Social determinants of health affect the lives of transgender people. When you see a transgender person in clinic, you are seeing them for a brief window of time. There is a whole world going on around that person that affects their lived experience.

Transgender people may have experiences that negatively affect their health and engagement in healthcare.¹ These may include experiences of discrimination or stigma and shame. They may have had to repress their identity for considerable lengths of time because they were not being accepted. They may lack legal protections in a range of areas or have difficulty obtaining updated identity documents, which can result in difficulty obtaining stable housing and employment.¹ People who lack stable employment or housing are at higher risk to become involved in sex work or drug trading for survival purposes, or have behavioral health or substance abuse issues.² In addition, transgender people may be exposed to physical abuse and violence, especially if there’s a lack of legal protections or hate crime laws.¹

All of these create a complicated interwoven web of factors that can affect the experience and lives of transgender people.

There is quite a lot we can do to make transgender patients more comfortable in the clinic. We can have clearly posted nondiscrimination and bathroom use policies.³ Our waiting rooms can include signs and posters, as you can see in the waiting room image here. Questionnaires about sexual behavior and family structures should be inclusive of transgender people. Discussion of sexual behavior should include the ways in which transgender and lesbian, gay, and bisexual people have sex.

Proper use of names and pronouns is very important in the care of transgender individuals. If you do not have a system to record pronouns in your electronic health record (EHR) and have staff properly use those pronouns once collected, then you will have people who will walk out of clinic before they are ever seen. Staff must be trained to use correct names and pronouns. Otherwise, you will miss an opportunity to identify health issues with patients because they will not engage in care.

Sexual orientation (who someone is physically, emotionally, and/or romantically attracted to) and gender (the internal sense of one’s gender) are 2 different entities.⁴ In primary care, it is important to collect sexual orientation and gender identity (SOGI) information. SOGI data include gender identity, the sex your patient was assigned at birth, and sexual orientation.⁴ These data can help inform quality improvement efforts and clinical care.

Regarding quality improvement efforts, these data can help us understand various factors about transgender healthcare. For example, we can identify if transgender patients are more likely to be lost to follow-up, or if they are less likely to be current on colon cancer screening. Unless you know which patients are transgender, there is no way to make those comparisons. SOGI data also can inform clinical care. To properly care for patients, you should know what organs your patient has. Knowing somebody’s sex assigned at birth is important for understanding certain risk factors.

It is important to maintain an accurate organ inventory for your transgender patients. The ideal situation is to include this in the EHR where it is linked to surgical history and the preventive health–reminder module.  For example, if somebody has not had a hysterectomy and they were assigned female at birth, they will have a uterus and a cervix, the presence of which would be linked to that preventive health–reminder module. If they have had a hysterectomy, that reminder would then be turned off automatically. Unfortunately, EHR systems are often not that robust. however, if a person goes to court and gets their identity documents changed so that they are legally male, there still needs to be a system in place to inventory in their chart that this patient has a cervix, for example, so you remember and can be reminded to appropriately screen that patient for cervical cancer.

Each person in the clinic plays a role in the experience of patients. In many ways, the people working at the front desk who check in patients have one of the most important jobs, because they welcome patients into the clinic. It is essential for all staff members to use patients’ proper names and pronouns. The next person the patient likely will encounter is the nurse or medical assistant who will bring the patient back to the examination room. This is an important opportunity to refer to the patient respectfully by their chosen name and pronoun. If you are unclear on what name or pronoun to use, pause and ask the patient to clarify.  For example, you can say, “May I ask you what name you use? What pronoun do you use?” I recommend against using honorifics such as sir or ma’am or Mr. or Mrs.

It often takes more than a single visit with a patient to develop a rapport where you can begin to have sensitive discussions about identity, sexual behavior, organs, or screening. Commonly in primary care when someone comes to clinic who has not seen a doctor for a while, they come in the room, are asked to gown-up before they see the provider, and then undergo a whole top to bottom physical including Pap smear on that day. In my clinic, no clothes come off when the patient comes in. The only time patients are asked to gown-up is if the provider decides that the patient should have a gown on. I often see patients for an initial visit and no skin touching occurs because we are still building that relationship. It is different from what most clinics are accustomed to, especially fast-paced, high-throughput primary care settings. However, if you think about it, most patients you are seeing in primary care do not need a gown, regardless of if they are transgender, cisgender, or nonbinary.

People talk a lot about cultural competency, which is really important. It is important to have knowledge about a particular culture. For example, what terminology is used? Is your own attitude accepting and welcoming for this community? Do you have compassion for people? You might also include empathy for people under the heading of cultural competency.

However, I recommend people go further and take on a cultural humility framework. With cultural humility, rather than making assumptions about people, you assume you know nothing.⁵ It does not matter how many lectures you went to or how many cultural trainings you have been to. At the end of the day, you recognize that the living person who is standing in front of you and telling you who they are is who you need to listen to. People may throw you curve balls, where you think, “‘That’s not what I learned about in that lecture,” but it still is important to let people tell you who they are.

Regarding hormone therapy and cardiovascular (CV) disease, as well as more broad metabolic conditions (lipid disorder, diabetes, etc), the approach should be to weigh the risks against all the benefits of hormone therapy. Hormone therapy can lead to significant improvements in psychosocial functioning, reduce stress and anxiety, and improve the overall sense of wellbeing and quality of life for transgender people.⁶ It also is important to consider the role that chronic stress, which can lead to chronic inflammation, can play in the development of chronic health conditions and unhealthy lifestyle factors such as overeating or tobacco or drug use. Not having a body that aligns with your identity or being discriminated against are examples of things that may drive chronic stress conditions for transgender people.⁷ When we practice gender-affirming measures, stress levels may go down, leading to improvements in quality of life and health outcomes.

When calculating CV risk to determine if a statin or other intervention is needed, the calculating system requires input if the person is male or female.⁸ Which do you pick for a transgender patient regarding this calculator? Determining this requires some critical thinking and is part of the art of medicine. You may need to consider how long the person has been on exogenous hormone therapy. For example, if a transgender female is 57 years of age and has only been on estrogen for 1 year, you are probably going to tick the male box. If a transgender woman is 52 years of age and been on estrogen since she was 19, you might check the female box or you might tick the male box because they did have a few years after puberty when they had testosterone in their body. You may need to take a weighted average of the 2. The reality is, the calculator will depend on what stage of transition the transgender person is from a chronology perspective.

There are 2 studies I would like to discuss regarding risk for CV events and hormone therapy. This first study is a retrospective chart review.⁹ Every transgender participant enrolled in the study was matched to 10 cisgender females and 10 cisgender males.

In the overall cohort of transfeminine people, the incidence of venous thromboembolism, stroke, and myocardial infarction (MI; ie, heart attack) were compared with cisgender people.⁹ The values in red are statistically significant. There was approximately 2-fold increase in hazard ratio of blood clots in transfeminine people compared with cisgender men. Compared with cisgender women there was a nearly 2-fold increase in all 3 of these outcomes.⁹

These numbers may set off alarms on their own, however there are some important items to consider. First, the most appropriate comparison group of transfeminine people and transgender women in this setting is cisgender men given the biologic basis before hormones are added into the mix. Second, it is important to calculate the number needed to harm, which is quite high. Although the relative risk is approximately double, the baseline risk of blood clot in just a walking and talking population is relatively low.⁹ Therefore, you have to treat 111 people with hormone therapy in this particular group to get 1 more unexpected blood clot. It is important to contextualize that information when conducting informed consent with patients in order for your patient to make an informed decision about whether they want to start hormone therapy. When we conduct risk to benefit assessments as a medical institution, it is important to think about because we want to do no harm in medicine.

In the transmasculine group in this study, there was no statistically significant difference between the transmasculine group and the cisgender male or cisgender female controls.⁹

This is the second study I would like to discuss regarding risk for CV events and hormone therapy. This study evaluated data from the Behavioral Risk Factor Surveillance System, which is a self-reported health survey sent out periodically by the US government.¹⁰ These are not chart-reviewed data like the previous study.⁹

In this study, there was no statistically significant difference in risk of MI in transgender women compared with cisgender men.¹⁰ There was an increased risk of MI in transgender men compared with cisgender men and, not a surprise, an even higher risk of MI when transgender men were compared with cisgender women.¹⁰ Transgender women did have a higher risk of MI compared with cisgender women, but that is not surprising given the main baseline comparison for this should be sex assigned at birth.

Although these data conflict with the prior study, if you conducted a number needed to harm analysis, it would be similar to the prior study with an absolute effect size difference that is not that large.

The take home message is that, if there is a risk of CV events with hormone therapy, it is not that large and should be put into context with the overall benefits of hormone therapy for transgender individuals.

Cancer screening should consist of an organ-based approach.¹¹ In medicine, we often focus on male and female cancer screenings, but the truth is we should be using and applying the organ inventory mentioned earlier when discussing cancer screenings. If the organ is present, appropriate cancer-screening guidelines should be applied.

Transgender men are much less likely than the general US population to be up to date on cervical cancer screening.¹² Exams for transgender men can be uncomfortable for various reasons, and transgender men have a higher preference for alternative approaches, such as self-sample.

In this study, we compared provider-collected samples with self-collected samples for HPV testing in 150 transgender masculine individuals. The negative predictive value (probability that a negative test is truly negative of HPV) was more than 94% with self-swab. The positive predictive value (the probability that a patient with a positive test has HPV) was still fairly good at 88%.¹³

If you have a patient in front of you saying, “I don’t want to do this test at all,” the self-swab option is really important. It provides patients an alternative for you to give them, “Well, what if we did the next best thing, which is have you to do self-sampling?”

In another analysis of the same cohort, we found that the risk of HPV infection is significantly increased among people who had sex with someone with a penis within their last 3 sex partners during the previous year.¹⁴ In this case, the data showed an approximately 5-fold increased odds of having a current high-risk HPV infection. Therefore, in some patients, especially those where considerations of cervical cancer screening are particularly difficult, it may be more appropriate to take an individualized approach to cervical cancer screening where risk factors such as types of sexual contacts and HPV vaccination status are considered as opposed to aggressive screening in every patient. This strategy, along with the possibility of self-swabbing, may provide a rational and patient-centered approach to cervical cancer screening in the future.

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The data for breast cancer screening in transgender people is limited. In addition, there may be harms associated with breast cancer screening including over screening which may cause unnecessary distress.¹⁵

In this retrospective chart review, the rates of breast cancer in transgender women were quite elevated compared with cisgender men but were lower than cisgender women.¹⁵ The overall rates in this study are quite low. There still are many more details to determine. The take-home message is that there does not appear to be an epidemic of breast cancer in transgender people.

The general recommendation is that breast cancer screening should be conducted for transgender women who are 50 years or older and have been on hormone therapy for 5 years or more.¹¹ Breast cancer screening for transgender men who have undergone chest surgery is a continued topic of debate, but should be discussed with patients. The post-operative anatomy may make mammograms technically difficult. Considerations in this group include self exams, ultrasound, or MRI, all of which have drawbacks and risks of false positives.

For patients who are amenorrheic, testosterone is generally safe and would not require evaluation for uterine cancer. However, patients looking to start testosterone therapy who have been amenorrheic without a known cause should be worked up, as you would with cisgender female patients. Furthermore, as with any cisgender females, unexplained sudden return of bleeding that cannot be attributed to changes in testosterone dose, BMI, or a new medication or medical condition should be explored.¹¹

This case series of amenorrheic transmasculine people found no significant endometrial abnormalities in patients on testosterone who were having their uteruses checked, which is consistent with other findings.¹⁶

Prostate cancer screening can be a bit tricky in transgender women, because people who have been on long‑term testosterone suppressive therapy will very likely have a prostate that is not palpable, besides the fact that prostate cancer screening guidelines are a bit murky in general. Furthermore, there have been no studies on the impact of long-term testosterone suppressive therapy on the risk of prostate cancer in transgender women.

My approach is to screen the organ the patient has based on current clinical guidelines and shared decision-making with the patient.^17-19 In my opinion, it is very reasonable in patients, particularly those in their 50s and 60s who started hormones or testosterone blocking later in life, to get regular prostate-specific antigen (PSA) tests.

Overall and cause-specific mortality among transgender people is higher compared with cisgender controls as demonstrated in 2 Dutch National Registry studies.^20,21 However, most of the mortality differences are attributable to social and societal factors involving things like substance use, suicide, and other factors.²² The effect size of biomedical cause-specific mortalities among transgender people was small and should be balanced with the benefits of hormone therapy.

The main takeaways are, 1) creating a welcoming environment can have a significant impact on the experience of transgender and gender-diverse patients in clinic; 2) CV mortality risks directly attributable to hormone therapy are marginal and are likely outweighed by the overall benefits of providing such treatment; 3) hormone- or sex-driven cancers do not appear to be elevated in transgender people compared with cisgendered people, and, in some cases, may be present at lower rates; and 4) cancer screening should be organ-based.