEA naturally slightly above the top of the range.
 
#22
Castaneda, we have some similar labs.

My T is in the 700 range, shbg averages 50ish (went to 80s on a vegan diet), E2 of 16, low saliva cortisol with large midday drop, and high reverse T3. RBC copper was low.

I'm looking to have labs done soon. If you have suggestions of a lab to include let me know. And if you figure something out, message me.
 
Thread starter #23
You talked about topical dhea/preg in your first post back in November. Round and round we go?
I don't follow you. I'm using Progesterone / DHEA now. No Pregnenolone. Completely different combination with completely different effects. "Round and round" would tend to indicate going no where. Improvement is not a circle. Sorry, try again.
 
Thread starter #24
This is a re-post form another thread, but wanted to get opinions here as well.

I beginning to think my provider is performing a wallet biopsy on me. They are giving me a 90G tube of cypionate liposomal cream at 200mg/G. They are charging $339 and asking me to apply 1g to the scrotum 2x a day. I've been doing that but am already running out of cream on the 21st day here.

These were my numbers on the last test:

Hemoglobin: 16.2 g/dl (13-17)
Hematocrit: 45.9% (37-49)
Platelets: 182 (130-400)
Estradiol 39.1 pg/ml (<=60.7)
Testosterone: 1082 ng/dl (300-890)
SHBG: 50.4 nmol/l (16.5-55.9)
Calc Free T: 204.5 pg/ml (47-244)

On another thread, I'm being told my SHBG is high enough to make my E2 low (calc'd E2). I'm just wondering if 1) I'm being swindled by the provider and 2) I'm putting way too much cream on the scrotum.

My libido has been in the gutter with this dose, but the doc says I have zero "high E2" symptoms due to lack of puffy nipples and irritability. Yes, low libido is also a sign of low E2 as well, but this little experiment of mine lately --- using 5mg:5mg solution of Progesterone / DHEA has brought libido back (in spades), and that combination is known to be anti-estrogenic at that dose, so I'm definitely wondering if I'm not going too high with the T dose.
 

fifty

Active Member
#25
I don't follow you. I'm using Progesterone / DHEA now. No Pregnenolone. Completely different combination with completely different effects. "Round and round" would tend to indicate going no where. Improvement is not a circle. Sorry, try again.
You posted the following a few posts back. Did you mean to say progesterone or am I just not following any of this right?

“Just as an experiment last night, I rubbed a topical solution of Pregnenolone / DHEA onto my forearms (5mg / 5mg) and literally within a couple of hours, I felt completely different. The weak erections immediately disappeared”
 
Thread starter #26
So since you’re pretty knowledgeable about the thyroid, I have a quick question. Here are my labs, what do you think is going on. I have average morning temps of 96.1, extreme brain fog, and a bunch of other hypothyroid symptoms. My guess is that my free T3 isn’t getting into the cells, and is pooling in my blood. So my questions are, what do you think is going on, and do you think NDT would help me? I’m thinking a trial of NDT would be the best option, but just curious if you had any insight. Thanks.

T3 total - 83 (76-181)
T4 total - 5.6 (4.5-10.5)
Free T3 - 3.7 (2.3-4.2)
Free t4 - 0.9 (0.8-1.8)
Rt3 - 11 (8-25)
TSH - 0.73 (0.4-4.5)
Thyroglobulin antibodies - (<1)
Thyroid peroxidase antibodies -(1) Range - (<9)
The problem with the thyroid labs is that they are hard to interpret in isolation. You made a passing remark about low cortisol and high DHEA, but would you mind sharing some specifics? For example, what kind of cortisol measurement was it? If it was a 4-point salivary measurement, did it show low cortisol throughout the day or only in the morning? Further, if the test doesn't look at cortisone, then we are really guessing altogether, because we need to see total metabolized cortisol which includes THE and THF. DUTCH Test does that, albeit not in the most scientific way (i.e spot urine).

That being said, your thyroid numbers look good except for free T4, which I prefer to see over 1.5. I don't even flag RT3 as a problem until it goes above 15, although the lower the better in most cases.

You can certainly try NDT, but given your free T3 is in the optimal zone, you could run the risk of jacking up your T4 and raising RT3 even higher. It could be that your thyroid receptors are not well expressed (sorry, I'm a geneticist, so that's just how I think). So even with adequate T3 levels, you are more sensitive to that small amount of RT3 clogging them up. In any case, NDT is going to raise your T4 and likely your RT3 as well.

One other thing I have seen in my practice is the tendency for high serotonin (and low dopamine) to cause body temperature to drop. I know, I know -- everyone thinks serotonin positively regulates body temps, but that's not my experience (and certainly not the experience of anyone that has ever had serotonin syndrome). Let me explain.…

When animals hibernate, their lack of food supply puts stress on their bodies, and this increases serotonin production.

https://www.sciencedirect.com/science/article/pii/0091305781903609

The same things happens with humans in winter (think seasonal depression). The psychiatrists have it all wrong. Serotonin (and lack of dopamine) causes depression in most cases. Most people out there taking SSRIs are overloading themselves. When serotonin elevates, it lowers temperature by decreasing metabolic rate. Google it if you don’t believe me… tryptophan and melatonin are also hypothermic. That’s why hypothyroid people need more medication in the winter. And here’s another tidbit: high estrogen will also raise serotonin, which is why pre-menopausal women are more frequently hypothyroid than men. And men with high aromatase expression tend to have lower body temps. Just a fact. All these things go hand in hand: low dopamine, lower metabolic rate, higher body fat, higher estrogen, etc.

Not to rant, but how is your mood? Dopamine agonists like Bromocriptine (or even L-DOPA / Mucuna) can have a heat generating effect. When my temps go south of 98 during the day, I can faithfully get them back to 98.6 or higher by pushing dopamine up. Coffee does that (and also increases cAMP which will push more T4 to T3). Forskolin does it. Exogenous androsterone will do it, though I’d not touch it with T therapy, as that would just tank estrogen.

Something else to think about – when there is excessive gut inflammation / irritation, enterochromaffin cells just explode with serotonin (and histamine). Most of the body’s serotonin is made in the gut and all these people out there complaining of low temps with normal thyroid labs never look at the gut. Sometimes, a simple stool test will show a Candida overgrowth, or something more sinister like E. Coli. And as soon as they run a course of antimicrobials, their serotonin goes back down, dopamine comes up, and temps stabilize. So looking at things from the perspective of thyroid can be misleading. Thyroid tends to adjust itself depending on what’s happening elsewhere in the body (with the exception of antibodies).

If you want my two cents, I’d take some high-powered Forskolin first thing in the morning as an experiment to see what happens. You don’t want to abuse it (i.e. don't take it more than 12 weeks at a stretch) due to liver stress, but I can tell you this: I didn’t need any thyroid support during the weeks in winter I was using Forskolin. I was taking cold showers and generating heat like a furnace. Why? Because it was pushing all my excess T4 to T3. And it raises dopamine too.

You don’t have a whole lot of T4 running around, but that could just be your “normal set point”. It’s still within range. As I said before, you might just be dealing with a metabolic problem outside the realm of thyroid. The body is complex. There are a lot of other things that could cause the problem. Low insulin output, for example. And that happens on low carb / high fat diets. I know a ton of people that have induced hypothyroidism with keto diets. Shoot me for saying that, but labs don’t lie.
 
Thread starter #27
You posted the following a few posts back. Did you mean to say progesterone or am I just not following any of this right?

“Just as an experiment last night, I rubbed a topical solution of Pregnenolone / DHEA onto my forearms (5mg / 5mg) and literally within a couple of hours, I felt completely different. The weak erections immediately disappeared”
Thanks for pointing that out. I mistyped. Let me go back and correct it.
 
#28
The problem with the thyroid labs is that they are hard to interpret in isolation. You made a passing remark about low cortisol and high DHEA, but would you mind sharing some specifics? For example, what kind of cortisol measurement was it? If it was a 4-point salivary measurement, did it show low cortisol throughout the day or only in the morning? Further, if the test doesn't look at cortisone, then we are really guessing altogether, because we need to see total metabolized cortisol which includes THE and THF. DUTCH Test does that, albeit not in the most scientific way (i.e spot urine).

That being said, your thyroid numbers look good except for free T4, which I prefer to see over 1.5. I don't even flag RT3 as a problem until it goes above 15, although the lower the better in most cases.

You can certainly try NDT, but given your free T3 is in the optimal zone, you could run the risk of jacking up your T4 and raising RT3 even higher. It could be that your thyroid receptors are not well expressed (sorry, I'm a geneticist, so that's just how I think). So even with adequate T3 levels, you are more sensitive to that small amount of RT3 clogging them up. In any case, NDT is going to raise your T4 and likely your RT3 as well.

One other thing I have seen in my practice is the tendency for high serotonin (and low dopamine) to cause body temperature to drop. I know, I know -- everyone thinks serotonin positively regulates body temps, but that's not my experience (and certainly not the experience of anyone that has ever had serotonin syndrome). Let me explain.…

When animals hibernate, their lack of food supply puts stress on their bodies, and this increases serotonin production.

https://www.sciencedirect.com/science/article/pii/0091305781903609

The same things happens with humans in winter (think seasonal depression). The psychiatrists have it all wrong. Serotonin (and lack of dopamine) causes depression in most cases. Most people out there taking SSRIs are overloading themselves. When serotonin elevates, it lowers temperature by decreasing metabolic rate. Google it if you don’t believe me… tryptophan and melatonin are also hypothermic. That’s why hypothyroid people need more medication in the winter. And here’s another tidbit: high estrogen will also raise serotonin, which is why pre-menopausal women are more frequently hypothyroid than men. And men with high aromatase expression tend to have lower body temps. Just a fact. All these things go hand in hand: low dopamine, lower metabolic rate, higher body fat, higher estrogen, etc.

Not to rant, but how is your mood? Dopamine agonists like Bromocriptine (or even L-DOPA / Mucuna) can have a heat generating effect. When my temps go south of 98 during the day, I can faithfully get them back to 98.6 or higher by pushing dopamine up. Coffee does that (and also increases cAMP which will push more T4 to T3). Forskolin does it. Exogenous androsterone will do it, though I’d not touch it with T therapy, as that would just tank estrogen.

Something else to think about – when there is excessive gut inflammation / irritation, enterochromaffin cells just explode with serotonin (and histamine). Most of the body’s serotonin is made in the gut and all these people out there complaining of low temps with normal thyroid labs never look at the gut. Sometimes, a simple stool test will show a Candida overgrowth, or something more sinister like E. Coli. And as soon as they run a course of antimicrobials, their serotonin goes back down, dopamine comes up, and temps stabilize. So looking at things from the perspective of thyroid can be misleading. Thyroid tends to adjust itself depending on what’s happening elsewhere in the body (with the exception of antibodies).

If you want my two cents, I’d take some high-powered Forskolin first thing in the morning as an experiment to see what happens. You don’t want to abuse it (i.e. don't take it more than 12 weeks at a stretch) due to liver stress, but I can tell you this: I didn’t need any thyroid support during the weeks in winter I was using Forskolin. I was taking cold showers and generating heat like a furnace. Why? Because it was pushing all my excess T4 to T3. And it raises dopamine too.

You don’t have a whole lot of T4 running around, but that could just be your “normal set point”. It’s still within range. As I said before, you might just be dealing with a metabolic problem outside the realm of thyroid. The body is complex. There are a lot of other things that could cause the problem. Low insulin output, for example. And that happens on low carb / high fat diets. I know a ton of people that have induced hypothyroidism with keto diets. Shoot me for saying that, but labs don’t lie.
Thank you so much for the long and detailed response! I’ll reply back when I have time. But really really appreciate all the effort that went into that reply. Definitely doesn’t go unappreciated.
 
Thread starter #30
Things have been taking a sinister turn for the worse lately. I went into the provider's office yesterday for a follow-up, and they put a transcranial EEG helmet on my head and asked me to respond to sounds, draw paths through numbers, and other such nonsense. From this, they deduced that I an in "autonomic overdrive". The doctor said the tachycardia alone (over 90 bpm pulse rate) was a sign that my cortisol was high. Apparently, he doesn't like the typical 4-point salivary testing. So the recommendation yesterday was to immediately start on 50mg of micronized DHEA per day. I protested that even micronized DHEA passes through the liver and is metabolized differently than transdermal, but the doctor didn't seem to understand the difference.

So on what now appears to me to be misguided advice, I went home and right before bed, took 50mg DHEA transdermally. I woke up this morning feeling completely emasculated. No morning wood, no drive, no energy, and a deep, dark depression (and anxiety) I haven't seen in years. I asked the doctor about it, and he said, "that's not a typical reaction". In other words, "I don't know, go f*** yourself".

What is interesting here is that my temperature has dropped as well. With that dose of DHEA, I have blunted the effects of Cytomel, and my body temps aren't going above 97.5. With the Progesterone, they were shooting up to 98.8. That's my sweet spot. So I went back and looked at my last labs. They show:

DHEA-S 186 (L)
Pregnenolone 208 (H)

That's my pattern. So it explains why I felt poorly with Preg + DHEA and better with Prog + DHEA. The only explanation I have for the DHEA results this morning is that 1) transdermal application requires far less to achieve the same effects as oral and 2) too much DHEA will suppress cortisol, even when it is high. I can come up with no other explanation. Too little cortisol, and thyroid goes south.

Pregnenolone is probably high because of my high fat / low carb diet. But, on the other hand, if you believe what the literature says, with a 17-alpha-hydroxylase deficiency, pregnenolone and progesterone may be elevated, along with 11-deoxycorticosterone. This could easily present in parallel with low DHEA, but then cortisol would also be low.

So I really have no idea how to proceed. With each day on T therapy, my energy levels, libido, and outlook on life go further into an abyss. I reached out to Defy Medical, but they also shrugged their shoulders (didn't want to take me on). So I'm left to puzzling through this on my own.

If things keep progressing at this rate, I'm going to be 6 feet under by the end of the year. Already feeling semi-suicidal. DHEA just pushed me clear off the edge. I wish there were medical professionals out there that really understood these pathways. It seems like the majority of them are just guessing and throwing darts blind-folded. And that's a recipe for disaster.

So to recap:

My Pregnenolone is high on the labs. DHEA is low. Taking DHEA causes severe depression and an obliteration of all male qualities. Doing nothing at all (just T therapy), I'm screwed. The closest I've gotten to feeling good is Progesterone + DHEA, but that goes south in a matter of 2-3 days if taken at 10mg:10mg per day. Trans-scrotal cypionate cream at 200mg, 2x a day is producing zero effects now. Absolutely nothing. Just feeling worse with each day.

So perhaps the answer is just taking that combo at 5:5mg and then only every 2-3 days. Although ... I would prefer to know why this is happening. Just finding the right combination teaches me nothing. I can't imagine I'm the only one out there with this chemistry.

The doc yesterday wanted to cut my T dose in half (suddenly) and add in 500mcg of HCG twice a week. I really don't think he has a clue, quite honestly. I will say I'm a step away from just flushing all this T down the toilet and going back to putting red light on the testicles. At least then, I felt like half a man. Right now, I'd be lucky to be a castrated eunuch. My wife has more testosterone than me.
 
#31
Was there a time in your life when you felt good and "on" in the ways you want to be feeling? You mentioned that you've had symptoms of low testosterone for a long time, so it may be worth thinking about how you felt before those symptoms started.

You seem very analytical and well researched. One downside to this is it makes it more likely for you to experience the placebo / nocebo effect, which can be quite strong. I'm not saying that's the case here, but it's something you should seriously consider.

For what it's worth, I experimented for a year with DHEA and pregnenolone before ultimately deciding on TRT. DHEA improved my mood, but it was a balancing act for me. It conferred mood benefits, but it had no benefits in the areas of energy / fatigue / muscle mass / exercise recovery. Interestingly, when my DHEA protocol was dialed in things felt a bit like this erowid report- "Every day felt like the first day of summer" (DHEA - Erowid Exp - 'Every Day Felt Like the First Day of Summer')

I found the usual dosages of DHEA to be excessive (25mg, 50mg/day, ..). Based on reading some of the studies, it looked like 2.5mg of DHEA twice a day was more than enough to bring my bottom-of-range DHEA-S level up to the top of range. I figured this out by looking at the dose-response relationship between DHEA-S and oral DHEA. You may want to try a much smaller dose of oral DHEA (this is what the studies are on), possibly somewhere around 2.5mg taken twice a day. The extra DHEA-S has to go somewhere, and in some cases I think it can go to undesirable hormone pathways.
 
Thread starter #32
Was there a time in your life when you felt good and "on" in the ways you want to be feeling? You mentioned that you've had symptoms of low testosterone for a long time, so it may be worth thinking about how you felt before those symptoms started.

You seem very analytical and well researched. One downside to this is it makes it more likely for you to experience the placebo / nocebo effect, which can be quite strong. I'm not saying that's the case here, but it's something you should seriously consider.

For what it's worth, I experimented for a year with DHEA and pregnenolone before ultimately deciding on TRT. DHEA improved my mood, but it was a balancing act for me. It conferred mood benefits, but it had no benefits in the areas of energy / fatigue / muscle mass / exercise recovery. Interestingly, when my DHEA protocol was dialed in things felt a bit like this erowid report- "Every day felt like the first day of summer" (DHEA - Erowid Exp - 'Every Day Felt Like the First Day of Summer')

I found the usual dosages of DHEA to be excessive (25mg, 50mg/day, ..). Based on reading some of the studies, it looked like 2.5mg of DHEA twice a day was more than enough to bring my bottom-of-range DHEA-S level up to the top of range. I figured this out by looking at the dose-response relationship between DHEA-S and oral DHEA. You may want to try a much smaller dose of oral DHEA (this is what the studies are on), possibly somewhere around 2.5mg taken twice a day. The extra DHEA-S has to go somewhere, and in some cases I think it can go to undesirable hormone pathways.
This is right on the money and in line with what I have been thinking about these pathways.

Last night, I took 5mg Progesterone + 5mg DHEA in tocopherol. Everything went back to normal and I feel perfectly balanced today. Nothing remotely like yesterday. Too much DHEA is, indeed, a bad thing, you are absolutely right ... it doesn't take much at all to handle a "deficit". Again, a lab range doesn't always mean a deficit. The body is smarter than we are.

So for whatever reason, my body seems to like very small doses of Progesterone + DHEA on a semi-regular basis. I will try every night, but as soon as libido takes a nose dive, I'll back off to every other day. We all have to find that sweet spot, and labs really can't get us there. Experimentation seems to be the only way.

If I were to guess, when we go on TRT, the majority of us have a biofeedback loop that slows down conversion of Pregnenolone to the sex steroids, as the body is saying "I've got enough down here, stand down". So those of us that are eating higher fat in the diet (and lower carbs) will see cholesterol go up, because it's not being used for that pathway at the level it used to before exogenous T.

What I am curious about (and will likely test) is where are my Progesterone levels at? I have a feeling this is a blind spot for a lot of guys. They think Progesterone is a female hormone, but it plays an important role in male physiology as well and if it goes too low -- watch out.

Progesterone, if used properly is androgenic. And consider this:

Testosterone and Progesterone, But Not Estradiol, Stimulate Muscle Protein Synthesis in Postmenopausal Women
 
#33
I've had some good results with Tribulus and Ginkgo Biloba. You may also look into Vitex, which is a hormone balancing herb. Usually defined as a woman's herb, guys will see their results at higher dosages-1500mg.

All 3 of these I began taking from reading recoveries of PFS.

Also, do you have stomach discomfort from eating? Sometimes I get it, and also can't concentrate. Maybe histamine? After researching stomach discomfort, I came across Pancreatitis. Then I found a study that Pancreatitis can cause low t3 levels, and higher reverse t3. Food sensitivities maybe?
 
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