Beyond the Binary: Prostate Cancer Among Transgender Women

If you're a transgender woman, you may wonder about your prostate health at times. Due to the risks of surgical removal (e.g. incontinence), the often overlooked prostate is typically left as it is, even for those who have transitioned or undergone gender-affirming surgery. While the prostate may be out of sight, you still remain susceptible to prostate cancer. It may be time to start giving prostate cancer some thought.

Transgender women are a population understudied in prostate cancer research. A study, drawing on 22 years of data from the US Veterans Affairs Health System, has found 155 trans women with prostate cancer. The median age of diagnosis for this group of patients was 61 years.

While such cases were initially thought to be quite rare, Dr Stephen J. Freedland, the lead researcher of this study, highlighted that these findings meant prostate cancer in trans women was “not a rare phenomenon”.

The team reported two main observations:

1. Despite having prostate glands like cisgender men, their risk of prostate cancer is much lower. The study suggested that the rate of prostate cancer among trans women is 14 cases per 10,000 individuals. In contrast, the prostate cancer rate in cis men, as reported by the American Cancer Society, is one case in every eight men.
2. Trans women tend to have delayed prostate cancer diagnoses.

However, researchers also suggested several factors for the observed disparities:

• Stigmas
• A lack of awareness for prostate-specific antigen (PSA) screening
• A lack of awareness regarding prostate cancer risks
• Underdiagnosis due to PSA reading misinterpretations for those on gender affirming hormone therapy
• The potential impact of estrogen used in gender affirming hormone therapy

Gender affirming treatments encompass both surgical and medication options. In surgical procedures, medical professionals may still retain the prostate glands while removing the testicles. In gender affirming hormone therapy, estrogen or drugs may be used to inhibit the effects of testosterone. Both methods aim to reduce testosterone, the key driver of PSA expression and of prostate cancer, thereby lowering the risk of prostate cancer.

The PSA test may face difficulties in identifying prostate cancer in transgender women undergoing hormone therapy, as PSA expression in prostate cancer is lowered by the absence of androgen stimulation. Magnetic resonance imaging (MRI) scans or androgen-independent biomarkers could therefore be considered to aid diagnosis in the future.

Genetic risk factors such as BRCA1/BRCA2 germline mutations must be also taken in account when assessing prostate cancer risk.

The risk of prostate cancer among trans women remains, albeit at a lower rate than in cisgender men. The same study indicated that those on gender affirming hormone therapy seemed to have a slightly more aggressive form of the disease by the time they were diagnosed. This increase in aggressiveness at the time of diagnosis could be explained by the lack of precision of the PSA test, leading to a delayed diagnosis. Additionally, these cancers may have already evolved to become castration-resistant and more difficult to treat.

In the US, nearly one-third of trans women live in poverty and many do not get proper healthcare for the fear of discrimination. A disheartening study revealed that their survival rates of prostate cancer are far worse than their cisgender counterparts.

Dr Freedland has urged trans women and clinicians to promote awareness for prostate cancer screenings. “Just because a woman walks into your office doesn't mean we shouldn't be thinking about prostate cancer,” he says. “These are women, they look like women, they, the world sees them as women. They are women, and yet they have a prostate.”

When mentioning how doctors should approach such a sensitive topic for trans women, his suggestion is to have a patient-centric conversation, like “I know they may well be sensitive, but you know, there are certain diseases that you may be at risk for based on your sex assigned at birth and how do you want to have this conversation?”

Dr. Heidi Rayala, a urologist and an editor of the Harvard Medical School Annual Report on Prostate Diseases added that, “many doctors are already familiar with other common drugs that alter PSA values… The same care needs to be taken in interpreting PSA values in transgender women.”

Another paper, published by Dr Freedland’s team, has investigated a possible way of interpreting PSA readings in trans women. This study may fill the recommendation gap for this susceptible minority.

While the standard PSA cutoff for cisgender men is 4 ng/mL of blood, the study suggests that PSA levels for individuals on gender-affirming hormone therapy would be significantly lower in general. To account for this while screening for prostate cancer, a lower PSA level threshold still needs to be needed to identify prostate cancer in trans women under hormone therapy.

In the absence of specific guidelines for this population, researchers also advise that individuals eligible for PSA screening based on age should undergo testing before starting gender-affirming hormone therapy to establish a baseline value. If specific genetic risk factors are identified, screening by imaging could be suggested.

Currently, prostate cancer in trans women is a new territory in research, needing more effort to understand its full impact. This topic definitely requires awareness and collaborative effort to:

• Foster inclusive and sensitive conversations between healthcare providers and transgender patients
• Tailor the approach in screening and treating prostate cancer for this minority group