High SHBG on Clomid or Enclomiphene? Fix It With TRT Instead

Why Your Total Testosterone Looks Great on Enclomiphene But You Still Feel Terrible

SHBG management, we get this a lot. And the reason we get this a lot is because we have a lot of guys on CIRMS. They take the Enchlomophen, they take the Clomid, obviously their SHBG numbers climb, they're free test plummets. They have higher testosterone levels, but they still feel like shit.

To understand why that happens, you have to know what testosterone actually does in the bloodstream, because it does not float around freely waiting for a receptor.

Most of it is attached to something called sex hormone binding globulin, or SHBG, which is a protein made in the liver that grabs onto testosterone and holds it tight. A smaller portion attaches loosely to albumin, another blood protein, and that bond is weak enough that the testosterone can come off when tissue needs it. And then there is the small fraction, usually somewhere around one to three percent, that is unbound and immediately available to enter a cell and do something.

So when a lab prints a total testosterone number, it is counting all three of those pools together, and it tells you nothing about how much of that hormone can actually reach a receptor.

That distinction has been formalized for decades. Vermeulen and colleagues laid out the calculation showing that free testosterone depends on total testosterone and SHBG together, meaning two men with identical total numbers can have completely different amounts of usable hormone depending on their binding protein.

Well, that's because your SHBG levels are elevated, which is binding up most of that free testosterone, which renders it basically useless.

Picture a warehouse with a thousand boxes on the floor. If nine hundred and eighty of them are chained to the wall, you have a thousand boxes and twenty you can move. That is what a high SHBG lab result means when it sits underneath a beautiful total testosterone number.

So how do we manage them? The quickest and easiest way to do it, if you're ready for the commitment, take the CIRM and throw it out the fucking window.

And I know in the past I have recommended CIRMS, they can be used as a tool for specific situations, especially with short term secondary hypogonadism, where we're trying to get somebody in check, fix their habits. Enclomiphene absolutely does what it says it does on the total testosterone side. Kaminetsky and colleagues showed oral enclomiphene citrate raised total testosterone into the normal range in men with low testosterone while maintaining sperm counts, which testosterone gel did not do.

That is a real result and it matters if fertility is the priority.

But if you're planning on being on this long term and you're okay with the TRT, testosterone is not going to elevate your SHBG. It's actually going to lower it and make you feel really good. I have never seen a study that landed cleanly on the exact magnitude of that drop, so I am telling you what I watch happen in bloodwork with clients rather than what the literature has settled.

There is another piece worth checking before you change anything, and it is body composition. La Vignera and colleagues ran a controlled pilot in men with obesity and metabolic hypogonadism, and tirzepatide raised total testosterone from 8.4 to 11.6 nmol/L alongside significant fat mass reduction, without any hormone being given directly.

Fat tissue and liver stress both push binding protein around, so if you are carrying extra weight, some of your SHBG problem is a body composition problem wearing a hormone costume.

Research: Kaminetsky J, Werner M, Fontenot G et al., J Sex Med, 2013. Vermeulen A, Verdonck L, Kaufman JM, J Clin Endocrinol Metab, 1999. La Vignera S, Cannarella R, Garofalo V et al., Reprod Biol Endocrinol, 2025.

References:

Kaminetsky J, Werner M, Fontenot G et al.. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. J Sex Med. 2013. https://pubmed.ncbi.nlm.nih.gov/23530575/

Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999. https://pubmed.ncbi.nlm.nih.gov/10523012/

La Vignera S, Cannarella R, Garofalo V et al.. Short-term impact of tirzepatide on metabolic hypogonadism and body composition in patients with obesity: a controlled pilot study. Reprod Biol Endocrinol. 2025. https://pubmed.ncbi.nlm.nih.gov/40604795/