SHBG, TRT, and making your dose actually work

Most men on TRT focus on the total testosterone number. The quiet spoiler is SHBG, a liver protein called sex hormone binding globulin. SHBG binds testosterone in your blood. Bound T is effectively neutralized and useless. Free T does the work. If SHBG is very high, you can have a decent total T number and still feel undertreated.

What SHBG does to your free T

SHBG is made in the liver and changes with health status. More SHBG means less free T for the same total T. That is why two men with a testosterone of “800 ng/dL” can feel totally different. Here’s where it gets confusing - Insulin resistance and liver fat tend to lower SHBG, while weight loss and fitness often raise it. Higher SHBG is not bad by itself; it’s a signal of the metabolic context your TRT is working inside. Trials and cohorts consistently show SHBG rises with intentional weight loss and structured exercise, while low SHBG tracks with diabetes risk and insulin resistance (journals.plos.org). Mechanistically, hepatic insulin signaling and steatosis down-regulate SHBG expression, tying low SHBG to poor metabolic health (2014–2015) (academic.oup.com).

So should you try to “lower” SHBG?

Not with shortcuts. You could drive SHBG down by becoming less healthy, but that trades free T for cardio-metabolic risk. Instead, correct causes of abnormally high SHBG, like over-replacement of thyroid hormone or untreated hyperthyroidism, which are classic drivers of elevated SHBG (pubmed.ncbi.nlm.nih.gov). If SHBG is high from being lean, highly active, or genetically set that way, you adjust how you replace testosterone rather than trying to suppress SHBG.

TRT tactics when SHBG is high or low

• Measure what matters. Don’t chase total T alone. Calculate free T with a validated equation that uses total T, SHBG, and albumin, or measure by equilibrium dialysis where available (academic.oup.com).

• Match dosing to SHBG. Lower SHBG men tend to have sharper peaks from larger, infrequent injections, which can provoke side effects; splitting the same weekly dose into smaller, twice daily topical application smooths the curve and often fixes symptoms. This is a practical clinic pearl echoed in our course materials.

• Check at the right time. For injections, draw labs at the trough (right before the next shot is due) to align numbers with how the patient feels day to day. For creams, consistency and symptom correlation matter more than isolated peaks, per our protocol, making lab testing even less frequent.

Lifestyle that makes TRT work better

These aren’t “SHBG hacks.” They are foundation of understanding that improve energy systems, reduce liver fat, and make any TRT regimen easier to dial in.

• Lose visceral fat at a steady pace. In overweight men, clinically supported weight-loss programs increased total T and SHBG and improved sexual function over months to years (journals.plos.org).

• Train with intent. Regular training improves insulin sensitivity and often raises SHBG as body composition improves. That can raise SHBG while improving symptoms, and you’ll adjust your TRT to maintain adequate free T as health improves (pmc.ncbi.nlm.nih.gov).

• Protect the liver. Limit (or preferably eliminate) alcohol, prioritize whole-food protein, and treat NAFLD (Fatty Liver Disease) risk factors. Hepatic fat and hyperinsulinemia suppress SHBG gene expression and lower circulating levels (academic.oup.com).

• Fix thyroid first if abnormal. Hyperthyroidism and overtreatment with thyroid hormone can elevate SHBG and distort free T calculations; correct the thyroid state before changing TRT (pubmed.ncbi.nlm.nih.gov).

• Lab cadence with context. Recheck after steady routines, not right after big diet or training shifts, so we aren’t chasing moving targets. Use the same lab and timing.

Takeaways

• Don’t try to “game” SHBG. Just know it exists and adjust as you improve metabolic health.

• Dose TRT to symptoms and free T, not total T alone.

• Use smaller, more frequent doses when SHBG is low or symptoms are peak-trough driven.

• Expect labs to evolve with training and fat loss; adjust dose of TRT instead of forcing SHBG down.

Kyndl perspective

We optimize the human system first, then the numbers. SHBG is one of many things we consider when we treat you, but it isn’t the only thing. We’ll use it to tune dosing cadence and aim at the healthiest way to achieve stable, therapeutic free testosterone.

This article is educational and not medical advice.

Evidence callouts

• Weight loss increases testosterone and SHBG in overweight men, improving sexual function (2016 randomized trial; 30-month follow-up lifestyle trial) (journals.plos.org).

• Low SHBG associates with insulin resistance and diabetes risk across cohorts (2010–2024) (drc.bmj.com).

• Insulin signaling and hepatic triglyceride content down-regulate SHBG expression in the liver (2014 mechanistic review) (academic.oup.com).

• Thyroid excess raises SHBG; hypothyroidism lowers it. Treat the thyroid disorder rather than aiming at SHBG itself (1986–2004; mechanistic 2013) (pubmed.ncbi.nlm.nih.gov).

• Free T should be calculated or directly measured when SHBG is atypical (guidance based on Vermeulen approach, 1999–2006) (academic.oup.com).

Sources

• Moran LJ et al. PLoS One. 2016; randomized weight-loss trial in overweight men (testosterone and SHBG). (journals.plos.org)

• Duggan C et al. Int J Obes. 2019; diet+exercise increased SHBG at 30 months. (pmc.ncbi.nlm.nih.gov)

• Winters SJ et al. J Clin Endocrinol Metab. 2014; hepatic fat, insulin resistance, and SHBG expression. (academic.oup.com)

• Aroda VR et al. BMJ Diabetes Res Care. 2020; SHBG inversely related to diabetes risk. (drc.bmj.com)

• de Nayer P et al. J Clin Endocrinol Metab. 1986; SHBG in thyroid states. (pubmed.ncbi.nlm.nih.gov)

• Meikle AW. Endocrinol Metab Clin North Am. 2004; thyroid–SHBG interrelationships. (pubmed.ncbi.nlm.nih.gov)

• Pulido MR et al. J Mol Endocrinol. 2013; thyroid hormones increase SHBG via HNF-4α. (jme.bioscientifica.com)

• Vermeulen et al. J Clin Endocrinol Metab. 1999; free T calculation; plus de Ronde 2006 comparison. (academic.oup.com)