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February 20, 2021
GENDER DYSPHORIA – the miserable feeling of contradicting one’s own gender – is one of the fastest growing medical complaints in children. America had a pediatric gender clinic in 2007. There are now at least 50. In the only pediatric gender clinic for England and Wales known by the acronym GIDS, referrals have increased 30 times in a decade. A similar pattern can be seen in the rich world.
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Many who visit such clinics are given gonadotropin releasing hormone (GNRH) agonists, or “puberty blockers”. Approved for the treatment of breast and prostate cancer, endometriosis, and “central premature puberty” – a rare condition in which puberty begins much earlier than normal – these drugs are prescribed off-label to stop the signals that cause The ramps of the testicles or ovaries to stimulate ramps increase sex hormone production. The idea is to delay puberty and give patients time to decide whether to proceed with cross-sex hormones and surgery to “die” as adults of the opposite sex.
All drugs offer a mixture of harm and benefit. Despite their popularity, the effects of puberty blockers remain unclear. Because they’re not approved for gender medicine, drug companies haven’t conducted studies. In many clinics, the records are poor. A 2018 review by researchers at the University of Melbourne described the evidence for its use as “inferior”. In December, UK judges also pointed to the lack of “solid evidence” when ruling that children are unlikely to be able to give meaningful consent to admission. The UK’s National Health Service recently withdrew an assertion made elsewhere that its effects were “completely reversible”.
The studies that exist are both weak and worrying. The day after the court ruling, GIDS published a study that found that children were happy to receive the medication. However, there was little other evidence of benefit – not even a reduction in gender dysphoria. Two older studies in Dutch patients given puberty blockers in the 1990s found that gender-specific dysphoria subsided afterwards. However, without a control group, it’s impossible to tell how the patients would have felt if they hadn’t taken the medication.
A 2020 paper analyzed the responses to an online survey and concluded that people who took puberty blockers were less prone to having thoughts of suicide. However, online surveys collect practical rather than representative samples. People can answer repeatedly or at random. Much of the data appeared to be misreported: many who reported taking puberty blockers were too old to plausibly do so.
In the absence of direct, robust evidence, researchers can attempt to extrapolate from other findings. Off-label prescribing is widespread in pediatric medicine because drug companies generally don’t like conducting studies on children. Hence, doctors look for used evidence from elsewhere in order to make their decisions. One source is studies examining how GNRH agonists are used to treat other conditions.
Interrupting normal adolescence is not the same as treating cancer, endometriosis, or precocious puberty. However, data from these conditions have indicated unpleasant side effects. Men who take GNRH agonists lose energy and sexual desire. (It is for this reason that some countries prescribe them to sex offenders.) Women are put into artificial menopause, an experience so uncomfortable that for endometriosis, drugs are usually prescribed for a maximum of six months. Adults taking puberty blockers for precocious puberty have filed several lawsuits against drug companies. They claim cognitive deficits, brittle bones, and chronic pain later in life, even though none made it to court.
Animal studies suggest such concerns may be worth investigating. A 2017 study looked at sheep that are experiencing a developmental surge similar to that of human youth. Sheep administered puberty blockers performed worse than controls on a maze navigation task, suggesting that their spatial memory was inferior. A 2020 study examining mice found, among other things, that women given puberty blockers were more shy in unfamiliar environments and earlier abandoned a “forced swim test”, which is often used to assess whether antidepressants are working .
A major concern is that puberty blockers reliably induce cross-sex hormones, what doctors refer to as a “cascade of interventions.” The best estimate from studies that began in the 1970s is that around 80% of gender dysphoric children who are free to express themselves but do not change socially – change their clothes, pronouns, and the like, to become members present the opposite sex – will be reconciled with their biological sex as they grow up. However, puberty blockers seem to prevent this reconciliation. In European clinics reporting figures, it happens that only 2-4% of children receive the medication. American clinics rarely publish figures, but anecdotally the picture is similar.
These figures led UK judges to decide that the effects of these subsequent treatments should be taken into account when assessing puberty blockers. In addition to their intended effects, such as breast or facial hair growth, cross-gender hormones also cause side effects. A 2018 study concluded that women who take testosterone are more likely to have cardiovascular disease, while men who take estrogen are at higher risk of blood clots and stroke. The additional risk increased the longer the patients received hormones.
Some doctors worry about osteoporosis. Bone density increases sharply during puberty, but blockers interfere with this process. If they are followed by cross-sex hormones, it is very likely that they will affect fertility even if the hormones are later stopped – although the lack of research means nobody knows how much, says Will Malone, an American endocrinologist and Society member for Evidence -Based Gender Medicine, a new group. If the cascade of intervention ends with the removal of the testicles or ovaries, the result is sterility.
Despite the uncertainties, professional associations have approved the drugs. In a 2018 position paper, the American Association of Paediatrics (AAP) described “gender-affirming” care as the only ethical approach. Not everyone is convinced. James Cantor, a Canadian clinical psychologist, published a paper accusing the AAP of misrepresenting the content of its quotes and “repeating the opposite of what the AAP attributed to them”. (When asked for comment, the AAP reiterated its position.) Marcus Evans, a psychoanalyst, resigned from the board that oversees GIDS over concerns about “experimental” treatments.
The best way to resolve such disputes is the same as in any other part of medicine: a large, well-conducted clinical trial. So far, no one is planning to do one, despite the increasing number of cases and puberty blockers that have been prescribed for decades.■
This article appeared in the Science & Technology section of the print edition under the heading “Arrested Development”.
