Transgender Women and Prostate Cancer: It’s Complicated

The Veterans Health Administration (VHA) provides care for about 10,000 transgender women, and clinicians must understand their distinctive needs for prostate cancer screening, a urologist told cancer specialists during a presentation at the 2024 annual meeting of the Association of VA Hematology/Oncology in Atlanta.

Even if they’ve undergone gender reassignment surgery, “all transgender women still have a prostate, so therefore they remain at risk of prostate cancer and could still be considered for prostate cancer screening,” said Farnoosh Nik-Ahd, MD, a resident physician at the University of California San Francisco. However, “clinicians and patients may not be aware of prostate cancer risk, so that they may not think [of screening] transgender women.”

Nik-Ahd also noted another complication: The results of prostate screening tests may be misleading in this population.

Transgender women were born biologically male but now identify as female. These individuals may have undergone gender reassignment surgery to remove male genitalia, but the procedures do not remove the prostate. They also might be taking estrogen therapy. “Prostate cancer is a hormonally driven cancer, and the exact impact of gender-affirming hormones on prostate cancer risk and development is unknown,” Nik-Ahd said.

In a 2023 study in JAMA, Nik-Ahd and colleagues identified 155 cases of prostate cancer in transgender women within the VHA (about 14 cases per year) from 2000 to 2022. Of these patients, 116 had never used estrogen, while 17 had used it previously and 22 used it at diagnosis.

The median age of patients was 61 years, 88% identified as White, and the median prostate-specific antigen (PSA) was 6.8 ng/mL. “Given estimates of 10,000 transgender women in the US Department of Veterans Affairs, 33 cases per year would be expected. Instead, only about 14 per year were observed,” the researchers wrote. “Lower rates may stem from less PSA screening owing to barriers including lack of prostate cancer risk awareness or stigma, the suppressive effects of estrogen on prostate cancer development, or prostate cancers being missed in transgender women because of misinterpretation of ‘normal’ PSA levels among those receiving gender-affirming hormone therapies.”

In the presentation, Nik-Ahd said, “PSA density, which is a marker of prostate cancer aggressiveness, was highest in transgender women who were actively on estrogen.”

She noted, “the existing thyrotropin reference ranges, which is what we use to interpret PSA values, are all based on data from cisgender men.” The ranges would be expected to be far lower in transgender women who are taking estrogen, potentially throwing off screening tests, she said, and “ultimately missing clinically significant prostate cancer.”

In the larger picture, there are no specific guidelines about PSA screening in transgender women, she said. 

A recent study published in JAMA by Nik-Ahd and colleagues examined PSA levels in 210 transgender women (mean age 60 years) treated within the VHA from 2000 to 2023. All were aged 40 to 80 years, had received estrogen for at least 6 months (mean duration 4.7 years), and didn’t have prostate cancer diagnoses.

“Median (IQR) PSA was 0.02 (0-0.2) ng/mL and the 95th percentile value was 0.6 ng/mL,” the report found. “PSAs were undetectable in 36% of patients (23% and 49% of PSAs in patients without and with orchiectomy, respectively).”

The researchers write that “the historic cut point of 4 ng/mL, often used as a threshold for further evaluation, is likely far too high a threshold for this population.”

Nik-Ahd noted, “clinicians should interpret PSA values in transgender women on estrogen with extreme caution. In this population, normal might actually not be normal, and a value that is considered normal might be very abnormal for somebody who is on estrogen. If you're unsure of whether a PSA value is appropriate for a transgender woman on estrogen, refer that patient to a urologist so they can undergo further evaluation.”

Farnoosh Nik-Ahd discloses consulting for Janssen.

The Veterans Health Administration (VHA) provides care for about 10,000 transgender women, and clinicians must understand their distinctive needs for prostate cancer screening, a urologist told cancer specialists during a presentation at the 2024 annual meeting of the Association of VA Hematology/Oncology in Atlanta.

Even if they’ve undergone gender reassignment surgery, “all transgender women still have a prostate, so therefore they remain at risk of prostate cancer and could still be considered for prostate cancer screening,” said Farnoosh Nik-Ahd, MD, a resident physician at the University of California San Francisco. However, “clinicians and patients may not be aware of prostate cancer risk, so that they may not think [of screening] transgender women.”

Nik-Ahd also noted another complication: The results of prostate screening tests may be misleading in this population.

Transgender women were born biologically male but now identify as female. These individuals may have undergone gender reassignment surgery to remove male genitalia, but the procedures do not remove the prostate. They also might be taking estrogen therapy. “Prostate cancer is a hormonally driven cancer, and the exact impact of gender-affirming hormones on prostate cancer risk and development is unknown,” Nik-Ahd said.

In a 2023 study in JAMA, Nik-Ahd and colleagues identified 155 cases of prostate cancer in transgender women within the VHA (about 14 cases per year) from 2000 to 2022. Of these patients, 116 had never used estrogen, while 17 had used it previously and 22 used it at diagnosis.

The median age of patients was 61 years, 88% identified as White, and the median prostate-specific antigen (PSA) was 6.8 ng/mL. “Given estimates of 10,000 transgender women in the US Department of Veterans Affairs, 33 cases per year would be expected. Instead, only about 14 per year were observed,” the researchers wrote. “Lower rates may stem from less PSA screening owing to barriers including lack of prostate cancer risk awareness or stigma, the suppressive effects of estrogen on prostate cancer development, or prostate cancers being missed in transgender women because of misinterpretation of ‘normal’ PSA levels among those receiving gender-affirming hormone therapies.”

In the presentation, Nik-Ahd said, “PSA density, which is a marker of prostate cancer aggressiveness, was highest in transgender women who were actively on estrogen.”

She noted, “the existing thyrotropin reference ranges, which is what we use to interpret PSA values, are all based on data from cisgender men.” The ranges would be expected to be far lower in transgender women who are taking estrogen, potentially throwing off screening tests, she said, and “ultimately missing clinically significant prostate cancer.”

In the larger picture, there are no specific guidelines about PSA screening in transgender women, she said. 

A recent study published in JAMA by Nik-Ahd and colleagues examined PSA levels in 210 transgender women (mean age 60 years) treated within the VHA from 2000 to 2023. All were aged 40 to 80 years, had received estrogen for at least 6 months (mean duration 4.7 years), and didn’t have prostate cancer diagnoses.

“Median (IQR) PSA was 0.02 (0-0.2) ng/mL and the 95th percentile value was 0.6 ng/mL,” the report found. “PSAs were undetectable in 36% of patients (23% and 49% of PSAs in patients without and with orchiectomy, respectively).”

The researchers write that “the historic cut point of 4 ng/mL, often used as a threshold for further evaluation, is likely far too high a threshold for this population.”

Nik-Ahd noted, “clinicians should interpret PSA values in transgender women on estrogen with extreme caution. In this population, normal might actually not be normal, and a value that is considered normal might be very abnormal for somebody who is on estrogen. If you're unsure of whether a PSA value is appropriate for a transgender woman on estrogen, refer that patient to a urologist so they can undergo further evaluation.”

Farnoosh Nik-Ahd discloses consulting for Janssen.

The Veterans Health Administration (VHA) provides care for about 10,000 transgender women, and clinicians must understand their distinctive needs for prostate cancer screening, a urologist told cancer specialists during a presentation at the 2024 annual meeting of the Association of VA Hematology/Oncology in Atlanta.

Even if they’ve undergone gender reassignment surgery, “all transgender women still have a prostate, so therefore they remain at risk of prostate cancer and could still be considered for prostate cancer screening,” said Farnoosh Nik-Ahd, MD, a resident physician at the University of California San Francisco. However, “clinicians and patients may not be aware of prostate cancer risk, so that they may not think [of screening] transgender women.”

Nik-Ahd also noted another complication: The results of prostate screening tests may be misleading in this population.

Transgender women were born biologically male but now identify as female. These individuals may have undergone gender reassignment surgery to remove male genitalia, but the procedures do not remove the prostate. They also might be taking estrogen therapy. “Prostate cancer is a hormonally driven cancer, and the exact impact of gender-affirming hormones on prostate cancer risk and development is unknown,” Nik-Ahd said.

In a 2023 study in JAMA, Nik-Ahd and colleagues identified 155 cases of prostate cancer in transgender women within the VHA (about 14 cases per year) from 2000 to 2022. Of these patients, 116 had never used estrogen, while 17 had used it previously and 22 used it at diagnosis.

The median age of patients was 61 years, 88% identified as White, and the median prostate-specific antigen (PSA) was 6.8 ng/mL. “Given estimates of 10,000 transgender women in the US Department of Veterans Affairs, 33 cases per year would be expected. Instead, only about 14 per year were observed,” the researchers wrote. “Lower rates may stem from less PSA screening owing to barriers including lack of prostate cancer risk awareness or stigma, the suppressive effects of estrogen on prostate cancer development, or prostate cancers being missed in transgender women because of misinterpretation of ‘normal’ PSA levels among those receiving gender-affirming hormone therapies.”

In the presentation, Nik-Ahd said, “PSA density, which is a marker of prostate cancer aggressiveness, was highest in transgender women who were actively on estrogen.”

She noted, “the existing thyrotropin reference ranges, which is what we use to interpret PSA values, are all based on data from cisgender men.” The ranges would be expected to be far lower in transgender women who are taking estrogen, potentially throwing off screening tests, she said, and “ultimately missing clinically significant prostate cancer.”

In the larger picture, there are no specific guidelines about PSA screening in transgender women, she said. 

A recent study published in JAMA by Nik-Ahd and colleagues examined PSA levels in 210 transgender women (mean age 60 years) treated within the VHA from 2000 to 2023. All were aged 40 to 80 years, had received estrogen for at least 6 months (mean duration 4.7 years), and didn’t have prostate cancer diagnoses.

“Median (IQR) PSA was 0.02 (0-0.2) ng/mL and the 95th percentile value was 0.6 ng/mL,” the report found. “PSAs were undetectable in 36% of patients (23% and 49% of PSAs in patients without and with orchiectomy, respectively).”

The researchers write that “the historic cut point of 4 ng/mL, often used as a threshold for further evaluation, is likely far too high a threshold for this population.”

Nik-Ahd noted, “clinicians should interpret PSA values in transgender women on estrogen with extreme caution. In this population, normal might actually not be normal, and a value that is considered normal might be very abnormal for somebody who is on estrogen. If you're unsure of whether a PSA value is appropriate for a transgender woman on estrogen, refer that patient to a urologist so they can undergo further evaluation.”

Farnoosh Nik-Ahd discloses consulting for Janssen.