Thyroid Worse on Testosterone Replacement

[DrMariano2]

Has anyone’s thyroid gotten worse when on trt?

Thyroid was pretty stable before TRT. And ever since TRT, my TSH has gone from below 1 to 4-6.

I was taking .250 synthroid before TRT. And now doc upped it to .275.

I’m starting to regret starting TRT. I was also taking HCG and have stopped it for now to see if that helps?

I also have hashimotos and antibodies are through the roof!

Usually, when I start testosterone replacement therapy (TRT), I also have to be ready to adjust thyroid hormone because exogenous testosterone can reduce thyroid signaling.

Changing one signal (as in testosterone) causes multiple downstream signaling changes in other systems. As long as one is ready to make the adjustments to thyroid hormone signaling and other signaling systems with TRT (such as estrogen signaling, adrenal signaling, nervous system, immune system, metabolism, nutrition, etc.), then one can avoid some complications with TRT, such as anxiety, fatigue, hypertension, insomnia, body aches, etc.

Off the top of my head, there are several possible ways TRT can reduce thyroid hormone signaling, including the following:

1. Exogenous testosterone suppresses testicular testosterone production AND testicular thyroid releasing hormone (TRH) production. This reduces brain TSH production, lowering thyroid hormone production from the thyroid gland.

2. Exogenous testosterone may reduce liver production of thyroid binding globulin. This reduces the half-life of thyroid hormone. This leads to a reduction in available thyroid hormone.

3. Exogenous testosterone can lead to a simultaneous conversion of testosterone to estradiol. The increase in estradiol can increase liver production of thyroid binding globulin. This can lead to a reduction in free thyroid hormone levels (Free T3, Free T4). This then reduces thyroid signaling.

4. Exogenous HCG (human chorionic gonadotropin) not only increases testicular production of testosterone and sperm but also increases aromatase enzyme production. The increase in aromatase enzyme can then lead to an increase in estradiol production from testosterone. This (as noted above) can lead to a reduction in thyroid signaling.

5. Exogenous testosterone can suppress ACTH (adrenocorticotropic hormone) production from the brain. And it can directly suppress adrenal cortical activity, including cortisol production. This can then lead to an increase in norepinephrine production, then immune system inflammatory signaling. This can then shift thyroid metabolism so that T4 is converted to reverse T3 (the waste product pathway) instead of being converted to T3 (the active thyroid hormone). This can reduce both T4 levels and T3 levels, leading to a reduction in thyroid signaling.

When possible, I usually prefer to consider first optimizing thyroid signaling, adrenal function, immune system function, nervous system function, metabolism and nutrition, to allow a smoother transition to testosterone replacement therapy.

There are times when adding testosterone simultaneously while addressing the other systems is important to help break some positive feedback loops between systems that contribute to illness. For example, high insulin/insulin resistance/diabetes, obesity, inflammatory signaling, stress/norepinephrine signaling, and lower testosterone production can be involved in multiple positive feedback loops which can cause significant illness. Adding testosterone when it is low in such a person can help unravel the self-perpetuating signaling loops that keep a person ill.

[DrMariano2]

Would you say that most men starting TRT have to raise or lower their thyroid
meds? Or is it the usual some need to raise, some lower, everyone’s different.
I thought testosterone was involved in the T4 to T3 conversion process. I
could’ve sworn I read on either the Testim or Androgel insert that men on
thyroid would need to be closely monitored cause chances were they’d have to
reduce their dose.

Most often, men will have to increase the dose of thyroid hormone after starting TRT. I have yet to see a need to lower thyroid hormone in men who start TRT.

Off the top of my head, one possible mechanism by which testosterone can lead to an increase in thyroid hormone is if there is significant inflammatory cytokine signaling resulting in a shift of T4 metabolism to Reverse T3 rather than T3.

If exogenous testosterone helps reduce inflammatory cytokine signaling, it can then help reduce reverse T3, leading to an increase in T3 production from T4.

On the other hand, increased inflammatory signaling can also lead to an increase in sympathetic nervous system norepinephrine production, i.e. stress signaling. This may then increase deiodinase enzyme production, increasing T4 to T3
conversion.

If Testosterone reduces stress/norepinephrine signaling – and testosterone is usually a very calming signal unless a lot is transformed to estradiol – then the addition of exogenous testosterone would negate norepinephrine’s increase in
T3 production.

This can possibly negating the gain from the above antiinflammatory effects of testosterone. This would lead to a wash in thyroid change from the addition of testosterone via these two mechanisms.

The sum of the above and other pathway influences on thyroid hormone would determine whether or not thyroid hormone increases or decreases with the addition of exogenous testosterone.

In my experience, usually, exogenous testosterone generally reduces thyroid hormone signaling. The population that I may see, however, may be different from that seen by other physicians.

[DrMariano2]

Thanks for the detailed answer Dr. Mariano. And does higher and higher
estradiol bind more thyroid, making you more hypo?

I’m thinking if estradiol is brought down with DIM or arimidex, it would then
free up your bound thyroid, meaning you’d lower your thyroid dose. Yes? No

It not that estradiol binds more thyroid hormone. Estradiol increases liver production of thyroid binding globulin which binds thyroid hormone, leaving less in the free form.

Reducing estradiol vis DIM or Arimidex works to a certain point, then worsens the situation.

Lowering estradiol would reduce thyroid binding globulin production. This increases free thyroid hormone. However, if thyroid binding globulin is reduced excessively, then the half-life of thyroid hormone is reduced. This results in an increased breakdown of thyroid hormone, leading to a reduction in total thyroid hormone.

Arimidex also has a limit in reducing estradiol. In some men, the body may compensate by increasing production of estradiol via alternative pathways when its production via the aromatase enzyme is reduced excessively. Thus there may be a ceiling in reducing estradiol after which the body uses other pathways to produce estrogen. Also other estrogens may be produced when estradiol is reduced excessively. One can’t also reduce estradiol excessively before the liver compensates by increasing cholesterol production.

It is a matter of balance. Estrogens are monitored more closely by the brain than testosterone in determining production of the reproductive hormones.

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