Increased Surveillance or Increased Scrutiny: Curbing Inappropriate Screening of Endometrial Cancer in Transgender Men

Abstract

Objective: The transgender male body is often considered a “black box” by even the most senior of attending physicians. Because of the stigma and fear associated with the utilization of Hormone Replacement Therapy (HRT) and the lack of clinical knowledge surrounding the subject, many transgender men will experience unnecessary testing for endometrial cancers.

Materials and methods: This narrative review looked through publicly available PubMed and GoogleScholar articles on the topic of the use of pelvic ultrasounds in gynecological screening in transgendered males. 18,000 articles were filtered by relevance, date, clarity of the topic, and clinical recommendations. Of these articles 37 were included for discussion.

Results: Of these 18,000 articles, only 37 were included for discussion. The resulting table, diagnostic tree, and discussion section are included within.

Conclusion: Herein, the authors discuss the current understanding of the role of imaging in the diagnosis and treatment of gynecological cancers in transgendered men and how unnecessary imaging studies can be curbed for the benefit of the patient and the medical system at large.

Introduction

While clear guidelines have been established for the role of imaging in screening transgender male patients for breast cancer, no such unified guidelines exist for the screening of endometrial cancers (1). While routine screening for endometrial cancer in any asymptomatic individuals with average risk is not recommended, historical misunderstandings about the effects of hormone replacement therapy have promoted unnecessary and invasive screenings in transgender men. Herein, the authors review the current literature on endometrial cancer in transgender patients, provide a diagnostic tree for the outpatient provider for screening purposes, and conclude with some general recommendations based on the currently available evidence in the literature.

Materials and methods

This narrative review looked through publicly available PubMed and GoogleScholar articles on the topic of the use of pelvic ultrasounds in gynecological screening in transgender patients. 18,000 articles were filtered by relevance, date, clarity of the topic, and clinical recommendations. Any articles not written in English, not relevant to the topic of transgender patients or found to be lacking in clinical recommendation for the imaging of these patients for pelvic conditions were excluded. Key details and recommendations were then collated and reviewed by three independent researchers, any disagreements were resolved through discussion and consensus.

Results

Of these 18,000 articles, only 37 were included for discussion based on the relevance to the topic of pelvic ultrasonography and the transgender patients. Most of the articles were excluded for the reason of a lack of relevance or discussion of other groups not pertaining to the transgender patients. The resulting table, diagnostic tree, and discussion section are included below.

Discussion

Hormone replacement therapy (HRT) is generally regarded as a safe and effective way for transgender and gender-diverse patients to enhance desired secondary sex characteristics, while reducing those characteristics that contribute to gender dysphoria (2, 3). While each patient’s personal gender expression is different, common HRT treatment goals for patients who are assigned female at birth (AFAB) include increased facial and body hair, changes in muscle and body fat composition, deeper voice, and cessation of menses (2). A full list of changes to the body of the patient is presented in Table 1. Persistent amenorrhea is often the benchmark at which testosterone levels are considered “physiologically male,” as serum testosterone values do not always directly correlate with the degree or rate of virilization achieved (2, 4-6).

Table 1.

Testosterone-Induced Changes in AFAB Patients

Bodily System	Change Experienced with the Use of Hormone Replacement Therapy	Timeframe from the Start of Hormone Replacement Therapy to see Some Effect	Timeframe from the Start of Hormone Replacement Therapy to see Maximum Effect
Reproductive Tract	Cessation of Menses	Two to Six Months	Two to Six Months
External Genitalia	Enlargement of the glans clitoris and atrophy of the vaginal tissues	Three to Twelve Months	Twelve to Twenty-Four Months (One to Two Years)
Adipose Tissue	Redistribution of body fat	Three to Six Months	Twenty-Four to Sixty Months (Two to Five Years)
Cardiovascular	Increase in the hematocrit within circulation.	Within Days	Around Six Months
Musculoskeletal	Increase in the patient’s muscular mass and distribution of the musculature.	Six Months to One year	One to Two Years
Musculoskeletal	Increase in the patient’s bone density	Six Months to One year	One to Two Years
Larynx	Increase in the anterior-posterior size of the larynx leading to a “deepening” of the voice	Three to Twelve Months	Twelve to Twenty-Four Months

While similar in many ways to the menopause experienced by cisgender women, the amenorrhea induced by exogenous testosterone administration is a unique physiologic process that has yet to be fully delineated. Theoretical concerns around the possibility of a testosterone-induced anovulatory state and subsequent “unopposed” estrogen production by the aromatization of free testosterone have led to the false assumption that testosterone HRT increases the risk of breast, endometrial, and ovarian cancer in transgender men (4). In the past, studies have suggested that transgender men were more likely to possess polycystic ovaries, even without a history of testosterone usage (9, 10). Routine histologic evaluations of ovaries taken from transgender men during gender-affirming oophorectomy have shown thecal and cortical hyperplasia similar to that seen in PolyCystic Ovarian Syndrome (PCOS), and increased incidence of polycystic appearance (11,12). The Rotterdam criteria for diagnosing PCOS states that 2 of 3 of the following findings must be present: at least one polycystic ovary identified on transvaginal US, oligomenorrhea, and clinical or biochemical evidence of hyperandrogenism (13).

Polycystic ovaries alone do not confer PCOS, but it was assumed that the intentional administration of exogenous testosterone to suppress menses satisfied the other criteria. However, more recent research confirms that exogenous testosterone administration in transgender men does not induce PCOS (14). Furthermore, data shows that while PCOS does increase the likelihood of developing endometrial cancer, there is currently no evidence to suggest an increased risk of breast and ovarian cancer secondary to this disorder (15, 16). While screening guidelines for cisgender women have been appropriately updated, considerations for transgender men have lagged, leaving patients open to the potential harms of inappropriate imaging. As written in a recent publication in the Cureus Journal of Medicine, no medical testing, treatment, or intervention is without its risks and effects on the entire bodily system (17). Many, if not all imaging studies are costly, and if there is a low chance that imaging results will change the management of a patient’s medical care, these studies serve only to raise the cost of the patient’s treatment without increasing the value received from that medical care (17).

Endometrial Cancer Screening

Endometrial cancer is the most common gynecologic cancer in the United States and is most often diagnosed in post-menopausal patients (18). It is directly related to long-term exposure to excess estrogen levels, but the vast majority of cancers are diagnosed in early, treatable stages when patients present with abnormal vaginal bleeding. Excessive or prolonged vaginal bleeding in pre/perimenopausal people or any amount of vaginal bleeding in post-menopausal people is the hallmark symptom of endometrial hyperplasia and cancer. Endometrial hyperplasia is considered a precursor lesion and can often be seen on a transvaginal ultrasound as part of the workup for abnormal vaginal bleeding (19). Nevertheless, tissue biopsy, as referred to in the classic statement “tissue is the issue”, is required to confirm the diagnosis (19). While some transgender men may experience persistent vaginal bleeding for several months after initiating testosterone HRT, most patients will experience amenorrhea in 6 months of initiating therapy, and virtually all bleeding resolves within 12 months of starting HRT (20). Breakthrough bleeding after this time frame is possible but is most likely a reflection of inaccurate or missed dosing, as both sub- and supraphysiologic levels of testosterone can result in abnormal vaginal bleeding (20, 21). It is principal to note that changes in body habitus can affect the dose needed to achieve physiologic levels, as people with more adipose tissue have both higher endogenous estrogen levels and increased peripheral aromatization of testosterone to estradiol (22). There are no current guidelines for the appropriateness of transvaginal US in evaluating abnormal vaginal bleeding in transgender men on HRT. Previous guidelines from the Endocrine Society suggested annual screening transvaginal ultrasounds for all amenorrheic transgender men with intact uteri, but there is no evidence that screening any patients with uteri for endometrial cancer leads to a decrease in mortality, and this practice risks false-positives and overtreatment (19, 23). The current UCSF Transgender Care and Treatment Guidelines state that, in the absence of missed or changed testosterone dosing, vaginal bleeding in transgender men with testosterone-induced amenorrhea should be evaluated (23). Long-term testosterone use at appropriate dosing has not been shown to increase endometrial proliferation in transgender men (13). One retrospective case-series study suggests testosterone HRT may even have a slightly protective effect due to endometrial atrophy, but further investigation is needed to fully characterize this claim (24). With these findings in mind, it is the authorial team’s highest recommendation that in transgender men with otherwise average cancer risk, transvaginal ultrasound should only be utilized in the assessment of persistent vaginal bleeding if:

• Patient has consistently been using testosterone HRT for at least 12 months

• Patient had previously achieved persistent amenorrhea on HRT

• Bleeding does not resolve with adjustments to HRT dose or frequency of administration

Costs of Inappropriate Screening

While transvaginal US has no radiation exposure and is a relatively low-cost test for insured patients, it is an invasive exam that comes with a high risk of negative psychological effects in transgender men. Transgender patients face higher rates of unemployment, poverty, and homelessness than their non-transgender peers and are more likely to be uninsured (25). With the national average price of a transvaginal ultrasound estimated between $89 and $142 for insured patients, this is not an insignificant cost to the patient or the healthcare system (26). Furthermore, according to the most recent US Transgender Survey (2015) one-third of respondents indicated they had at least one negative experience with a healthcare provider within the past year, including verbal harassment, refusal of treatment, or having to educate their provider on transgender identity and their own medical needs. One-quarter of respondents indicated that they declined to seek medical treatment within the last year out of fear of mistreatment by providers (27). Transgender men face unique challenges navigating the strongly gendered world of “women’s health,” where they are often met with confusion, invalidation, and even hostility. While transgender men are at increased risk of HPV infection, they are far more likely than cisgender women to have never received Pap testing due to a mix of prohibitive cost and psychological distress that leads them to avoid screening (28, 29). Limiting transvaginal ultrasound evaluation to only persistently symptomatic patients who have not responded to adjustments in HRT is a concrete step that can be made toward reducing the financial and emotional costs of healthcare for transgender men. Included is a diagnostic tree for improving decision making in the outpatient setting (Figure 1).

Figure 1.

This is a new diagnostic decision tree for pelvic US based on currently available resources (35-37).

Patient-Centered Care

One of the most important pieces of the treatment and care of transgender men is building a strong rapport with the patient. Like with all patients, this can be partially accomplished through explaining the steps that are being taken to ensure that the patient has an understanding of why the provider is ordering the imaging study or not, what the potential risks or benefit are to either ordering the testing or not, and finally what are warning signs that the patient should look for which would warrant further examination. However, special consideration should be taken when discussing anatomy, symptoms, and procedures that could potentially exacerbate gender dysphoria or trauma with transgender patients. Avoid gendering body parts (ex: “female organs” to refer to uterus and ovaries) and use the patient’s preferred terminology whenever possible to discuss their anatomy (ex: some transmen prefer the term “chest tissue” instead of “breasts”). Transgender patients are also more likely to be survivors of sexual violence, and the risk of re-traumatization should always be assessed against the potential benefits of invasive exams and procedures during clinical decision making (30). Through providing this dialogue early with the patient, ensuring that they have the necessary information to advocate for their own care, and then opening the space for the patient to ask questions regarding the clinical decision that was made - not only is the patient more likely to trust the physician, but compliance with medications and treatment also increases (31-33).

Conclusion

This article examined the current understanding of the role of imaging in the diagnosis and treatment of gynecological cancers in transgendered men and exhibited how unnecessary imaging studies can be curbed for the benefit of the patient and the medical system at large. As explained in the patient centered care section, through ensuring that patients are treated as humans first and foremost, clinicians will be able to provide the necessary care and compassion for the benefit of the overall patient’s health leading to increased compliance and trust from the patient. Further research into the risk ratios and the cost-benefit analysis of implementing less screenings for transgender patients and the resulting health outcomes on a longitudinal cohort remain necessary. It is the highest recommendation of the authorial team that this be conducted relatively soon. It is the highest desire of the authorial team that the care of the patient (financially, emotionally, and physically) be considered to guarantee that they are provided for holistically. As the famous father of modern medicine is quoted as saying, “The good physician treats the disease; the great physician treats the patient who has the disease” (34).

Conflict of Interests

Authors have no conflict of interests.

Notes:

Citation: Adams EC, Varkey TC, Aijaz A, Taboada J, Nguyen AM. Increased Surveillance or Increased Scrutiny: Curbing Inappropriate Screening of Endometrial Cancer in Transgender Men. J Family Reprod Health 2022; 16(3): 170-6.