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.

Dehydroepiandrosterone potentiates the effect of vitamin D on thyroid autoimmunity in euthyroid women with autoimmune thyroiditis: A pilot study.

The impact of androgens on the thyroid in women is poorly understood. The aim of the present study was to investigate whether vitamin D/dehydroepiandrosterone (DHEA) combination therapy is superior to vitamin D alone in affecting thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in young women with autoimmune thyroid disease. The study included 35 euthyroid women with untreated Hashimoto's thyroiditis and reduced sexual drive, allocated to one of two treatment groups. The first group (n = 19) received both vitamin D and DHEA, while the second (n = 16) was treated with only vitamin D. Serum thyroid antibody titres and concentrations of thyrotropin, free thyroid hormones, dehydroepiandrosterone-sulphate (DHEA-S), 25-hydroxyvitamin D, testosterone and estradiol were measured at baseline and 6 months later. Vitamin D administered alone or in combination with DHEA decreased serum titres of thyroid peroxidase and thyroglobulin antibodies, which correlated with baseline antibody titres, baseline 25-hydroxyvitamin D levels and treatment-induced increase in 25-hydroxyvitamin D levels. Apart from a stronger effect on antibody titres, vitamin D/DHEA combination therapy slightly decreased thyrotropin levels, as well as increased DHEA-S and testosterone levels. In this group of women, treatment-induced changes in antibody titres and thyrotropin levels correlated with the impact on DHEA-S and testosterone. The obtained results suggest that vitamin D/DHEA combination therapy may be a better treatment option for euthyroid women with Hashimoto's thyroiditis than vitamin D alone.

[Secondary hypogonadism after traumatic brain injury: a case report]. / Hipogonadyzm hipogonadotropowy po pourazowym uszkodzeniu mózgu: opis przypadku.

In the light of the recent studies it seems that traumatic brain injury-induced pituitary hormones deficiency occurs much more frequently than previously thought. Anterior pituitary hormone dysfunction may be an important feature of long-term morbidity in survivors of traumatic brain injury. The most common alterations appear to be somatotropin and gonadotropin deficiency, followed by corticotropin and thyrotropin deficiency. Clinical signs of hypopituitarism are, however, often subtle and may be masked by sequalae of traumatic brain injury, causing that the partial or complete insufficiency of anterior pituitary secretion may be underrecognized. Patients suffering from this condition may benefit from appropriate hormone replacement therapy. The authors report a case of a young male patient who developed hypogonadism and hyperprolactinemia several months after an accident. This case illustrates the need for clinical awareness of pituitary dysfunction in patients after traumatic brain injury.

[Precocious puberty in boys]. / Przedwczesne dojrzewanie plciowe u chlopców.

Precocious puberty in boys is defined as the onset of puberty before the age of 9 years. It is divided into two categories: central precocious puberty, characterized by the premature activation of the hypothalamic-pituitary-gonadal axis, and peripheral precocious puberty presents when premature sexual development is dependent on steroid production regardless of gonadotropin secretion. Although precocious puberty occurs more frequently in girls, in the case of boys it is more often associated with identifiable organic disorders of the central nervous system, adrenal glands or testes. The diagnosis should include detailed anamnesis and clinical examination, measurement of pituitary and sex hormones, assessment of bone age, and imaging of the hypothalamus, pituitary gland, adrenal glands and testes. Indications for treatment are based on the type of precocious puberty and its progression rate, advancement of bone age, predicted adult height and psychological evaluation. The purpose of this article was to discuss the etiopathogenesis of precocious puberty in boys and to provide the approach to its diagnosis, differentiation and treatment.

Impaired Cardiometabolic Effects of Bromocriptine in Men With Early-Onset Androgenic Alopecia.

Both hyperprolactinemia and early-onset androgenic alopecia are associated with increased cardiometabolic risk. The aim of this study was to assess whether early-onset male-pattern baldness modifies cardiometabolic effects of bromocriptine in men with prolactin excess. The study included 2 groups of men with prolactin excess: individuals with early-onset androgenic alopecia (group 1) and individuals with normal hair growth (group 2). Both groups were matched for age, smoking habits, body mass index, blood pressure, and prolactin levels. Over the entire study period (4 months), all participants were treated with bromocriptine (7.5 mg daily). Plasma levels of hormones (prolactin, total testosterone, and bioavailable testosterone), glucose homeostasis markers, lipids, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and the urinary albumin-to-creatinine ratio (UACR) were measured at the beginning and at the end of the study period. The two groups differed in total testosterone, bioavailable testosterone, insulin sensitivity, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, hsCRP, fibrinogen, homocysteine, and UACR. In both groups, bromocriptine reduced prolactin, increased total and bioavailable testosterone, improved insulin sensitivity, and decreased uric acid, hsCRP, and homocysteine. The impact on prolactin, insulin sensitivity, uric acid, hsCRP, and homocysteine was stronger in group 2 than in group 1. Only in group 2 did the drug increase HDL cholesterol and decrease triglycerides, fibrinogen, and UACR. The impact on cardiometabolic risk factors correlated with a reduction in prolactin levels and an improvement in insulin sensitivity, and, in group 1, inversely correlated with testosterone levels. The obtained results suggest that men with early-onset androgenic alopecia are partially resistant to the cardiometabolic effects of bromocriptine.

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.

Sexual Function and Depressive Symptoms in Young Women with Euthyroid Hashimoto's Thyroiditis Receiving Vitamin D, Selenomethionine and Myo-Inositol: A Pilot Study.

Thyroid autoimmunity is associated with an increased risk of sexual dysfunction. The aim of this study was to compare sexual functioning and depressive symptoms in women with Hashimoto's thyroiditis receiving different treatments. The study included euthyroid women with autoimmune thyroiditis, untreated or receiving vitamin D, selenomethionine, or myo-inositol. Apart from measuring antibody titers and hormone levels, all participants completed questionnaires evaluating female sexual function (FSFI) and depressive symptoms (BDI-II). In untreated women, the overall FSFI scores and domain scores for desire, arousal, lubrication, and sexual satisfaction were lower than in women receiving vitamin D, selenomethionine, and myo-inositol. In the vitamin D-treated women, the total FSFI scores and scores for desire and arousal were higher than in women receiving the remaining micronutrients. The BDI-II score was lowest in the vitamin D-treated women and highest in the untreated patients with thyroiditis. Vitamin D-treated women were also characterized by lower antibody titers and higher testosterone levels than the women receiving the remaining micronutrients. There were no differences in sexual functioning and depressive symptoms between the selenomethionine- and myo-inositol-treated women. The study results suggest that although all antibody-lowering treatments are associated with better sexual functioning and well-being in young women with euthyroid autoimmune thyroiditis, the greatest benefits are observed in patients receiving vitamin D.

Impaired Prolactin-Lowering Effects of Metformin in Women with Polycystic Ovary Syndrome.

The effect of metformin on prolactin concentration seems to be sex-dependent. The aim of this study was to determine whether the androgen status modulates the impact of metformin on plasma prolactin levels in women. This study included two matched groups of prediabetic women with hyperprolactinemia: 25 with PCOS and 25 control subjects with androgen levels within the reference range and with normal ovarian morphology. Glucose homeostasis markers, prolactin, the remaining anterior pituitary hormones, sex hormones, SHBG and IGF-1 were determined before and after six months of metformin treatment. At baseline, both groups differed in LH, LH/FSH ratio, testosterone, FAI, DHEA-S, androstenedione and estradiol. Although metformin improved insulin sensitivity and increased SHBG in both study groups, these effects were more pronounced in control subjects than in women with PCOS. In control subjects, the drug decreased total and monomeric prolactin and increased LH. In women with PCOS, metformin reduced LH, LH/FSH ratio, testosterone and FAI. In the control group, the impact on total and monomeric prolactin positively correlated with their baseline levels and with the degree of improvement in insulin sensitivity, as well as negatively correlated with testosterone and FAI. In women with PCOS, treatment-induced changes in testosterone and FAI positively correlated with the changes in LH and LH/FSH ratio. The obtained results suggest that the prolactin-lowering properties of metformin are less pronounced in women with coexisting PCOS than in women with elevated prolactin levels, probably owing to the increased production of endogenous testosterone.

Vitamin D Status Determines Cardiometabolic Effects of Cabergoline in Women with Elevated Prolactin Levels: A Pilot Study.

Both hyperprolactinemia and vitamin D deficiency appear to be associated with increased cardiometabolic risk. This study aimed to determine whether vitamin D status influences the cardiometabolic effects of cabergoline. The study included three matched groups of women with mild to moderate hyperprolactinemia: vitamin D-naive subjects with vitamin D insufficiency (group A), women with vitamin D deficiency/insufficiency successfully treated with vitamin D (group B), and vitamin D-naive individuals with normal vitamin D status (group C). Plasma prolactin, 25-hydroxyvitamin D, estradiol, glucose homeostasis markers, lipids, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and uric acid, as well as the urinary albumin-to-creatinine ratio (UACR), were measured at study entry and after four months of cabergoline treatment. Although cabergoline reduced prolactin levels and increased estradiol levels in all study groups, the effect on prolactin was more pronounced in groups B and C compared to group A. In groups B and C, the drug enhanced glucose homeostasis, increased HDL-cholesterol, and decreased triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR. In group A, only insulin resistance, hsCRP, and homocysteine were reduced by cabergoline. The effects on insulin sensitivity, HDL-cholesterol, triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR were proportional to the decrease in prolactin and baseline levels of 25-hydroxyvitamin D. The obtained results suggest that vitamin D status determines cabergoline's cardiometabolic effects.

Initial clinical, laboratory and radiological features of SARS-CoV-2-infected patients and their impact on the course of the disease.

BACKGROUND: On March 11, 2020, coronavirus disease (COVID-19) was declared a global threat by the World Health Organization (WHO). It quickly became apparent that reducing inpatient mortality rates and early phase prediction of possible deterioration or severe disease course relied on finding more specific biomarkers. OBJECTIVES: This retrospective study assessed initial clinical, laboratory and radiological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and explored their impact on mortality and the course of the disease. Such efforts aimed to facilitate the identification of high-risk patients and to improve the formulation of treatment plans for these individuals. MATERIAL AND METHODS: The cohort comprised 111 consecutive adult inpatients diagnosed with COVID-19 and hospitalized in the Internal Medicine Ward of the University Clinical Center of prof. K. Gibinski of the Medical University of Silesia in Katowice, Poland, a COVID-19 Treatment Unit, between November 16, 2020 and February 15, 2021. All available clinical, laboratory and radiological findings were extracted from electronic records and assessed as possible risk factors for poor prognosis. RESULTS: Clinicasl and radiological features with higher frequency in COVID-19 non-survivors included older age, history of smoking, concomitant cardiovascular diseases, low oxygen saturation (SpO2), and high infection risk assessed on admission as well as high opacity score, percentage of opacity and percentage of high opacity in computed tomography. Non-survivors had decreased serum lymphocytes, monocytes, calcium, magnesium, and hemoglobin oxygen saturation. They also had increased red cell distribution width (RDW), C-reactive protein (CRP), procalcitonin, alkaline phosphatase (ALP), creatinine, blood urea nitrogen (BUN), D-dimer, troponin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, as well as a base deficit. CONCLUSIONS: This retrospective study identified several markers associated with a fatal course of COVID-19. The early assessment of SARS-CoV-2-infected inpatients should consider these markers.

[Diagnosis and treatment of craniopharyngioma]. / Rozpoznawanie i leczenie czaszkogardlaka.

Craniopharyngioma is a benign, suprasellar brain tumour accounting for about 1 to 3% of all intracranial neoplasms. Because of the proximity of the tumour to the hypothalamus and pituitary gland its complete resection is often impossible. It still remains one of the most difficult tumours to the effective treatment and is associated with frequent recurrence. Currently, surgical excision followed by external beam irradiation, in cases of residual tumour, is the main treatment option. In this paper, the authors review different aspects of diagnostic and management of the craniopharyngioma. Particular attention is paid to the results of the studies published in the recent years. The reader is also provided with some practical recommendations on dealing with patients suffering from this tumour.

[Autoimmune polyendocrine syndrome type 3 in a patient after surgical treatment of Cushing syndrome]. / Autoimmunologiczny zespól wielogruczolowy typu 3 u chorej po operacyjnym leczeniu zespolu Cushinga.

In light of research carried out in recent years, it seems that autoimmune polyendocrine syndromes occur much more frequently than previously estimated. The underestimation of their real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical picture. On the basis of the clinical presentation, autoimmune polyendocrine syndromes may be divided into four different types. The most frequent of them, type 3, is composed of autoimmune thyroid disease associated with type 1 diabetes or other autoimmune conditions with the exception of Addison's disease and hypoparathyroidism. In this article, we report a case of a young woman, with a family history of autoimmune disorders, in whom type 3 autoimmune polyendocrine syndrome developed several months after adrenalectomy performed because of Cushing syndrome. We describe in details diagnostic and treatment strategies applied in our patient and their impact on the course and outcome of autoimmune polyendocrine syndrome. We conclude that immunosuppressive effects of glucocorticoid excess resulting from the presence of Cushing syndrome inhibited or reduced intensity of inflammatory processes responsible for the development of organ-specific autoimmune endocrine disorders. This case illustrates the need for clinical awareness of autoimmune polyendocrine syndromes in patients after surgically-induced normalization of adrenocortical hormone levels.

Impact of dehydroepiandrosterone on thyroid autoimmunity and function in men with autoimmune hypothyroidism.

Background Testosterone administration was found to have a protective effect on thyroid autoimmunity in men with autoimmune (Hashimoto's) thyroiditis. Objective The present study was aimed at assessing whether oral dehydroepiandrosterone affects thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with subclinical hypothyroidism induced by Hashimoto's thyroiditis. Setting The study was conducted at Medical University of Silesia, Katowice, Poland. Method The study enrolled 32 elderly men with autoimmune hypothyroidism and low dehydroepiandrosterone-sulfate levels. Based on patient preference, the participants either received oral dehydroepiandrosterone (50 mg daily; n = 16) or remained untreated (n = 16). Apart from measuring antibody titers and hormone levels, we calculated baseline and post-treatment values of three structure parameters of thyroid homeostasis. Main outcome measure Serum titers of thyroid peroxidase and thyroglobulin antibodies. Results At baseline, there were no significant differences in the investigated parameters between both groups of men. All participants completed the study. Oral dehydroepiandrosterone increased dehydroepiandrosterone-sulfate and testosterone levels, as well as had a neutral effect on estradiol levels. The increase in dehydroepiandrosterone-sulfate correlated with treatment-induced changes in serum testosterone. Moreover, dehydroepiandrosterone reduced titers of thyroid peroxidase and thyroglobulin antibodies, decreased serum thyrotropin levels, reduced Jostel's thyrotropin index as well as increased thyroid's secretory capacity. Treatment-induced changes in thyroid antibody titers, thyrotropin levels, Jostel's thyrotropin index and thyroid's secretory capacity correlated with the increase in dehydroepiandrosterone-sulfate and testosterone levels. Conclusion The obtained results show that exogenous dehydroepiandrosterone may exert a beneficial effect on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with autoimmune thyroiditis and subclinical hypothyroidism.

The Impact of Telmisartan on Cardiometabolic Risk Factors in Hypertensive Male Siblings of Women With Polycystic Ovary Syndrome.

Brothers of women with polycystic ovary syndrome (PCOS) were found to be at increased risk for cardiometabolic disorders. This risk may be exacerbated by concurrent poorly controlled hypertension. Angiotensin II receptor blockers are the most frequently used antihypertensive drugs. The aim of the present study was to compare blood pressure-lowering and pleiotropic effects of telmisartan between male siblings of PCOS probands and unrelated men. The study included 2 age-, blood pressure-, and mass index-matched groups of men with grade 1 hypertension: 24 brothers of women with PCOS (group A) and 26 brothers of healthy women (group B). All subjects were treated with telmisartan (80 mg daily). Blood pressure, glucose homeostasis markers, and plasma lipids, as well as plasma levels of total testosterone, bioavailable testosterone, androstenedione, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen, and 25-hydroxyvitamin D were measured before and after 12 weeks of therapy. At entry, there were between-group differences in the degree of insulin resistance, plasma levels of high-density lipoprotein-cholesterol, triglycerides, calculated bioavailable testosterone, androstenedione, hsCRP, and 25-hydroxyvitamin D. Although telmisartan reduced blood pressure in both study groups, this effect was stronger in group B. Irrespective of the study group, the drug improved insulin sensitivity and reduced circulating levels of uric acid and homocysteine, but these effects were more pronounced in group B than group A. Only in group B, telmisartan decreased hsCRP and fibrinogen, as well as increased 25-hydroxyvitamin D. The obtained results suggest that hypertensive male relatives of PCOS probands may gain less benefit from telmisartan treatment than unrelated hypertensive men.

Cardiometabolic Risk Factors in Men with Elevated Macroprolactin Content: A Pilot Study.

BACKGROUND: Macroprolactinemia is a condition associated with the presence of large amounts of high molecular weight complexes of prolactin. Despite high prevalence, clinical significance of macroprolactin remains poorly understood. OBJECTIVE: The aim of this study was to assess cardiometabolic risk in men with isolated macroprolactinemia. METHODS: The study population included 11 men with isolated macroprolactinemia, 14 subjects with monomeric hyperprolactinemia and 14 men with prolactin levels within the reference range. Glucose homeostasis markers, plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D were determined in all included patients. RESULTS: Compared to healthy counterparts, men with isolated macroprolactinemia had higher levels of 2-h postchallenge glucose, hsCRP and fibrinogen, lower levels of 25-hydroxyvitamin D and reduced insulin sensitivity. Patients with monomeric hyperprolactinemia were characterized by increased plasma levels of 2-h postchallenge glucose, triglycerides, uric acid, hsCRP, fibrinogen and homocysteine, reduced insulin sensitivity and decreased plasma concentrations of HDL cholesterol and 25-hydroxyvitamin D. Subjects with isolated macroprolactinemia differed from patients with monomeric hyperprolactinemia in postchallenge plasma glucose, insulin sensitivity, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D. In men with monomeric hyperprolactinemia, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D, while in men with elevated levels of macroprolactin, uric acid, hsCRP, fibrinogen and 25-hydroxyvitamin D correlated with a content of monomeric prolactin or macroprolactin, respectively, as well as with a degree of insulin sensitivity. CONCLUSIONS: The obtained results suggest that macroprolactinemia may increase cardiometabolic risk but to a lesser extent than monomeric hyperprolactinemia.

The Impact of Ethinyl Estradiol on Metformin Action on Prolactin Levels in Women with Hyperprolactinemia.

BACKGROUND: Metformin reduced prolactin levels only in women with hyperprolactinemia. OBJECTIVE: The purpose of this case-control study was to compare metformin action on lactoctrope function between women receiving oral contraceptive pills and women not using hormonal contraception. METHODS: The study included two groups of matched women with elevated prolactin levels and new-onset prediabetes or diabetes. The first group consisted of 20 women using oral contraceptive pills for at least 12 months before entering the study, while the second group included 20 patients not using any hormonal contraception. Over the whole study period, all women were treated with metformin (1.7-3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, adrenocorticotropic hormone, gonadotropins and insulin-like growth factor-1 were measured at the beginning and at the end of the study (16 weeks later). RESULTS: Thirty-eight patients completed the study. Metformin reduced plasma glucose levels and improved insulin sensitivity but the latter effect was stronger in women receiving oral contraceptive pills than in women not using any contraception. Although metformin treatment decreased plasma prolactin levels in both study groups, this effect was stronger in women taking oral contraceptive pills. Only in this group of women, metformin increased plasma luteinizing hormone levels. The changes in plasma prolactin correlated with their baseline insulin sensitivity and the effect of metformin on insulin sensitivity. Metformin did not affect plasma levels of thyrotropin, free thyroxine, free triiodothyronine, follicle-stimulating hormone, adrenocorticotropic hormone and insulin-like growth factor-1. CONCLUSIONS: The obtained results suggest that the effect of metformin on overactive lactotropes depends on estrogen levels.

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 impact of atorvastatin on cardiometabolic risk factors in brothers of women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are characterized by increased cardiometabolic risk. The aim of the current study was to compare the impact of atorvastatin on plasma levels of cardiometabolic risk factors between men whose sisters had either PCOS or were unaffected. METHODS: The study population consisted of two age-, fat-free mass index-, blood pressure- and plasma lipid-matched groups of men with elevated total and LDL cholesterol levels: 20 brothers of PCOS probands (group 1) and 20 brothers of healthy women (group 2). Both groups were then treated with atorvastatin (40 mg daily) for the following 6 months. At the beginning and at the end of the study, we assessed plasma lipid levels, glucose homeostasis markers and levels of dehydroepiandrosterone sulfate, testosterone, bioavailable testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen and 25-hydroxyvitamin D. RESULTS: At the beginning of the study, both treatment arms differed in the degree of insulin resistance, calculated bioavailable testosterone, as well as in plasma levels of dehydroepiandrosterone sulfate, uric acid, hsCRP and 25-hydroxyvitamin D. Although atorvastatin reduced total and LDL cholesterol levels, this effect was stronger in group 2 than group 1. In group 2, atorvastatin exerted also a more potent impact on hsCRP, fibrinogen and homocysteine. An unfavorable impact on insulin sensitivity was observed only in group 1; while, statistically significant changes in uric acid and 25-hydroxyvitamin D levels were found only in group 2. CONCLUSION: The obtained results suggest that cardiometabolic effects of atorvastatin are less pronounced in male siblings of PCOS probands than in brothers of unaffected women.

Plasma gonadotropin levels in metformin-treated men with prediabetes: a non-randomized, uncontrolled pilot study.

Metformin was found to reduce elevated, but not normal, thyrotropin and prolactin levels. This non-randomized, uncontrolled pilot study investigated hypothalamic-pituitary-testicular axis activity in men with primary hypogonadism receiving metformin. The study population included 29 men with prediabetes, 10 of whom had been diagnosed with primary hypogonadism. Throughout the study, the participants were treated with metformin (2.55-3 g daily). Glucose homeostasis markers (fasting glucose, glycated hemoglobin, and HOMA1-IR), as well as circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, thyrotropin, prolactin, estradiol, and creatinine, were assessed at the beginning of the study and 16 weeks later. Both groups differed in baseline gonadotropin and testosterone levels. Fasting glucose, glycated hemoglobin, and HOMA1-IR were lower after than before metformin treatment. The changes in fasting glucose and HOMA1-IR were more pronounced in hypogonadal men than in subjects with testosterone levels within the reference range. Only in hypogonadal men, plasma concentrations of FSH and LH were lower at the end than at the beginning of the study. Levels of the remaining hormones remained unchanged throughout the study period. The reduction in FSH and LH levels correlated with their baseline levels and with the changes in HOMA1-IR. The results of our study suggest that metformin may decrease FSH and LH levels in men with hypergonadotropic hypogonadism.

The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study.

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.