SHBG and hormone availability: what the science actually says

What did @heatherhirschmd actually say?

Dr. Hirsch explained that sex hormone binding globulin (SHBG) is a transport protein that binds estrogen and testosterone, leaving less "free" hormone available to act on your cells. She said high SHBG means you may need higher hormone doses to feel results, while low SHBG means smaller amounts can be highly effective. She also noted that birth control pills can raise SHBG over time, and that neither a high nor low number is inherently "bad." Her core point: total hormone levels on a lab report don't tell the whole story.

She was careful to frame this as educational, not personalized medical advice, and she avoided making promises about what fixing SHBG would do. That restraint matters here.

Does the science back this up?

Yes, mostly. The physiology she describes is well-established and not seriously contested. SHBG is produced primarily in the liver, and it binds sex hormones with high affinity, particularly testosterone and estradiol, reducing their bioavailability. The "free hormone hypothesis" underpins clinical measurement of free testosterone and free estradiol in practice.

A 2010 review by Hammond in the Journal of Endocrinology confirmed that only unbound hormone can enter cells via passive diffusion or receptor-mediated pathways, making free hormone concentrations clinically relevant. On the birth control point, she's also correct: combined oral contraceptives raise SHBG significantly. A 2006 study by Panzer et al. in the Journal of Sexual Medicine found that SHBG levels rose sharply in women on oral contraceptives and, in some cases, remained elevated even after stopping. That finding has clinical implications for women transitioning off the pill and starting hormone therapy.

One important nuance she glosses over: the free hormone hypothesis is well-supported for testosterone but more debated for estradiol, where albumin-bound fractions may also be bioavailable. This isn't a major error, but it is an oversimplification.

What did they get wrong (or right)?

She got the fundamentals right. The claim that "if you have a high SHBG, you might find you got to increase it and increase it" reflects real clinical experience and is consistent with how practitioners manage testosterone therapy in women with elevated SHBG.

Where she's slightly loose is the framing around control. She says "this is a number that you don't have that much control over," which is partially true but incomplete. Lifestyle factors like insulin resistance, obesity, and alcohol intake are associated with lower SHBG, while thyroid dysfunction and certain medications raise it. A 2014 paper by Perry et al. in PLOS Genetics identified genetic variants strongly linked to SHBG levels, supporting her point that much of it is constitutive, but modifiable factors exist and she undersells them.

She also doesn't mention that exogenous testosterone itself suppresses SHBG, which is a relevant feedback loop for anyone on TRT. That omission isn't wrong, but it's a gap worth flagging for anyone interpreting their labs mid-therapy.

What should you actually know?

If you're on hormone therapy and your labs show high total testosterone or estradiol but you still feel off, SHBG is a legitimate variable worth discussing with your provider. It's not exotic or fringe, it's standard endocrinology. Free testosterone assays, while imperfect, give more actionable information than total levels alone in patients with abnormal SHBG.

That said, "it's about how you feel" is not a complete clinical framework on its own. Symptoms are important data, but they're also nonspecific. Fatigue, low libido, and mood changes overlap with thyroid dysfunction, depression, sleep disorders, and a dozen other conditions. SHBG is one variable in a broader picture, not a master switch.

If your SHBG is abnormal and you haven't looked at thyroid function, liver health, or insulin sensitivity, those are reasonable next steps before adjusting hormone doses. The Endocrine Society's clinical practice guidelines on testosterone therapy emphasize individualized assessment, not chasing lab targets in isolation, which actually aligns with her broader message even if she doesn't spell out those specifics.