Statin Use and Benefits of Thyroid Function: A Retrospective Cohort Study

Abstract

PurposePrevious studies have suggested that cholesterol may influence thyroid function. Since statins are widely used for their cholesterol-lowering effect, we aimed to assess the association between statin use and thyroid function, and also to explore the role of the cholesterol-lowering effect in it.MethodsWe performed a retrospective cohort study derived from REACTION study. Eligible subjects receiving statin therapy were included in the statin group, and sex-, age-, total cholesterol (TC)-, and thyroid function-matched participants without lipid-lowering therapy were included in the control group. The median follow-up time was three years. Outcomes of thyroid function were evaluated at the end of follow-up. We used multivariable regression models to assess the association between statin use and outcomes of thyroid function, and also performed mediation analyses to explore the role of cholesterol in it.ResultsA total of 5,146 participants were screened, and 201 eligible subjects in the statin group and 201 well-matched subjects in the control group were analyzed. At the end of follow-up, TC and thyroid-stimulating hormone (TSH) levels in the statin group were lower than those in the control group (both p < 0.05), and the percentage of euthyroid subjects was higher in the statin group (88.06% vs. 76.12%, p = 0.002). The incidence rate of subclinical hypothyroidism (SCH) in euthyroid subjects was lower in the statin group (6.29% vs. 14.86%, p = 0.009), and the remission rate among subjects with SCH was higher in the statin group (50.00% vs. 15.38%, p = 0.008). In multivariable regression analyses, statin use was independently associated with lower TSH levels and higher odds to be euthyroid (OR 2.335, p = 0.004) at the end of follow-up. Mediation analyses showed the association between statin use and TSH levels were mediated by TC changes during follow-up.ConclusionStatin use was associated with benefits of thyroid function, and TC changes serve as a mediator of the association between statin use and TSH levels. Further studies are needed to clarify the possible underlying mechanism.

Effects of Antihypertensive Drugs on Thyroid Function in Type 2 Diabetes Patients With Euthyroidism

“…Previous study showed that statins use was associated with lower TSH levels and the relationship was mediated by TC declines ( Wang et al, 2021 ). Our investigation did not found this association might because TC reduction was not strong enough, which was partly consistent with Robert’s study ( Krysiak et al, 2019 ), or other hidden reason.…”

Association of longitudinal changes in serum lipids with the natural history of subclinical hypothyroidism: A retrospective cohort study using data from the REACTION study

“… 22 A retrospective cohort study found that statin use was associated with benefits for thyroid function, and TC served as a mediator of the association between statin use and TSH levels. 15 Endoplasmic reticulum (ER) stress may be one of the potential mechanisms of cholesterol-induced hypothyroidism. 23 , 24 , 25 , 26 The accumulation of too much cholesterol can cause ER stress, 23 , 24 which contributes to the occurrence of hypothyroidism.…”

“…14 Meanwhile, our previous cohort study revealed that statin use significantly improved the remission rate of SCH by reducing total cholesterol (TC). 15 These studies suggested that the thyroid gland may be attacked by lipids.…”

Rosuvastatin potentiates the thyrotropin‐lowering effect of metformin in men with non‐autoimmune subclinical hypothyroidism and prediabetes

“…Recently, HMG‐CoA reductase inhibitors have been found to activate the AMPK pathway and this mechanism seems to contribute to anti‐tumour, cardio‐protective, neuroprotective and hepato‐protective properties of these agents 17 . In a respective cohort study, statin therapy was associated with lower values of thyrotropin levels, a less frequent incidence of subclinical hypothyroidism and the increased remission rate of subclinical thyroid failure 18 . Short‐term (8‐week) simvastatin treatment of subjects with subclinical autoimmune hypothyroidism resulted in a reduction in thyrotropin levels and an increase in free thyroid hormone levels 19 .…”