Why TRT isn’t working for you and what to do about it

Ben House said that 80-85%+ of men quit TRT after 1 year of use (R).

This study found that adherence to topical TRT was very low. By 6 months, only 34.7% of patients had continued on medication; at 12 months, only 15.4% (R).

Why is that?

It’s for a variety of reasons, such as injection issues, not wanting to be on something their whole life and also because TRT didn’t do for them what they thought it would.

I’ve had many men contact me telling me that TRT didn’t do much for them.

Most men use it because of libido and sexual problems. As a side bonus, they expect more energy and maybe more assertiveness.

But after trying different esters, different doses, with or without AI, maybe even HCG, it just isn’t working.

What to do?

Vitamin D connection

The two studies I found most interesting that showed me that there was something to this were the following:

Progesterone, vitamin D and TBI

This 2011 study found that vitamin D deficient (Vit D-deficient) animals had elevated inflammatory proteins (TNFα, IL-1β, IL-6, NFκB p65) in the brain even without injury. Vit D-deficient rats with TBI, whether given progesterone or placebo, showed increased inflammation and greater open-field behavioral deficits compared to Vit D-normal animals. Although progesterone was beneficial in injured Vit D-normal animals, in Vit D-deficient subjects neurosteroid treatment conferred no improvement over vehicle (R).

But it’s not like vitamin D alone is the magic molecule here. This study shows that while vitamin D alone and progesterone alone both produced beneficial effects on neuronal cell survival in TBI, the combination of vitamin D and progesterone produced significantly more neuroprotection than either compound given alone and at their best individual doses (R).

So, progesterone was helpful at reducing brain edema and inflammatory markers, but without vitamin D, it conferred no improvement compared to placebo.

Strike 1: Progesterone needs vitamin D to work properly.

Testosterone, vitamin D and ED

This meta-analysis in 2020 found that those with low D, despite normal T, had a higher risk of ED than those with higher D and the same level of T (R).

…we found that eugonadal patients with severe ED have lower 25(OH)D3 levels than patients with mild ED. In conclusion, this meta-analysis suggests an association between vitamin D deficiency and the presence of severe forms of ED, independent of testicular function.” (R)

Strike 2: Low D equals ED, despite normal T.

To feel good on TRT, you need high vitamin D levels

It is worth emphasizing here that vitamin D is in fact not a vitamin, but rather a seco-steroid hormone with the same cholesterol backbone as other sex steroids (such as progesterone, testosterone, etc.) and its own class of nuclear steroid receptors and signaling mechanisms.

All steroids bind to nuclear receptors, where they influence DNA transcription and gene methylation.

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A few other interesting tidbit to consider

Dopamine

Testosterone improves mood, energy expenditure, focus and motivation by increasing dopamine and acetylcholine.

Vitamin D has also been shown to increase choline acetyltransferase and tyrosine hydroxylase activity, which are enzymes responsible for the synthesis of acetylcholine and dopamine (R).

Parkinsons is a condition where there is neurodegeneration doing on in the dopaminergic system. A high prevalence of vitamin D deficiency has been noted in Parkinson’s disease for at least the past two decades (R).

Androgen receptors

Vitamin D has androgen effects from multiple angles.

Vitamin D can:

  • bind to the androgen receptors directly (R, R)
  • prolong the duration that androgens bind to the androgen receptors
  • Increase androgen receptor mRNA, which lead to more androgen receptors (R)

Testosterone and vitamin D work together to prevent prostate cancer (R).

Think of anything that testosterone is good for; the liver, vascular system, bone, etc. For everything testosterone is beneficial, so is vitamin D. They synergize and are better together than either one alone.

Practical takeaway

Make sure your vitamin D is above 50ng/ml. I prefer to get sunlight for my vitamin D, since sunlight provides additional sexual, libido and mood benefits. Check it out here.

This alone should give you most of the benefits you need. Always be sure to eat a nutrient-dense diet as well, to provide all the cofactors for steroidogenesis and cellular function.

If you’re on testosterone alone, also consider adding pregnenolone and DHEA daily to backfill these prohormones that are suppressed by TRT.

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