Axis Activity In Women Research Articles

The Association between Vitamin D Status and the Impact of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Subclinical Hypothyroidism.

Metformin inhibits enhanced secretion of anterior pituitary hormones. Its impact on prolactin and gonadotropin concentrations is absent in individuals with hypovitaminosis D. The aim of this prospective cohort study was to investigate whether vitamin D status determines the effect of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-naïve women. The study included three groups of women of reproductive age with subclinical non-autoimmune hypothyroidism, which were matched for age, thyroid-stimulating hormone (TSH) concentration, and insulin sensitivity: untreated women with vitamin D deficiency/insufficiency (group A), women effectively supplemented with exogenous calciferol (group B), and untreated women with normal 25-hydroxyvitamin D concentrations (25OHD) (group C). Owing to concomitant type 2 diabetes or prediabetes, all subjects were treated with metformin. Concentrations of 25OHD, TSH, total and free thyroid hormones, glucose, insulin, glycated hemoglobin (HbA1c), prolactin, and peripheral markers of thyroid hormone action were assayed before metformin treatment and six months later. Based on hormone concentration, structure parameters of thyroid homeostasis were calculated. Except for 25OHD concentrations, there were no between-group differences in baseline values of the measured variables. Metformin reduced glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), and HbA1c in all study group, but these effects were less pronounced in group A than in the remaining groups. The reduction in TSH and Jostel's index was observed only in groups B and C, and its degree correlated with baseline TSH concentrations, baseline 25OHD concentrations, and the degree of improvement in HOMA1-IR. The drug did not affect circulating levels of 25OHD, free and total thyroid hormones, prolactin, other structure parameters of thyroid homeostasis, and markers of thyroid hormone action. The obtained results allow us to conclude that low vitamin D status in young women mitigates the impact of metformin on thyrotroph secretory function.

Impact of metformin on hypothalamic–pituitary–thyroid axis activity in women with autoimmune and non-autoimmune subclinical hypothyroidism: a pilot study

BackgroundMetformin reduces plasma TSH levels if these levels are elevated. No study has investigated whether the hormonal effects of metformin are impacted by thyroid autoimmunity. The current study aimed to compare the effect of metformin on hypothalamic–pituitary–thyroid axis activity between subjects with mild hypothyroidism of different origins.MethodsThe study population consisted of two groups of women with prediabetes and mildly elevated TSH levels, matched by age, insulin sensitivity, TSH, and thyroid hormone levels. Group A included 26 women with autoimmune thyroiditis, while group B enrolled 26 individuals with hypothyroidism of non-autoimmune origin. Both groups were treated with metformin (2.55–3 g daily). Circulating levels of TSH, total and free thyroid hormones, glucose, insulin, prolactin, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D, concentrations of thyroid antibodies, and structure parameters of thyroid homeostasis were assessed at baseline and 6 months later.ResultsAll patients completed the study. At baseline, both groups differed in concentrations of thyroid peroxidase antibodies, thyroglobulin antibodies, hsCRP, and 25-hydroxyvitamin D. The drug reduced TSH and Jostel’s index, with no difference between the study groups. The improvement in insulin sensitivity, observed in both groups, was more pronounced in group B than in group A. In women with autoimmune hypothyroidism, the drug increased SPINA-GT and decreased hsCRP levels. The remaining markers did not change throughout the study.ConclusionsThe obtained results suggest that, despite differences in thyroid output, the impact of metformin on TSH levels is similar in hypothyroid women with and without thyroid autoimmunity.

Insulin resistance attenuates the impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in women with autoimmune subclinical hypothyroidism.

Subjects with both subclinical hypothyroidism and autoimmune thyroiditis are frequently diagnosed with metabolic syndrome. The purpose of the current study was to investigate whether insulin sensitivity determines levothyroxine action on thyroid antibody titres and hypothalamic-pituitary-thyroid axis activity in young women with autoimmune subclinical hypothyroidism. The study population consisted of three age-, thyroid antibody- and thyrotropin-matched groups of women with autoimmune subclinical hypothyroidism: metformin-naive women with insulin resistance (group A, n=31), women receiving metformin treatment because of insulin resistance (group B, n=32), as well as metformin-naive women with normal insulin sensitivity (group C, n=35). Throughout the study, all subjects were treated with levothyroxine. Titres of thyroid peroxidase and thyroglobulin antibodies, as well as circulating levels of glucose, insulin, lipids, thyrotropin, free thyroid hormones, prolactin, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D were determined at the beginning of the study and 6months later. Except for two individuals, all patients completed the study. At baseline, group A differed from groups B and C in circulating levels of glucose, HDL-cholesterol, triglycerides, hsCRP, 25-hydroxyvitamin D and the homeostatic model assessment 1 of insulin resistance (HOMA1-IR). Although levothyroxine reduced thyroid antibody titres, decreased thyrotropin levels and increased free thyroid hormone levels in all studied groups, the effect on antibody titres and thyrotropin levels was more pronounced in groups B and C than in group A. The impact of levothyroxine on thyroid antibody titres correlated with baseline and treatment-induced changes in HOMA1-IR, thyrotropin, hsCRP and 25-hydroxyvitamin D. The results of the current study suggest that the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity is determined by insulin sensitivity.

The impact of combination therapy with metformin and exogenous vitamin D on hypothalamic-pituitary-thyroid axis activity in women with autoimmune thyroiditis and high-normal thyrotropin levels.

Metformin was found to decrease thyrotropin levels in subjects with non-autoimmune but not with autoimmune hypothyroidism. Vitamin D reduced thyroid autoimmunity without affecting thyrotropin and thyroid hormone levels. The aim of the current study was to investigate whether exogenous vitamin D modulates the impact of metformin on hypothalamic-pituitary-thyroid axis activity in young women with autoimmune thyroiditis. This case-control study included 32 prediabetic women with Hashimoto's thyroiditis, high-normal thyrotropin levels (2.5-4.5mIU/L) and vitamin D insufficiency. Based on patient preference, these individuals received either metformin (3g daily) plus vitamin D (4000IU daily) (n=17) or were treated with only metformin (3g daily) (n=15). Plasma levels of glucose, serum levels of insulin, thyrotropin, total and free thyroid hormones and 25-hydroxyvitamin D, as well as serum titres of thyroid antibodies, were assessed at baseline and 6months later. Thirty-one women completed the study. At baseline, there were no differences between the treatment groups. In both study arms, metformin reduced plasma glucose levels and improved insulin sensitivity but this effect was stronger in subjects receiving vitamin D. Only metformin administered with vitamin D decreased thyrotropin levels, increased 25-hydroxyvitamin D levels and reduced thyroid antibody titres. The impact on thyrotropin and antibody titres correlated with the increase in 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. This study has shown for the first time that exogenous vitamin D potentiates the impact of metformin on thyrotropin levels in women with autoimmune thyroiditis.

The impact of oral hormonal contraception on metformin action on hypothalamic-pituitary-thyroid axis activity in women with diabetes and prediabetes: A pilot study.

The impact of metformin on thyrotropin levels is sex-dependent. No previous study has assessed whether sex steroids determine metformin action on thyrotrope and thyroid cell functioning. The aim of the present study was to compare the effect of this agent on hypothalamic-pituitary-thyroid axis activity and thyroid function tests between women receiving oral contraceptive pills and women not using any contraception. The study population included 52 women with subclinical hypothyroidism and prediabetes or diabetes, 20 of whom had been using oral contraceptive pills for at least 12months before the beginning of the study. Over the entire study period (4months), all participants received oral metformin (1.7-3g daily). Circulating levels of glucose, insulin, thyrotropin, free thyroid hormones, oestradiol, gonadotropins and prolactin were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning and at the end of the study. The study groups differed in oestradiol, gonadotropins and prolactin levels and in structure parameter inference approach (SPINA)-GT. In both groups, metformin reduced glucose levels, homeostasis model assessment 1 of insulin resistance index (HOMA1-IR), thyrotropin levels and Jostel's thyrotropin index, as well as increased SPINA-GT. In women receiving oral contraceptive pills, the drug slightly decreased serum prolactin levels. The impact on metformin on HOMA1-IR, thyrotropin, prolactin, Jostel's thyrotropin index and SPINA-GT was more pronounced if women received oral contraception, as well as more pronounced in patients treated with higher doses of this agent. Treatment-induced changes in thyrotropin and Jostel's thyrotropin index correlated with their baseline values, baseline levels of oestradiol and gonadotropins, as well as with the degree of a reduction in HOMA1-IR. This study is the first one to have shown that oral oestrogens potentiate the effect of metformin on hypothalamic-pituitary-thyroid axis activity.

The Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Interferon-Induced Hypothyroidism: A Pilot Study

The Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Interferon-Induced Hypothyroidism: A Pilot Study

Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain

The objective of this study was to evaluate the perceived stress index, quality of life, and hypothalamus-pituitary-adrenal axis activity in women with endometriosis and chronic pelvic pain. For the study, 93 women with endometriosis and 82 healthy women volunteered. The visual analogue scale (VAS) (0 = no pain; 10 = severe pain) was used to determine pain intensity; the perceived stress questionnaire (PSQ) defined stress index, and the health-related quality-of-life (HRQOL)-SF-36 questionnaire was used to evaluate quality of life. Salivary cortisol was measured at 0800, 1600, and 2000 h and the awakening cortisol response was assessed to evaluate the hypothalamus-pituitary-adrenal axis activity. The results show that women with endometriosis and chronic pelvic pain of moderate intensity (4.1 ± 0.58, mean ± SEM) have higher levels of perceived stress (0.55 ± 0.01 versus 0.42 ± 0.01, p < 0.05), a poorer quality of life expressed as lower scores for all items of the inventory and hypocortisolism. Lower levels of salivary cortisol were observed in all three samples collected, as well as in the awakening cortisol response, for women with endometriosis (0.19 ± 0.09 μg/dl) when compared with controls (0.78 ± 0.08 μg/dl, p < 0.05 l), and it was independent of pain intensity and Mental health (MH) scores in SF-36. We concluded that women with endometriosis and chronic pelvic pain show low concentrations of salivary cortisol and a high level of perceived stress, associated with a poor quality of life. Whether the hypocortisolism was an adaptive response to the aversive symptoms of the disorder or a feature related to the etiology of endometriosis remains to be elucidated.

Cortisol secretary pattern and glucocorticoid feedback sensitivity in women from a Mediterranean area: relationship with anthropometric characteristics, dietary intake and plasma fatty acid profile

Chronic stress is associated with a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis consisting on disturbances on the cortisol response and lipid metabolism. To evaluate the HPA axis activity in women from a Mediterranean area, comparing three different measurements: daily cortisol secretory variability, postprandial cortisol secretion and glucocorticoid feedback sensitivity. In addition, HPA axis disturbance is correlated with dietary habits and plasma fatty acid profiles. The participants were 41 women born during the first 6 months of 1960 and living in a Mediterranean area (Murcia, Spain). They were of normal weight, with a waist circumference of 80.5 +/- 9.3 cm. Their salivary cortisol levels, 7-day dietary record and plasma fatty acid profile were evaluated. Daily cortisol variability and postlunch cortisol secretion were recorded and a dexamethasone suppression test is performed in order to detect possible HPA disturbance. Both the methods used for HPA axis evaluation were positively correlated (r = 0.448, P = 0.004). Subjects with normal diurnal curves (high cortisol variability) showed significantly higher cortisol values in the morning and postprandial cortisol secretion than women with pathological curves (medium and low variability). Cortisol variability was inversely correlated with waist circumference (r = -0.312, P = 0.047), suggesting that a disturbed HPA axis response may lead to an android pattern of body fat distribution. Dietary fat and saturated fatty acid intake were lower in the high cortisol variability group, while monounsaturated fatty acid intake was higher (P < 0.05). No major differences were reported in plasma fatty acid profile. A disturbed HPA axis is associated with abdominal fat distribution and a higher content of fat and saturated fatty acids in the diet. Women who chose a dietary pattern closer to the Mediterranean diet, with high monounsaturated fatty acid intake, showed lower levels on HPA axis disturbance.