MVIIIHealth The MVIII app
← Back

Research · Medication

Levothyroxine

In adults with subclinical hypothyroidism, levothyroxine brought TSH into range but did not change quality of life or thyroid symptoms in a meta-analysis of 21 trials. Restoring normal thyroid levels lowered weight 1 to 2 kg in overt hypothyroidism, not in subclinical. Trials in obesity showed no consistent weight effect. Over-replacement was linked to more heart rhythm problems and fractures.

Add to Bio HackChecked 2026-11-09
Status
Prescription drug in the US, FDA-approved to treat hypothyroidism and to suppress TSH in some thyroid cancers. The label carries a boxed warning that it is not for the treatment of obesity or for weight loss.
Also called
Synthroid, Levoxyl, Unithroid, Tirosint, Euthyrox, L-thyroxine, T4, thyroid hormone
Taken for
low thyroid, subclinical hypothyroidism, tiredness, energy, metabolism, weight loss, pregnancy

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help1

Reported risks4

What people take it for, and what was found

Shown to help1

Strong

Weight change when treating hypothyroidism

Shown to lower weight about 1.4 to 2.2 kg after treating hypothyroidism, in overt cases only. Weight did not change in subclinical hypothyroidism.

The numbers and sources
Effect
Across 23 studies, weight changed by -1.39 kg (95% CI -2.56 to -0.23) after levothyroxine restored normal thyroid levels. BMI changed by -0.39 kg/m², fat mass by -0.75 kg and lean mass by -0.95 kg. Weight and BMI fell in overt hypothyroidism but not in subclinical hypothyroidism, where lean mass fell [3]. Across 35 studies, weight fell 2.15 kg in overt hypothyroidism, mostly in the first 3 months, with no change in fat mass and a small fall in lean mass. In subclinical hypothyroidism, BMI, weight, fat mass and lean mass did not change [4].
Population
763 adults with hypothyroidism [3]; 1,116 adults, 672 with overt and 444 with subclinical hypothyroidism [4].
Sources
[3], [4]
Caveats
Both reviews pooled measurements taken before and after treatment, without an untreated comparison group. They disagree on fat mass [3][4].

Mixed results1

Moderate

Pregnancy outcomes with subclinical hypothyroidism or thyroid antibodies

Mixed results: fewer preterm and low birth weight births in one review, lower miscarriage in women with thyroid antibodies, and no difference in an NIH trial.

The numbers and sources
Effect
In randomized trials of women with subclinical hypothyroidism in pregnancy, levothyroxine was associated with less preterm birth (RR 0.56, 95% CI 0.41 to 0.77) and fewer low birth weight infants (RR 0.56, 95% CI 0.35 to 0.89). Small for gestational age and macrosomia did not differ [5]. In euthyroid pregnant women with thyroid peroxidase antibodies, miscarriage was lower (RR 0.78, 95% CI 0.63 to 0.98), while preterm birth (RR 0.78, 95% CI 0.55 to 1.13) and live birth (RR 1.05, 95% CI 0.99 to 1.12) did not differ [6]. In subclinical hypothyroidism, gestational hypertension (OR 1.03, 95% CI 0.85 to 1.25) and pre-eclampsia (OR 1.02, 95% CI 0.66 to 1.58) did not differ from controls [7].
Population
30 RCTs and cohort studies with 18,568 pregnant women with subclinical hypothyroidism [5]; 8 RCTs with 1,645 women [6]; trials and observational studies in pregnant women with subclinical or overt hypothyroidism or thyroid autoimmunity [7].
Sources
[5], [6], [7]
Caveats
[5] pooled RCTs with cohort studies, and the figures above are its RCT estimates. Preterm birth fell in [5] but not in [6], which studied a different group. The NIH trial of treatment from mid-pregnancy found no difference in pregnancy outcomes [8].

Not shown to help3

Strong

Symptoms and quality of life in subclinical hypothyroidism

Not shown to improve quality of life or thyroid symptoms in adults with subclinical hypothyroidism, including those 65 or older, though it brought TSH into range.

The numbers and sources
Effect
Thyroid hormone lowered mean TSH into the reference range (0.5 to 3.7 mIU/L against 4.6 to 14.7 on placebo) but did not change general quality of life (SMD -0.11, 95% CI -0.25 to 0.03) or thyroid-related symptoms (SMD 0.01, 95% CI -0.12 to 0.14) [1]. In adults aged 65 or older, the change in Hypothyroid Symptoms score at 1 year was 0.2 on both levothyroxine and placebo (difference 0.0, 95% CI -2.0 to 2.1). Tiredness scores did not differ (difference 0.4, 95% CI -2.1 to 2.9), and no secondary outcome improved [2].
Population
21 RCTs with 2,192 nonpregnant adults, 3 to 18 months [1]; 737 adults with mean age 74.4 and TSH 4.60 to 19.99 mIU/L [2].
Sources
[1], [2]
Caveats
Most participants had mildly raised TSH. [1] rated the evidence moderate to high quality. [2] was funded by the European Union FP7 and others.
Limited

Child IQ when treated in pregnancy

One trial found no difference in child IQ at 5 years when women with subclinical hypothyroidism or low free T4 were treated from mid-pregnancy.

The numbers and sources
Effect
Children of women treated for subclinical hypothyroidism had a median IQ of 97 against 94 on placebo (P = 0.71). In a parallel trial for low free T4, median IQ was 94 against 91 (P = 0.30). No other neurocognitive or pregnancy outcome differed [8].
Population
677 women with subclinical hypothyroidism and 526 with low free T4, starting at a mean 16.7 to 17.8 weeks of pregnancy, with children followed for 5 years [8].
Sources
[8]
Caveats
One trial. Treatment started at 8 to 20 weeks, so it does not describe treatment from conception. Funded by the National Institutes of Health [8].
Limited

Weight loss in obesity

Limited evidence: small studies could not establish a consistent effect of T3 or T4 on weight loss in obesity, and the therapy induced subclinical hyperthyroidism.

The numbers and sources
Effect
During calorie restriction in people with obesity, T3 lowered TSH and T4, but consistent effects of T3 or T4 on weight loss, protein breakdown, metabolic rate or heart rate could not be established. The review found the therapy induced subclinical hyperthyroidism [9].
Population
RCTs and prospective controlled studies of T3 or T4 in obesity [9].
Sources
[9]
Caveats
Few small studies of poor quality, with variable endpoints [9].

Doses studied

The trial in older adults reached a median dose of 50 µg a day [2]. The pregnancy trials adjusted levothyroxine to a normal TSH or free T4, against placebo with sham adjustment [8].

Risks

Reported risks4

LimitedHow often is not known

Toxicity at weight-loss doses (boxed warning)

The label warns thyroid hormones are not for weight loss, and doses beyond daily needs may produce serious or even life-threatening toxicity.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label's boxed warning states that thyroid hormones are not for obesity or weight loss, and that doses beyond daily hormonal needs may produce serious or even life-threatening toxicity. Adverse reactions are listed as those of hyperthyroidism from overdose, including arrhythmias, heart attack, tremor, insomnia, muscle weakness and heat intolerance [10]. In obesity studies, thyroid hormone therapy induced subclinical hyperthyroidism [9].
Population
Label [10]; obesity studies [9].
Sources
[10], [9]
Caveats
Label statements, not trial rates.
ModerateHow often is not known

Heart rhythm problems and cardiovascular disease with over- or under-replacement

Linked to more cardiovascular disease and heart rhythm problems in people on levothyroxine whose TSH was suppressed or high, not when TSH was low but unsuppressed.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against people on levothyroxine with TSH in the reference range, those with a suppressed TSH (0.03 mU/L or lower) had more cardiovascular disease (HR 1.37), dysrhythmias (HR 1.6) and fractures (HR 2.02). Those with a high TSH also had more of all three. Those with a low but unsuppressed TSH (0.04 to 0.4) had no increase [11]. The label warns of cardiac reactions, including atrial fibrillation, in older people and people with heart disease [10]. A systematic review found that cardiac, neuropsychiatric and muscle adverse events at replacement doses mostly did not differ from comparators. They occurred mainly when TSH was suppressed, and blinded placebo-controlled trials in people with normal thyroid levels showed no differences [12].
Population
17,684 people on long-term levothyroxine in Tayside, Scotland [11]; 12 studies with 1,817 people, 7 of them RCTs [12].
Sources
[11], [10], [12]
Caveats
Observational. In TRUST, serious adverse events of special interest were not raised at the doses used [2].
ModerateHow often is not known

Fractures and bone loss

Linked to more fractures in adults 70 or older, rising with dose, and in people on levothyroxine whose TSH was suppressed.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In adults aged 70 or older, current levothyroxine use was associated with fracture (adjusted OR 1.88, 95% CI 1.71 to 2.05) against remote use. Against low cumulative doses (under 0.044 mg a day), medium doses had an OR of 2.62 and high doses (over 0.093 mg a day) 3.45 [13]. A suppressed TSH was associated with fracture (HR 2.02) [11]. The label states over-replacement can increase bone resorption and decrease bone mineral density [10]. In a meta-analysis, people with overt hypothyroidism on levothyroxine had lower lumbar spine bone density than healthy controls (SMD -0.28, 95% CI -0.55 to -0.02). Hip sites did not differ, and no difference was found in subclinical hypothyroidism [14].
Population
213,511 levothyroxine users aged 70 or older in Ontario, 22,236 with a fracture over a mean 3.8 years [13]; 17,684 people in Scotland [11]; 13 studies [14].
Sources
[13], [11], [10], [14]
Caveats
[13] and [11] are observational. [14] compared treated patients with healthy people, not with untreated patients. The dose relation in [13] may partly reflect who receives higher doses.
LimitedHow often is not known

Acute overdose

Case reports: overdoses brought fast heart rate, confusion or fever, with one death. In larger studies over 90% had minimal or no symptoms.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In 95 published overdose cases, the median dose taken was 4,250 µg. Tachycardia occurred in 38.9%, confusion in 23.2%, fever in 18.9% and atrial fibrillation in 5.3%, and one death was reported. In larger retrospective studies, more than 90% had minimal or no symptoms, particularly children. Coma and heart failure occurred rarely, in adults after high doses [16].
Population
95 case reports and 6 retrospective studies with 11,513 patients [16].
Sources
[16]
Caveats
Case reports cannot give a rate, and severe cases are more likely to be published.

Checked, no increase found1

LimitedStudied in women

Breast cancer

Limited evidence: case-control studies found no statistically significant link to breast cancer, and certainty was rated low.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In 4 case-control studies, thyroid hormone treatment had an odds ratio for breast cancer of 1.43 (95% CI 0.90 to 2.28), which was not statistically significant. Heterogeneity was high (I² 94.3%), and the authors rated certainty low [15].
Population
221,254 women on thyroid hormone and 4,385,666 controls [15].
Sources
[15]
Caveats
Observational studies with substantial heterogeneity and possible confounding [15].

Claims tested and not found

  1. That levothyroxine relieves tiredness in mild hypothyroidism. In older adults with subclinical hypothyroidism, tiredness scores at 1 year did not differ from placebo [2], and pooled trials found no change in thyroid-related symptoms [1].

Sources

  1. Feller M, Snel M, Moutzouri E, et al. Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism. JAMA. 2018. https://doi.org/10.1001/jama.2018.13770
  2. Stott DJ, Rodondi N, Kearney PM, et al. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. New England Journal of Medicine. 2017. https://doi.org/10.1056/NEJMoa1603825
  3. Wolde Sellasie S, Ossola N, Piticchio T, et al. Levothyroxine therapy for euthyroidism restoration results in clinically insignificant weight and anthropometric changes: a systematic review and meta-analysis. International Journal of Obesity. 2026. https://doi.org/10.1038/s41366-026-02224-x
  4. Kretli-Souza D, Meireles-Oliveira G, Asevedo RA, et al. Levothyroxine monotherapy has limited effects on body composition in clinical and subclinical hypothyroidism: a systematic review and meta-analysis. Reviews in Endocrine and Metabolic Disorders. 2026. https://doi.org/10.1007/s11154-026-10093-y
  5. You Z, Zhang Y, Liu S, et al. Meta-analysis of the effects of levothyroxine therapy for subclinical hypothyroidism during pregnancy on offspring outcomes. Frontiers in Pediatrics. 2025. https://doi.org/10.3389/fped.2025.1530859
  6. Provinciatto H, Barbalho ME, da Câmara PM, et al. Levothyroxine in euthyroid pregnant women with thyroid peroxidase antibody: a systematic review and meta-analysis of randomized controlled trials. Revista Brasileira de Ginecologia e Obstetrícia. 2025. https://doi.org/10.61622/rbgo/2025rbgo75
  7. Goodarzi-Khoigani M, Aminorroaya A, Mohammadi R. Effect of Levothyroxine Therapy on Gestational Hypertension and Pre-eclampsia in Pregnant Women with Subclinical Hypothyroidism, Hypothyroidism, and Thyroid Autoimmunity: A Systematic Review and Meta-analysis. Cardiovascular & Hematological Disorders Drug Targets. 2025. https://doi.org/10.2174/011871529x324722250207072454
  8. Casey BM, Thom EA, Peaceman AM, et al. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. New England Journal of Medicine. 2017. https://doi.org/10.1056/NEJMoa1606205
  9. Kaptein EM, Beale E, Chan LS. Thyroid Hormone Therapy for Obesity and Nonthyroidal Illnesses: A Systematic Review. The Journal of Clinical Endocrinology & Metabolism. 2009. https://doi.org/10.1210/jc.2009-0899
  10. U.S. Food and Drug Administration. SYNTHROID (levothyroxine sodium) tablets, prescribing information. Revised 2024. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e11ad30-1041-4520-10b0-8f9d30d30fcc
  11. Flynn RW, Bonellie SR, Jung RT, et al. Serum Thyroid-Stimulating Hormone Concentration and Morbidity from Cardiovascular Disease and Fractures in Patients on Long-Term Thyroxine Therapy. The Journal of Clinical Endocrinology & Metabolism. 2010. https://doi.org/10.1210/jc.2009-1625
  12. Baskaran BS, Omrani MA, Muanda FT. Risk of cardiac, neuropsychiatric and musculoskeletal adverse events with levothyroxine: Systematic review. British Journal of Clinical Pharmacology. 2026. https://doi.org/10.1002/bcp.70455
  13. Turner MR, Camacho X, Fischer HD, et al. Levothyroxine dose and risk of fractures in older adults: nested case-control study. BMJ. 2011. https://doi.org/10.1136/bmj.d2238
  14. Li X, Zhang T, Zhang H, et al. Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis. BMC Endocrine Disorders. 2025. https://doi.org/10.1186/s12902-024-01819-7
  15. Kopanos S, Feldkamp JD, Tyssen J, et al. Thyroid Hormone Treatment and Breast Cancer Risk in Women: A Systematic Review and Meta-Analysis of Observational Studies. Metabolites. 2026. https://doi.org/10.3390/metabo16070465
  16. Ata F, Khan HA, Kashif A, et al. Clinical insights into levothyroxine overdose: A systematic review. World Journal of Methodology. 2026. https://doi.org/10.5662/wjm.v16.i2.111025

Everything in the library