The problem with having to get a doctor to prescribe gender-affirming hormone therapy is that doctors are trained to treat diseases. When you’re treating a disease you have a clearly defined goal - curing the disease, or minimising the suffering if it cannot be cured. This also extends to the scientific studies used to formulate treatment options, there is a clear and measurable definition of success. This is critical for normal patient care, doctors want to minimise the harm caused - and lets be clear, all medicines are harmful, just less harmful than what they’re treating - while maximising the effectiveness of the treatment.

This doesn’t work for gender-affirming care though. The effects you get from hormones depend a lot on your genetics and we don’t know enough about those to determine if a treatment is fully effective. In terms of M-F transition, we can’t establish if a certain breast size is the one genetically encoded, or if it has been restricted due to a lack of hormones. For those going F-M, is your voice fully deepened or has it stopped because of insufficient testosterone? Does the hormone level actually matter to either or is there just a threshold? We cannot design a study for this, especially given it would have to run for over 5 years to fully capture all the changes.

All of the uncertainty leads to doctors missing out on one half of the risk calculus - if you can’t tell what the target is you’re stuck with minimising the overall risk rather than balancing it against the effectiveness of treatment.

Now I’ll focus on one of the problems this causes

As always I’m looking at academic papers, so there will be medical language used some of which may be outdated.

Arbitrary medication limits

In the latest edition of the PATHA guidelines for gender affirming care, which is the document used by most doctors in New Zealand, there is this paragraph:

There is currently no evidence to suggest that a dose of ostrogen higher than 200mcg/24 hours via patch or 6mg daily orally is helpful, and, indeed, poor evidence to suggest any strong correlation between ostrogen doses at recommended levels and outcomes at all.

which cites as evidence

Moore E, Wisniewski A, Dobs A. Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects. The Journal of Clinical Endocrinology & Metabolism. 2003;88(8):3467-73.|

Time to get the paper! Here’s the summary of the paper on pubmed, your local library may have access to the journal if you want a copy.

At first glance, this paper suffers from very common issues in the field of transgender healthcare. It’s based on outdated medications and, the time period is unclear, some of the discussion compares to post-menopausal HRT, and it contains unjustified dose-level scaremongering.

Outdated medications

In this study the trans-feminine cohort were predominantly treated with ethinylestradiol or conjugated equine estrogens (CEE). There is one that used bio-identical oestrogen, but this was delivered as an injection for the first year.

These are not the medications we use in New Zealand. Both ethinylestradiol and CEE are no longer used for most GAHT because of the known adverse effects which are not present or greatly reduced when using bio-identical hormones, for example blood clots which aren’t a serious problem with bio-identical oestradiol.

It’s also important to note that non-human oestrogen has a different affinity for the various oestrogen receptors in the body. Two studies ^{1 2} found very different affinities for ethinylestradiol to the human oestrogen receptor, but neither of these had the same balance as human oestrogens do. Does this make a difference in GAHT? We have no way of knowing. CEE has a different binding profile as well.

Additionally most of the reports used cyproterone acetate in doses of 50-100mg per day which is a very high dose of a medication with known dose-dependant side effects, and is also known to be just as effective at much lower doses. Cyproterone acetate is a progestin, and has a very high affinity for progesterone receptors, which are implicated in breast development in animal models.

Study duration

It’s hard to pinpoint the duration of this study as it’s based on reports from multiple worldwide practices. They all seem to have different standards, but it takes several years for transition - puberty takes 8+ years and there’s nothing to indicate gender transition would be different - so studies have to run for a long time to see all the effects.

Comparison to menopausal HRT

This happens a lot in so many studies. Menopausal HRT and GAHT are not comparable in their goals and measures of efficacy. HRT for menopause has clearly defined symptoms so the dose can easily be adjusted to the lowest possible to relieve them, and lets remember that the surge of demand for HRT came after a TV documentary showed how badly treated women with menopause were by doctors, either through ignorance, not updating their knowledge about treatments, or plain dismissal of symptoms as important.

Menopausal HRT is aimed at reducing symptoms from a drop in hormones, not replacing hormones to effect a change. Doses for GAHT will have to be higher, we should be aiming for adult levels of hormones.

Dose level scaremongering

Quotes from the paper

Treatment that exceeded recommended estrogen dosages in M3F transsexual people was reported by eight subjects (45%), and five subjects (28%) reported three or more times the recommended dosage. […] Additionally, despite the hesitancy of providers to distribute injectable hormones to M2F transsexual people, 28% reported their use. In light of the older age of subjects, these high doses and complex regimens were particularly concerning for increased risk of adverse effects.

Doctors are always concerned about the risk of adverse effects, but they rarely seem concerned about the patient’s concern for these risks, or attempt to balance it against the mental distress of gender dysphoria.

All medications carry the risk of adverse effects, it should be up to the patient to determine their risk level.

My conclusions

I don’t think this study provides the evidence for any restriction of dose levels. There are reasons to had a maximum dose level, but this study doesn’t provide them. It reports on medications that we do not use, that have different absorption and biological effects, and seems more interested in commenting about how the doctors are concerned about the levels than the patients’ overall wellbeing.

While I’m not advocating for a hormone free-for-all I do wish that doctors would work with us rather than against us, ensure we know the long and short term risks and allow us to make our own choices.