11

Cancers of the Reproductive System

According to the American Cancer Society, over 2 million people are diagnosed with cancer each year, and more than 600,000 deaths due to cancer are recorded (Siegel et al., 2024). Cancer treatments can take a toll on anyone, but for some people, cancer treatment can be so intense and cause such severe side effects—including pain, cancer-related fatigue, nausea and vomiting, appetite loss, weight loss, bone density loss, heart problems, delirium, nerve problems, memory problems, and others—that they can limit a person’s ability to work or complete routine daily activities (NCI, n.d.). Pharmacological treatments available to address side effects can be costly and produce additional side effects (Devlin et al., 2017). Some people with cancer experience severe side effects that last for months or even years after treatment is completed (Stein et al., 2008). In addition, despite treatment, cancer may metastasize to other organs, causing additional complications and symptoms that further prevent cancer patients from engaging in substantial gainful activity. For these reasons, some people with cancer in advanced stages may apply for disability benefits through the Social Security Administration (SSA).

SSA’s adult disability Listings for cancer include several reproductive system cancers often associated with either cisgender women (including cancers of the uterus, uterine cervix, vulva, vagina, fallopian tubes, and ovaries) or cisgender men (including cancers of the prostate gland, testicles, and penis). Because these cancers are traditionally associated with one sex, SSA asked this committee to examine appropriate evaluation of these cancers for transgender and gender diverse (TGD) people and people with variations in

sex traits (VSTs) and to determine what changes in current disability criteria may be necessary for them to serve as medically appropriate indicators of severity for TGD applicants and applicants with VSTs.

This chapter examines the prevalence of cancer among TGD people and people with VSTs, describes the impact of gender-affirming care on people with cancer, presents current guidelines that aim to decouple gender from cancer, and offers a gender- and sex-inclusive approach to disability determination for people with reproductive cancers.

PREVALENCE OF AND SCREENING FOR REPRODUCTIVE CANCERS AMONG TRANSGENDER AND GENDER DIVERSE PEOPLE AND PEOPLE WITH VARIATIONS IN SEX TRAITS

Given that data on sexual orientation and gender identity are not (to date) routinely collected in prospective databases (see Chapter 4 of this report), it is difficult to determine the prevalence of cancer among TGD individuals and those with VSTs. One review estimates that cancer impacts fewer than 600 members of sexual or gender minority (SGM) groups (or 0.005 percent of the U.S. population) annually (Jackson et al., 2021), but this is likely a significant undercount. In addition, low cancer screening rates contribute to the difficulty of tracking cancer among SGM people, and many cases may go undiagnosed (Jackson et al., 2021). The literature shows that SGM people are less likely to participate in cancer screening relative to the general population. For example, Herriges and colleagues (2021) used the Health Information Network Trends Survey to determine the screening behaviors of lesbian, gay, and bisexual (LGB) people; they found that those with prostates were significantly less likely to undergo prostate-specific antigen blood testing compared with heterosexual men; likewise, LGB people with breasts and those with cervices were less likely to undergo mammography or Papanicolaou (Pap) tests, respectively, compared with heterosexual women (Herriges et al., 2021). Among TGD people, studies have found transgender men to be significantly less likely to be up to date on Pap testing compared with cisgender women (Oladeru et al., 2022; Peitzmeier et al., 2014a,b; Tabaac et al., 2018). Studies have also found lower rates of prostate-specific antigen screening among transgender women compared with cisgender men (Ma et al., 2021; Nik-Ahd et al., 2023; Tabaac et al., 2018).

Hostilities experienced by TGD people and people with VSTs in health care settings are a potentially important reason for these low cancer screening rates. For example, Mirza and Rooney (2018) found that among LGB or queer respondents to a survey from the Center for American Progress, 6 percent had been refused care, and 8 percent were refused being seen by a health care provider; among transgender respondents, these figures were

between 12 and 29 percent. In addition, where TGD populations receive care, that care may be less adequate than care provided to cisgender peers: one study found that transgender men who did receive Pap tests were 10 times more likely than cisgender women to have inadequate tests (i.e., the cell sample taken was insufficient for laboratory testing) (Peitzmeier et al., 2014b). Another study found that transgender women were significantly less likely than cisgender men to have ever had a discussion with a health care provider about the risks and benefits of prostate-specific antigen screening (Ma et al., 2021).

In addition, compared with their heterosexual counterparts, people from sexual and gender minority groups are more likely to be living in poverty; less likely to have health insurance; and for older individuals, twice as likely to be living alone (Sachdeva et al., 2021). Taken together, low screening rates, hostile and inadequate health care, and other health disparities may mean that TGD people may have a greater likelihood of presenting with more advanced disease compared with cisgender people. One study found transgender patients to be more likely to be diagnosed at later stages for lung cancer, and being transgender was associated with lower odds of treatment for kidney and pancreatic cancer (Jackson et al., 2021). Whether these same trends are true for reproductive cancers is difficult to evaluate given the lack of uniform data collection on sexual orientation and gender identity. Moreover, the literature evaluating the incidence and experience of cancer among people with VSTs is exceptionally limited and precludes any conclusions.

IMPACT OF GENDER-AFFIRMING MEDICAL CARE ON PEOPLE WITH CANCER

While the assumption that gender-affirming hormone therapy (GAHT) will increase the risk of hormonally sensitive cancers, such as prostate or ovarian cancer, in transgender individuals is common, the data do not support this assumption. A 2018 systematic review concluded that, based on the available retrospective studies, there was no association between GAHT and hormone-dependent tumors (McFarlane et al., 2018).

A few studies have examined this question for prostate cancer. In one study of the National Cancer Database (11,776,699 persons with cancer in the database, 589 of whom were transgender), transgender people were found to have higher rates of certain cancers (including anal cancer, liver cancer, nonmelanoma skin cancers, and Hodgkins and non-Hodgkins lymphoma) compared with their cisgender counterparts, but lower rates of prostate cancer (Jackson et al., 2021). Other studies support this finding. A 2022 review of the existing literature attempted to define the prevalence of prostate cancer in transgender women and identified only 24 publications, 10 of which were case reports; this review found that the risk of prostate

cancer among transgender women who have not undergone GAHT or any gender-affirming surgery is the same as for cisgender men; however, transgender women who have received GAHT or undergone gender-affirming surgery were found to have a lower incidence of prostate cancer compared to cisgender men (Bertoncelli Tanaka et al., 2022). A separate cohort study evaluated the incidence of prostate cancer in transgender females treated with antiandrogens, estrogen, and bilateral orchiectomy (N = 2,306) (Gooren and Morgentaler, 2014). Here, only one case of prostate cancer was detected, although the authors concluded this finding was likely due to a lack of prostate cancer screening in general and the overall younger age of the cohort studied. Another retrospective study including 2,281 transgender women found six cases of prostate cancer after a median of 17 years of hormone therapy (de Nie et al., 2020). The results of this study indicate that transgender women receiving GAHT have a substantially lower risk for prostate cancer compared with people assigned male at birth.

Given how much is unclear about cancer outcomes among transgender individuals, the question of how hormones interact with cancers is quite important. For example, there are now data indicating that cancer treatment–related toxicities are associated with gender. In a study that included more than 23,000 volunteers who participated in a Phase 2 or 3 trial over a nearly 20-year span, women had a 34 percent increased risk of a severe adverse event, regardless of treatment type (Unger et al., 2022). With regard to immunotherapy, women had a nearly 70 percent increased risk of a severe and symptomatic adverse event compared with men. These data point to potential biological differences between the sexes and the importance of dosing (often based on calculations that include gender) in drug metabolism and tolerance; they raise the question of what degree of risk a transgender person truly faces when exposed to cancer treatment.

In addition, there is a lack of evidence—and a lack of consensus—around the safety of GAHT with respect to cancer outcomes (e.g., recurrence or survival) in people diagnosed and subsequently treated for cancer. SSA adjudicators may see language from treating oncology specialists recommending against continuation or reinitiation of GAHT in cancer survivors. The committee points out that such recommendations are not based on data or guidelines and may reflect a paternalistic approach to TGD patients rather than reflect shared decision making that takes into account the patient’s own goals and desires.¹

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¹ “Paternalistic decision making” refers to a unidirectional flow of information from doctor to patient, with subsequent recommendations being made without patient input (Kane et al., 2014). In shared decision making, recommendations are based on bidirectional communication, whereby a patient’s values and preferences are solicited alongside the information needed to make decisions—a goal often referred to as patients’ values-aligned care (Barry and Edgman-Levitan, 2012; Charles et al., 1997).

GUIDELINES: DECOUPLING GENDER FROM CANCER

There is consensus today that disease is not associated with gender, but with specified organs. For example, the American Society of Clinical Oncology’s (2022) Center for Research and Analytics published guidance intended to ensure inclusion of SGM patients in clinical trials (ASCO, 2022). Among the recommendations of this guidance is decoupling gender, sex assigned at birth, and current anatomy by avoiding such phrases as “men with prostate cancer.” The guidance also advises that people receiving GAHT should be eligible to volunteer for clinical trials unless a clear contraindication exists. Both the American College of Obstetricians and Gynecologists (2021) and American Society for Colposcopy and Cervical Pathology (Perkins et al., 2020) have published on the topic of health care for TGD people, both recommending screening based on anatomy regardless of gender. The decoupling of gender and cancers is also more inclusive of people with VSTs, who may have organs that do not correspond to the sex assigned to them at birth.

Other organizations have modified language to be more gender inclusive. Examples include the following:

• The American Cancer Society (ACS, 2021) modified its language to eliminate gender–cancer associations. For example, screening and interventions are recommended for all “people with a cervix.” Likewise, ACS guidelines recommend that all “people with a uterus” receive appropriate endometrial cancer care and that all “people with a prostate” receive appropriate prostate cancer care.
• Instead of reserving prostate cancer screenings for males, the American Urological Association recommends screening for all people aged 45–50 and beginning at age 40 for “people at increased risk of developing prostate cancer” (Wei et al., 2023).
• National Comprehensive Cancer Network Guidelines for Prostate Cancer Early Detection follow a similar approach; updated in 2022, the guidelines specify that the recommendations are “for individuals with a prostate opting to participate” in an early detection program (Freedman-Cass et al., 2023).

Current U.S. Preventive Services Task Force Guidelines related to cancer screening are sex specific, but the task force has expressed a commitment to making its recommendations gender inclusive (Caughey et al., 2021).

CANCER AND SSA DISABILITY DETERMINATIONS

SSA asked the committee for this study to examine reproductive cancers under Listing 13.00, Cancer—Adult, as these cancers are traditionally associated with only one sex. Box 11-1 outlines the cancers examined in this chapter.

Similar to current guidelines that recommend screening based on anatomy rather than sex assigned at birth or gender identity, many of SSA’s criteria under its reproductive cancer Listings use inclusive language based on anatomy. For example, the category under Listing 13.24 is cancer of the “prostate gland,” rather than “men with prostate cancer.” The same is true for cancer of the testicles under 13.25 and cancer of the penis under 13.26. In theory, the current language under Listings 13.24, 13.25, and 13.26 is inclusive of transgender women who have prostate, testicular, or penile cancer (as well as other gender diverse applicants or applicants with VSTs who have these cancers) given that, in accordance with the language of the disability Listing, it does not matter what sex or gender is included in the applicant’s medical records, only that the applicant has the cancer at issue. While the applicant will still have to provide medical evidence to show the extent of their impairment in support of their disability application (which may include documentation of their treatment history, response

to anticancer therapy, cancer recurrence, evidence of metastasis, or other documentation included under Listing 13.00 Cancer—Adult or under the specific cancer Listing), the applicant need not document anything in relation to their sex or gender to qualify for disability benefits.

In contrast, the disability Listing 13.23, “Cancers of the female genital tract—carcinoma or sarcoma,” is not similarly inclusive of TGD people or people with VSTs who do not identify as female. While the specific cancers under 13.23 (cancers of the uterus, uterine cervix, vulva, vagina, fallopian tubes, and ovaries) are all listed by anatomy rather than sex or gender, the fact that these cancers fall under the category of “female” cancers may cause would-be applicants to assume that they cannot apply for benefits to which they would otherwise be entitled because their affirmed gender (or gender listed on medical or legal documents) is not female. Labeling these cancers as “female” could also cause professionals who may counsel would-be disability applicants (health care providers, social workers, disability lawyers, and others) to assume that one must be “female” to apply for disability under “cancers of the female genital tract.” The committee does not know whether SSA has rejected applicants who do not identify as female from qualifying under 13.23, but it appears possible from the way the Listing is written that disability adjudicators could reasonably deny benefits to TGD people or people with VSTs.

Furthermore, the fact that one reproductive cancer Listing is labeled “female” creates the inference that the other reproductive cancer categories must be “male.” This alone could dissuade people who do not identify as male from applying for disability under Listings 13.24, 13.25, and 13.26. Again, it appears possible to the committee that SSA adjudicators could deny benefits based on the assumption that these categories are reserved for people who identify as male.

A second portion of SSA’s disability criteria reinforces the idea that at least the ovarian cancer Listing (13.23E) does not include men. Section 13.00K7 explains criteria for evaluating primary peritoneal carcinoma (PPC),² which is included under the Listing for 13.23 (SSA, n.d.):

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² PPC is cancer of the peritoneum (a thin layer of tissue that lines and protects the abdomen), with presentation similar to that of ovarian cancer. PPC affects mainly people assigned female at birth, with only a few cases in males being reported in the medical literature. PPC is rare, with an estimated incidence of 6.78 cases per 1 million; given this condition’s rarity, this committee did not uncover research on PPC among TGD populations or populations with VSTs (Goodman and Shvetsov, 2009; Guellil, 2022).

Here, use of the terms “men” and “women” confers assignment of gender, as discussed in Chapter 2, and would appear to emphasize that it is only “women” who are eligible for disability under the ovarian cancer listing.

Furthermore, the language of Section 13.00K7 may create unnecessary boundaries—and confusion—for TGD disability applicants and applicants with VSTs, who do not fall neatly into the gendered categories of PPC. When these populations seek disability benefits based on a diagnosis of PPC, it is unclear what criteria should be used. Would transgender men be evaluated for PPC under Listing 13.23E because they were assigned female sex at birth or under 13.15A because their affirmed gender is male? The determining factor here may be the happenstance of how sex or gender is recorded in the person’s medical record, which (as discussed in Chapter 3) may not be accurate with respect to an individual’s sex, gender identity or anatomy. Being more intentional in the disability criteria for these Listings could make a real difference in terms of the medical evidence required to demonstrate disability. Box 11-2 compares SSA’s requirements under Listings 13.15A and 13.23E.

SSA would eliminate boundaries for TGD people and people with VSTs by removing differentiation of PPC in women versus men within the Listing and instead base disability determination on the histopathology.

The following suggested rewording under 13.00K7 emphasizes histology and uses inclusive language:

This approach would clarify for applicants that it is not gender that matters for PPC disability evaluation, but the histopathologic characterization of the cancer itself. This is consistent with current practice guidelines (Kindler et al., 2018). Such suggested language change under 13.00K7 recognizes that primary peritoneal mesothelioma can occur in all people regardless of the presence or absence of ovaries, while primary peritoneal adenocarcinoma is almost exclusively diagnosed in people with ovaries. Importantly, the committee prefers decoupling gender from the oncologic diagnosis by removing reference to “men” and “women” from the PPC Listing and referring instead to organs (e.g., ovaries, fallopian tube). Not only does this phrasing bring clarity for TGD people, but it acknowledges that people with VSTs—who may have ovaries and fallopian tubes but may have been assigned male sex at birth—could apply for disability with a PPC diagnosis.

Pertaining to the umbrella category “Cancers of the female genital tract” under 13.23, SSA might better serve TGD applicants and applicants with VSTs by choosing inclusive language that makes clear that these disability categories are open to anyone who has the cancer at issue, regardless of their gender identity or sex recorded at birth. A suggested way to reword 13.23 using inclusive language would be to call this category “Cancers of the uterus, uterine cervix, vulva, vagina, fallopian tubes, and ovaries.” Alternatively, SSA could split these cancers into separate categories as it does for cancers of the prostate gland, testicles, and penis.

SUMMARY OF KEY POINTS

TGD people and people with VSTs participate in reproductive cancer screening programs less commonly than cisgender people as a result of multiple barriers, including hostilities experienced from medical providers and lack of screening access. Lack of uniform data collection on sexual orientation and gender identity in medical records makes it difficult to determine the prevalence of reproductive cancers and stage of

presentation of these cancers among TGD people and people with VSTs. At this time, there are no data to indicate that GAHT increases the risk of a hormonally driven cancer. Whether GAHT has an impact on cancer survival is even less clear.

Organizations have begun to call for more gender-inclusive language in their cancer screening and treatment recommendations, language that moves away from an association between gender or sex recorded at birth and specific cancers to organ-specific considerations for malignancy. SSA might best serve TGD people and people with VSTs by being more intentional in its reproductive cancer Listings by not associating sex (e.g., woman or man; male or female) with any one cancer type.

REFERENCES

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