2018 study on T4 and T3 in breast cancer

Thyroid Hormones in CancerPublished August 2018, a new study of T4 and T3 hormones and obesity in relation to breast cancer risk found that higher levels of T4 hormone conferred greater risk, while higher T3 levels had a protective effect.

The article

  • Ortega-Olvera, C., Ulloa-Aguirre, A., Ángeles-Llerenas, A., Mainero-Ratchelous, F. E., González-Acevedo, C. E., Hernández-Blanco, M. de L., … Torres-Mejía, G. (2018). Thyroid hormones and breast cancer association according to menopausal status and body mass index. Breast Cancer Research : BCR, 20. Available online at PubMed Central https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085630/

Why it matters for thyroid patients too!

The standard T4 (Levothyroxine / Synthroid) therapy produces T4 levels that are, on average, 15 to 20% higher than T3 levels, compared to healthy controls (see Peterson, McAninch & Bianco, 2016, “Levothyroxine monotherapy”). Some thyroid patients on the standard therapy have a very significant divide between a higher T4 and much lower T3.

Their methods

This particular study analyzed over 600 patients with breast cancer and 600 control patients without breast cancer in Mexico between 2004 and 2007. They excluded anyone who reported a prior diagnosis of thyroid disease.

The study also used Total T3 and Total T4 measurements, rather than Free hormones. Estrogen replacement therapy and natural estrogen levels can significantly affect the Total : Free thyroid hormone ratio.


The average odds ratio (OR) was 5.98 in pre-menopausal women with higher TT4 values within the normal range (Table 4). In post-menopausal women, the OR for TT4 was 2.98, which is still significant. Overall, higher TT4 levels were associated with higher odds for breast cancer in this population. This means that women with higher TT4 in this population had 3-6 times the odds of breast cancer.

In comparison with TT4, the OR for TT3 levels was between 0.07 and 0.20, which is significant because any OR below 1.00 means that increasing levels of the indicator are “protective.” This means that higher TT3 levels (within the normal reference range) conferred between 80% and 93% reduced likelihood for breast cancer. The TT3 levels in breast cancer patients averaged 1.6-1.7 while TT3 in healthy controls averaged 2.4-2.6 nmol/L.

What about TSH and thyroid antibodies?

They stated “No significant associations were found with any other thyroid function parameters (TSH, Tg, Tg Ab, or TPO Ab).”

What was their TSH? — Among the premenopausal women, the average TSH was 1.6 mUI/L in those with breast cancer, and TSH was 1.7 in those without breast cancer. In postmenopausal women, TSH had the same average of 1.8 among those with and without breast cancer.

Did obesity make a difference?

In contrast with T4 and T3 levels, obesity as a risk factor by itself gave lower ORs, the highest being 1.16 for the most obese post-menopausal women.

Clearly, thyroid hormones are more important than obesity when it comes to breast cancer.

The researchers’ discussion

Their discussion section stated that “The addition of T4 to BC[Breast Cancer]-derived cell lines has been shown to increase cell proliferation [3], while in the presence of estrogen receptor (ER)-positive BC cell lines the addition of T3 inhibits cell proliferation [7].”

However, despite these past studies showing T4 and T3 have direct effects on breast cancer at the cellular level, they were still hesitant to say that high T4 / low T3 “causes” breast cancer in populations, since they reasoned that breast cancer illness may also contribute to problems with thyroid hormone conversion. They thought that perhaps Low T3 syndrome / “nonthyroidal illness” was a factor.

Future research

The researchers admit that collecting data on Free T4 and T3 would have been helpful, but only if one also collected data on women’s estrogen replacement, which alters thyroid hormone binding.

The researchers also suggested testing before disease & diagnosis to better understand a causal relationship between breast cancer and thyroid hormone levels:

In particular, prospective cohort studies in which T3 and T4 are collected prior to cancer diagnosis may be helpful in understanding the causal relationship between BC and thyroid hormones. In addition, a prospective study may also help to improve understanding of the relationship among thyroid hormones, BC, and obesity.

Our comments

TSH-uncrownClearly, it’s important to collect data on both T3 and T4 hormones in studies on thyroid and disease risk.

TSH is not always an important factor, especially when examining health within the normal TSH reference range. Normal-range TSH characterizes the vast majority of the population, including treated thyroid patients, whether they are sick or healthy.

Too many studies have examined TSH alone, or only at TSH and T4, blinded to the effects of T3, the most potent thyroid hormone.

Studies like this strengthen our campaign claims:

Keep doing studies on T3 hormone in relation to various diseases!

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