Vitamin D Status Determines the Impact of Metformin on Gonadotropin Levels in Postmenopausal Women.

Metformin was found to decrease elevated levels of anterior pituitary hormones. Its impact on lactotrope secretory function was absent in women with vitamin D insufficiency. This study investigated whether vitamin D status determines metformin action on overactive gonadotropes. We compared the effect of six-month metformin treatment on the plasma levels of gonadotropins, TSH, prolactin, ACTH, estradiol, free thyroid hormones, IGF-1, and 25-hydroxyvitamin D, as well as on glucose homeostasis markers between three matched groups of postmenopausal women at high risk for diabetes: untreated subjects with vitamin D insufficiency (group A), untreated women with normal vitamin D status (group B), and individuals receiving vitamin D supplementation with normal 25-hydroxyvitamin D levels (group C). Only in groups B and C did metformin reduce FSH levels and tend to decrease LH levels, and these effects correlated with baseline gonadotropin levels, baseline 25-hydroxyvitamin D levels, and the improvement in insulin sensitivity. Follow-up gonadotropin levels were higher in group A than in the other two groups. The drug did not affect circulating levels of TSH, prolactin, ACTH, estradiol, free thyroid hormones, IGF-1, or 25-hydroxyvitamin D. The obtained results suggest that the impact of metformin on gonadotropin secretion in women after menopause is determined by vitamin D status.

Myo-Inositol Potentiates the Inhibitory Effect of Metformin on Prolactin Levels.

INTRODUCTION: Metformin was found to reduce elevated levels of anterior pituitary hormones. Its thyrotropin-lowering effect was more pronounced in individuals receiving myo-inositol. The aim of the present study was to investigate whether the concomitant supplementation of myo-inositol determines the impact of metformin on prolactin levels. METHODS: The study population consisted of two groups of women with mild-to-moderate hyperprolactinemia. Group 1 included 24 individuals receiving myo-inositol preparations (2 g daily for at least 6 months), while 24 inositol-naïve women belonged to group 2. Both groups were matched for age, insulin sensitivity, and prolactin concentration. For the following 6 months, all women were treated with metformin (1.7 daily). Plasma glucose levels, the homeostatic model assessment of insulin resistance ratio (HOMA-IR), glycated hemoglobin, as well as plasma levels of total prolactin, monomeric prolactin, thyrotropin, free thyroid hormones, adrenocorticotropic hormone, and insulin-like growth factor-1 were measured at baseline and after 6 months of metformin treatment. RESULTS: Metformin reduced plasma glucose, HOMA-IR, and glycated hemoglobin in both study groups, but this effect was more pronounced in group 1 than group 2. Treatment-induced changes in total and monomeric prolactin levels were significant only in group 1. There were no differences between follow-up and baseline values of thyrotropin, free thyroxine, free tri-iodothyronine, adrenocorticotropic hormone, and insulin-like growth factor-1. Treatment-induced changes in prolactin concentration correlated with baseline prolactin levels, baseline values of HOMA-IR, and the impact of treatment on HOMA-IR. DISCUSSION: The obtained results suggest that myo-inositol supplementation potentiates the inhibitory effect of metformin on prolactin levels in women with hyperprolactinemia.

The impact of rosuvastatin on hypothalamic-pituitary-testicular axis activity in metformin-treated and metformin-naïve men with low testosterone levels: a pilot study.

BACKGROUND: Intense statin therapy was found to impair testosterone production in men. Metformin administered to subjects with hypergonadotropic hypogonadism decreased gonadotropin production. The current study was aimed at investigating whether metformin treatment modulates the impact of high-dose rosuvastatin therapy on hypothalamic-pituitary-testicular axis activity in men. METHODS: The study included 43 very high cardiovascular risk men with late-onset hypogonadism, 20 of whom had been treated with metformin (1.7-3 g daily) for at least 6 months. In all subjects, unsuccessful initial statin treatment was replaced with rosuvastatin (20-40 mg daily). Plasma lipid levels, glucose homeostasis markers, as well as circulating levels of gonadotropins, testosterone, bioavailable testosterone, dehydroepiandrosterone-sulfate, prolactin, estradiol and creatinine were measured at the beginning of the study and 4 months later in 28 individuals in whom rosuvastatin reduced LDL cholesterol levels to below 70 mg/dL. RESULTS: There were no differences between treatment-induced changes in plasma lipids. In both study groups, rosuvastatin reduced total and bioavailable testosterone levels. However, only in metformin-naïve men, rosuvastatin increased LH and FSH levels and slightly impaired insulin sensitivity. The impact on gonadotropin concentrations correlated with treatment-induced decrease in testosterone levels. There were no significant differences between baseline and posttreatment values of dehydroepiandrosterone-sulfate, prolactin, estradiol and the glomerular filtration rate. CONCLUSION: The obtained results suggest that metformin prevents the compensatory increase in gonadotrope function induced by intense statin therapy.

The effect of vitamin D and selenomethionine on thyroid antibody titers, hypothalamic-pituitary-thyroid axis activity and thyroid function tests in men with Hashimoto's thyroiditis: A pilot study.

BACKGROUND: Both selenium and vitamin D were found to reduce thyroid antibody titers in women with Hashimoto's thyroiditis. METHODS: The study enrolled 37 young drug-naïve euthyroid men with autoimmune thyroiditis, who were treated for 6 months with either exogenous vitamin D (group A, n = 20) or selenomethionine (group B, n = 17). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin and free thyroid hormones, serum levels of 25-hydroxyvitamin D, as well Jostel's thyrotropin, the SPINA-GT and the SPINA-GD indices were determined at the beginning and at the end of the study. RESULTS: At baseline, there were no differences between the study groups. Both vitamin D and selenomethionine reduced antibody titers and increased the SPINA-GT index. Only selenomethionine affected the SPINA-GD index, while only vitamin D increased 25-hydroxyvitamin D levels. Neither selenomethionine nor vitamin D significantly affected thyrotropin and free thyroid hormone levels. The effect of vitamin D on antibody titers correlated with baseline and treatment-induced changes in serum levels of 25-hydroxivitamin D. CONCLUSIONS: Both vitamin D and selenomethionine have a beneficial effect on thyroid autoimmunity in drug-naïve men with Hashimoto's thyroiditis.

The Relationship Between Statin Action On Thyroid Autoimmunity And Vitamin D Status: A Pilot Study.

BACKGROUND: Both vitamin D preparations and high-dose statin therapy were found to reduce thyroid antibody titers. OBJECTIVE: The purpose of this study was to assess whether vitamin D status determines the effect of statin therapy on thyroid autoimmunity. METHODS: The study population consisted of 39 euthyroid women with Hashimoto's thyroiditis and moderate or moderately high cardiovascular risk divided into two groups: women with vitamin D deficiency or insufficiency (group A; n=19) and women with normal vitamin D status (group B, n=20). All patients received atorvastatin therapy (20-40 mg daily) for the following 6 months. Plasma lipids, circulating levels of thyrotropin, free thyroid hormones, prolactin and 25-hydroxyvitamin D, titers of thyroid peroxidase and thyroglobulin antibodies, as well as Jostel's, the SPINA-GT and the SPINA-GD indices were assessed at the beginning and at the end of the study. RESULTS: The study completed all women. At baseline, with the exception of 25-hydroxyvitamin D, there were no significant differences between both study groups in plasma lipids, circulating hormone levels and titers of thyroid peroxidase and thyroglobulin antibodies. Despite improving plasma lipids in both study groups, atorvastatin reduced thyroid antibody titers only in women with normal vitamin D status. Moreover, in this group of patients, atorvastatin increased the SPINA-GT index. Circulating levels of the measured hormones, Jostel's thyrotropin index and the SPINA-GD index remained at a similar level throughout the study. CONCLUSIONS: The results of the study suggest that the effect of atorvastatin therapy on thyroid autoimmunity depends on vitamin D status.

Atorvastatin potentiates the effect of selenomethionine on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis.

OBJECTIVE: In many studies, selenium supplementation decreased serum titers of thyroid antibodies. The aim of the study was to investigate whether statin therapy determines selenium action on thyroid autoimmunity. METHODS: This prospective case-control study enrolled 42 euthyroid women with Hashimoto's thyroiditis and normal vitamin D status, 20 of whom had been treated with atorvastatin (40 mg daily) for at least 6 months. All patients received selenomethionine (200 µg daily) for 6 months. Plasma levels of lipids, serum titers of thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies, as well as serum levels of thyrotropin, free thyroid hormones, and 25-hydroxyvitamin D were determined at the beginning and at the end of the study. RESULTS: At baseline, there were no differences between both treatment arms in plasma lipids, titers of thyroid antibodies, serum levels of thyrotropin, free thyroid hormones, and 25-hydroxyvitamin D. Selenometionine decreased titers of TPOAb (from 843 ± 228 to 562 ± 189 U/mL) and TgAb (from 795 ± 286 to 501 ± 216 U/mL) in atorvastatin-treated women, as well as titers of TPOAb (from 892 ± 247 to 705 ± 205 U/mL) and TgAb (from 810 ± 301 to 645 ± 224 U/mL) in statin-naive women. The changes in antibody titers were more pronounced in women receiving atorvastatin (between-group difference: 94 [32-156] [TPOAb]; 129 [52-206] [TgAb]). Treatment-induced changes in TPOAb and TgAb correlated positively with baseline thyroid antibody titers. Circulating levels of lipids, free thyroxine, free triiodothyronine, and 25-hydroxyvitamin D remained at similar levels throughout the study. CONCLUSIONS: The obtained results indicate that the decrease in titers of thyroid antibodies was potentiated by atorvastatin use.

Moderate-dose simvastatin therapy potentiates the effect of vitamin D on thyroid autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and vitamin D insufficiency.

BACKGROUND: Vitamin D preparations reduce titers of thyroid antibodies in women with autoimmune thyroiditis. The same effect was induced by high-dose, but not moderate-dose-, statin therapy. No previous study has investigated the impact of concomitant treatment with a statin and vitamin D on thyroid autoimmunity. METHODS: The study included three matched groups of women with Hashimoto's thyroiditis and low vitamin D status. Groups B (n=19) and C (n=20) were treated with vitamin D (2000 IU daily). Because of coexistent hypercholesterolemia, groups A (n=18) and B received simvastatin (40mg daily). Plasma lipids, serum levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. RESULTS: At baseline, 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. In groups A and B, simvastatin reduced plasma levels of total and LDL cholesterol. Simvastatin produced no effect on thyroid antibody titers. Vitamin D decreased titers of thyroid peroxidase antibodies, as well as tended to decrease titers of thyroglobulin antibodies. Simvastatin-vitamin D combination therapy reduced serum titers of thyroid peroxidase and thyroglobulin antibodies and this effect was stronger than the effect of simvastatin and vitamin D administered alone. Treatment-induced changes in thyroid antibody titers correlated with baseline antibody titers, baseline levels of 25-hydroxyvitamin and treatment-induced changes in 25-hydroxyvitamin. CONCLUSIONS: The obtained results indicate that simvastatin may potentiate the impact of vitamin D on thyroid autoimmunity in vitamin D-deficient women with Hashimoto's thyroiditis.

The Effect of Vitamin D on Thyroid Autoimmunity in Levothyroxine-Treated Women with Hashimoto's Thyroiditis and Normal Vitamin D Status.

Background: Low vitamin D status is associated with autoimmune thyroid disease. Oral vitamin D supplementation was found to reduce titers of thyroid antibodies in levothyroxine-treated women with postpartum thyroiditis and low vitamin D status. Methods: The study included 34 women with Hashimoto's thyroiditis and normal vitamin D status (serum 25-hydroxyvitamin D levels above 30 ng/mL) who had been treated for at least 6 months with levothyroxine. On the basis of patient preference, women were divided into 2 groups, receiving (n=18) or not receiving (n=16) oral vitamin D preparations (2000 IU daily). Serum levels of thyrotropin, free thyroxine, free triiodothyronine and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: There were no significant differences in baseline values between both study groups. 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. No changes in hypothalamic-pituitary-thyroid axis activity and thyroid antibody titers were observed in vitamin-naïve patients. Vitamin D increased serum levels of 25-hydroxyvitamin D, as well as reduced titers of thyroid antibodies. This effect was more pronounced for thyroid peroxidase than for thyroglobulin antibodies and correlated with their baseline titers. Conclusions: Vitamin D preparations may reduce thyroid autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and normal vitamin D status.

[Adrenopause]. / Adrenopauza.

The hypothalamic-pituitary-adrenal axis activity in the aging people is characterised by an unexplained reduction of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) secretion while ACTH and cortisol production remains relatively unchanged. This decline in the biological activity of the zona reticularis, referred to as 'adrenopause', may contribute to the physiology of human aging. The reduced endogenous concentrations of DHEA and DHEAS found in advancing age have been correlated with a constellation of health problems. Because these steroids seem to play a role in the maintenance of immunity, musculoskeletal integrity, and cardiovascular health, age-associated declines in adrenal androgen production may lead to decreased immune function, osteoporosis, and atherosclerosis. Despite clear benefits of DHEA administration in patients with adrenal insufficiency, the results of DHEA supplementation in healthy euadrenal subjects are not so clear-cut. Studies assessing its action on sexual function, metabolism and cardiovascular functions have provided conflicting results. This paper summarises the present state of knowledge on the age-related changes in adrenal androgen production and discusses pros and cons of DHEA use in older people.

[Modern pharmacotherapy of benign prostatic hyperplasia]. / Wspólczesna farmakoterapia lagodnego rozrostu gruczolu krokowego.

Benign prostatic hyperplasia is the most common medical problem affecting elderly men throughout the world. With increasing awareness of health issues amongst males, the morbidity caused by this disease is not longer being accepted as just part of growing old. Until about 10 years ago, surgery was the only effective treatment for symptomatic benign prostatic hyperplasia. Now, many men suffering from this disorder may be effectively treated with a medical therapy. This article provides an overview of the efficacy and safety of 5alpha-reductase inhibitors, alpha1-adrenoceptor antagonists and herbal remedies, putting special emphasis on the current place of these agents in the modem therapy of benign prostatic hyperplasia. Wherever possible, our opinion is based on the detailed analysis of the results of available clinical trials.

[Prostate cancer chemoprevention]. / Chemoprewencja raka gruczolu krokowego.

Prostatic cancer is the most common malignancy diagnosed in men. Chemoprevention of prostatic cancer is a relatively new concept and seems to be a very promising strategy for preventing and arresting the development of this neoplasm. There is much evidence that the increased consumption of selenium, vitamins E and D, lycopen, soy and isoflavonoids and low-fat diet reduce the risk of the incidence of prostatic cancer. Similar effect is also exhibited by some drugs including finasteride, non-steroid anti-inflammatory drugs and lipoxygenase inhibitors. In this paper we summarize the results of published epidemiologic and scientific studies, trying to critically evaluate the potential clinical role and mechanism of action of these agents in modern chemoprevention of this cancer.