In high school, Charlie Manzano attempted to start gender-affirming hormone therapy, treatment that allows transgender individuals to acquire secondary sex characteristics more aligned with their gender identity. His pediatric endocrinologist, however, told him that the hormones cause cancer and were an “unnatural occurrence,” Mr. Manzano recalls. Mr. Manzano, a transgender man from Martinez, California, would subsequently learn just how common his experience was. After being diagnosed with melanoma, he cofounded the Transgender Cancer Patient Project with fellow cancer patient Roman Ruddick. (Ruddick identifies as nonbinary, a gender identity that falls beyond male or female categories, and uses the pronouns “they/them.”) Their project helps to raise awareness about the needs and challenges of gender minorities trying to navigate the US health care system. Many of the patients Mr. Manzano and Ruddick have talked to have had similar experiences of physicians emphasizing the “unnatural,” “bad,” or cancer-causing aspects of hormones. The subtext of such assertions, they say, is that transgender patients are somehow putting themselves at unnecessary risk by requesting gender-affirming hormone therapy. Similar to some other assumed risk factors, however, few studies have probed links between gender-affirming hormone therapy and cancer, and transgender health advocates say the risk assessments are almost never weighed against the potential benefits. For the transgender community, large gaps and conflicting evidence in peer-reviewed studies, lingering discrimination, inadequate or biased provider communication, and considerable barriers to health care access all have conspired against honest and helpful evaluations of cancer risks. Ash Alpert, MD, a hematology and medical oncology fellow at the Wilmot Cancer Institute of the University of Rochester Medical Center in Rochester, New York, says studies have so far yielded very little data about the long-term effects of gender-affirming hormone therapy. (Dr. Alpert uses the pronouns “they/them.”) “I think we've really let the community down by not really being able to allow people the opportunity for informed consent because we have so little data,” they say. Ruddick, an ovarian cancer patient from Medford, Oregon, points out that cisgender people (those whose gender identity matches the sex they were assigned at birth) sometimes use hormone replacement therapy too. Doctors have prescribed it to treat women's menopausal symptoms and prevent bone loss and fractures, even though large clinical trials have suggested that the therapy can increase the risk of cancer and other serious conditions. In those instances, patients and their providers have often determined that the benefits outweigh the risks. However, instead of a balanced discussion of risks and benefits, Ruddick says that the physicians of transgender patients routinely overemphasize the cancer links—something that trans patients in focus groups have told Dr. Alpert as well. Dr. Alpert, who is conducting oncology and hormone therapy research, says that message can raise questions in patients' minds about the true basis of their physicians' warnings. “I think it's a little hard to disentangle transphobia and stigmatization of trans people in general and within medical systems from how we're interpreting and communicating data,” Dr. Alpert says. “Are people thinking that there's a link between hormone therapy and cancer, or is it just another way of stigmatizing trans people for being trans?” Two recent reviews of previous studies found no significant increase in tumor risk among transgender individuals who were receiving gender-affirming hormone therapy, although both reviews acknowledged the need for better studies and risk assessments.1, 2 Madeline Deutsch, MD, MPH, an associate professor of clinical family and community medicine at the University of California at San Francisco and medical director of the Transgender Care program at the university's medical center, cautions that the absence of gathered evidence does not mean there is none to be had or no potential risk. “Any time a patient makes a decision to undergo a treatment, they are accepting some degree of unknown and some degree of risk,” she says. Nevertheless, she doubts whether hormones would raise the rate of hormone-sensitive breast cancers in transgender women beyond the rate observed in cisgender women. A new study from the Netherlands supports Dr. Deutsch's premise. The research included 2260 transgender women and 1229 transgender men receiving gender-affirming hormones at the VU University Medical Center Amsterdam's gender clinic. The study concluded that the breast cancer risk for the transgender women, who received mostly antiandrogen and estrogen therapy, was approximately 47-fold higher than the risk for Dutch cisgender men, but more than 3-fold lower than the risk for Dutch cisgender women.3 The risk for transgender men receiving testosterone therapy likewise was much higher than that for cisgender men but approximately 5-fold lower than the risk for cisgender women. “I think it's the clearest data we have that there's a connection between estrogen and breast cancer risk,” Dr. Alpert says. “And yet, for the trans women in the study, although their risk was dramatically increased compared to cisgender men, it was still less than cisgender women.” Based on the low overall risk, the authors concluded, transgender individuals should be able to follow the same breast cancer screening guidelines that cisgender people do. A 5-year, $5.7 million investigation launched by the National Institutes of Health in 2015 may help to fill some of the remaining gaps in knowledge. The study will follow young transgender individuals for life to gauge the effects of hormones on their relative risks for breast cancer and other malignancies. However, the initial data will not be available for another 15 years. In the meantime, Dr. Alpert says, “Whenever we're talking about risks of hormone therapy, we also have to talk about risks of not being on hormone therapy for trans people, including a potential increase in risk of suicidal ideation.” A 2018 study of 206 transgender veterans, for example, found that access to transition-related medical interventions, especially to both hormone therapy and surgical transition interventions, significantly reduced their frequency of suicidal ideation and depressive symptoms.4 Cancer, therefore, needs to be viewed within the larger context of health outcomes. Hormone therapy is not the only risk factor for which the available data conflict. Several small studies have suggested that transgender individuals are more likely to use tobacco than their cisgender counterparts. However, the 2015 US Transgender Survey of nearly 28,000 respondents suggested that trans individuals do not smoke at higher rates: 57% reported smoking all or part of a cigarette at any point in their lives, compared with 63% of the US population. Approximately 22% of transgender respondents said they had smoked within the past 30 days, compared with 21% of the US population. “I wouldn't want to dissuade anyone from having smoking cessation programs specifically for transgender people, because I think that a lot of our health care services may be inaccessible to trans people,” Dr. Alpert says. Nonetheless, the mixed data suggest a need to clarify the contributions of risk factors “and room for us to do a lot more work to take better care of trans people in oncologic and other settings,” they say. In fact, Dr. Deutsch says more research regarding cancer risks related to discrimination, emotional trauma, stress, and other physiologic wounds experienced by transgender people is badly needed. Studies have suggested that such experiences can increase levels of inflammation and stress hormones such as cortisol. In turn, chronic inflammation and higher cortisol levels have been linked to cancer. “So we don't know as much as we should about what being trans means for your cancer risk, regardless of hormone use,” she says. Filling in the gaps is far more difficult when medical institutions do not routinely collect information regarding gender identity, Dr. Alpert says. Likewise, assessing risks based on family and medical histories can be complicated when transgender patients' records are listed under different names. Whether physicians communicate cancer risks effectively and empathetically can be critical as well, given that many transgender patients have cited negative experiences with providers as barriers to seeking out health care. For example, when Ruddick arranged an informational meeting to discuss gender-affirming hormone therapy, the endocrinologist, who was unfamiliar with their cancer history, made a dismissive and ill-informed recommendation. The doctor advised Ruddick to “just get a hysterectomy” to eliminate gynecologic cancer risk as a potential side effect of hormone therapy. “It felt really insensitive because it was just a very broad assumption that all trans people want to and should get rid of those organs,” Ruddick says. “I think their hope, because they don't know what to do with it, is that we just get it cut out.” Many physicians appear to be scared of trans patients, Ruddick adds. “They're not sure how to talk to us, and they're not sure about the care that we need that's different. A lot of them don't know what hormones do, they don't know what surgeries trans people get, and they're afraid to ask.” Learning how to do so, advocates say, could make the difference between life and death.