Recently there has been much discussion over the use of gender affirming care for children and young adults. One such concern focuses on the claim that if otherwise healthy teens use puberty blockers it could cause irreversible harm to their bone density.
Luckily for transgender teens, parents and curious third parties, a group of Dutch endocrinologists and pediatricians are investigating how puberty blockers affect bone density. JAMA Pediatrics published the results of their most recent study in October 2023.
In this study they followed up on transgender adults who had used puberty blockers as teens before they started hormone therapy. The researchers measured their bone density ten years later to see if the puberty blockers had lasting, long-term effects. So are puberty blockers safe for growing kids? A bit like gender identity, the answer is not a yes/no binary.
Are puberty blockers bad for growing bones?
In this context when we talk about safety, what we really mean is, ‘Do they cause long term effects that prevent a teenager’s bones from growing strong and healthy?’ Based on this 2023 study, the response would be ‘it depends how you use them’. The evidence in this cohort study showed that a decade after using puberty blockers followed by hormone treatment, trans men had bone mineral density scores appropriate for their age. In contrast, trans women had normal bone density in their hips, but on average had lower bone density scores in their lumbar spine.
Before we probe the observations made by the clinicians, we will review the context behind this study. We’ll learn what puberty has to do with bone mass, what puberty blockers are and who gets them.
What does puberty have to do with bone mass?
So let’s get into the specifics. Why would puberty blockers mess with your bones in the first place? The most important thing to understand is that the onset of sexual maturity starts a count down to when your bones stop growing. On average people finish skeletal development in their late teens, occasionally into their early twenties. The bone mass and bone mineral density that we acquire in the womb, as infants and as teens is referred to as our ‘bone bank’.
We reach peak mineral density in our late 20s, and for the next few decades, gradually we lose it. Bone mass at the end of puberty matters because the more bone density you have to start off, the longer it takes for your bones to lose mass. When people lose a certain amount of bone density, their bones become weak and fracture easily, or crumble.
Delayed puberty causes less bone density
Over many years, doctors have discovered that both boys and girls who start puberty very late have lower bone mineral density as adults. Careful study of these children and the general population allowed researchers to discover that most of the bone mineral density a person acquires happens during adolescence.
In practical terms this means that our skeleton accumulates most of its bone mass and density during the time when sex hormones like testosterone and oestrogen start ramping up. The older a child is when they start the process, the shorter the window there is for bones to acquire mass and get strong.
In fact, when smaller than average kids use puberty blockers to give them a chance to grow more before they reach sexual maturity, they have lower than average bone mass as adults. A longitudinal study followed 163 healthy teens of normal stature through bone development. They found that not only does the age you start puberty negatively correlate to bone mass and density, but that the starting prepubertal bone mass of a child did not influence their bone mass at skeletal maturity.
Given the impact of sex hormones on bone development and maintenance, some people have expressed worries that puberty blockers might cause skeletal problems later in life. So are we right to be concerned that puberty blockers for trans teens might be setting them up for osteoporosis later in life?
What do puberty blockers do?
Puberty blockers are a class of drugs that prevent the pituitary gland from releasing the hormone that tell your body to produce sex hormones. These sex hormones trigger the changes that humans go through to transition to sexual maturity. Puberty blocking drugs usually come in the form of an injection and they need to be administered at regular intervals (every few weeks or months depending on the dose or type of drug) to maintain the pause. Once a patient stops taking the drug, the pituitary gland can start making hormones again.
Gonadotropin-releasing hormone (GnRH) is the messenger that tells your pituitary gland that it needs to release the hormones that control sexual development and reproduction. Sex hormones are produced by cells in the pituitary gland, adrenal glands and the gonads (testes or ovaries) in a cascade. The pituitary gland sits at the top and is turned on and off by Gonadotropin-releasing hormone.
Pausing puberty
What we refer to as ‘puberty blockers’ are Gonadotropin-releasing hormone agonists. These are molecules that bind to the receptors that the pituitary gland uses to sense GnRH. If the receptors are blocked, the GnHR can’t get into the pituitary gland’s cells to turn on sex hormone production.
The idea is that Gonadotropin-releasing hormone agonists will pause the release of sex hormones slowing down or stopping puberty and the formation of secondary sexual characteristics.
Usually, doctors prescribe puberty blockers to children who need to prevent very early puberty. Or, in children with growth problems who need a couple of years more to grow taller before they start the count down to bone growth plate fusion. Medics use the same drugs to slow down prostate cancer in older men, to treat women with endometriosis or as part of fertility treatments amongst other applications.
Why would doctors prescribe puberty blockers?
In 2017 American Association of Clinical Endocrinologists, American Society of Andrology, European Society for Paediatric Endocrinology, European Society of Endocrinology, Paediatric Endocrine Society and World Professional Association for Transgender Health collaborated to produce an updated guide to clinical best practice for people suffering with gender dysphoria.
Gender dysphoria happens when a person’s gender identity does not match their sex and it causes them distress. The important concept here is that the mismatch can make the person very unhappy, to the point that they are unable to live a normal life. Many countries have since used these guidelines as the basis for their policy on how best to treat people struggling with gender dysphoria.
Adolescence is a major trigger for gender dysphoria. As children begin to develop secondary sexual characteristics, it can be very distressing if those changes exacerbate the difference between their self-image and appearance.
The endocrinologists and psychiatrists who created the clinical recommendations suggest that teens with gender dysphoria use Gonadotropin-releasing hormone agonists AKA puberty blockers, to pause puberty. They advise that a brief pause can give a child a chance to work with a therapist to understand whether they have gender dysphoria, and how best to move forward. Their reasoning being that if a teen resolves their feelings, they can just stop taking the medication and resume puberty. If the adolescent and their doctor think it appropriate, the they might continue to use puberty blockers and begin hormone therapy that helps their appearance align more with their gender identity.
When do kids get puberty blockers?
The clinical guidelines suggest that doctors only prescribe puberty blockers in the situation where the teen has reached specific developmental markers of puberty and are in distress because of it.
When we are talking about trans kids talking puberty blockers, we are not talking about 10-year-olds, we are talking about adolescents who have already started developing secondary sexual characteristics. Children who have not started puberty don’t get puberty blockers. In order to be a candidate for GnRH agonists, a teen assigned female at birth would have started developing breast tissue, and assigned male at birth teens would be noticing changes to their testes.
Gender dysphoric teens don’t get hormones the moment they start puberty. The process of getting a gender dysphoria diagnosis and being referred to a gender identity clinic takes time. By 2017, in the Netherlands teens suffering with gender dysphoria were aged around 15 years old by the time they started using puberty blockers. To put this in perspective, the US National Institutes of health puts puberty as normally starting at between 8 and 13 years old for girls and 9-14 years old for boys.
Making a Plan
In a typical treatment plan, a teen would present with gender dysphoria, get GnRH agonists and pause puberty. Once the child reached age 16, if they were still suffering from gender dysphoria, they could start taking low dose hormone therapy. Over time they would increase the dose, in a way mimicking the hormonal changes that take place during puberty. At age 18 after at least a year of hormone therapy, if they wished clients could continue their path, receiving gonadectomy (trans women) or the maximum dose of testosterone therapy (trans men) and ending their course of puberty blockers. Patients would then continue their gender affirming hormone treatment indefinitely.
So now we are up to speed on the context behind the research study it’s time to dig in.
What was this study about?
The researchers were investigating whether there were long-term negative bone mass consequences for trans-teens who used puberty blockers. Studies on kids treated for precocious puberty or children with endocrine disorders that delayed puberty, show that starting puberty late leads to lower bone mass. The absence of increasing levels of sex hormones prevents their bones from reaching optimal bone mineral density before they finish growing.
In theory, giving trans teens puberty blockers should have the same result. Blocking puberty for a few years should stop the bones from accumulating mineral density. In practice, however, trans teens do pause puberty, but after a year or two they start using gender affirming hormone therapy that replaces those missing sex hormones.
Trans kids on gender affirming hormone therapy are experiencing increasing levels of oestrogen or testosterone for the last few years of puberty and into young adulthood. The doctors wanted to know, do these years of hormone therapy make up for the interval between starting puberty blockers and starting hormone therapy? Does pausing puberty cause worse long-term bone health?
Who took part in the study?
Between 2020 and 2021, the researchers contacted patients who had visited the gender identity clinic of Amsterdam UMC and received puberty blockers before age 18 and had since used hormone therapy for at least nine years. They managed to track down 143 former clients, 75 of whom were willing to take part: 25 people who were assigned male at birth, 50 people who were assigned female at birth.
The team looked through the files kept by the clinic to find information about the bone density and health of the participants. They were able to collect records from the initial visits to the clinic before starting treatment, and then a few years later for a check-up. The doctors then invited the participants to attend a clinic appointment where they measured participants’ bone mineral density again for a long-term follow-up.
The interval between starting gender affirming hormone therapy and the final follow up was between 10 and 14.7 years, with most participants being on the lower end. Participants were aged between 26 and 31, with most clustered around 28 years old. We can estimate then that most of them began hormone treatment approximately 11 years prior – so between 15 and 17 years old.
The point of these long intervals was to investigate whether hormone replacement therapy with opposite sex hormones made up for the loss of the sex hormones blocked by the puberty blockers.
Bone mass measurements
The researchers measured bone density using DXA testing. This method uses X-rays to measure how dense your bones are. You lie on a table, and a radiologist will scan areas of interest with an X-ray machine or a CT scanner. The denser the bones, the less radiation will make it through the bone to the X-ray detector. This will produce a picture, like a regular X-ray, but instead of a piece of film, they use a very sensitive digital camera/radiation detector.
The radiologist then uses special software to compare how much radiation penetrated the bones in each picture. By comparing the amount of penetration to a standard, the radiologist can give a relative rating of how dense the bones are. Once they have an idea of how dense the bones are, the specialists will compare your bone density score to the norm. You will get a ’T score’ and a ‘Z score’ based on how close to the average your bone density is.
Mind your Ts and Zs
Your T score is how many standard deviations you are away from the bone density of an average healthy adult between 23 and 35 who shares your sex and ethnicity. If you have a positive T score, your bones are as dense or more dense than an average young adult. If you have a negative T-score, it means your bones are less dense than the average young, healthy adult. The bigger your T-score, the more extreme the difference is.
The Z-score is very similar, this time instead of comparing you to a healthy 25–35 year-old, the radiologist will compare your score to that of the average person of your age, sex and ethnicity. Your Z-score, like your T-score, is the number of standard deviations from the mean density your bone density results are. A positive number means you have stronger bones than average and a negative score shows that you have less dense bones than we would expect for your age.
If your score is between -1 and +1 your bone density is within normal limits.
The researchers measured bone density in three key places so that came could get an overall impression of bone health. They took measurements of bone density in the lumbar spine, hip and the femoral neck of the nondominant hip. These are parts of the skeleton that are especially sensitive to bone mineral loss.
How did puberty blockers affect trans men?
The researchers tracked the Z scores of each participant at four time points. They followed so see where they started off, how puberty blockers affected the Z-score and then how gender affirming hormone therapy affected density. They calculated Z scores using the birth sex of each participant so that they could make before and after comparisons – did the hormone blockers and hormone therapy make a difference?
What they observed was a pattern a little like a check mark. The assigned female at birth transgender teens aged between 15 and 17 at their initial DXA test, had scores of less than 0. This is normal and what you would expect.
The kids then started using GnHR agonists. The next DXA scan was taken between one and three years after they began using puberty blockers, just before they began using testosterone hormone therapy. As expected, the researchers saw a drop in the density scores. Pausing puberty also slowed down bone mineral acquisition.
At the next follow up visit around the time they stopped using puberty blockers and had been using testosterone for a few years, the bone density readings increased. It seems the hormone therapy had triggered bone mass accumulation.
Finally, at the last follow up 10–14 years after starting gender affirming hormone therapy their Z scores had increased back to levels close to 0.
Testosterone takes the prize
What does this mean? Quite simply, in all three regions of the skeleton, using puberty blockers for a short time and then supplementing with gender affirming hormone treatment made little difference to bone health. Even though initially the trans boys bone density took a hit from the puberty blockers, they made up the gap in the years following once they started cross sex hormone therapy. The Z scores at the end of the study were between -1 and +1 for all the trans men. This means they came out at the end with normal bone mass.
How did puberty blockers affect trans women?
The researchers did the same analysis on test results from the trans women. They compared readings taken before the start of puberty blockers, at the start of gender affirming hormone treatment with 17β-estradiol. Then at the early follow up around the time they would stop puberty blockers and then the final follow up between 10 and 15 years later.
Like trans men, the trans women started with Z scores in the normal range before starting puberty blockers. After a year or two on puberty blockers Z scores in all three regions (hips, femoral neck of hip and lumbar spine) dipped. On average the Z scores were below -1 indicating that the teens had not been laying down enough bone mass. At the next check up at around age 22, Z scores for the hip and femoral neck of the hip had improved after a few years of oestrogen therapy. The lumbar spine readings, however, had got worse.
These trends continued over time. A decade or later, each of the trans women had better Z scores in their hip or femoral neck of the hip. Their bone mass was not significantly different to the average male of the same age and ethnicity, but it was on the lower side. The readings for the lumbar spine, on the other hand, were not good. The Z scores dropped once the teens started using puberty blockers and did not recover. By the end of the study Z scores in the lumbar spine were on average below -1. This was a clinically significant result.
So what does this mean?
These results indicate that if kids assigned female at birth start using gender affirming hormone therapy after a couple of years on puberty blockers it generally has little effect on their bone health. By theirn late 20s, the trans men ended up back where they started or with slightly stronger bones than the average woman of the same age and ethnicity. While these results only represent 50 individuals, the spread of the results is pretty small. There are not huge variations between scores or big changes in either direction so for now it seems like bone density is not a pressing worry.
The story was less encouraging for trans women, but maybe not as bad as it looks at first glance. First, we have to consider that on average men’s bones are denser than women’s. The researchers calculated trans women’s z scores using a male reference so that the researchers could follow each participant’s relative changes. What this means in practice is that the z-score are slightly underestimating the final bone density. If they calculate a Z-score comparing trans women to age and ethnicity matched female bone density, the scores might be closer to zero for the hip and femural neck of the hip.
Back Up Plans Needed
This does not apply to the lumbar spine. All 25 trans women had low bone density readings in their lumbar spine, this was consistent finding. The authors of the study discuss some possible reasons for this. They suggest that maybe the oestrogen therapy needs to start earlier as the bones of the lumbar spine are more sensitive to sex hormones than other parts of the skeleton. It’s also possible that changes in lifestyle might be responsible. One of the ways we build our bone density is through physical activity. If the trans women were doing less load-bearing exercise in their 20s, there’s a chance that this could affect their spinal strength.
The researchers end by pointing out that the low bone mass measurements at ages 28–30 in trans women are not necessarily a reason to forgo therapy. Now that doctors are aware that hormone therapy might not help lumbar spine bone density recover, they can help patients to manage their risk of osteoporosis and osteopenia.
Are puberty blockers safe for transgender teens?
So are puberty blockers bad for bone health in trans-teens? The answer is mixed. For assigned female at birth trans-teens, testosterone counters the effect on bone density. There does not seem to be cause for anxiety. For people assigned male at birth, while oestrogen helps, they will need long-term monitoring and help with managing bone health.
Here’s the biggest problem with drawing firm conclusions: so few people in the Netherlands were receiving puberty blockers as gender affirming care as teens in the 2010s that there are not many people available to study.
The researchers only found 143 who fit the bill, and only 75 of them were willing to take part. Not only were there few patients to follow, but most kids didn’t get their puberty blockers until they were in their mid to late teens but some recieved them several years younger than others. In addition to these difficulties, the small number of subjects and the nature of the data meant the researchers were not able to make comparisons between participants that could reveal the presence of confounding factors that could influence how well a young adult’s peak bone mass accumulates.
These factors make it difficult to give a firm answer on how puberty blockers affect bone mineral density in gender dysphoric teens in general. The Amsterdam based doctors were, however, able to conclude that under the norms of prescribing in the 2010s, puberty blockers did not cause clinically significant bone problems in trans men and may or may not be an issue for trans women.
Weighing the risks
Some experts have expressed concern about the fact that children who use puberty blockers for endocrine disorders have lower bone density than is optimal. It’s fair to consider the idea in weighing harms. For children delaying puberty to give them time to grow, parents might feel that the loss of bone mass is out weighed by the benefits of having time to grow taller. Likewise children using puberty blockers to delay precocious puberty. Trans teens and their parents deciding whether to treatment with pursue puberty blockers will also be weighing up the potential harms of preventing bone mass accumulation against the distress caused by gender dysphoria.
Now to the more critical point, the teens using puberty blockers were not using puberty blockers alone. Unlike the children with endocrine disorders, the kids in this study were not lacking sex hormones for long. Between one and three years after they hit the pause button, trans kids choose whether to discontinue treatment or to continue the puberty blockers while receiving hormone therapy. This would mean that the teens would receive age appropriate doses of the sex hormone associated with their preferred gender place of the hormones blocked by the puberty blockers. These sex hormones mostly cancel out the effects of pausing puberty on bone development, as they would kick-start the bones to build mineral density again.
The work continues
This study only followed 75 subjects and the time points were not exactly matched so there was a lot of variability introduced that made absolute comparisons difficult. By plotting all the Z scores against years, the researchers were able to show trends. Closer time matching of records would paint a clearer picture. A more standardized approach to data collection rather than having to throw whatever records were available into the mix would help the researchers to draw more robust conclusions. They themselves recognize that this work needs to be expanded to cover a larger cohort with more consistent data collection. We are not shown how using puberty blockers and then discontinuing treatment for gender dysphoria affected long-term bone health. This would probably be useful information for doctors and patients.
Overall, this is encouraging data for assigned female at birth teens considering putting a pause on puberty, while assigned male at birth teens might need to consider their options more carefully. Making an informed decision about your long term health is hard when there are conflicting stories making the rounds, and much of the information is buried behind unproductive discussions about hypotheticals and extreme outliers. It’s time to get serious about understanding the evidence before making policy decisions.
References
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Casteel CO, Singh G. Physiology, Gonadotropin-Releasing Hormone. In: StatPearls. StatPearls Publishing; 2025. Accessed February 10, 2025. http://www.ncbi.nlm.nih.gov/books/NBK558992/
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Recently there has been much discussion over the use of gender affirming care for children and young adults. One such concern focuses on the claim that if otherwise healthy teens use puberty blockers it could cause irreversible harm to their bone density. Luckily for transgender teens, parents and curious third parties, a group of Dutch endocrinologists and pediatricians are investigating how puberty blockers affect bone density. JAMA Pediatrics published the results of their most recent study in October 2023. In this study they followed up on transgender adults who had used puberty blockers as teens before they started hormone therapy. The researchers measured their bone density ten years later to see if the puberty blockers had lasting, long-term effects. So are puberty blockers safe for growing kids? A bit like gender identity, the answer is not a yes/no binary. In this context when we talk about safety, what we really mean is, ‘Do they cause long term effects that prevent a teenager’s bones from growing strong and healthy?’ Based on this 2023 study, the response would be ‘it depends how you use them’. The evidence in this cohort study showed that a decade after using puberty blockers followed by hormone treatment, trans men had bone mineral density scores appropriate for their age. In contrast, trans women had normal bone density in their hips, but on average had lower bone density scores in their lumbar spine. Before we probe the observations made by the clinicians, we will review the context behind this study. We’ll learn what puberty has to do with bone mass, what puberty blockers are and who gets them. So let’s get into the specifics. Why would puberty blockers mess with your bones in the first place? The most important thing to understand is that the onset of sexual maturity starts a count down to when your bones stop growing. On average people finish skeletal development in their late teens, occasionally into their early twenties. The bone mass and bone mineral density that we acquire in the womb, as infants and as teens is referred to as our ‘bone bank’. We reach peak mineral density in our late 20s, and for the next few decades, gradually we lose it. Bone mass at the end of puberty matters because the more bone density you have to start off, the longer it takes for your bones to lose mass. When people lose a certain amount of bone density, their bones become weak and fracture easily, or crumble. Over many years, doctors have discovered that both boys and girls who start puberty very late have lower bone mineral density as adults. Careful study of these children and the general population allowed researchers to discover that most of the bone mineral density a person acquires happens during adolescence. In practical terms this means that our skeleton accumulates most of its bone mass and density during the time when sex hormones like testosterone and oestrogen start ramping up. The older a child is when they start the process, the shorter the window there is for bones to acquire mass and get strong. In fact, when smaller than average kids use puberty blockers to give them a chance to grow more before they reach sexual maturity, they have lower than average bone mass as adults. A longitudinal study followed 163 healthy teens of normal stature through bone development. They found that not only does the age you start puberty negatively correlate to bone mass and density, but that the starting prepubertal bone mass of a child did not influence their bone mass at skeletal maturity. Given the impact of sex hormones on bone development and maintenance, some people have expressed worries that puberty blockers might cause skeletal problems later in life. So are we right to be concerned that puberty blockers for trans teens might be setting them up for osteoporosis later in life? Puberty blockers are a class of drugs that prevent the pituitary gland from releasing the hormone that tell your body to produce sex hormones. These sex hormones trigger the changes that humans go through to transition to sexual maturity. Puberty blocking drugs usually come in the form of an injection and they need to be administered at regular intervals (every few weeks or months depending on the dose or type of drug) to maintain the pause. Once a patient stops taking the drug, the pituitary gland can start making hormones again. Gonadotropin-releasing hormone (GnRH) is the messenger that tells your pituitary gland that it needs to release the hormones that control sexual development and reproduction. Sex hormones are produced by cells in the pituitary gland, adrenal glands and the gonads (testes or ovaries) in a cascade. The pituitary gland sits at the top and is turned on and off by Gonadotropin-releasing hormone. What we refer to as ‘puberty blockers’ are Gonadotropin-releasing hormone agonists. These are molecules that bind to the receptors that the pituitary gland uses to sense GnRH. If the receptors are blocked, the GnHR can’t get into the pituitary gland’s cells to turn on sex hormone production. The idea is that Gonadotropin-releasing hormone agonists will pause the release of sex hormones slowing down or stopping puberty and the formation of secondary sexual characteristics. Usually, doctors prescribe puberty blockers to children who need to prevent very early puberty. Or, in children with growth problems who need a couple of years more to grow taller before they start the count down to bone growth plate fusion. Medics use the same drugs to slow down prostate cancer in older men, to treat women with endometriosis or as part of fertility treatments amongst other applications. In 2017 American Association of Clinical Endocrinologists, American Society of Andrology, European Society for Paediatric Endocrinology, European Society of Endocrinology, Paediatric Endocrine Society and World Professional Association for Transgender Health collaborated to produce an updated guide to clinical best practice for people suffering with gender dysphoria. Gender dysphoria happens when a person’s gender identity does not match their sex and it causes them distress. The important concept here is that the mismatch can make the person very unhappy, to the point that they are unable to live a normal life. Many countries have since used these guidelines as the basis for their policy on how best to treat people struggling with gender dysphoria. Adolescence is a major trigger for gender dysphoria. As children begin to develop secondary sexual characteristics, it can be very distressing if those changes exacerbate the difference between their self-image and appearance. The endocrinologists and psychiatrists who created the clinical recommendations suggest that teens with gender dysphoria use Gonadotropin-releasing hormone agonists AKA puberty blockers, to pause puberty. They advise that a brief pause can give a child a chance to work with a therapist to understand whether they have gender dysphoria, and how best to move forward. Their reasoning being that if a teen resolves their feelings, they can just stop taking the medication and resume puberty. If the adolescent and their doctor think it appropriate, the they might continue to use puberty blockers and begin hormone therapy that helps their appearance align more with their gender identity. The clinical guidelines suggest that doctors only prescribe puberty blockers in the situation where the teen has reached specific developmental markers of puberty and are in distress because of it. When we are talking about trans kids talking puberty blockers, we are not talking about 10-year-olds, we are talking about adolescents who have already started developing secondary sexual characteristics. Children who have not started puberty don’t get puberty blockers. In order to be a candidate for GnRH agonists, a teen assigned female at birth would have started developing breast tissue, and assigned male at birth teens would be noticing changes to their testes. Gender dysphoric teens don’t get hormones the moment they start puberty. The process of getting a gender dysphoria diagnosis and being referred to a gender identity clinic takes time. By 2017, in the Netherlands teens suffering with gender dysphoria were aged around 15 years old by the time they started using puberty blockers. To put this in perspective, the US National Institutes of health puts puberty as normally starting at between 8 and 13 years old for girls and 9-14 years old for boys. In a typical treatment plan, a teen would present with gender dysphoria, get GnRH agonists and pause puberty. Once the child reached age 16, if they were still suffering from gender dysphoria, they could start taking low dose hormone therapy. Over time they would increase the dose, in a way mimicking the hormonal changes that take place during puberty. At age 18 after at least a year of hormone therapy, if they wished clients could continue their path, receiving gonadectomy (trans women) or the maximum dose of testosterone therapy (trans men) and ending their course of puberty blockers. Patients would then continue their gender affirming hormone treatment indefinitely. So now we are up to speed on the context behind the research study it’s time to dig in. The researchers were investigating whether there were long-term negative bone mass consequences for trans-teens who used puberty blockers. Studies on kids treated for precocious puberty or children with endocrine disorders that delayed puberty, show that starting puberty late leads to lower bone mass. The absence of increasing levels of sex hormones prevents their bones from reaching optimal bone mineral density before they finish growing. In theory, giving trans teens puberty blockers should have the same result. Blocking puberty for a few years should stop the bones from accumulating mineral density. In practice, however, trans teens do pause puberty, but after a year or two they start using gender affirming hormone therapy that replaces those missing sex hormones. Trans kids on gender affirming hormone therapy are experiencing increasing levels of oestrogen or testosterone for the last few years of puberty and into young adulthood. The doctors wanted to know, do these years of hormone therapy make up for the interval between starting puberty blockers and starting hormone therapy? Does pausing puberty cause worse long-term bone health? Between 2020 and 2021, the researchers contacted patients who had visited the gender identity clinic of Amsterdam UMC and received puberty blockers before age 18 and had since used hormone therapy for at least nine years. They managed to track down 143 former clients, 75 of whom were willing to take part: 25 people who were assigned male at birth, 50 people who were assigned female at birth. The team looked through the files kept by the clinic to find information about the bone density and health of the participants. They were able to collect records from the initial visits to the clinic before starting treatment, and then a few years later for a check-up. The doctors then invited the participants to attend a clinic appointment where they measured participants’ bone mineral density again for a long-term follow-up. The interval between starting gender affirming hormone therapy and the final follow up was between 10 and 14.7 years, with most participants being on the lower end. Participants were aged between 26 and 31, with most clustered around 28 years old. We can estimate then that most of them began hormone treatment approximately 11 years prior – so between 15 and 17 years old. The point of these long intervals was to investigate whether hormone replacement therapy with opposite sex hormones made up for the loss of the sex hormones blocked by the puberty blockers. The researchers measured bone density using DXA testing. This method uses X-rays to measure how dense your bones are. You lie on a table, and a radiologist will scan areas of interest with an X-ray machine or a CT scanner. The denser the bones, the less radiation will make it through the bone to the X-ray detector. This will produce a picture, like a regular X-ray, but instead of a piece of film, they use a very sensitive digital camera/radiation detector. The radiologist then uses special software to compare how much radiation penetrated the bones in each picture. By comparing the amount of penetration to a standard, the radiologist can give a relative rating of how dense the bones are. Once they have an idea of how dense the bones are, the specialists will compare your bone density score to the norm. You will get a ’T score’ and a ‘Z score’ based on how close to the average your bone density is. Your T score is how many standard deviations you are away from the bone density of an average healthy adult between 23 and 35 who shares your sex and ethnicity. If you have a positive T score, your bones are as dense or more dense than an average young adult. If you have a negative T-score, it means your bones are less dense than the average young, healthy adult. The bigger your T-score, the more extreme the difference is. The Z-score is very similar, this time instead of comparing you to a healthy 25–35 year-old, the radiologist will compare your score to that of the average person of your age, sex and ethnicity. Your Z-score, like your T-score, is the number of standard deviations from the mean density your bone density results are. A positive number means you have stronger bones than average and a negative score shows that you have less dense bones than we would expect for your age. If your score is between -1 and +1 your bone density is within normal limits. The researchers measured bone density in three key places so that came could get an overall impression of bone health. They took measurements of bone density in the lumbar spine, hip and the femoral neck of the nondominant hip. These are parts of the skeleton that are especially sensitive to bone mineral loss. The researchers tracked the Z scores of each participant at four time points. They followed so see where they started off, how puberty blockers affected the Z-score and then how gender affirming hormone therapy affected density. They calculated Z scores using the birth sex of each participant so that they could make before and after comparisons – did the hormone blockers and hormone therapy make a difference? What they observed was a pattern a little like a check mark. The assigned female at birth transgender teens aged between 15 and 17 at their initial DXA test, had scores of less than 0. This is normal and what you would expect. The kids then started using GnHR agonists. The next DXA scan was taken between one and three years after they began using puberty blockers, just before they began using testosterone hormone therapy. As expected, the researchers saw a drop in the density scores. Pausing puberty also slowed down bone mineral acquisition. At the next follow up visit around the time they stopped using puberty blockers and had been using testosterone for a few years, the bone density readings increased. It seems the hormone therapy had triggered bone mass accumulation. Finally, at the last follow up 10–14 years after starting gender affirming hormone therapy their Z scores had increased back to levels close to 0. What does this mean? Quite simply, in all three regions of the skeleton, using puberty blockers for a short time and then supplementing with gender affirming hormone treatment made little difference to bone health. Even though initially the trans boys bone density took a hit from the puberty blockers, they made up the gap in the years following once they started cross sex hormone therapy. The Z scores at the end of the study were between -1 and +1 for all the trans men. This means they came out at the end with normal bone mass. The researchers did the same analysis on test results from the trans women. They compared readings taken before the start of puberty blockers, at the start of gender affirming hormone treatment with 17β-estradiol. Then at the early follow up around the time they would stop puberty blockers and then the final follow up between 10 and 15 years later. Like trans men, the trans women started with Z scores in the normal range before starting puberty blockers. After a year or two on puberty blockers Z scores in all three regions (hips, femoral neck of hip and lumbar spine) dipped. On average the Z scores were below -1 indicating that the teens had not been laying down enough bone mass. At the next check up at around age 22, Z scores for the hip and femoral neck of the hip had improved after a few years of oestrogen therapy. The lumbar spine readings, however, had got worse. These trends continued over time. A decade or later, each of the trans women had better Z scores in their hip or femoral neck of the hip. Their bone mass was not significantly different to the average male of the same age and ethnicity, but it was on the lower side. The readings for the lumbar spine, on the other hand, were not good. The Z scores dropped once the teens started using puberty blockers and did not recover. By the end of the study Z scores in the lumbar spine were on average below -1. This was a clinically significant result. These results indicate that if kids assigned female at birth start using gender affirming hormone therapy after a couple of years on puberty blockers it generally has little effect on their bone health. By theirn late 20s, the trans men ended up back where they started or with slightly stronger bones than the average woman of the same age and ethnicity. While these results only represent 50 individuals, the spread of the results is pretty small. There are not huge variations between scores or big changes in either direction so for now it seems like bone density is not a pressing worry. The story was less encouraging for trans women, but maybe not as bad as it looks at first glance. First, we have to consider that on average men’s bones are denser than women’s. The researchers calculated trans women’s z scores using a male reference so that the researchers could follow each participant’s relative changes. What this means in practice is that the z-score are slightly underestimating the final bone density. If they calculate a Z-score comparing trans women to age and ethnicity matched female bone density, the scores might be closer to zero for the hip and femural neck of the hip. This does not apply to the lumbar spine. All 25 trans women had low bone density readings in their lumbar spine, this was consistent finding. The authors of the study discuss some possible reasons for this. They suggest that maybe the oestrogen therapy needs to start earlier as the bones of the lumbar spine are more sensitive to sex hormones than other parts of the skeleton. It’s also possible that changes in lifestyle might be responsible. One of the ways we build our bone density is through physical activity. If the trans women were doing less load-bearing exercise in their 20s, there’s a chance that this could affect their spinal strength. The researchers end by pointing out that the low bone mass measurements at ages 28–30 in trans women are not necessarily a reason to forgo therapy. Now that doctors are aware that hormone therapy might not help lumbar spine bone density recover, they can help patients to manage their risk of osteoporosis and osteopenia. So are puberty blockers bad for bone health in trans-teens? The answer is mixed. For assigned female at birth trans-teens, testosterone counters the effect on bone density. There does not seem to be cause for anxiety. For people assigned male at birth, while oestrogen helps, they will need long-term monitoring and help with managing bone health. Here’s the biggest problem with drawing firm conclusions: so few people in the Netherlands were receiving puberty blockers as gender affirming care as teens in the 2010s that there are not many people available to study. The researchers only found 143 who fit the bill, and only 75 of them were willing to take part. Not only were there few patients to follow, but most kids didn’t get their puberty blockers until they were in their mid to late teens but some recieved them several years younger than others. In addition to these difficulties, the small number of subjects and the nature of the data meant the researchers were not able to make comparisons between participants that could reveal the presence of confounding factors that could influence how well a young adult’s peak bone mass accumulates. These factors make it difficult to give a firm answer on how puberty blockers affect bone mineral density in gender dysphoric teens in general. The Amsterdam based doctors were, however, able to conclude that under the norms of prescribing in the 2010s, puberty blockers did not cause clinically significant bone problems in trans men and may or may not be an issue for trans women. Some experts have expressed concern about the fact that children who use puberty blockers for endocrine disorders have lower bone density than is optimal. It’s fair to consider the idea in weighing harms. For children delaying puberty to give them time to grow, parents might feel that the loss of bone mass is out weighed by the benefits of having time to grow taller. Likewise children using puberty blockers to delay precocious puberty. Trans teens and their parents deciding whether to treatment with pursue puberty blockers will also be weighing up the potential harms of preventing bone mass accumulation against the distress caused by gender dysphoria. Now to the more critical point, the teens using puberty blockers were not using puberty blockers alone. Unlike the children with endocrine disorders, the kids in this study were not lacking sex hormones for long. Between one and three years after they hit the pause button, trans kids choose whether to discontinue treatment or to continue the puberty blockers while receiving hormone therapy. This would mean that the teens would receive age appropriate doses of the sex hormone associated with their preferred gender place of the hormones blocked by the puberty blockers. These sex hormones mostly cancel out the effects of pausing puberty on bone development, as they would kick-start the bones to build mineral density again. This study only followed 75 subjects and the time points were not exactly matched so there was a lot of variability introduced that made absolute comparisons difficult. By plotting all the Z scores against years, the researchers were able to show trends. Closer time matching of records would paint a clearer picture. A more standardized approach to data collection rather than having to throw whatever records were available into the mix would help the researchers to draw more robust conclusions. They themselves recognize that this work needs to be expanded to cover a larger cohort with more consistent data collection. We are not shown how using puberty blockers and then discontinuing treatment for gender dysphoria affected long-term bone health. This would probably be useful information for doctors and patients. Overall, this is encouraging data for assigned female at birth teens considering putting a pause on puberty, while assigned male at birth teens might need to consider their options more carefully. Making an informed decision about your long term health is hard when there are conflicting stories making the rounds, and much of the information is buried behind unproductive discussions about hypotheticals and extreme outliers. It’s time to get serious about understanding the evidence before making policy decisions. Branch NSC and O. Bone Mineral Density Tests: What the Numbers Mean. National Institute of Arthritis and Musculoskeletal and Skin Diseases. May 5, 2023. Accessed February 12, 2025. https://www.niams.nih.gov/health-topics/bone-mineral-density-tests-what-numbers-mean Casteel CO, Singh G. Physiology, Gonadotropin-Releasing Hormone. In: StatPearls. StatPearls Publishing; 2025. Accessed February 10, 2025. http://www.ncbi.nlm.nih.gov/books/NBK558992/ Emmanuel M, Bokor BR. Tanner Stages. In: StatPearls. StatPearls Publishing; 2025. Accessed February 7, 2025. http://www.ncbi.nlm.nih.gov/books/NBK470280/ Finkelstein JS, Neer RM, Biller BM, Crawford JD, Klibanski A. Osteopenia in men with a history of delayed puberty. N Engl J Med. 1992;326(9):600-604. doi:10.1056/NEJM199202273260904 Gilsanz V, Gibbens DT, Carlson M, Boechat MI, Cann CE, Schulz EE. Peak trabecular vertebral density: a comparison of adolescent and adult females. Calcif Tissue Int. 1988;43(4):260-262. doi:10.1007/BF02555144 Gilsanz V, Chalfant J, Kalkwarf H, et al. Age at Onset of Puberty Predicts Bone Mass in Young Adulthood. J Pediatr. 2011;158(1):100-105.e2. doi:10.1016/j.jpeds.2010.06.054 Matkovic V, Jelic T, Wardlaw GM, et al. Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model. J Clin Invest. 1994;93(2):799-808. Moreira-Andrés MN, Cañizo FJ, de la Cruz FJ, Gómez-de la Cámara A, Hawkins FG. Evaluation of radial bone mineral content in prepubertal children with constitutional delay of growth. J Pediatr Endocrinol Metab. 2000;13(6):591-597. doi:10.1515/jpem.2000.13.6.591 Sabatier JP, Guaydier-Souquières G, Laroche D, et al. Bone mineral acquisition during adolescence and early adulthood: a study in 574 healthy females 10-24 years of age. Osteoporos Int. 1996;6(2):141-148. doi:10.1007/BF01623938 van der Loos MATC, Vlot MC, Klink DT, Hannema SE, den Heijer M, Wiepjes CM. Bone Mineral Density in Transgender Adolescents Treated With Puberty Suppression and Subsequent Gender-Affirming Hormones. JAMA Pediatrics. 2023;177(12):1332-1341. doi:10.1001/jamapediatrics.2023.4588 1. Yap F, Högler W, Briody J, Moore B, Howman-Giles R, Cowell CT. The skeletal phenotype of men with previous constitutional delay of puberty. J Clin Endocrinol Metab. 2004;89(9):4306-4311. doi:10.1210/jc.2004-0046
Are puberty blockers bad for growing bones?
What does puberty have to do with bone mass?
Delayed puberty causes less bone density
What do puberty blockers do?
Pausing puberty
Why would doctors prescribe puberty blockers?
When do kids get puberty blockers?
Making a Plan
What was this study about?
Who took part in the study?
Bone mass measurements
Mind your Ts and Zs
How did puberty blockers affect trans men?
Testosterone takes the prize
How did puberty blockers affect trans women?
So what does this mean?
Back Up Plans Needed
Are puberty blockers safe for transgender teens?
Weighing the risks
The work continues
References
