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

Abstract

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. Video Summary: http://links.lww.com/MENO/A783.

Understanding the female athlete: molecular mechanisms underpinning menstrual phase differences in exercise metabolism

“…plasma free T3 concentration was found to be higher coincident to a greater leucine oxidation rate in the ML versus EF phase in one study (Lariviere et al 1994). P4 binds PR within the thyroid gland to promote T3/thyroxine (T4) secretion and reduce its binding to the plasma protein, thyroid-binding globulin to maximise free T3 availability (Torre et al 2020;Kaminski et al 2021) thereby accounting for the higher resting metabolic rate (Benton et al 2020) and thus possibly protein catabolism reported in the luteal phase compared with follicular phase.…”

Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study

“…It modulates the synthesis of TSH in the pituitary gland [24,25]. Estrogen can also impact the levels of thyroid-binding proteins in the bloodstream, which, in turn, affects the transport and availability of thyroid hormones for cellular uptake and metabolism [26]. Moreover, elevated estrogen levels have been positively associated with developing autoimmune thyroid disorders, such as Hashimoto's thyroiditis [25].…”

Effects of the Menstrual Cycle and Hormonal Contraceptive Use on Metabolic Outcomes, Strength Performance, and Recovery: A Narrative Review

“…In addition to the impact of female sex hormones on substrate utilization, estrogen and progesterone also impact resting energy expenditure. Recent works demonstrate estrogen can increase the pituitary gland to secrete key hormones that regulate the metabolic rate, such as thyroid hormones and growth hormone [42,43]. At rest, EUM females exhibit heightened fat oxidation, as indicated by a decreased respiratory exchange ratio, and a 2.5-11.5% higher resting energy expenditure during the LP of the menstrual cycle when ovarian hormones peak [44,45].…”