The following potential confounders were included in our model: (a) medications known or suspected to modify the risk of some cancers, including aspirin (ATC code: B01AC06),19-22 statins (ATC code: C10AA),19, 23, 24 and angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARB) (ATC codes: C09A and C09C),19, 25-27 exposure to any of which was defined as being prescribed within at least 60 days during a 3-year period prior to the index date; (b) prior diagnoses of diseases known or suspected to modify the risk of some cancers, established within 3 years prior to the index date, including chronic pulmonary disease (composite measure of diagnoses [ICD-9:490.x-505.x, 506.4]), myocardial infarction (ICD-9:410.x, 412.x), congestive heart failure (ICD-9:428.x), peripheral vascular disease (ICD-9:443.9, 441.x, 785.4, V43.4), cerebrovascular disease (ICD-9:430.x-438.x), dementia (ICD-9:290.x), rheumatic disease (ICD-9:710.0, 710.1, 710.4, 714.0-714.2, 714.81, 725.x), peptic ulcer disease (ICD-9:531.x-534.x), liver disease (ICD-9:571.2, 571.4-571.6, 456.0-456.21, 572.2-572.8), diabetes (ICD-9:250.x), hemiplegia or paraplegia (ICD-9:344.1, 342.x), renal disease (ICD-9:582.x, 583-583.7, 585.x, 586.x, 588.x), and age-adjusted Charlson comorbidity index (ACCI) scores.28. The prevalence of chronic hepatitis B in Taiwan was once estimated to be 15%-20% in the general population and has plunged to <1% in the younger generation since the launch of the nationwide mass vaccination program against hepatitis B in 1984.31 Given the mean age of 60.47 years in both groups in this study, the cases and controls, among whom HBV infection was highly prevalent, were predisposed to chronic hepatitis B and liver diseases. The mechanism of the association between levothyroxine and the risk of cancer remains unclear. An effect of cumulative duration of filled prescriptions (categorized as 60-364 days and ≥1 year) was evaluated to find the possible magnitude of the association. My Interpretations and Recommendations. In the current study, levothyroxine use was significantly associated with increased risk of breast cancer. trouble getting pregnant. Levothyroxine helps prevent cancer in our situation. Applies to levothyroxine: oral capsule liquid filled, oral solution, oral tablet Other dosage forms: 1. Levothyroxine therapy is provided to inactivate abnormal thyroid tissue growth or function and to restore the clinical and biochemical euthyroid state in the thyroid gland.5, 6 Recently, concerns have been raised regarding the use of levothyroxine medication and its adverse effects, for example, on bone and cardiac function.7. Your dose needs may be different during pregnancy. We excluded 400 474 cancer patients who were aged <20 years or who had only one cancer diagnosis. Use the link below to share a full-text version of this article with your friends and colleagues. Previous studies have demonstrated that oxidative stress can impair cell function and, consequently, leads to several chronic morbid conditions, including cancer and autoimmunity.10, 11 Furthermore, biological mechanisms could also support this association. The relationship between levothyroxine use and cancer risk is largely underdetermined. Fifth, we could not obtain information from the HSDC database on whether or not the hypothyroid patients were overtreated with levothyroxine. Store at room temperature away from moisture and heat. Overdose symptoms may include headache, leg cramps, tremors, feeling nervous or irritable, chest pain, shortness of breath, and fast or pounding heartbeats. 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. Based on the 3-year average daily dose (in DDD), the patients were categorized into three groups: <0.34, 0.34-≤0.67, and >0.67 DDD per day. Working off-campus? Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. 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. This association could possibly be explained by the fact that thyroid medications enhance the activation of the mitochondrial function responsible for overproduction of ROS. Levothyroxine is used to treat hypothyroidism (low thyroid hormone). weight gain or loss. The relationship between levothyroxine use and cancer risk is largely underdetermined. A P-value ≤.05 was considered statistically significant. We comply with the HONcode standard for trustworthy health information. Author information: (1)Department of Family Medicine & Supportive Care Center, Samsung Medical Center, Seoul, Republic of Korea. If you use any of the following drugs, avoid taking them within 4 hours before or 4 hours after you take levothyroxine: calcium carbonate (Alka-Mints, Caltrate, Os-Cal, Oyster Shell Calcium, Rolaids Soft Chew, Tums, and others); sodium polystyrene sulfonate (Kalexate, Kayexalate, Kionex); stomach acid reducers - esomeprazole, lansoprazole, omeprazole, rabeprazole, Nexium, Prilosec, Prevacid, Protonix, Zegerid, and others; or. Why, that many of them had to fight for years for a diagnosis, and when they finally got one, couldn't persuade their doctors to treat the symptoms instead of the infallible TSH. Our study has several strengths. I’ve been noticing several articles coming out the past week about a strong association between hypothyroidism and a twice the risk of liver disease and liver cancer, especially in females. J-Shaped Association Between Postoperative Levothyroxine Dosage and Fracture Risk in Thyroid Cancer Patients: A Retrospective Cohort Study. 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. Increased risks of bladder (AOR: 1.32, 95% CI: 1.06-1.65), lung (AOR: 1.30, 95% CI: 1.16-1.45), pancreatic (AOR: 1.30, 95% CI: 1.01-1.68), and esophageal cancers (AOR: 1.23, 95% CI: 0.69-2.2) were also identified in female patients using levothyroxine. Table 1 shows the demographic characteristics of cases and controls. However, we found the associated excess risk of thyroid cancers in men with levothyroxine treatment especially among men below 50 years of age, and thus possible survivors of thyroid cancers from before 1998, and “re-detected” as cancers during our time frame 2009–2015, could not other than marginally explain the excess thyroid cancer risk associated with levothyroxine … Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Effect of not taking medicine after thyroid removal. Available for Android and iOS devices. Many other medicines can be affected by your thyroid hormone levels. Please check your email for instructions on resetting your password. Certain other medicines may also increase or decrease the effects of levothyroxine. If you do not receive an email within 10 minutes, your email address may not be registered, [] found no association between hypothyroidism (i.e. You may need frequent medical tests. Risk for colon cancer appeared to be slightly reduced, but this finding was not statistically significant. antacids that contain aluminum or magnesium - Gaviscon, Maalox, Milk of Magnesia, Mintox, Mylanta, Pepcid Complete, and others. Conclusion The results of the present study are the first to suggest that levothyroxine use increased the risk of breast cancer. Short-term (60-<365 days) and long-term (≥1 year) use of levothyroxine were significantly associated with the overall cancer risk (AOR: 1.46, 95% CI: 1.40-1.53; AOR: 1.52, 95% CI: 1.4-1.59, respectively). The injection is given as an infusion into a vein. symptoms of a heart attack (chest pain or heavy feeling, pain spreading to the jaw or shoulder, nausea, sweating, general ill feeling). Avoid the following food products, which can make your body absorb less levothyroxine: grapefruit juice, infant soy formula, soybean flour, cotton seed meal, walnuts, and high-fiber foods. redness of the face, neck, arms, and occasionally, upper chest. Levothyroxine oral tablet is used to treat hypothyroidism. One case-control study mentioned that levothyroxine might be an effective agent against colorectal cancer,9 while another study found a direct correlation with lung cancer but not with breast, colorectal, or gastric cancer.8 A review article concluded that clinical studies were needed given the limited knowledge and evidence of the causality between levothyroxine and breast cancer risk.37 Studies on the association between levothyroxine use and cancer risk are to date still inadequate. Synthroid, Armour Thyroid, liothyronine, Euthyrox, Levoxyl, Tirosint, Cytomel, NP Thyroid. Other side effects not listed may also occur in some patients. The results indicated that levothyroxine use increased the risk of overall cancer when compared with non–users. However, other studies had dissimilar findings. chest pain, pain spreading to your jaw or shoulder; weakness, tiredness, sleep problems (insomnia); memory problems, feeling depressed or irritable; vomiting, diarrhea, appetite changes, weight changes. Shin DW(1), Suh B(2), Lim H(3), Yun JM(4), Song SO(5), Park Y(6). 1 Levothyroxine doses are based on weight in children. Increased incidence of mostly autoimmune thyroid disease has been associated with breast and other malignancies, and thyroid hormone levels might also be associated with risk of colorectal cancer (CRC). All subjects in the database used in this study were de-identified, and, therefore, the requirement for informed consent was waived. trouble sitting still. In addition, we suggest considering gender-based and appropriate dose-related therapy, so that physicians can provide appropriate drug dosage, efficient treatment, and improved drug safety. Keep using this medicine even if you feel well. Levothyroxine is a synthetic T(4) hormone commonly used to treat thyroid disease. We found that use of levothyroxine was associated with a significant increase in breast cancer risk (OR 1.24, 95% CI 1.15–1.33; P < 0.001). In other words, cases and controls were matched on the index date. Despite clinical benefits of levothyroxine, concern about its overall safety has further been raised because of its connection to cancer risk. Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, Inclusion and exclusion criteria of cases and controls, I have read and accept the Wiley Online Library Terms and Conditions of Use, 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum, Higher risk for thyroid diseases in physicians than in the general population: a Taiwan nationwide population-based secondary analysis study, Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India, Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), The clinical implications of sunitinib-induced hypothyroidism: a prospective evaluation, Management of patients with thyroid disease: oral health considerations, Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition, Levothyroxine and lung cancer in females: the importance of oxidative stress, A case–control study of levothyroxine and the risk of colorectal cancer, A comparative study of the oxidative profile in Graves’ disease, Hashimoto’s thyroiditis, and papillary thyroid cancer, Oxidant/antioxidant balance in patients with thyroid cancer, Statins are associated with a reduced risk of gastric cancer: a population-based case–control study, Risk factors for ectopic pregnancy in the Taiwanese population: a retrospective observational study, The impact of different surgical procedures on hypoparathyroidism after thyroidectomy: a population-based study, Rosiglitazone reduces breast cancer risk in Taiwanese female patients with type 2 diabetes mellitus, Centers for Disease Control and Prevention, International classification of diseases, ninth revision, clinical modification, Compared to what? However, you may not be able to take this medicine if you have certain medical conditions. If your thyroid has been removed (thyroidectomy), your body can no longer make the thyroid hormone it needs. The National Health Insurance covers more than 99% of the 23 million inhabitants of Taiwan, who receive all forms of healthcare services, including outpatients, inpatients care, Chinese traditional medicine, dental care, childbirth, physical therapy, preventive health care, home care, and rehabilitation for chronic mental illness.12-15 This database also contains information regarding patient demographic characteristics (with encrypted patient identification numbers, birthdates, and sex) and inpatient or outpatient data on prescriptions, diagnoses, and pharmacy records. Some studies have found that such association is linked to increased oxidative stress resulting from overproduction of reactive oxygen species (ROS) in the body,10, 11 and oxidative stress is considered the main factor for various chronic conditions such as cancer and autoimmunity. In contrast, decreased risks of esophageal (AOR: 0.80, 95% CI: 0.55-1.17) and cervical (AOR: 0.75, 95% CI: 0.62-0.91) cancers were observed in levothyroxine users. CI, confidence interval; DDD, defined daily dose. We compared cases and controls with regard to the difference in covariate distribution using the McNemar test for categorical variables and paired t-test for continuous variables. 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. restlessness. This study showed that levothyroxine use was associated with a significantly increased risk of overall cancer, as well as brain, skin, prostate, pancreatic, female breast, lung, and colorectal cancers, in levothyroxine users when compared to non–users. All authors declare no conflicts of interest. the risk peaks earlier for women (who are most often in their 40s or 50s when diagnosed) than for men (who are usually in their 60s or 70s). Learn more. Do not give this medicine to a child without medical advice. Taking adequate amounts of levothyroxine keeps TSH low and is demonstrated to reduce the risk of recurrent thyroid cancer. More than 60,000 of the study participants had an underactive thyroid, and more than 80,000 had an overactive thyroid. Swallow the tablet or capsule whole, with a full glass (8 ounces) of water. Eligible cases were defined as all Taiwanese individuals who were ≥20 years with a histologically verified primary cancer diagnosis. Table 5 represents the effects of 3-year average daily dose of levothyroxine use on cancer risk. Doses in this study were standardized by dividing a levothyroxine user’s overall 3-year dose by 0.15 mg, which was the defined daily dose (DDD) of levothyroxine, either for oral or for parenteral use.18 A patient’s 3-year average daily dose (in DDD) was then calculated by dividing the 3-year total number of DDD by 1095 days. Second, our current study showed the high statistical power of the main and the subgroup analyses. This retrospective case-control study was performed using de-identified data of a large cohort of patients retrieved from the Health and Welfare Data Science Center (HWDC) database, Ministry of Health and Welfare, Taiwan. Do not share this medicine with another person, even if they have the same symptoms you have. Last updated on May 4, 2021. Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Not all possible interactions are listed here. Measure liquid medicine carefully. So it's the excess oestrogen - more common than people think - that increases the risk of breast cancer. You will need to take thyroid hormone (levothyroxine) pills to replace the natural hormone and help maintain normal metabolism and possibly lower your risk of the cancer coming back. Increased incidence of mostly autoimmune thyroid disease has been associated with breast and other malignancies, and thyroid hormone levels might also be associated with risk of colorectal cancer … Table 4 shows the effect of cumulative duration of levothyroxine use and cancer risk. Levothyroxine is used to treat hypothyroidism (low thyroid hormone). This medicine is given when your thyroid does not produce enough of this hormone on its own. More relevant studies in diverse populations and countries and meta-analyses are needed to examine the causality of the association and to clarify its mechanism. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Version: 14.02. Generic Name: levothyroxine (oral/injection) (LEE voe thye ROX een) Levothyroxine is a synthetic form of the thyroid hormone thyroxine (T4) that's used to treat an underactive thyroid, known as This study was approved by the Taipei Medical University-Joint Institutional Review Board (TMU-JIRB), Taiwan (TMU JIRB No. A conditional logistic regression model was used to estimate the adjusted odds ratios (AOR) with 95% confidence intervals (CI) for quantifying the magnitude of the association between levothyroxine use and cancer risk. Furthermore, specific data on the medications prescribed, laboratory and diagnostic tests, dates of visits, lengths of hospitalization, and diagnoses are stored based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).16 This study retrieved and analyzed data between 2001 and 2011, which offered a great opportunity to explore the relationship between levothyroxine use and the risk of cancer. To ensure safe and effective treatments, physicians and other healthcare providers should take these findings into consideration while prescribing this medication. Risk of rectal cancer was more than 30% lower in men who used levothyroxine for at least 5 years, relative to the referent group (Table 1). Data sources include IBM Watson Micromedex (updated 3 May 2021), Cerner Multum™ (updated 4 May 2021), ASHP (updated 3 May 2021) and others. 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. A study presented at the 2017 Cancer Survivorship Symposium revealed a long-term cardiovascular risk associated with administration of levothyroxine. unusual tiredness or weakness. Warnings Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Another reason for adapting this approach was that we considered it very unlikely that recent exposure within 3 years would contribute to cancer risk. A total of 1 434 933 cancer patients and approximately 21.6 million non–cancer patients were identified between 2001 and 2011. TSH is the main promoter of thyroid cancer. Levothyroxine should not be used to treat obesity or weight problems. 172-1, Sec. Is angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy protective against prostate cancer? Finally, we analyzed the effect of daily doses on the association during the 3-year study period. Thyroid disease is a major public health concern worldwide.1 The number of individuals with thyroid disorders is expected to continue to grow, having reached approximately 750 million globally in 2012.2 Hypothyroidism is the most common type of thyroid disorder, and women’s risk of hypothyroidism is five to eight times higher than that of men.3 In the USA, the prevalence of biochemical and clinically evident hypothyroidism is 4.6% and 0.3%, but this can vary considerably by age.4 Levothyroxine is a first-line treatment for the hypothyroidism. Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Two biological studies reported a potential consequence of excessive oxidative stress; they showed a possible biological pathway connecting impairment or destruction of DNA activity due to oxidative stress. Certain side effects may be more likely in older adults. Several epidemiological studies have attempted to assess the magnitude of the association between levothyroxine use and cancer risk, but their findings have been inconclusive. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. The risk of cancer incidence varied depending on the type of cancer studied. Online Version of Record before inclusion in an issue. Medications in the HWDC database were coded according to the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification system.18 Levothyroxine was defined as a prescribed medication with the ATC code H03AA01. It is well known that overt hypothyroidism has negative effects on the heart function that improve with levothyroxine treatment. Select one or more newsletters to continue. Compared with no use levothyroxine, the adjusted odd ratio was 1.22 (95% CI 1.11-1.35; P = 0.01) for the group having been prescribed levothyroxine 2 months to 1 year, and 1.26 (95% CI 1.12-1.41; P < 0.01) for the group with more than 1 year. If you notice any other effects, check with your healthcare professional. In conclusions, levothyroxine treatment was associated with an excess cancer risk, including many different types of cancer, especially among women. This approach has immense benefits to the drug prevalence among cases and can, therefore, avoid reverse causation bias (ie a spurious association between levothyroxine use and cancer risk).
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