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Taiwan retrospective population study shows levothyroxine use significantly associated with increased risk of cancer including PCa

Graham49 profile image
10 Replies

Levothyroxine is commonly taken for an under active thyroid.

“Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46-1.54; P < .0001) compared with non–users.”

I take it and will be querying the necessity and dose with my doctor.

Risk of cancer in long-term levothyroxine users: Retrospective population-based study

Chieh-Chen Wu, Md. Mohaimenul Islam, Phung-Anh Nguyen, Tahmina Nasrin Poly, Ching-Huan Wang, Usman Iqbal, Yu-Chuan (Jack) Li, Hsuan-Chia Yang

First published: 01 April 2021

doi.org/10.1111/cas.14908

Abstract

Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case-control study was conducted using Taiwan’s Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ≥20 years and had a first-time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46-1.54; P < .0001) compared with non–users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48-2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17-1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01-1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15-1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients’ condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms.

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Graham49
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10 Replies
Jpburns profile image
Jpburns

hmmm… but no mention of prostate cancer? I’m trying to not discount nor believe any connection, but read this because I’ve been on Levothyroxine for untold years (at least 15? I forget…).

Eh… too late to do anything about it now.

Graham49 profile image
Graham49 in reply to Jpburns

prostate cancer is mentioned in the main report: "prostate (AOR: 1.26, 95% CI: 1.06-1.5". AOR means adjusted odds ratio, in other words 26% more likely to have prostate cancer. It may be too late for PCa however its probably best not to get any of the other cancers as well.

Gl448 profile image
Gl448 in reply to Graham49

Does of the report motioned Armor Thyroid use? I wonder if the natural stuff having bits of all the different thyroid hormones in them give it a non-cancer advantage over the synthetic stuff

garythomas profile image
garythomas

I have been on medication for underactive thyroid for many years and have Gleason 4+5 PCa.

GAdrummer profile image
GAdrummer

Which came first, the chicken or the egg? My husband had two different cancers (leiomyosarcoma and prostate cancer) 15 years before Keytruda treatment left him essentially hypothyroid and he had to start taking Levothyroxine.

Keytruda is used in treating many different cancers, and one of it's side effects is possibly skewing the results of the survey. Maybe his genes paired with his occupational hazards (exposure to chemicals), made him susceptive to developing cancers and to the treatment side effects.

Searching a patient data base for "Levothyroxine" and a particular type of "cancer" would give results that should be individually reviewed to determine which came first. If a cancer came first, any other cancer may pop up after starting on Levothyroxine, and in that case, the survey cannot discriminate a cause between Levothyroxine and/or the person's genes and exposure to other carcinogens. If you throw out that case, you need to increase your error. If you don't throw it out, then you have to make a choice - and that is biasing the result.

We are quietly waiting for the next type of cancer to be found. Crossed fingers...

MouseAddams profile image
MouseAddams in reply to GAdrummer

Amen. I agree with your assessment. My hubby also had that same issue.

j-o-h-n profile image
j-o-h-n in reply to GAdrummer

Depends.......... raw, boiled or scrambled?........

Good Luck, Good Health and Good Humor.

j-o-h-n

Graham49 profile image
Graham49

Here’s another older study. In this case it’s mostly people with natural thyroxine (called FT4 in this study) that’s being measured. Higher levels still increase risk of solid organ cancer especially lung cancer.

“Excluding participants with thyroid function–altering medication resulted in similar risk estimates, but the association with breast cancer lost statistical significance (Table 4). There was no effect modification by age or sex (P > .05 for all interaction terms) (Supplemental Table 1). Risk estimates of the most adjusted models also remained similar when cancer cases that were not pathology based were included as outcome (Supplemental Table 2) and when the first 2 years of followup were excluded (Supplemental Table 3).”

The report discusses the mechanisms that might lead to increased cancer. With respect to prostate cancer it states:

“In prostate cancer cells, thyroid hormone can down-regulate B cell translocation gene 2 (BTG2), resulting in increased proliferation (2). Furthermore, thyroid hormone can alter the expression level of cyclin D1, a protein that regulates the cell cycle, and of cyclin-dependent kinases, leading to various tumor types, such as breast cancer and neural cancers (1). Action of thyroid hormone on estrogen and androgen receptors may also contribute to breast and prostate cancer, respectively (29, 30)”.

Thyroid Function and Cancer Risk: The Rotterdam Study

Samer R. Khan, Layal Chaker, Rikje Ruiter, Joachim G. J. V. Aerts, Albert Hofman, Abbas Dehghan, Oscar H. Franco, Bruno H. C. Stricker, Robin P. Peeters Author Notes

The Journal of Clinical Endocrinology & Metabolism, Volume 101, Issue 12, 1 December 2016, Pages 5030–5036, doi.org/10.1210/jc.2016-2104

Published: 20 September 2016

Context:

In vitro and in vivo experiments have assigned both oncosuppressive and oncogenic properties to thyroid hormones. Population-based studies have found inconclusive results.

Objective:

We aimed to prospectively assess the relation between thyroid function and incident cancer in a population-based setting.

Design, Setting, and Participants:

The current study is a prospective population-based cohort study including 10 318 participants for whom baseline measurements of free T4 (FT4) and/or TSH were available.

Main Outcome Measures:

Cox proportional hazards models were used to assess hazard ratios (HRs) of any solid non-skin cancer, as well as lung, breast, prostate, and gastrointestinal cancer specifically.

Results:

Higher FT4 levels were associated with a higher risk of any solid cancer (HR, 1.42; 95% confidence interval [CI], 1.12–1.79), lung cancer (HR, 2.33; 95% CI, 1.39–3.92) and breast (HR, 1.77; 95% CI, 1.10–2.84) cancer. The risk estimates were similar after exclusion of thyroid-altering medication, but the association lost significance for breast cancer. Compared with the lowest FT4 tertile, the highest tertile was associated with a 1.13-fold increased risk of any solid, 1.79-fold increased risk of lung, and 1.14-fold increased risk of breast cancer (P for trend <.05 for all). For TSH levels we found no associations with cancer risk. There was no differential effect of sex or age on the association between thyroid function and cancer risk.

Conclusions:

Higher FT4 levels are significantly associated with an increased risk of any solid, lung, and breast cancer. Further research should elucidate the underlying pathophysiological mechanisms.

Nwdx profile image
Nwdx

Thank you for posting that. My last blood test TSH was really low (unexpected) now trying to change dosage same exam time as high PSA discovery, both were out. I have been taking Levoxl for 30 years and changed dosage various times, who knows if this contributed partially to my cause of PC. Vitamin D level was low also on same blood exam.

Graham49 profile image
Graham49

For anybody still interested here’s some interesting data from an even earlier study for prostate cancer.

Thyroid Function and Cancer Risk: A Prospective Population Study

Alf Inge Hellevik; Bjørn Olav Åsvold; Trine Bjøro; Pål R. Romundstad; Tom Ivar L. Nilsen; Lars J. Vatten

Cancer Epidemiol Biomarkers Prev (2009) 18 (2): 570–574.

doi.org/10.1158/1055-9965.E...

Thyrotropin = TSH, HR = hazard ratio

Thyrotropin (mU/L ) <0.50 HR (95%) 1.97 (1.04-3.76)

Thyrotropin (mU/L ) 0.50-1.4 HR (95%) 1.0 (Reference)

Thyrotropin (mU/L ) 1.5-2.4 HR 0.93 (0.73-1.2)

Thyrotropin (mU/L ) 2.5-3.5 HR 0.78 (0.54-1.13)

Thyrotropin (mU/L) >3.5 HR 0.86 (0.55-1.35)

The other individual cancers investigated differ slightly. The data for all cancers suggest a Thyrotropin of <0.5 should be avoided. Total cancer also indicated lowest HR for Thyrotropin (mU/L ) 2.5-3.5.

Therefore based on this one study a good target for TSH would be Thyrotropin (mU/L ) 2.5-3.5.

This might not be a good target for other aspects of health. Doctors often use a target of 0.5 to 5.0. UCLA health state:

“Some people with a TSH value over 2.0 mIU/L, who have no signs or symptoms suggestive of an under-active thyroid, may develop hypothyroidism sometime in the future. Anyone with a TSH above 2.0 mIU/L, therefore, should be followed very closely by a doctor.”

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