Effect and safety
Some studies, including those discussed in a previous article in the Journal of the Norwegian Medical Association (1), emphasise positive patient experiences and highlight the importance of relatively short-term outcomes. However, it is important to recognise that puberty blockers, in addition to the subsequent treatment with exogenous sex hormones (which the majority of those receiving puberty blockers eventually undergo (5, 6)), must still be considered experimental. There is currently insufficient clinical evidence of lasting health benefits, in terms of empirical data (7, 8) and systematic evaluations of study quality (9, 10). Existing studies are often characterised by methodological challenges such as considerable variation in study design, low scientific quality due to high dropout rates, relatively short follow-up periods, heterogeneous study populations and insufficient sample sizes to draw definitive conclusions (7–10).
Furthermore, hormone-modulating therapy can cause serious adverse effects such as infertility (11, 12), irreversible damage to the genital organs (13, 14), osteoporosis (15), dyslipidaemia, elevated haematocrit and an increased risk of cardiovascular complications (thrombosis, infarction and sudden death) (16–19). Patients who subsequently undergo surgery face additional risks of complications, including infections, haemorrhage, impaired wound healing and surgical side effects such as scar contractures, fistula formation, necrosis, urinary incontinence and voiding dysfunction, accompanied by psychosocial problems and chronic pain (20–23). Surgical removal of the native genitalia generally results in permanent sterility (24).
Although gender incongruence is no longer classified as a mental disorder, experience and research indicate that many of these children and young people also have mental health problems, and the high prevalence of psychiatric comorbidity is a major concern (25, 26). However, mental health is not always thoroughly evaluated before irreversible treatment interventions are initiated. In some cases, this can impair a patient's overall health, which several of us have encountered.
There are few longitudinal studies in this field. In a well-known Swedish study that followed 324 adults for up to 30 years (with an average follow-up of 10 years) after gender reassignment via hormone therapy and surgery, suicide rates remained high in the follow-up period (27). The overall rate was 19 times higher than that of age-matched controls, and 40 times higher among individuals who had transitioned from female to male.
A subsequent Swedish registry study (28) found evidence that surgical interventions, but not hormone therapy, improved mental health in individuals with gender incongruence. In response to criticism from the medical community, the editor-in-chief of the American Journal of Psychiatry (29), which published the study, prompted an independent statistical review. This review refuted the main conclusion of the original study. In a subsequent reanalysis, the authors compared two equal-sized groups with gender incongruence: one that had undergone surgery and one that had not (30). No significant long-term differences in mental health were found, and overall, the findings did not support the notion that 'gender-affirming' interventions have a documented positive long-term effect on mental health.