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Cited by 90Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryHormonal and reproductive studies

Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age

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Devdhar, Madhuri, Drooger, Rebecca, Pehlivanova, Marieta, Singh, Gurdeep, Jonklaas, Jacqueline·2011·Thyroid
DOI 10.1089/thy.2011.0029PMC PMC3148125
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Abstract

BACKGROUND: Body weight (BW) and age have been shown to affect the dose of levothyroxine (LT(4)) that results in normalization of serum thyroid-stimulating hormone (TSH) in hypothyroid patients. Our objective was to determine whether gender, menstrual status, and ideal BW (IBW) also affect the LT(4) dose required to achieve a serum TSH within the normal range. METHODS: We retrospectively reviewed the charts of patients being treated for primary hypothyroidism who had TSH values within a normal range. We selected patients aged 18-85 years who were taking LT(4) without any confounding medications, and who had no serious chronic conditions. Their LT(4) doses, referred to here as LT(4) dose requirements, based on both BW and IBW were documented. The relationship between gender, menstrual status, age, serum TSH concentrations, and the degree of overweight on LT(4) dose requirements were determined using multivariate analyses. RESULTS: Women were significantly more overweight than men (ratio of BW/IBW was 1.35 for women vs. 1.17 for men, p <0.0001). LT(4) requirements based on BW did not differ by gender when age was included in the model. However, when degree of overweight was also included, men required lower LT(4) doses than both premenopausal women (1.34 μg/kg vs. 1.51 μg/kg, p = 0.038) and menopausal women (1.34 μg/kg vs. 1.49 μg/kg, p = 0.023). When examining IBW using a model incorporating age, men also required lower LT(4) doses than both premenopausal women (1.64 μg/kg vs. 1.92 μg/kg, p = 0.0033) and menopausal women (1.64 μg/kg vs. 1.90 μg/kg, p = 0.0024). Serum TSH concentrations were not significantly different in any of the gender groups. There was no relationship between serum TSH and either age or BW. The initial serum TSH concentration was by design with the normal range, but the concentration within that range was not a significant predictor of the LT(4) replacement dose in any of the models. CONCLUSION: In contrast to previous studies suggesting that age affects LT(4) replacement requirements, we found that age-based differences in doses are secondary to differences in BW and gender. In addition, in contrast to prior studies showing that lean body mass, but not gender, affected LT(4) dose, we instead found a significant impact of gender. Gender-based differences in dose requirement only became apparent either when IBW was used to correct for the dose or when degree of overweight was included in the model. Gender differences in LT(4) dose requirement exist, but are masked unless gender-based differences in degree of overweight are also considered.

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  • Ideal body weight is a better predictor of LT4 dose than actual body weight, suggesting LT4 dose requirement may depend on lean body mass.

    “Two studies have shown that ideal body weight is a better predictor of LT 4 dose than actual body weight (214,225), thus suggesting that LT4 dose requirement may depend on lean body mass.”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [214]

    The Discussion (page unavailable) concludes that LT4 dose is primarily driven by ideal body weight and suggests a role for the lean body compartment. The Introduction attributes the specific finding that ideal body weight is a better predictor than actual body weight to Santini et al.; this paper does not itself establish that direct comparison, although the citing sentence presents it as one of two studies that did. (LLM, conf=0.82)

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  • Most studies examining factors affecting LT4 dose were retrospective chart reviews, but some were prospective.

    “Most studies examining this issue were retrospective chart reviews (47,212-224), but some studies were prospective (38,225-229).”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [214]

  • Studies examining the effect of sex, menopausal status, and the DIO2 Thr92Ala polymorphism on LT4 dose requirement have produced inconsistent findings.

    “In contrast to consistency of the findings reported in the above studies, studies examining the effect of sex (214,215, 221), menopausal status (214,215,221), and the presence of the type 2 deiodinase gene ( DIO2 ) Thr92Ala polymorphism (222,224) have produced inconsistent findings.”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [214]

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Authors
Devdhar, M., Drooger, R., Pehlivanova, M., Singh, G., & Jonklaas, J.
Affiliations
  • Georgetown University Medical Center (US)
  • MedStar Health Research Institute (US)
Corresponding author
Jonklaas, Jacqueline
ORCID
Venue
Thyroid
Publisher
SAGE Publications
Published
2011-08
Volume
21
Issue
8
Pages
821-827
ISSN
  • 1050-7256 (ISSN-L)
  • 1557-9077
DOI
10.1089/thy.2011.0029
PMC
PMC3148125
OpenAlex
W1967592306
Cited by
90
References
34
Citations by year
2026: 4 · 2025: 10 · 2024: 7 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 8 · 2012: 7
FWCI
6.56
Type
journal article
Language
en
Open access
Licence
www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations
  • Thyroid (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Georgetown University
  • National Institutes of Health
  • National Center for Research Resources (UL1RR031975)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
levothyroxine, hypothyroidism, body weight, ideal body weight, sex differences, menstrual status, menopause, age, serum TSH, dose normalization, overweight, body weight ratio
MeSH terms
Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Body Weight, Female, Humans, Hypothyroidism, Male, Middle Aged, Retrospective Studies, Sex Factors, Thyrotropin, Thyroxine

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