Effects of Long-Term Use of Raloxifene, a Selective Estrogen Receptor Modulator, on Thyroid Function Test Profiles

Abstract

Estrogen (1)(2)(3)(4)(5) may increase hepatic production of thyroxine-binding globulin (TBG) and decrease TBG clearance (6), thus increasing serum total thyroxine (tT4) (3)(4) and, to a lesser extent, total triiodothyronine (tT3) (3)(4). As a result, increased tT4 and tT3 are seen in states of excessive estrogen and/or progestin, such as pregnancy, estrogen replacement therapy (HRT) (5), and oral contraceptive usage (1). This phenomenon may cause problems in clinical diagnoses when tT4 or tT3 is used for these patients. On the other hand, estrogen has been shown to increase thyroid-stimulating hormone (TSH) and to decrease free thyroxine (fT4) through a mild inhibitory effect on the thyroid gland (4). Compound that are analogs of estrogens, such as tamoxifen, have been shown to increase TSH without decreasing fT4 (7)(8). Recently, a new category of therapeutic agents, collectively termed selective estrogen receptor modulators (SERMs), has been developed to treat patients with postmenopausal osteoporosis (9). Raloxifene …