Levo and increased risk of cancer long term use

[Sharcott]

Any thoughts please pubmed.ncbi.nlm.nih.gov/337...

My consultant wants me off HRT because I am at risk of breast cancer

[Aurealis]

The consultant wants you off thyroid replacement?How much is the increase in risk?

[Sharcott in reply to Aurealis]

Long term levo is 50% more so it makes the small risk much bigger.

[Aurealis in reply to Sharcott]

But is it 1 case per 100 more, or 1 case per 100 million more. They can easily scare us with these stats.

[Sharcott in reply to Aurealis]

Not sure I am dyslexic

[jimh111 in reply to Aurealis]

HRT or thyroid treatment?

[Catfur]

In my opinion this is a deeply flawed study. It’s not actually saying there is a link between levothyroxine and cancer and what that mechanism is.

It is saying that people who take levothyroxine have been anecdotally linked with a potentially higher risk of cancer. However the study has not taken into account smoking and other factors which are known to be linked to higher risks of cancer.

In fact it states it’s own limitations in the article as below :

Our study also had several limitations. First, some potential factors such as family history, smoking status, body mass index, and alcohol consumption information related to cancer risk were not included in our main and subgroup analyses because the HWDC database does not provide such information.40, 43, 44 Despite the lack of smoking status data in the HWDC database, we included chronic obstructive pulmonary disease, which could be regarded as a surrogate for smoking status, in the confounding comorbidities and adjusted it in the analysis of cancer risk. Second, the current study was conducted in populations in Taiwan, and, hence, our findings might be different from other studies in other populations with different races or ethnicities. Third, a dose-response association for gender was not included in our analysis, and this may weaken the observed association because male and females respond differently to the same dosage.45 Fourth, cancer stages were not included in our main analyses due to lack of information. Fifth, we could not obtain information from the HSDC database on whether or not the hypothyroid patients were overtreated with levothyroxine. Finally, the association between levothyroxine exposure and various types of cancer risk was analyzed and identified in this study, yet its biological or metabologic mechanism could not be clarified using our study design.

In fact COPD is not a surrogate for smoking plenty of people have COPD without ever having smoked. Yes people who smoke may have COPD but that is not the only reason to have it.

In fact the excerpt above undermines any statements made in this article.

This article is a load of twaddle and unfounded scaremongering which is not worth the absence of paper it is not printed on.

[Hashiboy]

Thanks for this Sharcott. The paper reports an association between being on levo and an increased risk of being diagnosed with cancer in Taiwan. It doesn’t show being on levo is the cause of the increased risk and isn’t designed to say how levo might cause increased risk. I bet the association is higher for ever having smoked, ever having a glass of wine or ever having a ham sandwich, ever being overweight or sunbathed. The authors of the paper recommend being cautious interpreting the data and suggest a 20 to 25 year study to truly establish the relationship between Levo and increased cancer risk. Maybe your consultant has good reason but I think they should at least explain why they think this risk is so clear and why they think it’s much more important than other risks they have to weigh up. Good luck.

[jimh111]

I posted this healthunlocked.com/thyroidu... which tries to give a balanced explanation of how higher T4 levels carry cancer risk.

Any risk between T4 and breast cancer is not clear, it seems that higher T3 or T4 may increase risk.

Please note I have no cancer expertise.

[RedApple Administrator]

Sharcott, The abbreviation HRT usually refers to sex hormone replacement such as oestrogen, progesterone and testosterone. These are the hormones usually referred to in conjunction with breast cancer.

Levothyroxine is an absolutely essential hormone for anyone who doesn't have a fully working thyroid. It's not something to 'come off', and it's not usually associated with breast cancer.

[radd]

Sharcott,

Your risk of using Levothyroxine causing cancer is a separate issue to your HRT causing cancer. Which are you referring to?

[Sharcott in reply to radd]

Both as I am on Levo and HRT

[radd in reply to Sharcott]

Sharcott,

The cancer risk associated with Levothyroxine is applied mainly when FT4 levels have remained too high or at over- range levels. This is common in people medicating T4-mono therapy who are unable to convert sufficient T3 levels, so keep increasing their meds.

The risk of breast, ovarian and womb cancer is less with body-identical HRT than older versions and for many the benefits outweigh the risk. However, if you have cancer in your family then the risk increases somewhat and must be taken into consideration.

I have not read it is beneficial to evaluate the cancer risks of taking both Levo & HRT together even though it is commonly known that thyroid hormones heavily influence sex hormones, and vice versa. I guess it's dependant upon your individual cancer risk and T4 -T3 conversion abilities.

[Sharcott in reply to radd]

My T4 remained high because I don't convert well I am on T3 as well. T4 normally in range .

[radd in reply to Sharcott]

Sharcott,

Medicating thyroid hormone replacement meds are essential in addressing deficiencies, and a small amount of T3 can help convert more T4 to T3, so achieving a higher value than the amount medicated. This is how the deiodinases (thyroid enzymes) work, so a much healthier approach that is more in line with our body when we have conversion issues.

"My consultant wants me off HRT because I am at risk of breast cancer". Then that would need careful considerations to analyse the benefits against the risk of cancer if you are deemed vulnerable.

[jimh111]

Keep these risks in proportion. Breast cancer accounts for 7% of all cancer deaths (but affects mainly women). To me the studies seem inconclusive, it appears that higher thyroid hormone levels are associated with increased breast cancer risk. I feel more confident that higher T4 levels are associated with overall cancer risk and so it seems reasonable to keep fT4 around the lower part of its reference interval, if you can.

I don’t know about the extent that HRT affects breast cancer risk, you will have to research this and make a judgement. Bear in mind that we make these risk / benefit decisions all the time, such as our diet or amount of exercise.

As regards thyroid hormone I’ve always thought it best to take the lowest effective dose that resolves our symptoms (but at least enough to get a normal TSH). If we need higher levels to lead a normal life we have to accept the extra risk. In medicine there are always risks and benefits to balance.

[helvella Administrator Thyroid UK]

This paper, which cites the paper from the original post, ends with this:

The overarching aim is to ensure the maintenance of cancer patient quality of life in keeping with the notion of “treating patients not numbers”.

The Clinical Relevance of Hypothyroidism in Patients with Solid Non-Thyroid Cancer: A Tantalizing Conundrum

Maria V. Deligiorgi* and Dimitrios T. Trafalis

Abstract

Hypothyroidism in patients with solid non-thyroid cancer is a tantalizing entity, integrating an intriguing thyroid hormones (THs)–cancer association with the complexity of hypothyroidism itself. The present narrative review provides a comprehensive overview of the clinical relevance of hypothyroidism in solid non-thyroid cancer. Hypothyroidism in patients with solid non-thyroid cancer is reminiscent of hypothyroidism in the general population, yet also poses distinct challenges due to the dual role of THs in cancer: promoting versus inhibitory. Close collaboration between oncologists and endocrinologists will enable the prompt and personalized diagnosis and treatment of hypothyroidism in patients with solid non-thyroid cancer. Clinical data indicate that hypothyroidism is a predictor of a decreased or increased risk of solid non-thyroid cancer and is a prognostic factor of favorable or unfavorable prognosis in solid non-thyroid cancer. However, the impact of hypothyroidism with respect to the risk and/or prognosis of solid non-thyroid cancer is not a consistent finding. To harness hypothyroidism, or THs replacement, as a personalized anticancer strategy for solid non-thyroid cancer, four prerequisites need to be fulfilled, namely: (i) deciphering the dual THs actions in cancer; (ii) identifying interventions in THs status and developing agents that block tumor-promoting THs actions and/or mimic anticancer THs actions; (iii) appropriate patient selection; and (iv) counteracting current methodological limitations.

Keywords: cancer prognosis, cancer risk, hypothyroidism, levothyroxine, liothyronine, solid non-thyroid cancer, thyroid hormones, thyroid hormone receptors, thyroid stimulating hormone

Deligiorgi MV, Trafalis DT. The Clinical Relevance of Hypothyroidism in Patients with Solid Non-Thyroid Cancer: A Tantalizing Conundrum. J Clin Med. 2022 Jun 14;11(12):3417. doi: 10.3390/jcm11123417. PMID: 35743483; PMCID: PMC9224934.

ncbi.nlm.nih.gov/pmc/articl...

[jimh111 in reply to helvella]

I have a bad cold and am struggling to read the study you quoted. Some general comments. The review shows that hypo and hyper thyroidism can have beneficial / harmful effects on cancer risk and progression. The studies I've seen show a sort of '80/20' effect, that a low normal fT4 is beneficial for about 80% (very rough number) of cancer cases and fatalities. So, when placing your bets it's better to have a low normal fT4.

If we should unfortunately get cancer it's important the oncologist looks at the evidence for that type of cancer and thyroid therapy. Once you know what cancer it is you don't play the odds game anymore.

The complexity of this subject tells me we should perhaps push for combination therapy and if we get cancer leave it to the oncologist but asking them about our thyroid therapy.

[helvella Administrator Thyroid UK in reply to jimh111]

Though 80:20 seems very much population based statistics - and not directly applicable to individuals. (As ever.)

[jimh111 in reply to helvella]

It's a very rough example as 80/20 is in common usage. Individuals will get, or be at special risk of, specific cancers.

[SlowDragon Administrator]

As a sweeping generalisation….hypothyroid patients often gain weight ….becoming over weight or obese

Weight gain appears to increase risk of cancer

cancer.org/latest-news/how-...

breastcancernow.org/informa...

[Jazzw in reply to SlowDragon]

And following along the correlation not causation argument—many people with hypothyroidism aren’t diagnosed until it’s far advanced. And even then, are often left on too low a dosage of thyroid hormone replacement for a long time too.

I don’t have any studies to hand to back anything up, but it strikes me that being left chronically deficient in thyroid hormones for sometimes years at a time is likely to be far more detrimental to one’s long term health than having high in range FT4 levels as a result of being on a decent amount of levothyroxine.

Isn’t it more likely that it’s the years of not having enough thyroid hormone on board that does the cell damage rather than the thyroid hormone replacement itself?

[SlowDragon Administrator in reply to Jazzw]

My thoughts exactly

[Sharcott in reply to SlowDragon]

Yes I strongly agree

[jimh111 in reply to Jazzw]

Hypothyroidism is generally protective against cancer, but not all cancers. A specific role for T4 promoting cancer has been identified, i.e. T4 binding to the integrin alphaVbeta3 receptor (my keyboard doesn’t have the Greek letters). The argument is that we should use combination therapy so that hypothyroidism can be treated with lower fT4 levels and hence less cancer.

Untreated hypothyroidism carries risks, especially cardiac risks.

[RedApple Administrator in reply to jimh111]

jimh111 'Hypothyroidism is generally protective against cancer, but not all cancers.'

Can you expand on that please? If you are hypothyroid, surely it's not a 'protection', more a hindrance for growth of a cancer.

Have you read Oliver Sacks story about Uncle Toby?

[RedApple Administrator in reply to RedApple]

Cold StorageOliver Sacks

‘Uncle Toby was alive, but suspended, apparently, in some strange icy stupor.’

granta.com/cold-storage/

[jade_s in reply to RedApple]

Fascinating! I wasn't able to access that article, but found this publicly available account via google books: books.google.be/books?id=_H...

[RedApple Administrator in reply to jade_s]

Excellent, thanks for that! It's years since I read it, so I'm delighted to find it available.

[helvella Administrator Thyroid UK in reply to RedApple]

It is available on the Wayback Machine (Internet Archive)!

You have to sign up to an account. That is free. Then you can "borrow" the copy of Granta for an hour. (If an hour isn't long enough, you can re-borrow repeatedly.)

First link should be to the exact page - the second is to the copy of Granta:

archive.org/details/granta2...

archive.org/details/granta2...

jade_s

[RedApple Administrator in reply to helvella]

Thanks, good to know

[jade_s in reply to helvella]

Handy! Thanks!!

[jimh111 in reply to RedApple]

For a long time there has thought to be a protective effect of hypothyroidism regarding cancer. More recently hypothyroxinemia (low T4) has been found to be the protective mechanism rather than hypothyroidism per se. There was an intervention study that showed this effect doi.org/10.1634/theoncologi... . This wasn’t placebo controlled so further studies are needed to be sure.

Hypothyroidism is not protective against e.g. liver cancer, probably because it causes high lipid levels. On balance, hypothyroidism is more protective than promoting of cancers.

I’m not advocating hypothyroidism! Not least because it does a lot of cardiac harm and wrecks lives. I mention hypothyroidism because it describes the history of how the link between higher T4 and cancer was found.

[RedApple Administrator in reply to jimh111]

Well no doubt you and the researchers concerned know far more about it than I do.

My simplistic way of thinking says too little thyroid hormone could slow or temporarily prevent cancer growth, whereas too much thyroid hormone could speed it up.

[jimh111 in reply to RedApple]

That seems perfectly reasonable and was my elementary impression but when looking at studies on possible use of T3 to treat COVID I came across the link between T4 and cancer. The subject is incredibly complex so I just look at the numbers, links between higher T4 levels and cancer.

I always had the view that levothyroxine monotherapy was fine for people with primary hypothyroidism who did well on it. I’ve now changed my view because I believe it leads to higher risk of cancer and cardiac disease.

[Sharcott in reply to jimh111]

Interesting they removed all my meds when I had covid and sent me very hypo thought I was dying I couldn't breath

[jimh111 in reply to Sharcott]

I don't understand why they did that. In hospital I believe they remove meds so they can monitor what meds you are on. They should continue regular meds in most cases, certainly stopping thyroid meds is only going to make you worse. (the body alters its T4 to T3 conversion in illness, so there may be some merit in reducing T3 intake during serious illness. This is hypothetical, nobody knows what is best).

[Sharcott in reply to jimh111]

Removed all no aim of putting me back on, huge mistake.

[Lovecake]

My GP wanted me to come of HRT patches a year ago. She said pessaries would be better. (Total rubbish)I’m 56. Had an emergency hysterectomy 12 years ago due to a large growth on my ovary. Thankfully was benign.

HRT tablets made me very ill 24/7 migraines. Patches much better.

I was finally diagnosed with Hashimoto’s in 2016 but had been struggling for years before.

So, I came of the patches for 12 weeks - BIG mistake - felt dreadful and it messed up my thyroid levels/symptoms too.

Went back on them (increased slowly over a few weeks). Spent 6 months sorting my thyroid levels again (and I know it wasn’t going back on the patches that caused problems, it was coming off them that upset the balance and many other issues within my body)

I weighed up my quality of life being off the patches to the very slight chance of cancer risk.

You need to decide what is best for you. If you have a pretty good QoL on HRT, would it be worse to come off the HRT and have a poor QoL? Or you might be ok?

Some brilliant and informative answers from other people as always on here.

[MrsSuzuki]

I've been on levothyroxine for over 11 years and was on HRT for the same amount of time. I had to stop the HRT when I was diagnosed with breast cancer in 2014. My choice to take HRT but I had to take levothyroxine.

My doctor told me that there was research to suggest that taking levothyroxine

could lead to a small increased risk of breast cancer. I was also on HRT which increased the risk again. My two maternal aunties also died from breast cancer in their fifties, so I guess I was a prime case for the cancer.

At the end of the day it's all about statistics and percentages; some of us have problems and the lucky ones don't.

Lily