How safe is transgender hormone therapy?

Few have been examining that question more closely in recent years than Dr. Joshua Safer, the first director of the new Center for Transgender Medicine and Surgery at Mount Sinai in New York. So far, the answers he is finding are encouraging.

In 2014, Safer and fellow researchers found that the existing scientific literature suggests that transgender hormone therapy is “safe without a large risk of adverse events when followed carefully for a few well-documented medical concerns.”

In 2017, Safer co-authored a study finding that out of the 31 percent of transgender women he saw at Boston Medical Center who smoked, a staggering 64 percent quit while undergoing hormone therapy in order to reduce their risk of blood clots.

In 2018, he and a research team learned that testosterone treatment for transgender men seems to reduce estrogen levels on its own, potentially reducing the need for “other estrogen-reducing strategies.”

Most recently, Safer helped find in an April study that prolactin levels did not rise significantly among a sample of transgender women taking the traditional combination of estradiol and the anti-androgen spironolactone, suggesting that “it may be unnecessary to monitor prolactin in women on this treatment combination.”

“The theme,” Safer tells The Daily Beast, “is that the studies to date have tended to reassure that transgender hormone treatments are safer than people realized.”

Safer was part of a team of endocrinologists, or hormone specialists, who updated the Endocrine Society’s guidelines for transgender treatment in late 2017.

Prior to that, the inaugural set of guidelines were published in 2009–a landmark step forward for transgender health care, despite how cautious those initial recommendations were.

“The 2009 guidelines were very conservative,” Safer recalls. “But they were really enormous in their impact because it was a conventional medical organization that took this on, and it just changed the entire conversation.”

Nearly a decade after those guidelines were first published, Safer says there is still “a lot of work to be done” to refine them through “much bigger, more comprehensive studies.”

But so far, every time Safer has examined a fear that physicians might have about transgender hormone therapy, the results have helped alleviate those fears.

Take blood clots, for example. Estrogens can increase the risk of getting them. That’s not a situation unique to transgender women, as Safer tells The Daily Beast, given that some of the “worst offenders” for blood clot risk can be found in “birth control pills given to millions of [cisgender] women.”

But as recently as a few years ago, as Safer recalls, some physicians would go so far as to deny estrogen to transgender women who smoked, for fear of increasing their risk of blood clots.

Safer took a different approach: Instead of denying them the medically-necessary treatment that is hormone therapy, he was “pretty aggressive” in petitioning his transgender female patients to give up cigarettes as they medically transitioned.

When Safer and a student of his later looked through the files of his patients who agreed to be included in his 2017 study on the subject, they found that the transgender women smokers quit at a rate about ten times higher than the 6.2 percent of adult smokers who “successfully quit in a given year.”

And because smoking increases the risk of blood clots far more than estrogens do, that encouraging trend was a net gain for his patients as a whole.

“ While some physicians raise concern over morbidity from hormone therapy, in our experience, good health habits initiated with care in our system more than outweigh the modest risks currently described ”

“Just counting out those who managed to quit smoking more than offset the total risk of blood clots from all that estrogen being given to everybody,” he says.

Indeed, the benefits of getting these transgender women hooked into the health care system—rather than turning them away—proved to be much greater than the increased risk of blood clots that may come with an estrogen prescription.

As the abstract for the study notes: “While some physicians raise concern over morbidity from hormone therapy, in our experience, good health habits initiated with care in our system more than outweigh the modest risks currently described.”

Safer tells The Daily Beast that his work lately has largely been about “addressing fears.”

As he explains it: “That’s exactly where you want to begin: What is everybody worried about?”

He doesn’t necessarily begrudge his peers in the medical community for being cautious about administering transgender hormone therapy, attributing their hesitations around the area “almost exclusively” to the Hippocratic promise to “do no harm.” By now, doctors recognize the enormous mental health cost of leaving gender dysphoria untreated—and major medical associations have long affirmed the necessity of transition-related health care for those who suffer from it.

But fine-tuning the hormone regimens for transgender men and transgender women, and evaluating their risks remains a challenging task—one that will require frustratingly slow and methodical labor.

Contrary to popular belief, says Safer, it’s not the size of the transgender population that makes it so difficult to carry out longitudinal studies with large samples. According to the latest estimate, about 1.4 million adults in the United States are transgender, which is certainly small by percentage of the population but not in terms of total number.

“The numbers of [transgender] people are bigger than for a lot of medical conditions, so I don’t think that’s the biggest barrier,” he tells The Daily Beast.

The problem, says Safer, is that the population isn’t “well-identified,” meaning it is hard to sue out through “conventional medical records” which of the patients in large databases of medical information are transgender.

Add to that a delay in funding being directed toward this issue—it wasn’t until September 2017 that the National Institutes of Health added a funding opportunity for research on transgender health—and you get what Safer calls “a little bit of a lag in getting high-quality, sophisticated research done.”

That’s not to say that there isn’t solid research to support the current state of transgender hormone therapy. The Endocrine Society would never have published guidelines on the topic if there weren’t. And in fact, Safer says that, in his opinion, even the new 2017 guidelines are “overly conservative in a few areas.”

“Yes, I will be very honest,” he admits, laughing. “I already can see opportunities to revise the revision.”

For example, the new 2017 guidelines direct physicians to monitor the levels of prolactin in transgender women undergoing hormone therapy, for fear that higher levels could lead to growths or tumors on the pituitary gland.

Safer’s most recent study, however, found evidence in the medical records of 98 transgender women treated at Boston Medical Center that there was “no significant rise in prolactin” when treated with the regimen that is customary in the United States. Now, Now, Safer can’t help but wonder if “we might have dropped that recommendation” about prolactin monitoring had that study come out before the revision process began.

What has helped fuel research in this area is the overwhelming willingness of transgender patients to participate in it. Several of Safer’s studies use anonymized data from the patient records at his previous position at Boston Medical Center and, as he tells The Daily Beast, “almost every single patient [they] asked” gave their consent.

“I think people felt very mission-driven,” says Safer, noting that they seemed concerned about helping other transgender people get quality health care.

Safer, too, seems mission-driven, although he is not transgender himself. Circumstance is what led to him to this understudied discipline—and to his new job at Mount Sinai, where he hopes to provide a “model” for comprehensive transgender treatment around the country.

“For me, it’s a little bit of an accident, honestly,” Safer says.

“ I knew nothing. And all of a sudden, I had to really ramp up my knowledge ”

In the early 200s, when Safer was faculty at Boston University, a fellow working beneath him—Dr. Vin Tangpricha, a transgender endocrinology expert in his own right and the president-elect of the World Professional Association of Transgender Health—left the practice. Tangpricha’s transgender patients fell into Safer’s care.

“I knew nothing,” he remembers. “And all of a sudden, I had to really ramp up my knowledge.”

Now, Safer has not only learned about as much as any researcher can learn on the subject, he is helping lead the charge to learn more. But more so than feeling proud, Safer says he feels “lucky” to have been in a position to help advance health care for a minority that has long struggled to access it.

“I would characterize it as a very cool experience,” he says, “to be able to be somewhat useful.”

[Disclosure: Dr. Tangpricha, Dr. Safer’s former fellow mentioned briefly above, is the author’s physician.]