The Unstudied Effects Of Hormone Replacement Therapy: What Do Transgender Patients Need To Know?

"Larger, long-term studies are needed in transgender medicine," says endocrinologist Joshua Safer.

Many transgender individuals seek out hormone replacement therapy (HRT) during their transition. This typically requires trans women to take estrogen and an anti-androgen (a testosterone blocker), and for trans men to take testosterone. Throughout treatment, feelings of dissonance between a patient's gender identity and body often lessen, leading to a person who is happier and more at home in his or her own skin. While many studies assert the safety of HRT when undertaken under the guidance of a healthcare professional, research on long-term effects of HRT are practically nonexistent, raising the question: What impact could hormones have on bodies later in life?

For many trans people, partaking in HRT is not a stopgap: Those that choose to undergo it will likely continue for the remainder of their lives. Inquiring about long-term effects, therefore, is necessary. For instance, does the risk of blood clots, insulin insensitivity, and/or diabetes increase over time? Is literature proposing that dementia might be exacerbated by synthetic estrogen supported by ample data? There exists a great gap in scientific knowledge.

Syringe with medical supplies on blue background. 3d illustration

On the other hand, short-term effects are well-studied. An article published in the Journal of Clinical and Translational Endocrinology, which drew information from over 70 respectable papers and studies, suggests HRT is very safe—whether it’s undertaken by cisgender or transgender men or women. The article's authors, doctors Jamie Weinand and Joshua Safer, medical director of the Center for Transgender Medicine and Surgery at Boston University Medical Center, asserts that the risks of undergoing HRT for an otherwise healthy trans adult are minimal.

Current literature suggests [HRT] is safe when followed carefully for certain risks. The greatest health concern for [HRT] in transgender women is venous thromboembolism [blood clots, most typically in the legs]. [HRT] among transgender men appears to cause polycythemia [an increase in the volume of red blood cells]. Both groups experienced elevated fasting glucose. There is no increase in cancer prevalence or mortality due to [HRT].

The study suggests that the highest incidence rate of blood clots in trans women is among those taking an infrequently prescribed form of estrogen (ethinylestradiol) and those whose risk is already elevated: smokers, patients immobilized for long periods of time following surgeries, or patients with a hypercoagulable disorder (an abnormality of blood coagulation). The risk of increased red blood cells in trans men, and elevated fasting glucose in both trans men and women are, according to Dr. Safer, inconclusive, and unlikely to be significant.

“Although current data support the safety of [HRT] with physician supervision,” the article concludes, “larger, long-term studies are needed in transgender medicine.”

Female scientist about to view a human sample under a microscope

When asked why he thought these long-term studies hadn’t been conducted, Dr. Safer told NewNowNext, “You have to remember that the entire field has not been part of conventional medicine and conventional scientific investigation for very long... Nobody's been funding this research, nobody's been doing this research—but that isn't totally surprising.” Dr. Safer believes that the growing recognition that gender identity has a biological component “takes the entire field and puts it into the realm of conventional medicine and science."

He points to an announcement made by the National Institutes of Health in September 2017 that requested more research into transgender care; NIH began welcoming submissions in January. While this is encouraging news for the trans community, it’s unfortunate that it took the NIH—one of the world’s foremost medical research centers—this long to acknowledge the seriousness of long-term trans health, especially considering the World Professional Association for Transgender Health released its first standards of care document for transgender adults nearly 40 years ago.

But is the NIH moving in the right direction?

“I'm always an optimist,” says Dr. Safer, “and as somebody who's been active in this field, I'm made more optimistic over time… Until very recently there would be no specific opportunity to even ask for funding from the National Institutes of Health, and pharmaceutical companies would specifically not want their product associated with transgender care for fear of negative publicity.”

Regardless, Dr. Safer isn’t sure that long-term research of HRT will yield any negative implications.

"My honest expectation is to find very little, if any, negative consequence. We [employ] science because we don't really know the answer, but my guess is that there's going to be one of two things: either there is a small harm or there is not. If there is a small harm, it will simply be a part of our pattern where we will say, 'Okay, this is your risk, is it worth it to you?' And most of the patients will say, 'Sure.'"

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