Effects of oral versus transdermal estradiol plus micronized progesterone on thyroid hormones, hepatic proteins, lipids, and quality of life in menopausal women with hypothyroidism: a clinical trial

Objective: The aim of the study was to evaluate the effects of usual doses of oral estradiol with transdermal estradiol and the effects of these estrogens plus micronized progesterone (MP) in menopausal women with primary hypothyroidism.

Methods: Twenty women were randomized to 12 weeks of treatment with estradiol 1 mg tablets or estradiol 1 mg gel. Then, women with a uterus received a 100 mg capsule of oral MP. Thyroid function, thyroxine-binding globulin (TBG), sex hormone-binding globulin (SHBG), insulin-like growth factor 1 (IGF-1), lipid profiles, and quality of life were measured at baseline and after 12 and 24 weeks.

Results: Oral estradiol led to an increase in total T4 levels (5.84 ± 1.11 vs 8.41 ± 1.61 μg/dL; P < 0.001); changes in thyroid-stimulating hormone (TSH) levels were clinically important in 3 of 10 participants who needed to increase their dose of levothyroxine. Significant changes were detected in hepatic proteins with oral estradiol: TBG and SHBG levels increased (15.29 ± 3.87 vs 20.84 ± 5.49 μg/mL, P < 0.001; 61.85 ± 33.6 vs 121.4 ± 49.36 nmol/L, P < 0.001; respectively), whereas IGF-1 levels decreased (152 ± 38.91 vs 96 ± 17.59 ng/mL; P < 0.001). Transdermal estradiol alone did not significantly affect the thyroid function. Transdermal estradiol plus MP led to a decrease in TSH levels (1.79 ± 1.05 vs 1.09 ± 0.52 mIU/L; P = 0.04), while total T4 levels increased (7.54 ± 1.34 vs 9.95 ± 2.24 μg/dL; P = 0.01). Hormonal therapy had a greater impact on depressed mood and vasomotor symptoms.

Conclusions: Total T4 and TBG levels increase after oral estradiol in women with hypothyroidism and it may cause clinical changes in TSH levels. Conversely, transdermal estradiol alone or plus MP does not cause major changes in thyroid function in these women.