Sex Organ Specific Screening Recommendations: Transfeminine Patients
GAHT in transfeminine patients can include GnRH antagonists to shut down an individual's natal sex hormone production in addition to the administration of exogenous estrogen. The administration of these hormones makes the complex interactions between sex and cancer risk more complicated as they may not only affect the risk of sex-specific cancers but also for other cancers that may contain sex-receptors. As with the female sex organs there is no evidence that GAHT increases oncologic risk of the male sex organs.
Cis-males should have annual physical examinations to monitor for any testicular masses. There have been two reported cases of testicular cancer in transfeminine patients: one was found incidentally after orchiectomy and the other was discovered when the patient had rising testosterone levels despite being on feminizing hormones.[59,60] It is recommended that patients that still have testicles undergo annual physical exam to check for any testicular masses at any point in their transition.
Prostate cancer screening recommendation for cis-males is patients over 50 have their PSA checked and digital rectal examination. This screening should occur earlier in high risk patient: African-Americans and patients with a positive family history. The risk of prostate cancer in transfeminine patients is lower than cis-males but it is not zero.
Even though the prostate is not removed during surgical transition, there are few studies looking at the prevalence of prostate cancer in the transfeminine population. Gooren et al. reported a prevalence of 0.04% in their cohort of over 2,300 patients, however these patients were not screened for prostate cancer and the actual prevalence maybe higher. This lack of screening for prostate cancer has been shown in other studies too. Tabaac et al. also found that transfeminine patients were less likely to discuss prostate issues with a physician and were less likely to have had a PSA test compared to cis-males. This may have been considered a nonissue in transfeminine patients because "dissemination of prostate cancer is inhibited by eliminating androgens or neutralizing their effect with the injection of estrogens". More recent studies and case reports, including the 10 cases of prostate cancer in transfeminine patients of which 6 were metastatic on presentation, are beginning to question this dogma. The patients in all reported cases of prostate cancer had undergone extended estrogen therapy and some studies have suggested that estrogen may play a role prostate cancer development.[62–64] Although none of these studies have been conducted in the transgender population. Both the WPATH and the Endocrine society recommend transfeminine patients follow the current prostate cancer screening guidelines for cis-men with the caveat that 1 ng/mL should be considered the upper threshold of normal.[56,65,66] This guideline should be followed at any point in a patient's transition.
There is currently insufficient evidence to support cancer screening for penile cancer in the cis-gender population. Diagnosis is made based on physical exam and confirmed with a biopsy. There have been no reported cases of penile cancer in the transgender population. However, patients that still have a penis should report any lesions to their physician.
There is not sufficient evidence to support breast cancer screening in cis-males and as previously stated cis-females should be screening with routine mammograms. Brown et al., using data from the Veteran Health Administration, found three cases of breast cancer in transfeminine patients, most patients had undergone some GAHT. The overall incidence was 20/100,000 patient years regardless of hormone exposure, which was not higher than the expected rate. De Blok et al. found 15 cases of breast cancer out of 2,260 transfeminine patients, and one study from the Netherlands found transfeminine patients have a 46-fold increased risk of breast cancer compared to cisgender men. Most tumors presented in a typically female pattern, they were ductal carcinomas and receptor positive. It should be noted that the rate of breast cancer in transfeminine individuals was still lower than cisgender females (incidence ratio of 0.3).
Transfeminine patients have an overall lower exposure to estrogen and little exposure to progesterone compared to cisgender females, which could explain their lower cancer risk. The presence of estrogen and progesterone receptors is a major factor in the prognosis and treatment of cis-females and cis-males with breast cancer. Androgen receptors can have tumor suppressive or tumor proliferative effects depending on the type of breast cancer, and while there isn't evidence to suggest GAHT increases cancer risk the effect of exogenous hormones on cancer risk or cancer treatment is still unknown.[28,29] There is also evidence to suggest testosterone is protective and the loss of circulating testosterone combined with the increased circulating estrogen levels results in the increased risk for transfeminine patients compared to cismales. Transfeminine patients commonly have dense breasts, which is both an independent risk factor for breast cancer and increases the rate of false-negative mammograms.
There is no current data or recommendations on how GAHT affects breast cancer risk for patients with BRAC-1 mutations, only 6% of cisgender men with BRAC-1 mutation develop breast cancer compared to 78% of cisgender females. There has been one case report of a transgender female with a BRCA-1 mutation. This patient refused prophylactic mastectomy, continued GAHT after her vaginoplasty and bilateral orchiectomy, and is undergoing screening based on the established guidelines for cisgender women.
Breast cancer screening guidelines are an evolving area of medicine, with respect to what age to begin screening and frequency, which is made more complicated in transgender women by a poor understanding of the effect of GAHT and the lack of reliable epidemiologic data. However, for transfeminine patients' mammograms are recommended every two years in patients over 50 and who have 5–10 years of GAHT treatments. All screening should be based on shared decision making, and patients and providers may want to start screening at an earlier age or shorter number of years of hormone exposure in patients with a significant family history.
Transl Androl Urol. 2020;9(6):2771-2785. © 2020 AME Publishing Company