Hormone drugs taken by a rapidly rising number of transgender patients may raise their risk of a deadly stroke or heart attack by nearly seven times, a study suggests.
People assigned male at birth are typically prescribed estrogen, while biological females receive testosterone to achieve the physical attributes of the opposite sex.
The long-term risks of the drugs in gender dysphoria patients have been under-studied, with previous research focusing on younger women using hormone-based birth control or on older women following a hysterectomy or during menopause.
Now experts from Mercy Catholic Medical Center in Darby, Pennsylvania, have found that trans patients who take the drugs are up to seven times more likely to suffer an ischemic stroke compared to trans patients who are not prescribed them.
They were also nearly six times more likely to suffer myocardial infarction – the most serious type of heart attack – and had a five times higher risk of pulmonary embolism, a blockage in an artery in the lung.
The above map shows the population of transgender adults and children across America in 2020, according to the Williams Institute at the University of California, Los Angeles. Its estimate for children aged 13 to 17 has doubled since 2017. It shows the highest population is in southern states, followed by those along the east coast
A Massachusetts-based detransitioner who goes by the name Shape Shifter transitioned from male to female, but encountered appalling medical issues. He has since detransitioned, identifying as a gay man with a feminine look
Dr Ibrahim Ahmed, lead author of the study and resident at the hospital, warned that medically transitioning is ‘not a risk-free endeavor’.
‘It’s all about risks and benefits. Starting transitioning is a big part of a person’s life and helping them feel more themselves, but hormone replacement therapy also has a lot of side effects.’
Both estrogen and testosterone are known to increase the clotting activity of blood, which could explain the increased risk.
But those taking hormone replacement therapy also had higher rates of substance use disorder and hypothyroidism, which both raise the risk of clots and cardiovascular problems.
The researchers stressed that although there was an up to seven times higher risk, the absolute risk remains small.
One limitation of the study is that it only accounted for whether individuals had ever used any type of hormone replacement therapy.
To better inform clinical decisions, researchers said it would be helpful to assess whether the duration of treatment, the age at which it is initiated or the type of hormone therapy used affects the risks.
An estimated 1.6million Americans 13 years or older identify as transgender, according to a University of California Los Angeles report – a number that has rocketed in recent years amid growing acceptance about gender dysphoria.
Gender-affirming care for US adults and adolescents can include a number of medical, behavioral and social changes, as well as surgery.
For adolescents who have not yet gone through puberty, puberty-blocking medication can suppress the release of the sex hormones testosterone and estrogen, which halts the development of secondary sex characteristics like breasts and facial hair.
Whether or not original puberty was blocked, trans adults and adolescents can also begin hormone therapy, which essentially initiates the puberty of their gender identity.
These hormones can be taken as pills, patches and gels, and are taken continuously throughout adulthood, or until the desired physical traits are achieved.
Surgical options include facial, chest and genital altering procedures, and are generally the last step of the transition process.
Sinead Watson, from Glasgow, Scotland, lived as man from the age of 23 and had a double mastectomy, but realized at age 27 that she had made a terrible mistake, and de-transitioned at 28. She spoke out on social media this week about widespread harassment from the transgender community she was leaving: ‘I was sent rape and death threats,’ posted Watson, pictured earlier this year. ‘I was called a hideous freak show.’
For the latest study, set to be presented at an American College of Cardiology research session Thursday, researchers gathered data from 21,000 people with gender dysphoria.
Data was gathered in 2019, but members of the sample had begun their treatment in the years preceding.
Researchers used medical record data to determine which teens had suffered cardiac events in the time since starting the therapy.
Among that group, 1,675 underwent hormone therapy.
Hormone therapy is an umbrella term for drugs that boosts the levels of hormones naturally created by a person of the opposite sex, giving a person the desired characteristics.
Transmen will usually receive testosterone, while transwomen will receive estradiol.
The drugs have long been used to treat low testosterone in men or issues related to fertility and menopause in some women.
In recent years, their use off-label has surged as doctors have begun prescribing them for transitioning patients.
Researchers found that, across the study population, people who suffered from gender dysphoria and received the treatment were 7.15-fold more likely to suffer an ischemic stroke than those who did not.
This occurs when blood clotting blocks crucial arteries blood uses to travel to the brain. Around 17 percent of these events result in death.
Pulmonary embolisms, when blood clotting the artery block blood to the lungs, were also 4.92-fold more common in people who received hormone treatments.
Myocardial infarctions, one of the most deadly forms of heart attack, also caused by blood clotting, is 5.9-fold more common in people who underwent hormone therapy.
While some have disputed the link, large-scale studies have linked pill forms of hormone treatments to an increased risk of blood clotting, especially in women.
A 2019 study by UK researchers found that women who took the oral treatment were at a 58 percent increased risk of developing potentially deadly blood clotting.
In the same study, other forms of therapy were not found to have a significant effect on risk.
‘I’m curious to see if the method of administration alters the outcomes,’ Dr Ahmed said.
‘Is one way of giving hormone replacement therapy better or associated with a lower risk of cardiovascular outcomes? If so, then that should be the focus for how we give these patients their hormone replacement therapy going forward.’
There are outside factors that could be at play, though.
Transgender people are more likely to suffer from mental health issues such as depression and anxiety, which are also linked to an increased risk of this cardiovascular problems.
This could be controlled for by using only patients suffering from gender dysphoria in the study, like this study did.
Still, Dr Ahmed wants doctors to do more to screen patients before putting them on these therapies and to make them aware of potential risks.
‘I’m curious to see if the method of administration alters the outcomes,’ he said.
‘Is one way of giving hormone replacement therapy better or associated with a lower risk of cardiovascular outcomes? If so, then that should be the focus for how we give these patients their hormone replacement therapy going forward.’
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