Effect of Estrogen Replacement Therapy upon Bone Mineral Density in Thyroxine-Treated Postmenopausal Women with a Past History of Thyrotoxicosis

Abstract

We have shown that previous thyrotoxicosis and subsequent levothyroxine (L-T4) therapy are together associated with reduction in femoral and lumbar vertebral bone mineral density (BMD) in postmenopausal women. To determine whether estrogen replacement therapy exerts a beneficial effect upon bone loss in this situation, we performed a cross-sectional study comparing BMD measurements of the femur and lumbar spine in four groups of women (n = 15 in each group) matched for age and duration of menopause: (i) those with a previous history of thyrotoxicosis who were subsequently receiving both L-T4 and estrogen replacement therapy for at least 3 years (L-T4 + HRT group), (ii) previously thyrotoxic women matched to group (i) for L- dose and duration who had never used estrogen replacement (L-T4 alone group), (iii) those with no history of thyroid disease who had received estrogen replacement therapy for at least 3 years (HRT alone group), and (iv) those with no history of thyroid disease who had never received estrogen replacement therapy (control group). BMD measurements were higher at each site in the HRT alone group than in controls (6.0-13.6% increases in BMD, p < 0.05 for measurements at femoral neck, Ward's triangle, and trochanter) while measurements of BMD were lower at each site in the L-T4 alone group than in controls (3.3-6.1% reductions in BMD), although values did not reach statistical significance. Measurements at each site in the L-T4 + HRT group were higher than those from the L-T4 alone group (2.2-16.1% increases in BMD, p < 0.05 for measurements at lumbar spine), although lower than in the group receiving HRT alone (p < 0.05 for femoral neck and Ward's triangle) and similar to those in untreated controls. Our results indicate that estrogen replacement therapy abolishes reduction in femoral and vertebral BMD in postmenopausal women with previous thyrotoxicosis and subsequent L-T4 therapy. This potentially beneficial influence of estrogen replacement upon both BMD and fracture risk in postmenopausal women with a history of thyroid disease suggests that estrogen administration should be encouraged in this group.