Why Your Testosterone Is Low Even With Normal Bloodwork: Aromatase Explained

Why Your Testosterone Can Be Low While Your Bloodwork Looks Fine

Most men who get a low testosterone result assume their testicles have quit on them, and that assumption sends them straight toward replacement therapy without anyone ever asking where the testosterone actually went.

Start with the full chain, because the number on the lab report is the last step in a long loop, not the first.

We're producing testosterone at the testicles, and that production is not running wide open. Your brain releases two signaling hormones, LH and FSH, and those tell the testicles how hard to work.

And part of the thing that throttles the production of more testosterone so we don't get too much is the presence of estrogen, and that brake is what keeps the loop holding you in a range rather than letting the number climb forever. What presses the brake is estrogen, and where estrogen comes from is the part almost nobody explains properly.

Estrogen in men is converted from testosterone, and the conversion is done by an enzyme called aromatase, which takes a testosterone molecule and chemically rearranges it into estradiol. Aromatase is expressed in several tissues in the body including fat, muscle, skin and the brain, and the amount of expression varies by tissue and by age (Nelson and Bulun, 2001).

The commonly repeated version of this is that aromatase lives mostly in body fat, so the fatter you get, the more testosterone gets converted. I cannot point you to a study that establishes fat as the primary site of aromatase in men, and no study has shown that the low testosterone seen in obese men with normal LH and FSH is driven by peripheral conversion rather than something happening in the testicles themselves.

What I will say is that aromatase activity in fat tissue does increase with age, and Bulun and colleagues documented that rise in their work on aromatase in aging (Bulun et al., 1999).

The more estrogen we have, the more we are going to suppress the signal from our brain to produce more testosterone. I am describing the feedback loop as it is generally taught, and the research hasn't settled how much of the suppression in any individual man traces back to conversion happening outside the testicles.

Here is why this matters in a clinic room.

When you go to the doctor, you get your blood drawn, and what usually comes back is normal or even elevated estrogen sitting alongside LH and FSH that read as normal too, while the testosterone number itself lands low.

A doctor reading that panel sees a signal being sent correctly and a gland failing to respond, which looks like a testicle problem, and the standard answer to a testicle problem is exogenous testosterone.

Why? Because your body's producing what it should be producing but you're getting so much of that testosterone converted to estrogen that your T numbers are crashed and everything else is working properly upstream. That is the reading I favor when the upstream signal is intact and the estrogen is high, though I have seen this pattern clinically more than I can cite it from a controlled trial.

Picture a bucket with a hole in the side, slowly losing water no matter how much you pour in. You can keep pouring more water in, which is what testosterone replacement does, or you can find the hole. Adding water works, and it works fast, and it also shuts down your own production entirely because the brain reads the incoming testosterone as proof it no longer needs to send the signal.

The simplest place to start is body composition, because reducing fat mass reduces the tissue where conversion happens and it does so without touching the signaling loop at all.

Research: Bulun et al., Semin Reprod Endocrinol 1999; Nelson and Bulun, J Am Acad Dermatol 2001; Iorga et al., Biol Sex Differ 2017.

References:

Bulun SE, Zeitoun K, Sasano H et al.. Aromatase in aging women. Semin Reprod Endocrinol. 1999. https://pubmed.ncbi.nlm.nih.gov/10851574/

Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001. https://pubmed.ncbi.nlm.nih.gov/11511861/

Iorga A, Cunningham CM, Moazeni S et al.. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol Sex Differ. 2017. https://pubmed.ncbi.nlm.nih.gov/29065927/