Shedding light on sex differences in differentiated thyroid cancer

By Naveed Saleh, MD, MS | Fact-checked by Barbara Bekiesz
Published May 6, 2022

Key Takeaways

  • Physicians are trained to think of thyroid cancer as more common in women than in men. And on the surface, this phenomenon holds.

  • On further analysis, microcarcinoma rates may be similar in men and women.

  • Women are more likely to be screened and treated for thyroid cancer than men, who present with more advanced cases.

Sex dimorphism (ie, gender difference) plays a big role in tumor biology. Most cancers are more common in men, but thyroid cancer is the only non-reproductive system cancer more frequent in women, with a three to four times higher incidence.[]

Historically, women are more likely to develop thyroid cancer compared with men.

This difference has become even more pronounced lately in the US and other countries.

But this may be an oversimplification. Although gender differences underlying thyroid cancer have yet to be elucidated, experts have looked into the topic and made some clinical suggestions.

Discrepancies in differentiated thyroid cancer

Throughout the world, rates of differentiated thyroid cancer have increased over the past few decades. According to an article published in the International Journal of Molecular Sciences, “This has been explained in part by changes in clinical practice. Indeed, the set-up of a systematic screening in some countries has led to an epidemy of small cancers, overdiagnosis, and overtreatment, as this was not associated with a change in mortality, whereas the increase in more clinically relevant thyroid cancer was of a more limited amplitude.”[]

According to the authors, papillary thyroid cancer (PTC) rates have increased for women around the world. There has been a significant increase in microcarcinomas (5–10 mm) in women vs men, with increasing female/male ratios affecting women between beginning at around 15 years of age and then decreasing ratios by 50–55 years of age, a pattern which could be tied to reproduction.

Is this an oversimplification?

Men tend to be diagnosed with thyroid disease later in its course, when tumors are larger.

For women, the reason for the ultrasound exam on which the thyroid carcinoma was detected is frequently unknown.

Autopsy data also point to equal probability for men and women to develop microcarcinoma. Women, however, are more likely to experience tumor growth, possibly due to sex hormones.

The frequency of thyroid carcinoma has been found to be similar in boys and girls, with differences arising at pubertal age. In other words, tumor growth is dependent on sex hormones, whereas a tumor’s initial manifestation may be due to environmental factors and molecular injury.

Results from a recent cohort study and meta-analysis published in JAMA further support the notion that thyroid cancer’s predominance in women is an oversimplification.[]

The authors found that the gender disparity is more pronounced regarding small, subclinical PTCs, which are noted at similar rates in men and women at autopsy but detected more commonly in women during clinical practice. As the thyroid cancer type becomes more deadly, investigators found, the numbers tend to even out and approach a 1:1 ratio.

Clinical implications

These findings have important clinical implications.

For instance, given the large reservoir of subclinical papillary cancers that exists, coupled with clinicians’ ingrained thinking about thyroid cancer incidence in women, practitioners may be inclined to look for—and find, and then treat—these subclinical lesions in women. The benefits of such aggressive targeting are unclear, as potential harm and adverse events may be associated with it.

On the other hand, men are more likely to be diagnosed later, with advanced disease, because the differential diagnosis for them gives precedence to other conditions besides thyroid cancer.

Healthcare utilization could also play a role. Women often pursue health care visits more actively than men—even accounting for reproductive visits. This increased access and exposure to healthcare could bolster opportunities to discover thyroid nodules and result in perceived differences in thyroid cancer numbers between the sexes.

Role of hormones

The influence of sex hormones as an explanation for the larger number of thyroid cancers in women may also need to be reexamined. The authors of the JAMA study pointed to mixed results from in vitro and animal studies on the possible link between estrogen and the thyroid, although some mechanisms demonstrate thyroid tissue sensitivity to estrogen.

“The findings of the present study suggest that women may benefit from guidelines aimed at promoting more focused use of thyroid imaging,” the authors concluded. “While men are also at risk of having subclinical disease detected, they may be diagnosed with clinical disease at later stages because they present for health care less often and may have thyroid cancer placed lower in the differential than women with similar symptoms.”

As far back as 2013, research showed that male sex is not an independent prognostic factor for survival in thyroid cancer. That study also attributed the worse survival in men to more advanced disease at time of presentation.[]

What this means for you

Physicians shouldn’t buy into the hype that thyroid cancer is a “woman’s cancer.” It’s very possible that rates between men and women are comparable, based on recent research. It’s advisable to limit overzealous thyroid treatment in women, and to screen men more diligently. When clinical findings in men suggest thyroid cancer, this diagnosis should take its proper place on the list of differential diagnoses.

Related: The connection between thyroid disease and weight
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