Reader donations fund Those Nerdy Girls. Help keep the lights on by becoming a paid subscriber today. Q: Are puberty blockers helpful or harmful to trans youth? A: Current evidence suggests that puberty blockers, which hit the pause button on puberty and are reversible, significantly improve the mental health of trans youth while reducing the risk of needing future surgeries.
I find it concerning that this blog claims expertise in "evidence-based medicine" but when addressing questions of mental health effectiveness, harm, and "reversability" of puberty blockers cites a single observational study when there are existing systematic evidence revews that address the same questions, but come to different answers.
For example, the Ludviggsson et al systematic review finds that bone health measures did not recover to pre-treatment levels after puberty suppression in all subjects, and that mental health benefits were inconclusive. https://onlinelibrary.wiley.com/doi/10.1111/apa.16791
These results undercut the argument that denying access to puberty blockers would harmful because we don't actually know if the blockers are beneficial. And even the linked study appears to have "denied access" to 398 study participants (unclear without the full text).
How do you reconcile this with claims to be "evidence based"?
Excellent question. Most of the data we have on bone health shows that, although, as expected, bone mineral density decreases or stays the same (rather than increasing as it would during puberty), this then improves once either the blockers are stopped or cross-sex hormone therapy is administered. The best long-term data we have is from studies of puberty blockers used for other medical conditions, and they show no long-term detriment on bone health. We also know that in some studies, trans girls start out with abnormally low bone density (before any medical intervention), which may be due to lack of sufficient vitamin D (many studies show they tend to be deficient) or calcium and/or lack of participation in exercise/sports. After treatment they continue to have lower bone density, but it may be due to these other pre-existing factors more than the treatment with puberty blockers. https://academic.oup.com/jcem/article/105/12/e4252/5903559 It's also important to remember that bone density measurements are scaled according to the population averages for people of the same age. During puberty, bone density increases, so we see, at the population level, large increases in the averages during the teen years. Therefore, anyone with a delayed puberty will score "low" relative to their other peers. Also, in the linked study, they did not deny puberty blockers to 398 participants - those were patients who for whatever reasons had not used them. (They are actually quite difficult for most people to access.)
Studying and understanding bone health in adolescents treated with puberty blockers for gender dysphoria is important and must continue - I agree that we need better data, but given historical long-term data on their use for other conditions showing no long-term adverse effects on bone health, the several studies showing mental health benefit that we linked in the article, and the known prevention of harmful irreversible physical changes, at this point the risk/benefit analysis seems to tilt toward benefit. That said, a well-informed decision must be made by the family, considering all knowns and unknowns.
We agree on some technical things but you haven't addressed the question: Why does the post link to a single study when systematic evidence reviews are available and these contradict your claims? You must be familiar with the "hierarachy of evidence"? Systematic reviews trump single non-randomised studies. You cannot claim to be an 'evidence based' blog if you cherry pick.
We agree that bone density decreases or stays the same when it would otherwise increase under puberty suppression. We disagree that bone density necessarily increases when blockers are stopped. It might increase but all the studies on this follow kids who went on to hormones not ones that stopped treatments altogether, so there isn't evidence for this case. Its also important to note that studies deal with average measures so it may not be increasing in an important subset. One paper showed that up to 1/3 of subjects had bone density more than 2 standard deviations below the population mean for some measure after blockers –the same level for paediatic osteoporosis https://www.degruyter.com/document/doi/10.1515/jpem-2021-0180/html
You apply the results of bone density recovery from other medical conditions rather than the direct evidence that it *didn't* recover from normally timed puberty in males. This is highly misleading. The systematic review I linked to inlcudes the Schagen et al study you link to but conclues that it it only "partially" recovers https://onlinelibrary.wiley.com/doi/full/10.1111/apa.16791
Time to Think reports a young adult patient previously on GnRHa with osteoporosis. The patient’s doctor believes that “there are others with cases like mine”. https://swiftpress.com/book/time-to-think/
The New York Times also reported on the issue in 2022 and highlighted the case of a teen who developed osteoporosis after 2 years of GnRHa treatment.
https://archive.ph/XKI76. The NYT commisssions a review that comes to the same conclusion as the one I linked to.
"“There’s going to be a price,” said Dr. Sundeep Khosla, who leads a bone research lab at the Mayo Clinic. “And the price is probably going to be some deficit in skeletal mass.”
Did these teens develop osteoporosis simply because of lifestyle factors? Yes lifestyle factors contributed but blockers have made very likely made it worse .
Yes adolescents wih suppressed puberty will score low in relative to their same-age peers. This is a sign of compromised bone health. How could it not be? You repeat this with scare quotes is as if its data artefact rather than direct evidence that their bone health has been compromised.
Finally, it would great to clarity on the reasons that 398 controls did not take blockers. The reasons could point to other confounding differences between the groups that may explain the results
As for bone health, the potential that it could be lost (or not gained, anyhow) is the reason why we included in our post that therefore most clinicians watch this very carefully with bone density tests and other measures to promote bone health. All medications have potential risks and unknowns. The key is to weigh these against potential benefit, given all of the best evidence at hand and the particular situation of the individual patient involved.
The post advertised the treatment as "reversible". If it has a potential negative impact on lifetime bone density, do you thik its wise to describe it as "reversible"?
Thank you for pointing out that we hadn't answered the question about why this one study rather than an evidence review. The answer is that the evidence review published in 2023 is unfortunately already far out of date (it only looked at studies through 2021, and lots has been published since then) and was missing some important studies, including some published in 2020. Also, it's important to point out that that review, in its text, talked about the several studies which showed significant improvement in mental health, but they decided that the studies were not robust enough (due to small numbers, etc.) to be conclusive. They did not say that the evidence showed no benefit, just that the benefit was "unknown."
The study we wrote about is one of the largest to look at puberty blockers specifically, which means it is some of the strongest evidence we have - therefore it is a useful example. All of the studies on this issue are observational rather than randomized, and many of the recent ones have shown significant benefit.
Here are three that were not included in the review you cited:
Van der Miesen in J. Adol. Health in 2020 studied over 1000 adolescents, both trans and cis, and found that those trans teens who'd had puberty blockers (n=178) had significantly fewer emotional and behavioral symptoms compared to trans teens without them (n=272) and scored similarly to their cisgender peers (n=651). https://www.jahonline.org/article/S1054-139X(20)30027-6/fulltext
We are limited by our type of platform, as our place is not to write an entire evidence review but rather to sift through the most current data and hold up a representative study that we can explain to readers. It's very tricky when talking about trans youth, as there has been a lot of noise in this space and, unfortunately, a lot of fear mongering as well. We try to be as clear-eyed as we can and represent the current scope of the evidence as best we can. Right now, the evidence points toward benefit for mental health and social functioning.
I find it concerning that this blog claims expertise in "evidence-based medicine" but when addressing questions of mental health effectiveness, harm, and "reversability" of puberty blockers cites a single observational study when there are existing systematic evidence revews that address the same questions, but come to different answers.
For example, the Ludviggsson et al systematic review finds that bone health measures did not recover to pre-treatment levels after puberty suppression in all subjects, and that mental health benefits were inconclusive. https://onlinelibrary.wiley.com/doi/10.1111/apa.16791
These results undercut the argument that denying access to puberty blockers would harmful because we don't actually know if the blockers are beneficial. And even the linked study appears to have "denied access" to 398 study participants (unclear without the full text).
How do you reconcile this with claims to be "evidence based"?
Excellent question. Most of the data we have on bone health shows that, although, as expected, bone mineral density decreases or stays the same (rather than increasing as it would during puberty), this then improves once either the blockers are stopped or cross-sex hormone therapy is administered. The best long-term data we have is from studies of puberty blockers used for other medical conditions, and they show no long-term detriment on bone health. We also know that in some studies, trans girls start out with abnormally low bone density (before any medical intervention), which may be due to lack of sufficient vitamin D (many studies show they tend to be deficient) or calcium and/or lack of participation in exercise/sports. After treatment they continue to have lower bone density, but it may be due to these other pre-existing factors more than the treatment with puberty blockers. https://academic.oup.com/jcem/article/105/12/e4252/5903559 It's also important to remember that bone density measurements are scaled according to the population averages for people of the same age. During puberty, bone density increases, so we see, at the population level, large increases in the averages during the teen years. Therefore, anyone with a delayed puberty will score "low" relative to their other peers. Also, in the linked study, they did not deny puberty blockers to 398 participants - those were patients who for whatever reasons had not used them. (They are actually quite difficult for most people to access.)
Studying and understanding bone health in adolescents treated with puberty blockers for gender dysphoria is important and must continue - I agree that we need better data, but given historical long-term data on their use for other conditions showing no long-term adverse effects on bone health, the several studies showing mental health benefit that we linked in the article, and the known prevention of harmful irreversible physical changes, at this point the risk/benefit analysis seems to tilt toward benefit. That said, a well-informed decision must be made by the family, considering all knowns and unknowns.
We agree on some technical things but you haven't addressed the question: Why does the post link to a single study when systematic evidence reviews are available and these contradict your claims? You must be familiar with the "hierarachy of evidence"? Systematic reviews trump single non-randomised studies. You cannot claim to be an 'evidence based' blog if you cherry pick.
We agree that bone density decreases or stays the same when it would otherwise increase under puberty suppression. We disagree that bone density necessarily increases when blockers are stopped. It might increase but all the studies on this follow kids who went on to hormones not ones that stopped treatments altogether, so there isn't evidence for this case. Its also important to note that studies deal with average measures so it may not be increasing in an important subset. One paper showed that up to 1/3 of subjects had bone density more than 2 standard deviations below the population mean for some measure after blockers –the same level for paediatic osteoporosis https://www.degruyter.com/document/doi/10.1515/jpem-2021-0180/html
You apply the results of bone density recovery from other medical conditions rather than the direct evidence that it *didn't* recover from normally timed puberty in males. This is highly misleading. The systematic review I linked to inlcudes the Schagen et al study you link to but conclues that it it only "partially" recovers https://onlinelibrary.wiley.com/doi/full/10.1111/apa.16791
There have also been news reports of puberty suppressed teenagers who now have osteoporosis. In Sweden a 14 year old was diagnosed with osteoporosis after 4.5 years of puberty suppression. https://www.svt.se/nyheter/granskning/ug/uppdrag-granskning-avslojar-flera-barn-har-fatt-skador-i-transvarden
Time to Think reports a young adult patient previously on GnRHa with osteoporosis. The patient’s doctor believes that “there are others with cases like mine”. https://swiftpress.com/book/time-to-think/
The New York Times also reported on the issue in 2022 and highlighted the case of a teen who developed osteoporosis after 2 years of GnRHa treatment.
https://archive.ph/XKI76. The NYT commisssions a review that comes to the same conclusion as the one I linked to.
"“There’s going to be a price,” said Dr. Sundeep Khosla, who leads a bone research lab at the Mayo Clinic. “And the price is probably going to be some deficit in skeletal mass.”
Did these teens develop osteoporosis simply because of lifestyle factors? Yes lifestyle factors contributed but blockers have made very likely made it worse .
Yes adolescents wih suppressed puberty will score low in relative to their same-age peers. This is a sign of compromised bone health. How could it not be? You repeat this with scare quotes is as if its data artefact rather than direct evidence that their bone health has been compromised.
Finally, it would great to clarity on the reasons that 398 controls did not take blockers. The reasons could point to other confounding differences between the groups that may explain the results
As for bone health, the potential that it could be lost (or not gained, anyhow) is the reason why we included in our post that therefore most clinicians watch this very carefully with bone density tests and other measures to promote bone health. All medications have potential risks and unknowns. The key is to weigh these against potential benefit, given all of the best evidence at hand and the particular situation of the individual patient involved.
The post advertised the treatment as "reversible". If it has a potential negative impact on lifetime bone density, do you thik its wise to describe it as "reversible"?
Thank you for pointing out that we hadn't answered the question about why this one study rather than an evidence review. The answer is that the evidence review published in 2023 is unfortunately already far out of date (it only looked at studies through 2021, and lots has been published since then) and was missing some important studies, including some published in 2020. Also, it's important to point out that that review, in its text, talked about the several studies which showed significant improvement in mental health, but they decided that the studies were not robust enough (due to small numbers, etc.) to be conclusive. They did not say that the evidence showed no benefit, just that the benefit was "unknown."
The study we wrote about is one of the largest to look at puberty blockers specifically, which means it is some of the strongest evidence we have - therefore it is a useful example. All of the studies on this issue are observational rather than randomized, and many of the recent ones have shown significant benefit.
Here are three that were not included in the review you cited:
Van der Miesen in J. Adol. Health in 2020 studied over 1000 adolescents, both trans and cis, and found that those trans teens who'd had puberty blockers (n=178) had significantly fewer emotional and behavioral symptoms compared to trans teens without them (n=272) and scored similarly to their cisgender peers (n=651). https://www.jahonline.org/article/S1054-139X(20)30027-6/fulltext
Tordoff et al in Pediatrics in 2022 studied 104 trans and non-binary youth and found that the 66% who had access to medical therapy had a 60% lower odds of depression and 73% lower odds of suicidality after one year. https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2789423
Turban et al in Pediatrics in 2000 surveyed over 20,000 trans and non-binary adults. Of the approximately 3500 who had wanted puberty blockers when younger, the 2.5% who'd actually received them had a 70% lower rate of suicidality. https://publications.aap.org/pediatrics/article/145/2/e20191725/68259/Pubertal-Suppression-for-Transgender-Youth-and
We are limited by our type of platform, as our place is not to write an entire evidence review but rather to sift through the most current data and hold up a representative study that we can explain to readers. It's very tricky when talking about trans youth, as there has been a lot of noise in this space and, unfortunately, a lot of fear mongering as well. We try to be as clear-eyed as we can and represent the current scope of the evidence as best we can. Right now, the evidence points toward benefit for mental health and social functioning.