Lack of Substantial Effects of Raloxifene on Thyroxine-Binding Globulin in Postmenopausal Women: Dependency on Thyroid Status
Abstract
Long-term estrogen therapy can modify thyroid hormone kinetics by increasing serum concentration of thyroxine-binding globulin (TBG). Raloxifene is a recently developed selective estrogen receptor modulator (SERM) for the treatment of osteoporosis, which possesses estrogenic and antiestrogenic properties. In a prospective and randomized study, we investigated the effects of raloxifene on TBG levels and on the serum concentrations of free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) in controls and in patients receiving TSH-suppressive doses of levothyroxine (LT4). Twenty-nine postmenopausal osteopenic (n = 14) and osteoporotic (n = 15) women were investigated over a period of 6 months. Group 1 (n = 15) included control patients and group 2 (n = 14) patients receiving TSH-suppressive dose of LT4. All patients were treated with raloxifene hydrochloride, 60 mg/d, for a period of 6 months. Serum basal TBG values were found higher in Group 1 compared to Group 2 (26.2 2 microg/mL vs. 21.4 2.1 microg/ml; p < 0.01). The TBG levels raised slightly in group 1 from 26.2 2 microg/mL to 28.6 3.1 microg/mL; p < 0.05 (in group 2 from 21.4 2.1 microg/mL to 22.2 2.3 microg/mL, not significant) after 3 months of treatment and failed to show any further significant change until the end of the study. Serum concentrations of T4, FT4, T3, and TSH levels changed insignificantly in both groups up to the completion of the study. Moreover, patients remained clinically euthyroid. Our findings may provide evidence that TBG levels, and consequently, thyroid function are not substantially affected by treatment with raloxifene. Additionally, TBG levels may also be influenced by small variations of thyroid function as subclinical hyperthyroidism.
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Estrogen, tamoxifen, raloxifene, clofibrate, opioids, mitotane, fluorouracil, and capecitabine increase serum TBG.
“Examples of drugs that increase serum TBG from insignificant to significant degrees, include estrogen (201), tamoxifen (202), raloxifene (203), clofibrate (204), opioids (205), mitotane (206), fluorouracil (207), and capecitabine (208).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [203]
With the exception of estrogen, drugs that increase TBG have either not been associated with altered TSH or were shown in case reports only.
“With the exception of estrogen, these drugs have either not been associated with an altered TSH (202-207), or were shown in case reports only (208).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [203]
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Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928 · see citing works
“Examples of drugs that increase serum TBG from insignificant to significant degrees, include estrogen (201), tamoxifen (202), raloxifene (203), clofibrate (204), opioids (205), mitotane (206), fluorouracil (207), and capecitabine (208).”
- Authors
- Duntas, L. H., Mantzou, E., & Koutras, D. A.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- ORCID
- Duntas, Leonidas H.
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2001-08
- Volume
- 11
- Issue
- 8
- Pages
- 779-782
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2105292969
- Cited by
- 14
- References
- 19
- Citations by year
- 2021: 1 · 2020: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- raloxifene, thyroxine-binding globulin, selective estrogen receptor modulators, postmenopausal women, osteoporosis, levothyroxine, thyroid function, free thyroxine, triiodothyronine, thyroid-stimulating hormone, subclinical hyperthyroidism, estrogen therapy
- MeSH terms
- Aged, Bone Diseases, Metabolic, Dose-Response Relationship, Drug, Female, Humans, Kinetics, Middle Aged, Prospective Studies, Reference Values, Thyroid Gland, Thyrotropin, Thyroxine, Thyroxine-Binding Proteins, Triiodothyronine, Osteoporosis, Postmenopausal, Postmenopause, Selective Estrogen Receptor Modulators, Raloxifene Hydrochloride
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