Thyroid Cancer Increase Observed in Transgender Female Veterans

WASHINGTON, DC — Transgender female veterans are more likely to have thyroid cancer at rates comparable to cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

"In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year," first author John Christensen, MD, of UC Davis Health, Division of Endocrinology, Diabetes & Metabolism, in Sacramento, California, told Medscape Medical News. He presented their findings this month at the American Thyroid Association (ATA) Annual Meeting and Centennial Celebration.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to US cancer statistics for 2020 from the National Cancer Institute.

"About one third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy (GAHT) may be a potentially important risk factor," Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

"There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer," Christensen said. "So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line."

To investigate the issue in a larger population, Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Administration Informatics and Computing Infrastructure (VINCI) database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients' thyroid cancer subtypes, 22 were papillary cancer, five were a follicular variant of papillary cancer, five were both papillary and follicular cancer, four were follicular cancer, three were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well-established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study's important limitations, Christensen urged a cautious interpretation of the findings.

"We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis-generating — not conclusive," he added. "I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first."

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the Cedars-Sinai Transgender Surgery and Health Program at Cedars-Sinai Medical Center, in Los Angeles, California, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

"With an estimated 1.5 to 1.6 million people in the US who are transgender, with many of them receiving GAHT, we haven't observed a bump or high incidence of any kind of cancer among these people so far," he said.

"There's certainly a high potential that hormone therapy, whether it's feminizing or masculinizing hormone therapy, can affect an individual's cancer risk," he added. "But we don't know of any [definitive evidence] yet of an increase, and, there's also even the question of whether there could be an opposite effect."

Regarding the thyroid cancer data, Garcia agreed that the preliminary nature of the study is a key limitation. "It's hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer," he said.

"Until more statistical analysis is done, I think all that can be said is that it's speculative."

Garcia, who co-authored a review published this month on Cancer Screening for Transgender Individuals, underscores that despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, "the point is that we cannot forget to screen them at all."

Christensen and Garcia had no disclosures to report.

American Thyroid Association (ATA) Annual Meeting and Centennial Celebration. Presented September 29, 2023. Late Breaking Poster #490.

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