madman
Super Moderator
Abstract
The effect of metformin on thyrotrope function seems to be sex dependent.The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on hypothalamic-pituitary-thyroid axis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age,weight,insulin sensitivity,and thyrotropin levels.The first group (n = 11) included subjects with low serum testosterone levels,while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated with metformin (2550-3000 mg daily).Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and free thyroid hormones were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformin decreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel’s thyrotropin index, and increased SPINA-GT. Metformin-induced changes in thyrotropin and Jostel’s index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.
Some study limitations merit comment. The most important limitation is the small sample size, resulting from difficulties in including in one research center a larger group of untreated patients with new-onset type 2 diabetes mellitus, nonautoimmune subclinical hypothyroidism, and late-onset hypogonadism. Second, because the real meaning of changes in Jostel’s thyrotropin index and SPINA-GT is still unclear, the obtained results should be interpreted with caution. Moreover, taking into account that the participants were characterized by low selenium status34 and adequate iodine intake,35 it is not certain whether the impact of metformin is the same in areas with adequate selenium and inadequate iodine consumption. Furthermore, it remains to be elucidated whether metformin affects hypothalamic-pituitary-thyroid axis activity in men with thyroid hypothyroidism of autoimmune origin. Finally, the question of whether endogenous testosterone determines metformin action on thyrotrope function in subjects with normal or only slightly impaired insulin sensitivity requires further research.
To sum up, despite improving glucose homeostasis in both study groups, metformin decreased thyrotropin levels, lowered Jostel’s thyrotropin index, and increased SPINA-GT only in men with low testosterone levels. The effect of treatment on thyrotropin and Jostel’s thyrotropin index depended on baseline levels of thyrotropin and testosterone, as well as correlated with the impact of metformin on insulin sensitivity. These findings suggest that metformin action on the hypothalamic-pituitary-thyroid axis activity depends on the androgen status of a patient. Because of the small sample size, the current study should be regarded as a pilot study, and larger multicenter trials are required to confirm the obtained results.
The effect of metformin on thyrotrope function seems to be sex dependent.The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on hypothalamic-pituitary-thyroid axis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age,weight,insulin sensitivity,and thyrotropin levels.The first group (n = 11) included subjects with low serum testosterone levels,while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated with metformin (2550-3000 mg daily).Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and free thyroid hormones were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformin decreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel’s thyrotropin index, and increased SPINA-GT. Metformin-induced changes in thyrotropin and Jostel’s index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.
Some study limitations merit comment. The most important limitation is the small sample size, resulting from difficulties in including in one research center a larger group of untreated patients with new-onset type 2 diabetes mellitus, nonautoimmune subclinical hypothyroidism, and late-onset hypogonadism. Second, because the real meaning of changes in Jostel’s thyrotropin index and SPINA-GT is still unclear, the obtained results should be interpreted with caution. Moreover, taking into account that the participants were characterized by low selenium status34 and adequate iodine intake,35 it is not certain whether the impact of metformin is the same in areas with adequate selenium and inadequate iodine consumption. Furthermore, it remains to be elucidated whether metformin affects hypothalamic-pituitary-thyroid axis activity in men with thyroid hypothyroidism of autoimmune origin. Finally, the question of whether endogenous testosterone determines metformin action on thyrotrope function in subjects with normal or only slightly impaired insulin sensitivity requires further research.
To sum up, despite improving glucose homeostasis in both study groups, metformin decreased thyrotropin levels, lowered Jostel’s thyrotropin index, and increased SPINA-GT only in men with low testosterone levels. The effect of treatment on thyrotropin and Jostel’s thyrotropin index depended on baseline levels of thyrotropin and testosterone, as well as correlated with the impact of metformin on insulin sensitivity. These findings suggest that metformin action on the hypothalamic-pituitary-thyroid axis activity depends on the androgen status of a patient. Because of the small sample size, the current study should be regarded as a pilot study, and larger multicenter trials are required to confirm the obtained results.
