Preventive Health for Transgender Men and Women

Abstract

Transgender men and women experience an incongruity between their assigned sex at birth and their identified gender. Gender dysphoria is defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) as clinically significant distress or impairment resulting from misalignment in assigned and experienced gender. Transgender people have a history of negative experiences in health care and efforts should be made to create a welcoming environment through staff training, gender neutral restrooms, and gender inclusive electronic medical record systems. Transgender men and women face unique preventive health concerns in areas of metabolic screening, cancer screening, immunizations, and anticipatory guidance secondary to cross-sex hormone therapy, gender confirming surgical procedures, and certain high-risk behaviors. Here, the available data are reviewed and suggested best practices are outlined to optimize the preventive health for this patient population.

Keywords

transgender - gender dysphoria - preventive health

Transgender men and women have a sense of incongruity in their assigned sex at birth and their identified gender in many cases, leading to distress or impairment and a diagnosis of gender dysphoria.[1] Many transgender individuals need cross-sex hormones to treat gender dysphoria by aligning their secondary sex characteristic with their experienced gender. Typical cross-sex hormone therapy may include testosterone for transgender men and estradiol plus an androgen blocking medication such as spironolactone for transgender women.[2] Transgender men and women may undergo several gender confirming surgical procedures that result in removal or alteration of their natal organs, see article by Unger in this issue.[3] It is imperative for clinicians providing care for transgender individuals to obtain a careful and detailed surgical and hormonal history to understand how to apply recommended screening guidelines. While many of the recommendations for preventive health are the same for transgender persons and non-transgender persons, there are important considerations for the clinician caring for transgender patients.

Diagnosis of Gender Dysphoria

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) defines gender dysphoria as “distress which may accompany an incongruence between one's experienced/expressed gender and one's assigned gender.”[1] For adult patients, the diagnosis can be made when gender dysphoria is present for at least 6 months, manifested by at least two of the following: a marked incongruence between one's experienced/expressed gender and primary and/or secondary sex characteristics; a strong desire to be rid of one's primary and/or secondary sex characteristics because of a marked incongruence with one's experienced/expressed gender; a strong desire for the primary and/or secondary sex characteristics of the other gender; a strong desire to be of the other gender (or some alternative gender different from one's assigned gender); a strong desire to be treated as the other gender (or some alternative gender); a strong conviction that one has the typical feelings and reactions of the other gender (or some alternative gender). Additionally, this incongruence causes clinically significant distress or impairment in social, occupational, or other important areas of functioning for the patient.[1]

Creating a Welcoming Space

As many as one-third of transgender patients report negative experiences with healthcare providers, including refusal of treatment, verbal harassment, and physical assault. Fifty percent of transgender patients have to teach their provider about transgender health issues to get appropriate care.[4] This highlights the importance of both increasing medical knowledge among providers and the intentional creation of an open and welcoming space through ongoing cultural competency training for all staff. More information can be found in this issue in article by Cook et al.[5]

Staff should be trained to maintain a nonjudgmental posture and avoid making assumptions about a patient's sexual orientation or gender identity. Additionally, training should include a basic introduction of terminology often used by, and about, the transgender community. In addition to cultural competency training, the physical environment can provide patients with visual indications of inclusive care. This can be accomplished with LGBTQ themed magazines, pamphlets, and artwork.

In 2015, as many as 17 states introduced anti-transgender bills aimed at bathrooms and locker rooms.[6] Thus, it is incredibly important to provide transgender patients with a safe place to use the bathroom by posting policies stating that patients may use any bathroom in which they feel comfortable or labeling single-stall bathrooms as “gender-neutral.”

While challenging to implement, a gender-inclusive electronic medical record (EMR) system is an important way to create a welcoming space for transgender patients. Recommendations for EMR systems include distinct demographic fields for preferred name, assigned sex at birth, gender identity, and pronouns of reference. Preferred name should show up on schedules and track boards to operationalize its consistent use among all staff. EMR systems should include an organ inventory and medical and/or surgical transition history.[7]

Limitations and Challenges of Preventive Health Data for Transgender Patients

There is a disparate amount of health-related data about transgender people for multiple reasons, including lack of gender identity as a demographic variable in electronic health records and research databases. While there are no national guidelines specific to preventive health care for transgender patients, the recommendations below include screening considerations for transgender persons compiled using available outcome data for transgender persons as well as inferences from data with non-transgender persons using hormone therapy. The provision of medically and culturally competent preventive health care for transgender persons is integral to striving for health equity for this population.

Metabolic Screening Recommendations

Cardiovascular Disease

The pooled cohort equation uses male sex as one of the risk factors for calculating 10-year risk of cardiovascular disease (CVD) and determining the indication for low-dose aspirin therapy for primary prevention of CVD.[8] The United States Preventive Services Task Force (USPSTF) recommends low-dose aspirin therapy for primary prevention of CVD for persons aged 50 to 59 with a 10-year CVD event risk of 10% or greater.[9] Depending on the age of cross hormone therapy initiation and the total length of exposure, it is advisable to use either the transgender patient's assigned sex at birth or affirmed gender, or an average of both, in the calculation of 10-year CVD risk.[10]

Transgender Men

Evidence suggests testosterone treatment in transgender men has no effect on risk of cardiovascular events.[11] [12] Non-transgender men treated with testosterone for androgen deficiency have been shown to have increases, decreases, and no change in cardiovascular events.[13] [14] [15] Maintaining physiological levels of testosterone, as opposed to supraphysiologic levels, in transgender men is recommended to reduce cumulative risk of CVD.[16]

Transgender Women

The long-term use of ethinyl estradiol in transgender women has been associated with a threefold increased risk of cardiovascular death.[12] Similarly, there are increased risks of cardiovascular events among postmenopausal non-transgender women on hormone therapy, as shown in the Women's Health Initiative (WHI) trial. In the group taking combination estrogen and progesterone, there was a probable increased risk of stroke, heart attack, and venous thromboembolism.[17] The estrogen-only arm demonstrated an increased risk of stroke and venous thromboembolism while having no effect on cardiac events.[18] The estrogen primarily used in the WHI trial was oral conjugated estrogen and it is unknown if this confers similar risk to the estrogen preparations more commonly used by transgender women—oral 17-β estradiol, transdermal estradiol, intramuscular estradiol valerate, or intramuscular estradiol cypionate. The use of transdermal estradiol, as compared with oral estrogen, has been shown to have a reduced risk for venous thromboembolism, markers of coagulation, and dyslipidemia.[19] [20] In transgender women older than 50 years and/or with other risk factors for CVD (smoking, family history, diabetes, etc.), it may be prudent to use transdermal estrogen and minimize the use of progesterone therapy.[21]

Hypertension

The goal blood pressure for transgender men and women is the same as that for non-transgender men and women.[22] Blood pressure should be monitored at every visit.[21]

Transgender Men

There is an increased prevalence of polycystic ovarian syndrome (PCOS) seen in pre–cross-hormone treatment transgender men.[23] [24] PCOS has been shown to increase the risk for hypertension in non-transgender women; thus, transgender men should be screened for symptoms of PCOS before initiating hormones.[2]

Transgender Women

Estrogen therapy has been shown to minimally increase blood pressure; however, the clinical significance of this is unclear.[2] [25] Spironolactone, with its antiandrogen properties, is often used as a part of a feminizing regimen for transgender women, and can be used to treat blood pressure to the defined target based on age.

Type 2 Diabetes Mellitus

Transgender men and women should be screened for diabetes mellitus using the same guidelines used for non-transgender men and women.[10] [26] Consider annual diabetes screening with a hemoglobin A_1c, fasting glucose, or with an oral glucose tolerance test for transgender men and women taking cross-sex hormones if they have a family history of diabetes or weight gain of >5 kg since starting medication(s).[21]

Transgender Men

There is no evidence that testosterone therapy increases the risk for diabetes in transgender men.[2] However, transgender men before starting hormone therapy have increased rates of PCOS, a condition known to be associated with increased risk for impaired glucose tolerance and type 2 diabetes mellitus in non-transgender women.[25] [27] Transgender men should be screened for symptoms associated with PCOS (hirsutism, acne, anovulation) before initiating therapy, and, if present, should be routinely screened for diabetes regardless of their age.

Transgender Women

Treatment for transgender women with estradiol has been shown to increase fasting insulin levels, weight, and percentage body fat and decrease insulin sensitivity.[23]

Dyslipidemia

Screening and treatment of cholesterol abnormalities in transgender men and women should follow the same guidelines as for non-transgender persons.[8] [28] As mentioned earlier, when calculating a 10-year CVD event risk, it is advisable to use either a patient's assigned sex at birth or affirmed gender or an average of the two depending on the age of cross-sex hormone initiation and/or the total length of time a transgender person has been on hormones.[10] The USPSTF recommends that persons aged 40 to 75 without a history of CVD who have one or more risk factors (dyslipidemia, diabetes, smoking, or hypertension) and a calculated 10-year CVD event risk of >10% be started on low- to moderate-dose statin therapy. For the same group of people with a 10-year CVD event risk of 7.5 to 10%, it is recommended that low- to moderate-intensity statin therapy be offered depending on individual circumstances.[28] Transgender men and women on cross-sex hormones should have annual screening for dyslipidemia with fasting lipid profiles.[2]

Transgender Men

Treatment with testosterone may lead to unfavorable lipid changes, namely, increases in total cholesterol, low-density lipoprotein (LDL), and triglycerides, and decreases in high-density lipoprotein (HDL).[29]

Transgender Women

Estrogen therapy in transgender women has been associated with increased HDL and decreased LDL.[23] [29] Transdermal estrogen is the preferred route of administration for transgender women with hypertriglyceridemia.[30] Estrogen therapy in transgender women should be considered a cardiovascular risk factor and should be taken into account when calculating the 10-year CVD risk and determining if lipid lowering therapy is indicated for primary prevention of CVD.[21]

Osteoporosis

Transgender Men and Women

The recommendations for osteoporosis prevention is the same for transgender and non-transgender persons—adequate calcium and vitamin D intake, weight-bearing exercise, smoking cessation, and moderation of alcohol consumption.[31] Because of insufficient data to determine long-term effects of cross sex-hormone therapy on bone density, both transgender men and women should be screened for osteoporosis with a DXA scan starting at the age of 65 years. Similarly, both transgender men and women aged 50 to 64 years with a 10-year fracture risk of >9.3% as calculated with the FRAX (Fracture Risk Assessment) tool (available at https://www.shef.ac.uk/FRAX/tool.jsp) should have DXA testing. The FRAX tool and DXA test include sex as a variable and clinicians should utilize either the patient's assigned sex at birth or affirmed gender or an average of the two depending on the age of cross-sex hormone initiation and/or the total length of time a transgender person has been on hormones. Osteoporosis risk is increased in transgender persons if cross-sex hormones are underutilized status post gonadectomy. DXA testing is recommended for transgender persons of any age status post gonadectomy who have had 5 years or more without cross-sex hormones.[10]

Cancer Screening Recommendations

Cervical Cancer Screening

Transgender Men

Transgender men with a cervix should follow the same cervical cancer screening guidelines as for non-transgender women.[32] [33] However, transgender men face unique challenges to adequate screening, including access to care, dysphoria regarding genital exams, technically difficult pap smears, and unsatisfactory pap smears.[34] [35] Pap adherence is lower for transgender men than for non-transgender women, and providers and other health care personnel should facilitate comfortable, safe, and technically successful pelvic examinations for transgender patients.[36] Tips for a successful exam include using culturally sensitive language, interviewing the patient prior to disrobing, having the patient disrobe only from the waist down, and allowing the patient to have a support person present during the exam. A virginal or Pederson speculum with a small amount of water-based lubricant can improve patient comfort. Transgender men have a 10-fold higher incidence of an unsatisfactory pap smear result compared with non-transgender women, correlated with the length of testosterone exposure and the presence of vaginal atrophy.[35] It is important to notify the pathologist that the patient is taking testosterone and consider high-risk human papillomavirus (HPV) DNA testing, as it can be helpful in determining whether cytologic changes are related to HPV infection or atrophy. Transgender men who have undergone hysterectomy should follow the same ASCCP screening guidelines as for non-transgender women who have undergone hysterectomy.[32]

Transgender Women

Vaginal pap smears for transgender women who have undergone vaginoplasty are not indicated. However, because of documented cases of neovaginal condyloma, a physical exam may be warranted to visually inspect for genital lesions on an annual basis or if symptoms arise.[37]

Breast Cancer

Numerous agencies have published recommendations regarding breast self-examination, clinical breast exams, mammography, and genetic screening for breast cancer.[38] [39] While recommendations vary regarding patient age range and frequency of screening from agency to agency, all groups encourage discussion about the patient's values regarding benefits and harms of screening strategies. This should apply to patients of all genders. Additional considerations include family history of breast cancer and familial cancer syndromes.

Transgender Men

Transgender men who have not undergone chest surgery should be screened according to guidelines for non-transgender women. Transgender men who have undergone male chest reconstruction do not need screening mammography.[21] While there are no recommendations regarding chest wall exams after surgery, there are reports of breast cancer in residual tissue, and patient's concerns about changes in the chest wall should be promptly addressed.[40]

Transgender Women

Screening mammography for transgender women with past or current hormone use is recommended per guidelines for non-transgender women.[38] Mammography can be delayed until the transgender woman has been on hormone therapy for 5 to 10 years.[10] Transgender women with a current or past history of estrogen therapy who have undergone breast augmentation procedures should still undergo mammography. Breast augmentation has not been shown to increase the risk of breast cancer, but may make screening mammography more challenging.[41] Additional information can be found in article by Deutsch et al in this issue.[42]

Endometrial Cancer in Transgender Men

Currently, there is no recommended routine screening test for endometrial cancer in non-transgender women or transgender men.[43] Risk factors for endometrial cancer are numerous, which include nulliparity, menstrual irregularities, obesity, and hypertension. Transgender men may have a higher incidence of PCOS, which is a risk factor for developing endometrial cancer.[23] [24] For transgender men with a uterus, routine office visits should screen for abnormal uterine bleeding (AUB) and post-menopausal bleeding, as this may indicate endometrial atrophy from testosterone use, endometrial hyperplasia, or endometrial carcinoma. Unexplained vaginal bleeding should prompt evaluation with a transvaginal ultrasound and/or endometrial biopsy. Though hysterectomy is not recommended for primary prevention of endometrial cancer, persistent AUB, even with a negative endometrial biopsy, may be an indication for hysterectomy.[10]

Ovarian Cancer in Transgender Men

There are no current ovarian cancer screening recommendations for non-transgender women or transgender men.[44] [45] Although many transgender men may have risk factors for ovarian cancer, including nulliparity, and/or infertility treatments including oocyte cryopreservation, there is no evidence that testosterone therapy increases the risk of ovarian cancer.[10] All individuals should be evaluated for symptoms of ovarian cancer, and a careful family history should be taken. Those who may be at risk to carry the BRCA gene mutations should be offered genetic counseling and risk-reducing surgery.

Anal Cancer in Transgender Men and Women

Similar to cervical cancer, anal cancer is associated with high-risk HPV, with types 16 and 18 causing the majority (79%) of cases.[46] While HIV infection is an independent risk factor for anal cancer, other risk factors include receptive anal intercourse; cervical, vaginal, or vulvar dysplasia; and smoking.[47] [48] While the CDC and USPSTF do not provide recommendations for anal cancer screening, multiple organizations advocate screening for high-risk populations, including all HIV-positive individuals.[49] [50] The New York State Department of Health recommends screening all HIV-positive individuals annually for symptoms of anal cancer such as itching, bleeding, diarrhea, and pain. Additional recommended annual screening includes a visual inspection of the perianal region and a digital anorectal exam (DARE). Annual anal cytology should be performed on HIV-positive patients with a history of receptive anal intercourse, anogenital condyloma, and abnormal cervical and/or vulvar histology.[50] [51]

Anal cytology is completed by inserting a moistened Dacron swab into the anus at least 2 cm from the anal verge to sample the squamocolumnar transition zone. The swab is rotated in a spiral motion while being moved in and out without complete withdrawal. The swab is then placed in a methanol-based preservative solution and agitated for 60 seconds. Patients with abnormal cytology results should be further evaluated with high-resolution anoscopy.[50]

There are no routine anal cancer screening recommendations for HIV-negative persons, even those who are higher risk including men who have sex with men (MSM) or transgender men and women who have sex with men. However, if a patient has symptoms concerning for anal cancer, evaluation should include a visual perianal exam, DARE, and anoscopy.[52]

Prostate Cancer in Transgender Women

Current USPSTF guidelines for non-transgender men aged 50 to 69 years recommend providers consider a patient's risk for prostate cancer and life expectancy in addition to discussing the limited potential benefits and substantial risks associated with screening for prostate cancer with a prostate-specific antigen (PSA) test and only perform the test if patients express a clear preference for the test.[53] These guidelines should also be applied to transgender women. Transgender women on estrogen therapy and antiandrogen therapy have decreased prostatic volume and PSA blood levels, thus further decreasing the utility of the PSA test as a screening or diagnostic tool.[54] However, transgender women who have undergone genital gender confirmation surgery will still have an intact prostate and there have been case reports of prostate cancer in transgender women.[2] If a prostate exam is needed in a transgender woman who has undergone vaginoplasty, a neovaginal approach is most useful as the prostate lies anterior to the neovagina.[10]

Immunizations

The vaccination recommendations and schedules are the same for transgender patients and non-transgender patients.[21] [55]

Human Papillomavirus

As of May 2017, nonavalent Gardasil (Gardasil-9) will be the only available vaccine in the United States to prevent HPV infection. It is approved for both boys and girls aged 9 to 26 years and should be offered regardless of variances in gender identity. Gardasil-9 is given over a 6-month period with either two or three doses depending on age at the time of first vaccination.[55] [56]

Meningococcal Vaccine

Transgender adults are living with HIV at a rate of nearly five times that of the population at large.[4] HIV-infected persons are at higher risk of invasive meningococcal disease with serogroups C, W, and Y. Persons with HIV infection or at high-risk for HIV should be vaccinated with meningococcal conjugate vaccine (Menactra or Menveo) and then receive a booster dose every 5 years if risk factors remain.[55] [57] The meningococcal serogroup B vaccine (Trumenba or Bexsero) is not recommended for HIV-infected individuals.[55]

Hepatitis A and B

Transgender adults who have chronic liver disease, use intravenous drugs, participate in high-risk sexual behaviors, or have anal sex should receive both hepatitis A virus and hepatitis A virus (HBV) vaccines. Recommendations for the HBV vaccine is the same for transgender men and women as it is for non-transgender persons, including those with HIV or who are pregnant.[55]

Anticipatory Guidance

Contraception

All transgender individuals who retain their natal reproductive organs and engage in penile-vaginal sexual activity are at risk for pregnancy and should be counseled on the need for contraception. Transgender spectrum patients such as nonbinary or androgynous individuals may not take doses of hormones high enough to suppress normal reproductive function. Additionally, access to hormone therapy may be intermittent, allowing for resumption of sperm production or ovulation. It is important not to assume sexual behavior or orientation based on one's gender identity. A sensitive and careful sexual history including details about partners' assigned sex at birth, gender identity, and functioning gonads will help the provider evaluate the risk of pregnancy.

Transgender Women

Transgender women should be counseled that androgen blockers can reduce the ability to have and maintain erections, as well as decrease sperm production and impair fertility. However, transgender women may still produce sperm and should be cautioned about the risk of pregnancy in intimate partners.

Transgender Men

Testosterone therapy often effectively suppresses ovulation; however, unintended pregnancies in transgender men occur.[58] The use of traditional hormonal contraceptives is often not acceptable to transgender men wishing to avoid natal hormones, but many may be open to discussing options such as a nonhormonal or hormonal intrauterine device.[59] Surgical sterilization including tubal ligation can be offered, in addition to gender affirming surgery such as hysterectomy and oophorectomy.

Sexually Transmitted Infections

While there are no guidelines specific to transgender populations, transgender men and women who have sex with non-transgender men should be considered to be high risk for sexually transmitted infections (STIs) and guidelines for MSM can be utilized.[60] [61] Transgender women have the highest rates of HIV among any other population group with prevalence rates as high as 28%.[62] It is important to recognize that gender identity is independent of sexual orientation and sexual behavior. Decisions regarding STI screening tests should be based on a thorough history that includes current anatomy, sexual behavior, and injection drug use.[61] [63] Specifically, STI screening should be performed at all exposed anatomic sites, including oropharyngeal and anal swabs, based on sexual behavior.[63] Gender inclusive STI prevention strategies should account for each individual's anatomy and specific sexual practices. When indicated, barrier protection should be discussed, as it relates to anal and vaginal penetration as well as with oral intercourse.

HIV Prevention

HIV pre-exposure prophylaxis (PrEP) with daily oral fixed-dose combination tenofovir disoproxil fumarate (TDF) 300 mg and emtricitabine (FTC) 200 mg was first shown to be effective in the iPrEx Study, with participants including MSM and transgender women.[64] Overall efficacy was 43%, increasing to 92% if the drug was taken as prescribed resulting in detectable blood levels.[64] PrEP is recommended for persons at substantial risk of contracting HIV based on sexual behavior or intravenous drug use. The medication is contraindicated in the presence of a creatinine clearance less than 60.[65] The World Health Organization recommends transgender women who have receptive anal sex with men be evaluated for PrEP therapy in the same manner as the MSM population.[66]

Conclusion

Transgender men and women have unique preventive health concerns secondary to the use of cross-sex hormones, gender confirming surgical procedures, and certain high-risk behaviors. Clinicians providing care for transgender individuals have the opportunity to reverse the trend of transgender persons having negative experiences in healthcare settings by providing evidence-based medical care in a culturally competent manner. Providers providing primary care, including gynecologists, can successfully integrate preventive health care for transgender patients into their daily practice by creating an environment where the patient feels safe disclosing their gender identity and sexual practices, thus enabling the provider to customize screening recommendations and optimize patient's well-being.

No conflict of interest has been declared by the author(s).

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