Sex and Age Differences in Levothyroxine Dosage Requirement
Abstract
Objective To examine the performance of weight-based formulae for estimating the levothyroxine dosage requirement in athyreotic patients and to determine whether formula performance is affected by age, sex, or menstrual status.Methods In this prospective study, euthyroid study participants aged 18 to 65 years were followed up after total thyroidectomy at 4 time points: 6-8 weeks, 12-16 weeks, 6 months, and 1 year. Patient weight, serum thyrotropin concentration, and levothyroxine dosage required were recorded at each time point. The postoperative starting levothyroxine dosage was 1.7 mcg/kg daily for patients with benign thyroid disease and 2.2 mcg/kg daily for patients with thyroid cancer. Actual body weight was used to calculate the initial dosage. At steady state, adjustments were made in each patient's levothyroxine dosage until the target thyrotropin concentration was reached. The levothyroxine dosage required to achieve this goal was documented.Results Fifty patients were included (37 women, 13 men). Formulae based on actual body weight were accurate in achieving a normal thyrotropin concentration in 48% to 75% of participants. Final dosages to achieve normal thyrotropin values were similar in men (1.43 mcg/kg daily) and menopausal women (1.68 mcg/kg daily), but higher in premenopausal women (2.10 mcg/kg daily). When a formula based on ideal body weight was used, the requirement for menopausal women (2.34 mcg/kg daily) was similar to that of premenopausal women (2.44 mcg/kg daily), but the requirement for men (1.73 mcg/kg daily) remained lower than that observed in both female groups.Conclusions When actual body weight was used to calculate levothyroxine dosage requirement, premenopausal women appeared to have a greater requirement than either menopausal women or men. When ideal weight was used, the requirement of all women was greater than that of men. Perhaps with formulae using actual weight, this apparent sex difference is masked by the greater weight, older age, or altered hormonal milieu of menopausal women.
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LT4 replacement doses tend to decrease with age when they are titrated based on serum TSH.
“LT4 replacement doses tend to decrease with age when they are titrated based on serum TSH (213,215,216,219,220).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [215]
Hypothyroid patients with minimal endogenous thyroid function require LT4 doses of 1.6-1.8 μg/kg actual body weight.
“Based on body weight, hypothyroid patients with minimal endogenous thyroid function require LT4 doses of 1.6-1.8 l g/kg of actual body weight (38,47,212,213,215-217,226,227), although some studies estimate higher doses of 2.0-2.1 l g/kg for some patient groups (212,213,226).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [215]
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 [215]
Thyroid cancer patients requiring TSH suppression generally require LT4 doses of 2.1-2.7 μg/kg.
“LT4 doses in thyroid cancer patients requiring TSH suppression are generally higher and on the order of 2.1-2.7 l g/kg (38,212,215).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [215]
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 [215]
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- Authors
- Jonklaas, J.
- Affiliations
- Georgetown University Medical Center (US)
- Corresponding author
- Jonklaas, Jacqueline
- ORCID
- Jonklaas, Jacqueline
- Venue
- Endocrine Practice
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 16
- Issue
- 1
- Pages
- 71-79
- ISSN
- 1530-891X (ISSN-L)
- OpenAlex
- W2024081395
- Cited by
- 72
- References
- 36
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 1 · 2019: 7 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 4 · 2012: 3
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Practice (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (M01RR023942, K23RR016524)
- 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 › Thyroid Cancer Diagnosis and Treatment
- Keywords
- levothyroxine dosage, sex differences, age differences, menstrual status, menopause, premenopausal women, ideal body weight, actual body weight, total thyroidectomy, thyroid cancer, thyroid-stimulating hormone, euthyroid patients, thyroid hormone replacement
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Body Weight, Female, Humans, Male, Middle Aged, Retrospective Studies, Sex Factors, Thyroid Diseases, Thyroid Neoplasms, Thyroidectomy, Thyrotropin, Thyroxine, Young Adult
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