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Posted on March 31, 2019 at 4:33 PM

by Florence Ashley B.C.L., LL.B

Hormonal interventions for trans youth are subject to controversy in the media and certain clinical circles. A recent blog post for BMJ EBM Spotlight described hormonal interventions for trans youth as “largely experimental” and cautioned that the available evidence didn’t allow informed clinical decision making. This assessment stands in stark contrast with the commonplaceness of hormonal interventions in trans youth care.

Determining how much evidence is needed for a practice to be deemed sufficiently safe involves a value judgement. Although more evidence on various hormonal regimens is welcomed by trans health clinicians, current evidence demonstrates enough safety to justify the prescription of puberty blockers and hormone replacement therapy. Transition-related care is unlike traditional medicine insofar as it doesn’t aim at curing an illness, but rather at enabling self-actualisation and promoting bodily autonomy. Being trans, as the World Professional Association for Transgender Health states, is not an illness but part of normal human variation.

The present blog article aims at providing a gender-affirmative perspective on the reported data, highlighting the normative component of evaluating safety, and addressing some common misconceptions about the risks of hormonal interventions.

Size of trans youth populations and the clinical picture

The prevalence estimates of 1 in 27,000 to 1 in 10,000 offered by the BMJ EBM blog post are misleading: They do not represent the proportion of people who are trans or have gender dysphoria, but rather the proportion of youth attending gender identity clinics (GICs). A report by the Williams Institute, which draws from population-based surveys, estimates that the number of youth from ages 13 to 17 who identify as transgender is closer to 1 in 145. No authoritative explanation for the discrepancy has been offered by GICs, but fear of parental rejection and community distrust for GICs are likely contributors. Being trans is common.

Photo by Zackary Drucker from The Gender Spectrum Collection, used under a Creative Commons license.

The authors also report that approximately ¾ of pre-pubescent children will “change their minds as they age”. As experts in trans health explain, this statistic is misleading for a number of reasons: Many children referred to GICs never claimed to have a gender different from the one they were assigned at birth and didn’t meet the full criteria for diagnosis, and various theoretical and methodological assumptions artificially inflated the reported percentage.

Most importantly, those numbers are irrelevant to puberty blockers and hormone replacement therapy. The ¾ statistic is based on flawed studies and only refers to pre-pubertal youth, whereas puberty blockers and hormone replacement therapy are only offered after the beginning of puberty. A 2011 study conducted at the clinic from which the ¾ statistic arises has shown that children who decide to initiate puberty blockers all continued to be trans years later.

Puberty blockers

The primary evidence base regarding the safety of puberty suppression is the use of GnRHa for precocious puberty. Since the underlying biology remains the same, the primary difference between GnRHa for precocious puberty and as part of puberty suppression is the length of treatment, especially in relation to bone density. Because longer use of GnRHa leads to poorer bone density compared to peers of the same age, many clinicians recommend initiating hormone replacement therapy before 16 years old among youth who have been on blockers for multiple years.

The impact of puberty blockers on bone density is a common concern. As reported by the BMJ blog, a 2015 study found decreased bone density for trans girls which “did not increase following oestrogen treatment.” However, their bone density was being compared to the bone density of age-matched cisgender (not transgender) men rather than cisgender women and was a relative measurement rather than a measurement of absolute density. This is an inappropriate comparator when attempting to establish safety profiles.

To the extent that long-term use of puberty blockers may have an impact on bone density, initiating hormone replacement therapy earlier may be indicated. This would also allow youth to undergo puberty alongside their peers, reducing risks of ostracization.

Hormone replacement therapy

Different hormone replacement therapy regimes come with different safety profiles. In the past, ethinyl estradiol was commonly prescribed; it was associated with significant risks of adverse cardiovascular events and is no longer commonly prescribed. Cyproterone acetate is associated with depressive symptoms and, more recently, with risks of brain tumours. Other options should be considered, where appropriate, and suppression with only estrogen should be considered.

Hormone replacement therapy impacts haematocrit levels. The blog post cites a 2017 study as showing significant elevation in haemoglobin and haematocrit among trans men. However, both haematocrit and hemoglobin are on average higher in men than in women, and the increase in both counts merely bridges that gap. The haematocrit of 44.5% and hemoglobin count of 15.0 g/dL reported in the study are well within normal ranges for men and do not pose significant concerns.

Data on the metabolic impact of hormone replacement therapy should be read cautiously, keeping in mind that many metrics vary between cis men and women, and that undergoing hormonal interventions will impact metabolic parameters accordingly. In adults, higher rates of adverse cardiovascular events were found in transfeminine individuals but may be due to higher rates of smoking and stress. Nonetheless, the incidence of venous thrombosis incidence was lower for trans women than for cis women on birth control, suggesting that it is well within acceptable risks. Where risk factors such as smoking and stress are present, non-oral forms of estrogen can be used to further lower risk.

Frames of evaluation

Assessing safety is relative and value-laden. We accept greater negative effects before we call a cancer treatment unsafe than we do for Ibuprofen. Our evaluation of the importance and purpose of hormonal interventions sets the preliminary threshold for assessing whether a treatment is sufficiently safe to be indicated.

Hormonal interventions are offered because trans people deserve to have a gendered body that suits their self-image, just like cis people, even if this requires bodily interventions. Much like access to abortion, it is a matter of fundamental bodily autonomy. Access to hormonal interventions is correlated with better mental health and quality of life in both youth and adults. These metrics are admittedly subjective, as the blog authors point out, but this is a by-product of interventions justified by bodily autonomy and psychological wellbeing—psychology and psychiatry, by and large, work from such subjective measures.

Physical health is difficult to compare to mental health, let alone abstract notions like bodily autonomy. This makes hormonal interventions ethically atypical: they are not a cure for an illness, unlike most endocrinological interventions, but a tool of self-actualisation. This difference in the fundamental logic of puberty blockers and hormone replacement therapy makes adopting a high evidentiary threshold for safety unreasonable. Would we prohibit abortions because their safety hasn’t been sufficiently proven, especially when little interest has been historically shown in exploring its safety?

Although hormonal interventions raise some safety concerns and better studies are needed in elucidating the comparative benefits of different regimens, they are sufficiently safe for current practices. According to the systematic review Hormonal Treatment in Young People With Gender Dysphoria which the blog authors relied upon: “Overall, hormonal treatments for transgender youth were observed to be relatively safe but not without potential adverse effects.”


Longitudinal studies comparing different hormonal regimes are necessary to the development of trans health. These studies will inevitably be neither blinded nor randomised, as blinding is impossible, and randomisation would be impractical and unethical. Controlled groups should be used and matched on risk factors such as stress levels, physical activity, and smoking.

The current practice of prescribing puberty blockers and hormone replacement therapy to trans youth is legitimate. The positive impacts on bodily autonomy and mental health outweigh the apparent risks. A critical reading of the scientific literature is necessary, as studies do not always frame their data in the most informative way for subsequent analysis. The risks of hormonal interventions should not be overstated, as can happen when comparing trans participants to controls of the same gender assigned at birth. Risk can be minimised through individualised hormonal regimens, and remaining concerns about risk are appropriately addressed by obtaining properly informed consent or assent.

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