But we're not talking about pregnancy. We're not actually suggesting that people do pregnancy-level E long term. I did it once on a lark to see what it felt like. My long-term numbers are more in the 300-400 range.

The point is that hormones are incredibly safe medications, far safer than most OTC medications. Searching for LD50 values for various estradiol formulations suggest numbers around 1000 mg/kg of body weight in rat studies. A typing oral E dose is in the 4-8 mg/day range. You could literally take an entire decade's worth of oral estradiol all at once, and odds are it wouldn't kill you.

I agree that you should generally aim for the lowest effective dose, but doctors and patients often fundamentally disagree on how to define that. The dichotomy I often see is:

Patients: I want the dose that maximizes masculinization/feminization and produces the absolute best physical results I can get on E/T. I know there's not studies showing superior effects and experiences in the 300-400 range vs the 100-200 range, but subjectively I feel better and anecdotally I get better results. There aren't studies I can point at to support this, as the studies haven't been done. I want to find the minimum dose to produce maximum changes.

Doctors: I practice evidence-based medicine. Research on transition-related care is horribly underfunded, but that's not my problem. What evidence I do have suggests that HRT can reduce the risk of suicide. I'll prescribe the minimum dose proven to affect suicide rates among trans people.

One approach says, "trans identities are valid and I want to help facilitate them as best I can." The other is, "trans women are at their core delusional males. However, giving them HRT is a proven way to prevent them from hurting themselves. Give them the minimum E dose to prevent self-harm."