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Low prolactin levels have been found to impair libido and arousal, as well as to reduce wellbeing in young women.The aim of this study was to investigate whether drug-induced hypoprolactinaemia affects male sexual function and depressive symptoms.The study population consisted of three groups of young and middle-aged men. Two groups were treated with dopamine agonists because of previous hyperprolactinaemia but differed in current prolactin levels, which were3ng/ml (n=12; group 1) or within the reference range (3-20ng/ml) (n=20; group 2). The control group (group 3) included 24 dopamine agonist-naïve normoprolactinaemic men. During the study, doses of dopaminergic agents in group 1 were reduced by 25-50% compared to doses before the start of the study. Circulating levels of prolactin, testosterone, free calculated testosterone, dehydroepiandrosterone-sulphate, oestradiol and gonadotropins were measured upon enrolment in the study and six months later. Moreover, at the beginning and the end of the study, all men enrolled completed questionnaires assessing sexual functioning (IIEF-15) and depressive symptoms (BDI-II).Group 1 differed from groups 2 and 3 in domain scores for sexual desire and erectile function, and in the overall BDI-II score. It was also characterised by lower levels of total testosterone and calculated free testosterone. Reduction of drug doses normalised sexual desire and erectile function, reduced BDI-II scores and increased prolactin as well as total and free calculated testosterone. Groups 2 and 3 did not differ from each other in sexual functioning, depressive symptoms or hormone levels.The results obtained indicate that men with dopamine agonist-induced hypoprolactinaemia are characterised by impaired sexual functioning and reduced wellbeing. These disturbances are a consequence of subnormal prolactin levels and do not seem to reflect adverse effects of dopamine agonists.

Background Nonalcoholic fatty liver disease (NAFLD) awareness is low. NAFLD diagnosis and management by gastroenterologists (GEs) and general practitioners (GPs) in Poland were evaluated. Methods RESTORE was an observational, noninterventional, retrospective cross-sectional survey performed among GEs and GPs with at least 3 years' experience. Computer-assisted web interviews were completed. GEs provided information from patient records. Results Mean experience was 14.2 (95 GEs) and 22.6 (115 GPs) years. Mean patient numbers with liver disorders consulted per month were 36 (13%; GEs) and 51 (6%; GPs); ~50% were patients with NAFLD. All GEs/GPs used ultrasound; most evaluated transaminases and gamma-glutamyl transferase. More GEs used other imaging techniques and a larger spectrum of laboratory tests than GPs. Physician-identified NAFLD key symptoms were similar for GEs/GPs. GEs noticed less obvious symptoms (abdominal discomfort, drowsiness, fatigability, lack of energy) vs. GPs (abdominal pain/discomfort, dyspepsia). Common comorbidities in NAFLD were similar in GE/GP responses. NAFLD interventions by GEs/GPs (% patients) were diet/lifestyle/pharmacological interventions (54%/59%), diet/lifestyle changes alone (41%/31%) or pharmacological interventions alone (5%/10%). The top three criteria for supportive pharmacological selection were efficacy, tolerability and quality of life improvement for GEs/GPs. The five supportive treatments most commonly prescribed by GEs/GPs were essential phospholipids, ursodeoxycholic acid, timonacic, silybinin/silymarin and ornithine + choline. Information from patient records (n = 380) confirmed GEs responses. Conclusions NAFLD is not a silent disease as physicians and patients reported many, albeit nonspecific, symptoms. This cross-sectional survey provides important insights into clinical management of NAFLD by GEs and GPs in Poland.

What is known and objective Metformin was found to reduce elevated gonadotropin levels. The aim of the present study was to determine whether metformin modulates the impact of discontinuation of testosterone therapy on hypothalamic-pituitary-gonadal axis activity and sexual function in men with low testosterone levels. Methods The study included 28 men with late-onset hypogonadism (defined according to the criteria of the European Male Aging Study group) receiving testosterone undecanoate (120 mg in three equal doses), 12 of whom had been treated with oral metformin (1.7-3 g daily). Both testosterone and metformin had been administered for at least six months before enrolment. In all patients, testosterone replacement required to be discontinued. The control group included 16 testosterone- and metformin-treated men with late-onset hypogonadism who during the entire study period continued their treatment. Glucose homeostasis markers, as well as plasma levels of insulin, gonadotropins, testosterone, calculated bioavailable testosterone, dehydroepiandrosterone-sulphate, oestradiol, thyrotropin, free thyroxine, prolactin, insulin-growth factor-1 and cortisol were measured at the beginning of the study and four months later. Moreover, at the beginning and the end of the study, all enrolled patients completed a questionnaire assessing their sexual functioning (IIEF-15). Results and discussion Discontinuation of testosterone therapy resulted in a decrease in total testosterone and bioavailable testosterone (by 42% and 45% in metformin-treated patients, and by 52% and 54% in metformin-naive patients), as well as impaired all aspects of male sexual function. Changes in bioavailable testosterone, as well as in erectile function, orgasmic function and sexual desire were less pronounced if subjects received metformin. Only in metformin-naive men, follow-up FSH and LH levels were higher than at baseline (by 75% and 62%). Moreover, discontinuation of testosterone therapy in metformin-naive men increased glycated haemoglobin, as well as worsened insulin sensitivity. There were no differences between baseline and follow-up levels of the remaining hormones. In metformin-naive subjects, the increase in gonadotropin levels correlated with the changes in testosterone levels and insulin sensitivity. No effect on glucose homeostasis markers, hormone levels and sexual functioning was observed in the control group. What is new and conclusion The obtained results suggest that metformin treatment mitigates the unfavourable effect of discontinuation of testosterone treatment on hypothalamic-pituitary-testicular axis activity and sexual function in men with late-onset hypogonadism.

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.

What is known and objective Metformin was found to normalize secretory function of overactive pituitary cells. Its effect on circulating thyrotropin levels was more pronounced in women receiving exogenous vitamin D. The aim of the current study was to investigate whether vitamin D status determines the impact of metformin on prolactin levels in premenopausal women with hyperprolactinaemia. Methods The study population consisted of three groups of women with prediabetes and elevated prolactin levels: vitamin D-naive women with vitamin D insufficiency (group 1; n = 19), women receiving vitamin D preparations because of vitamin D deficiency (group 2 n = 20), as well as vitamin D-naive women with normal vitamin D status (group 3 n = 23). All participants were then treated with metformin (2.55-3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin were determined at baseline and six months later. Results and discussion At baseline, prolactin levels were higher in group 1 than in the remaining groups of patients. Although metformin decreased glucose levels and improved insulin sensitivity in all treatment groups, this effect was more pronounced in groups 2 and 3. Only in subjects with 25-hydroxyvitamin D levels within the reference range, metformin reduced prolactin levels. The impact on prolactin levels correlated with 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. The drug produced a neutral effect on circulating levels of thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin D. What is new and the conclusion The results of the current study suggest that the impact of metformin on secretory function of overactive lactotropes depends on the vitamin D status of patients.

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.

Cardiovascular diseases are the leading cause of mortality worldwide. Prevention, diagnosis and treatment of these diseases are one of the major challenges in modern medicine. Despite a large number of pharmacological agents significantly reducing the cardiovascular risk, it is still high in many patients. Due to the multifactorial aetiology and complex pathomechanism of cardiovascular diseases, the development of a more effective therapy remains an open issue. It was found in the 1980s that a diet rich in polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid in particular, was associated with a lower incidence of cardiovascular diseases. For this reason, polyunsaturated fatty acids have become the subject of many clinical trials aimed at understanding their mechanism of action and determining their exact impact on cardiovascular risk. Polyunsaturated fatty acids are known to affect many aspects that are key factors in the development of cardiovascular disease. They are characterised mainly by a positive effect on the structure and functioning of cell membranes, the ability to reduce inflammation and blood pressure, anticoagulant and antiplatelet effects, antiarrhythmic activity, the ability to improve myocardial contractility and a beneficial effect on the lipid profile. The latest analyses of the available clinical trials show that these compounds reduce cardiovascular risk in both primary and secondary prevention. Therefore, they represent a promising therapeutic option. It is worth noting that the effect seems to depend on the type of polyunsaturated fatty acids, their dose and individual factors. Nevertheless, this issue is extremely complex and requires further research to fully understand the mechanism of action and establish ideal therapeutic doses to improve patient prognosis.

Streszczenie Konwertazy probiałkowe (PCs, proprotein convertases) to rodzina 9 proteaz serynowych (PC1/3, PC2, furyna, PC4, PC5/6, PACE4, PC7, SKI-1), której przedstawicielem jest również konwertaza probiałkowa typu 9 o aktywności subtylizyny/keksyny (PCSK9). Poszczególni członkowie tej rodziny, są głównym elementem w potranslacyjnej obróbce białek prekursorowych, prowadzącej do powstania biologicznie czynnych cząsteczek, takich jak hormony, enzymy, czynniki transkrypcyjne oraz czynniki wzrostu. W związku ze zdolnością aktywacji dużej liczby substratów, PCs odgrywają znaczącą rolę w przebiegu procesów fizjologicznych, takich jak embriogeneza, aktywność ośrodkowego układu nerwowego, metabolizm lipidów, a także w stanach patofizjologicznych m.in. infekcjach wirusowych i bakteryjnych, osteoporozie, hiperglikemii, chorobach sercowo-naczyniowych, neurodegeneracyjnych oraz nowotworowych. Zahamowanie funkcji konwertazy proproteiny typu 9 o aktywności subtylizyny/keksyny (PCSK9, proprotein convertase subtilisin/kexin 9) przez przeciwciała, takie jak alirokumab czy ewolokumab zmniejsza tempo degradacji receptora LDL (lipoproteina o małej gęstości). Wiąże się to z redukcją stężenia cholesterolu LDL w osoczu, którego normalizacja jest jednym z głównych celów służących ograniczeniu ryzyka sercowo-naczyniowego. Inhibitory PCSK9 (alirokumab, ewolokumab, bococizumab) zostały stworzone m.in. z myślą o pacjentach, u których mimo stosowania optymalnych dawek dostępnych leków hipolipemizujących (statyn, ezetymibu) nie udało się uzyskać pożądanych wartości stężeń cholesterolu LDL we krwi. Wydaje się, że ze względu na dużą skuteczność, przyszłe zastosowanie inhibitorów PCSK9 (PCSK9i) w codziennej praktyce klinicznej będzie bardziej powszechne. Uwzględniając działania plejotropowe substancji dotychczas stosowanych w hiperlipidemii, takich jak statyny, omówiono piśmiennictwo pod kątem innych, poza hipolipemizującymi, możliwych skutków działania inhibitorów PCSK9 oraz oceniono ich potencjalne zalety lub wady.

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.

What is known and objective Metformin was found to reduce thyrotrophin levels in subjects with hypothyroidism. This case-control study was aimed at comparing metformin action on hypothalamic-pituitary-thyroid axis activity between levothyroxine-treated and levothyroxine-naive women with non-autoimmune thyroid hypofunction. Methods The study included two groups of thyroid antibody-negative women with thyrotrophin levels in the range between 4.5 and 10 mIU/L and untreated prediabetes, matched for age, body mass index, thyrotrophin levels and glucose homeostasis markers. The first group had been treated for at least 6 months with levothyroxine, whereas the second group had not received thyroid hormones. All these women were then managed with metformin (3 g daily). Circulating levels of glucose, insulin, glycated haemoglobin, thyrotrophin, total and free thyroid hormones and prolactin were assessed at baseline and 6 months later. Results and discussion Thirty-two women (16 in each treatment arm) completed the study. At baseline, both groups differed only in free and total thyroxine levels. Metformin reduced glucose levels and glycated haemoglobin, improved insulin sensitivity and decreased thyrotrophin levels. The impact on insulin sensitivity and thyrotrophin was stronger in women simultaneously treated with levothyroxine than in women not receiving this hormone. In levothyroxine-treated patients, metformin slightly reduced prolactin levels. In both study groups, metformin treatment exerted a neutral effect on free and total thyroxine and triiodothyronine. The thyrotrophin-lowering effect of metformin correlated with the improvement in insulin sensitivity and in levothyroxine-treated women with the changes in prolactin levels. What is new and conclusion The obtained results suggest that metformin/levothyroxine combination therapy may be an interesting treatment option in women with non-autoimmune hypothyroidism poorly tolerating high-dose levothyroxine treatment.

Objective Dopamine agonist treatment may result in hypersexuality in men. The aim of this study was to investigate for the first time female sexual functioning and depressive symptoms in women with very low prolactin levels. Design A prospective case-control study. Patients and measurements The study population consisted of three age-matched groups of young women with normal, regular menstrual cycles: 15 subjects with cabergoline-induced hypoprolactinaemia (group A), 25 cabergoline-treated individuals with prolactin levels within the reference range (group B) and 30 dopamine agonist-naive women with normoprolactinemia. Because of low prolactin levels, the dose of cabergoline in group A (but not in group B) was then reduced. Apart from measuring serum levels of prolactin, testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulphate, estradiol and gonadotropins, at the beginning of the study and 6 months later, all included women filled in questionnaires evaluating female sexual function (FSFI) and depressive symptoms (BDI-II). Results At the beginning of the study, there were no differences between groups B and C in the mean total FSFI score, all domain scores and in the BDI-II score. In group A, the total FSFI score and domain scores for desire and arousal were lower, while the BDI-II score was higher than in the remaining study groups. Compared with groups of B and C, women with cabergoline-induced hypoprolactinaemia were also characterized by lower total testosterone levels and lower values of the free androgen index. Cabergoline dose reduction normalized the FSFI score, desire, arousal, the BDI-II score, as well as normalized prolactin, total testosterone and the free androgen index. Conclusions The obtained results suggest that dopamine agonist-induced hypoprolactinaemia impairs sexual functioning and well-being in young women, as well as that these disturbances are secondary to low prolactin levels, not to specific properties of cabergoline.

What is known and objective 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. Methods This case-control study included 32 prediabetic women with Hashimoto's thyroiditis, high-normal thyrotropin levels (2.5-4.5 mIU/L) and vitamin D insufficiency. Based on patient preference, these individuals received either metformin (3 g daily) plus vitamin D (4000 IU daily) (n = 17) or were treated with only metformin (3 g 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 6 months later. Results and discussion 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. What is new and conclusion 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.

WHAT IS KNOWN AND OBJECTIVE Vitamin D administered together with selenomethionine has been reported to markedly reduce thyroid antibody titres in patients with autoimmune thyroiditis. Hyperprolactinaemia exerts a complex pro-inflammatory effect. This study was aimed at investigating whether prolactin excess determines the effect of vitamin D/selenomethionine combination therapy on thyroid autoimmunity. METHODS The study included two age-, body mass index-, hormone- and thyroid antibody-matched groups of young euthyroid women with Hashimoto's thyroiditis: 19 women with mild-to-moderate hyperprolactinaemia and 19 individuals with prolactin levels within the reference range. All participants were then treated with vitamin D (4000 IU daily) and selenomethionine (200 µg daily). Serum titres of thyroid peroxidase and thyroglobulin (TgAb) antibodies, serum levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin and 25-hydroxyvitamin D, as well as the calculated parameters of thyroid homeostasis, were determined at baseline and 6 months later. RESULTS AND DISCUSSION All women completed the study. With the exception of prolactin and 25-hydroxyvitamin D levels, there were no differences between the study groups in the investigated parameters. In both study groups, vitamin D/selenomethionine combination therapy reduced thyroid peroxidase and TgAb antibody titres, decreased the free thyroxine:free triiodothyronine ratio and increased 25-hydroxyvitamin D levels and SPINA-GD. The decrease in antibody titres, as well as the improvement in vitamin D status, was more pronounced in subjects with prolactin levels within the reference range than in subjects with hyperprolactinaemia and was inversely correlated with prolactin levels. Moreover, only in normoprolactinaemic women, the treatment reduced thyrotropin levels and increased SPINA-GT. WHAT IS NEW AND CONCLUSION The obtained results suggest that hyperprolactinaemia attenuates the impact of vitamin D/selenomethionine combination on thyroid autoimmunity.

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.

Background Autoimmune (Hashimoto’s thyroiditis) is characterized by a strong female preponderance, which may suggest that sex hormones have an impact on thyroid autoimmunity. The aim of this study was to investigate whether testosterone determines vitamin D action on thyroid antibody titers and thyroid function tests in men with autoimmune thyroiditis and low testosterone levels. Methods The study included 36 men with testosterone deficiency, 17 of whom had been treated for at least 26 weeks with oral testosterone undecanoate (120 mg daily). Because of coexistent euthyroid Hashimoto’s thyroiditis, all participants were then treated with vitamin D (100 μg daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin, free thyroid hormones, testosterone and 25-hydroxyvitamin D, as well as Jostel’s thyrotropin index, SPINA-GT and SPINA-GD were assessed before vitamin D treatment and 26 weeks later. Results With the exception of testosterone levels, there were no significant differences between both study groups in serum hormone levels, antibody titers and thyroid function tests. All participants completed the study. In addition to increasing 25-hydroxyvitamin D levels, vitamin D increased SPINA-GT and reduced thyroid peroxidase and thyroglobulin antibody titers. In testosterone-treated men, vitamin D increased testosterone levels. Vitamin D did not affect serum levels of thyrotropin, free thyroid hormones, Jostel’s thyrotropin index and SPINA-GD. Treatment-induced changes in thyroid antibody titers and SPINA-GT were more pronounced in testosterone-treated than testosterone-naive men. Conclusions The obtained results suggest that the beneficial effect on thyroid autoimmunity and thyroid secretory function is stronger in men receiving testosterone therapy.

Metformin was found to reduce elevated prolactin levels in women but not in men. The current study was aimed at investigating whether endogenous testosterone determines the impact of metformin on lactotroph function in men. This prospective case-control study included 28 men with recently diagnosed type 2 diabetes mellitus and mild or moderate hyperprolactinaemia, 14 of whom had low testosterone levels, while in the remaining 14 ones' testosterone levels were within the reference range. All participants received metformin (2.55-3 g daily) for the following 4 months. Circulating levels of glucose, insulin, prolactin, testosterone, oestradiol, gonadotropins, sex hormone-binding globulin adrenocorticotropic hormone, insulin-like growth factor-1, thyrotropin and free thyroid hormones were measured at the beginning and at the end of the study. Although metformin reduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels. Only in patients with abnormally low testosterone levels, the drug decreased prolactin levels. This effect, which was accompanied by an increase in luteinizing hormone levels, was inversely correlated with baseline testosterone and calculated free testosterone levels, and positively with treatment-induced improvement in insulin sensitivity. In both treatment groups, metformin produced a neutral effect on plasma levels of the remaining hormones. The obtained results suggest that endogenous testosterone may attenuate the impact of metformin on lactotropic cells.

Introduction: The predominance of high-molecular-weight forms of prolactin in plasma is referred to as macroprolactinaemia. Unlike monomeric hyperprolactinaemia, no previous study has investigated cardiometabolic risk factors in subjects with elevated macroprolactin content. Material and methods: We studied two age-, weight-, and blood pressure-matched groups of premenopausal women: 11 women with macroprolactinaemia and 11 women with prolactin levels within the reference range. The outcomes of interest included: 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. Results: Circulating levels of hsCRP and 2-h postchallenge plasma glucose, as well as the homeostatic model assessment 1 of insulin resistance ratio, were higher, while levels of HDL cholesterol and 25-hydroxyvitamin D were lower in women with macroprolactinaemia than in women without elevated levels of prolactin. In women with elevated levels of big-big prolactin, values of hsCRP and 25-hydroxyvitamin D correlated with the degree of insulin resistance and, similarly to HDL cholesterol and 2-h postchallenge plasma glucose, with macroprolactin content. There were no differences between the study groups in concentrations of fasting glucose, total cholesterol, LDL cholesterol, triglycerides, uric acid, fibrinogen, and homocysteine. Conclusions: The obtained results indicate that young women with macroprolactinaemia seem to be characterised by slightly increased cardiometabolic risk.

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.

Background Elevated prolactin levels were found to be associated with impaired sexuality. Study question The aim of the study was to compare the impact of bromocriptine and cabergoline on sexual functioning in both genders. Study design The study enrolled 39 young women and 18 young men receiving bromocriptine treatment. In 19 women and 8 men, because of poor tolerance, bromocriptine was replaced with cabergoline, whereas the remaining ones continued bromocriptine treatment. Measures and outcomes Apart from measuring serum levels of prolactin and insulin sensitivity, at the beginning of the study and 16 weeks later, all included patients completed questionnaires evaluating female or male sexual functioning (Female Sexual Function Index; International Index of Erectile Function-15). Results Irrespective of the gender, posttreatment prolactin levels were lower in cabergoline-treated patients than in bromocriptine-treated patients. Baseline sexual functioning did not differ between patients well and poorly tolerating bromocriptine treatment. Neither in men nor in women receiving bromocriptine, posttreatment sexual functioning differed from baseline one. In both genders, cabergoline improved sexual desire. Moreover, in men, the drug improved erectile and orgasmic function, whereas in women, it improved sexual arousal. All these effects correlated with the impact of this drug on prolactin levels and on insulin sensitivity. Conclusions Cabergoline is superior to bromocriptine in affecting male and female sexual functioning and should be preferred in hyperprolactinemic men and women with sexual dysfunction.

Hashimoto (autoimmune) thyroiditis develops much less frequently in men than in women, suggesting that androgens have a protective effect against thyroid autoimmunity. The current study was aimed at investigating whether the effect of selenomethionine on thyroid antibody titers and thyroid function tests in euthyroid men with autoimmune thyroid disease depends on testosterone levels. The study population consisted of 2 age-matched, weight-matched, and thyroid antibody titer-matched groups of euthyroid men with Hashimoto thyroiditis and testosterone deficiency: 18 patients receiving intramuscular testosterone enanthate (100 mg once weekly) and 19 testosterone-naive men. All subjects were than treated with selenomethionine (200 µg daily) for 6 months. Serum titers of thyroid antibodies, thyrotropin, free thyroid hormones, and testosterone as well as calculated parameters of thyroid homeostasis were assessed at the beginning and at the end of the study. At baseline, except for testosterone, there were no differences between the 2 treatment arms in thyroid antibody titers, serum hormone levels, or values of all calculated indices. Although selenomethionine reduced thyroid peroxidase and thyroglobulin antibody titers in both treatment arms, these effects were stronger in testosterone-treated than in testosterone-untreated men. Only in men receiving testosterone, selenomethionine altered the free thyroxine/free triiodothyronine ratio, testosterone levels, and structure parameter interference approach-GT and structure parameter interference approach-GD. Selenomethionine-induced changes in thyroid antibody titers correlated with the effect of treatment on structure parameter interference approach-GT and testosterone. The obtained results suggest that testosterone determines the strength of selenomethionine action in euthyroid men with autoimmune thyroiditis.

Objective Despite high prevalence in a female population, surprisingly little is known about sexual functioning of women with thyroid hyperfunction. This study was aimed at assessing female sexual function and depressive symptoms in women with overt hyperthyroidism of autoimmune and non-autoimmune origin. Study design The study included three age-matched groups of young women inhabiting the Upper Silesia (a selenium-deficient and iodine-sufficient area): individuals with overt hyperthyroidism induced by Graves’ disease (group A, n = 31), women with overt hyperthyroidism caused by toxic multinodular goiter or toxic adenoma (group B, n = 30) and women with normal thyroid function (group C, n = 34). Apart from measuring serum hormone levels, serum antibody titers and determining calculated parameters of thyroid homeostasis, all women completed questionnaires evaluating femalesexual function (FSFI) and depressive symptoms (BDI-II). Results The mean total FSFI score and all domain scores were lower while the overall BDI-II score was higher in both groups of women with overt hyperthyroidism than in the control group, and correlated with thyrotropin and free thyroid hormone levels, as well as with the SPINA-GT index. The FSFI score as well as domain scores for desire, arousal and sexual satisfaction were lower, while the BDI-II score was higher in group A than in group B. In group A, the total FSFI score, desire, arousal, sexual satisfaction and severity of depressive symptoms correlated with TRAb and TPOAb titers. Conclusion The obtained results suggest that excessive thyroid hormone production and thyroid autoimmunity have an additive effect on sexual functioning and mood.

Colchicine is an effective anti-inflammatory agent used to treat gout, coronary artery disease, viral pericarditis, and familial Mediterranean fever. It has been found to act by preventing the polymerization of the protein called tubulin, thus inhibiting inflammasome activation, proinflammatory chemokines, and cellular adhesion molecules. Accumulating evidence suggests that some patients with coronavirus disease 2019 (COVID-19) suffer from "cytokine storm" syndrome. The ideal anti-inflammatory in this setting would be one that is readily available, cheap, orally administered, with a good safety profile, well-tolerated, and that prevents or modulates inflammasome activation. The researchers selected colchicine for their study. This paper is a review of the literature describing the effects of colchicine, which is a drug that is being increasingly used, especially when standard therapy fails. Colchicine was shown to reduce inflammatory lung injury and respiratory failure by interfering with leukocyte activation and recruitment. In this publication, we try to systematically review the current data on new therapeutic options for colchicine. The article focuses on new data from clinical trials in COVID-19, rheumatic, cardiovascular, and other treatment such as familial Mediterranean fever, chronic urticaria, and PFAPA syndrome (periodic fever, aphthous, stomatitis, pharyngitis, and cervical adenitis). We also summarize new reports on the side effects, drug interactions, and safety of colchicine.

Metformin was found to reduce elevated thyrotropin levels in subjects with hypothyroidism. The impact on thyrotropin levels was stronger in women receiving oral contraceptive pills than in women not using any contraception. The aim of the present study was to determine whether physiological levels of oestradiol determine the effect of metformin on hypothalamic-pituitary-thyroid axis activity. The study population included 40 postmenopausal women with prediabetes and untreated non-autoimmune subclinical hypothyroidism, using (group A; n = 18) or not using (group B; n = 22) oestradiol replacement therapy. Over the entire study periods, all subjects were treated with metformin (2.55-3.00 g daily). Plasma levels of glucose, lipids, insulin, thyrotropin, free thyroxine, free triiodothyronine, prolactin, gonadotropins and oestradiol were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning of the study and 6 months later. At entry, both groups differed in gonadotropin and oestrogen levels. Despite improving insulin sensitivity, thyrotropin levels and Jostel's thyrotropin index in both study groups, these effects were stronger in group A than group B. Only in group A, metformin increased SPINA-GT, while only in group B the drug decreased FSH levels. Levels of the other variables remained at a similar level throughout the study. The effect of treatment on thyrotropin levels correlated with its baseline values, as well as with the improvement of insulin sensitivity. The results obtained suggest that the impact of metformin on hypothalamic-pituitary-thyroid axis activity depends on the oestrogen status of patients.

Introduction: Administration of testosterone or dehydroepiandrosterone to subjects with low levels of these hormones was found to reduce thyroid antibody titres. Male-pattern baldness is accompanied by mildly increased androgen levels. The present study was aimed at investigating whether early-onset androgenetic alopecia determines the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity in young men with autoimmune hypothyroidism. Material and methods: The study included 2 thyroid-antibody-matched groups of men with autoimmune hypothyroidism: subjects with early-onset androgenetic alopecia (group 1; n = 24) and subjects with no evidence of hair loss (group 2; n = 24). All patients were treated with exogenous levothyroxine. Circulating titres of thyroid peroxidase and thyroglobulin antibodies, as well as levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin, total testosterone, calculated bioavailable testosterone, dehydroepiandrosterone-sulphate, and oestradiol were measured before levothyroxine treatment and 6 months later. Results: In both study groups, levothyroxine decreased thyroid antibody titres, reduced thyrotropin levels and increased free thyroid hormone levels. However, these effects were less pronounced in the men with early-onset male-pattern baldness than in the control men. The degree of reduction in antibody titres and thyrotropin levels correlated with baseline levels of total and calculated bioavailable testosterone, as well with baseline insulin sensitivity and treatment-induced improvement in insulin sensitivity. Concentrations of the remaining variables remained unchanged throughout the study period. Conclusions: The results of the current study suggest that the benefits of levothyroxine therapy in men with autoimmune hypothyroidism are less pronounced in individuals with early-onset androgenetic alopecia.

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 6 months 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.

Women with polycystic ovary syndrome are at a high cardiometabolic risk. Early-onset male-pattern baldness is considered the phenotypic equivalent of polycystic ovary syndrome in men. The aim of this study was to assess whether early-onset androgenetic alopecia modifies cardiometabolic effects of lisinopril in men with arterial hypertension. The study population consisted of 62 young men with grade 1 hypertension, 31 of whom were diagnosed with early-onset male-pattern baldness (group A). Thirty-one blood pressure-matched men with normal hair growth (group B) served as a control group. All participants were treated with lisinopril (10-40 mg daily). Blood pressure, glucose homeostasis markers, urinary albumin-to-creatinine ratio (UACR), as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, total and calculated free testosterone, dehydroepiandrosterone sulfate, and estradiol were assessed before lisinopril treatment and 6 months later. At baseline, levels of all cardiometabolic risk factors were higher in group A than group B. Although lisinopril reduced systolic and diastolic blood pressure, UACR, hsCRP, and fibrinogen in both study groups, these effects were stronger in group B than in group A. Only in group B, the drug decreased levels of uric acid and homocysteine, as well as improved insulin sensitivity. The impact of lisinopril on uric acid, hsCRP, fibrinogen, homocysteine, and UACR correlated weakly with its hypotensive properties, androgen levels, and insulin sensitivity. The obtained results suggest that cardiometabolic effects of lisinopril in men are less pronounced in case of coexisting early-onset androgenetic alopecia.

Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.

Background Early-onset androgenic alopecia is regarded as the phenotypic equivalent of polycystic ovary syndrome in men. Women with polycystic ovary syndrome are at high risk of autoimmune thyroiditis. The aim of the current study was to investigate whether early-onset androgenic alopecia determines the impact of exogenous vitamin D on thyroid autoimmunity and thyroid function in men with autoimmune thyroiditis. Methods The study included 67 young men with autoimmune thyroiditis, 25 of whom had early-onset androgenic alopecia (group A). All 25 men with alopecia and 23 out of the 42 men with no evidence of hair loss, matched for age, antibody titers and thyrotropin levels (group B), were then treated with vitamin D (100 μg daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin, free thyroid hormones, total and calculated free testosterone, dehydroepiandrosterone-sulfate, estradiol, prolactin and 25-hydroxyvitamin D, as well as the calculated parameters of thyroid homeostasis were assessed before vitamin D treatment and 6 months later. Results At baseline, thyroid antibody titers were higher in subjects with than without alopecia and correlated with calculated free testosterone levels. Vitamin D reduced antibody titers in both groups but this effect was stronger in group B than group A. Only in group B, vitamin D increased SPINA-GT. The impact of vitamin D on antibody titers correlated with 25-hydroxyvitamin D levels, calculated free testosterone, treatment-induced increase in 25-hydroxyvitamin D levels and the improvement in insulin sensitivity. Conclusion This study suggests that euthyroid men with early-onset androgenic alopecia may benefit to a lesser degree from vitamin D treatment than other subjects with autoimmune thyroiditis.

Background Hypothyroidism, hyperprolactinemia, macroprolactinemia and low vitamin D status were found to impair pleiotropic effects of hypolipidemic agents. The aim of the current study was to investigate whether cardiometabolic effects of atorvastatin in men are determined by endogenous testosterone. Methods We studied three groups of men matched for age, BMI, plasma lipids and blood pressure: 19 untreated subjects with low testosterone levels (group A), 19 normotestosteronemic men receiving testosterone preparations (group B) and 21 untreated men with testosterone levels within the reference range (group C). Because of coexistent hypercholesterolemia, all subjects were managed with atorvastatin (40 mg daily) for 6 months. Glucose homeostasis markers, plasma lipids, as well as circulating levels of testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D were determined at the beginning and at the end of the study. Results At baseline, group A was more insulin-resistant and was characterized by higher levels of hsCRP, fibrinogen and homocysteine, and lower levels of 25-hydroxyvitamin D than the remaining groups of patients. Despite reducing total and low-density lipoprotein cholesterol and hsCRP levels in all treatment groups, this effect was stronger in groups B and C than in group A. In groups B and C, atorvastatin use was also associated with a decrease in uric acid, fibrinogen and homocysteine concentrations and with an increase in 25-hydroxyvitamin D levels. In group A, but not in the remaining groups, the drug decreased insulin sensitivity. Conclusion The obtained results suggest that untreated hypotestosteronemia may attenuate cardiometabolic effects of atorvastatin in men.

Introduction Glucagon-like peptide receptors (GLP-R) expression in epicardial (EF) and pericardial (PF) fat depots might be involved in the pathogenesis of cardiovascular (CV) diseases. Objectives We sought to evaluate the messenger RNA (mRNA) expression of GLP-1R and GLP-2R in EF and PF and their associations with the renin-angiotensin-aldosterone system (RAAS) in patients with multivesslel disease coronary artery disease (MVD). Patients and methods Consecutive stable patients with MVD requiring elective coronary artery bypass grafting were enrolled. Clinical data, anthropometric parameters and the quantity of fat depots (cardiovascular magnetic resonance and abdominal ultrasound) were obtained. The fat samples (EF, PF, subcutaneous [SF]) were taken from patients during cardiac surgery. Relative mRNA expression of GLP-1R, GLP-2R and RAAS components (Angiotensin II Receptor Type 1 [AGTR1], Angiotensinogen [AGT], Angiotensin I Converting Enzyme 1 [ACE1] and Angiotensin I Converting Enzyme 2 [ACE2]) were assessed in those fat depots. Results Fifty-three patients (64.7 [7.4] years) were included in the final analysis. We found that only GLP-2R relative expression were lower in PF and compared to SF (reference). Ultrasound abdominal fat depots were associated with both GLP-1R and GLP-2R in PF. GLP-1R and GLP-2R showed significant correlations with RAAS components, in both EF and PF depots. Conclusions In stable patients with MVD, the relative mRNA expression for both GLP receptors revealed significant associations with majority of analysed RAAS components.

Background: he internal mammary artery (IMA) is routinely used as an arterial graft for coronary artery bypass grafting with an excellent long‑term patency rate, but its protective mechanism is unclear. Aims: We evaluated the differences between the expression of several gene in perivascular adipose tissue from the IMA (PVAT‑IMA) as compared with other fat depots in patients with severe coronary artery disease. Methods: A total of 53 patients (13 women) with severe coronary artery disease and preserved left ventricular ejection fraction were scheduled for coronary artery bypass grafting. Clinical assessment, anthropometric parameters, and quantification of fat depots were performed in all patients. The relative expression of the following genes were obtained in PVAT‑IMA, as well as epicardial, pericardial, and subcutaneous (SF) fat samples: angiotensinogen (AGT), angiotensin I converting enzyme 1 and 2 (ACE1and ACE2), glucagon‑like peptide receptors type 1 and 2 (GLP1R and GLP2R), phospholipid transfer protein (PLTP), adiponectin (ADIPOQ), omentin‑1 (ITLN1), and uncoupling protein 1 (UCP1). Results: The expression of UCP1 (median [interquartile range [IQR], 2.5 [0.91–16.6]; P < 0.01) and AGT(2.22 [0.65–6.2]; P < 0.01) was higher in PVAT‑IMA compared with the SF depot. ADIPOQ expression was lower in pericardial and epicardial fat depots (median [IQR], 0.44 [0.23–2.3]; P < 0.01). The expression of ITLN1 was increased in PVAT‑IMA as compared with epicardial and pericardial fat (P < 0.001). Conclusions: PVAT‑IMA revealed differences in the expression of selected genes in relation to SF. We found a higher expression of ITLN1 in PVAT‑IMA compared with other adipose tissue depots, which could be associated with protective mechanisms against atherosclerosis in IMA. However, this remains a subject for further studies.

Vitamin D deficiency is a risk factor for cardiometabolic disease. The aim of this study was to determine the role of vitamin D status in the impact of fenofibrate on plasma levels of cardiometabolic risk factors. The study population (n = 61) consisted of three matched groups of women with atherogenic dyslipidaemia: vitamin D-naive women with vitamin D insufficiency (group A), women receiving vitamin D preparations because of vitamin D deficiency (group B), as well as vitamin D-naive women with normal vitamin D status (group C), who were treated with micronized fenofibrate (200 mg daily). Glucose homeostasis markers, plasma lipids, as well as plasma levels of 25-hydroxyvitamin D, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine were determined at the beginning of the study and 6 months later. At entry, group A was characterized by lower levels of 25-hydroxyvitamin D, reduced insulin sensitivity and higher concentrations of uric acid, hsCRP, fibrinogen and homocysteine. Apart from a weaker effect on HDL-cholesterol and triglycerides in group A, there were no differences between the treatment arms in the effect of fenofibrate on plasma lipids. However, only in groups B and C the drug improved insulin sensitivity and reduced circulating levels of uric acid and hsCRP, as well as increased levels of 25-hydroxyvitamin D and these effects correlated with the degree of improvement in insulin sensitivity. Treatment-induced increase in homocysteine was observed only in group A. The results of the study indicate that cardiometabolic effects of fibrates may depend on the vitamin D status of patients.

Introduction: Although hyperthyroidism is characterised by female predominance, its presence may lead to the development of numerous complications in both sexes. This study was aimed at investigating sexual function and depressive symptoms in men with overt hyperthyroidism of autoimmune and non-autoimmune origin. Material and methods: The study population consisted of three age-matched groups: men with overt hyperthyroidism and Graves’ disease (group A; n = 20), men with overt hyperthyroidism and toxic multinodular goitre or toxic adenoma (group B; n = 21), and men with normal thyroid function (group C; n = 23). As well as measuring serum hormone levels and antibody titres, and determining calculated parameters of thyroid homeostasis, all included patients filled in questionnaires evaluating sexual function (International Index of Erectile Function-15: IIEF-15) and assessing the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition – BDI-II). Results: Compared with control subjects, men with overt hyperthyroidism obtained lower scores for erectile function, intercourse satisfaction, orgasmic function and overall satisfaction. Scores for erectile function, orgasmic function, and sexual desire differed between both groups of men with thyroid hyperfunction and inversely correlated with thyrotropin receptor antibody titres. The BDI-II score was higher in patients with Graves’ disease than in men with normal thyroid function. Conclusions: The obtained results indicate that overt hyperthyroidism in men causes multidimensional impairment of sexual function, which is particularly pronounced if excessive hormone production results from Graves’ disease.

Background Elevated prolactin levels are associated with increased cardiometabolic risk. No previous study has compared the effect of hypolipidemic therapy on plasma levels of lipids and other cardiometabolic risk factors in patients with and without hyperprolactinemia. Methods The study included three age-, weight-, blood pressure- and lipid-matched groups of premenopausal women: 18 women with untreated hyperprolactinemia, 19 women with bromocriptine-treated hyperprolactinemia and 20 drug-naive women with normal prolactin levels. Because of concomitant atherogenic dyslipidemia, all patients were treated with fenofibrate (200 mg daily) for 12 weeks. Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were assessed at baseline and at the end of hypolipidemic treatment. Results Unlike similar baseline lipid levels, plasma concentrations of the remaining investigated cardiometabolic risk factors were higher in women with elevated prolactin levels than in patients with normal prolactin levels. The impact of fenofibrate on total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels, as well as on uric acid, hsCRP, homocysteine, and fibrinogen was less pronounced in women with untreated hyperprolactinemia than in women with bromocriptine-treated hyperprolactinemia and drug-naive women with normal prolactin levels. Conclusions The results of our study indicate that cardiometabolic effects of fenofibrate depend on plasma prolactin levels.

Because of contradictory results, clinical significance of elevated levels of macroprolactin (macroprolactinemia) remains unclear. The aim of this study was to investigate whether macroprolactinemia determines levothyroxine action on hypothalamic-pituitary-thyroid axis activity and thyroid antibody titers in women with autoimmune hypothyroidism. The study population included 2 age-, body mass index-, hormone-, and thyroid antibody-matched groups of premenopausal women with untreated autoimmune subclinical hypothyroidism: 15 subjects with coexisting macroprolactinemia and 29 individuals with prolactin levels within the reference range. All included patients were then treated with levothyroxine for 6 months. Serum levels of thyrotropin, free thyroid hormones, prolactin and 25-hydroxyvitamin D, titers of thyroid peroxidase and thyroglobulin antibodies, as well as macroprolactin content were assessed at the beginning and at the end of the study. Except for 25-hydroxyvitamin D levels and macroprolactin content, there were no significant differences between both study arms in the investigated markers. All participants completed the study. In both treatment arms, levothyroxine treatment decreased thyrotropin levels, increased free thyroxine and free triiodothyronine levels, as well as reduced thyroid peroxidase titers, but this effect was less pronounced in women with macroprolactinemia. In women with normal prolactin levels, levothyroxine reduced also thyroglobulin antibody titers and increased 25-hydroxyvitamin D levels. In this group of patients, treatment-induced changes in hormone levels and thyroid antibody titers correlated with treatment-induced changes in 25-hydroxyvitamin D levels. The obtained results suggest that macroprolactin excess attenuates the impact of levothyroxine on hypothalamic-pituitary-thyroid axis activity and thyroid autoimmunity.

Gestational diabetes mellitus (GDM), i.e. a carbohydrate metabolism disorder at pregnancy, is one of the most common metabolic complications that occur during this period. Pancreatic b-cell dysfunction and insulin resistance during pregnancy are considered the main causes of the condition. It is currently estimated that GDM is confirmed in 1-25% of patients. Diagnosis and appropriate management allow to reduce the risk of complications in newborns and the perinatal mortality rate and also improve the prognosis for mother and offspring. Metformin is taken by many patients before pregnancy due to both previously diagnosed type 2 diabetes and in the treatment of prediabetes, obesity and polycystic ovary syndrome (PCOS) as part of therapy for insulin resistance. The use of metformin in pregnancy has been controversial for many years, particularly in terms of the safety of continuation of drug therapy. Available scientific data indicate both benefits and possible drug-related adverse effects in offspring of metformin-treated patients. This problem is related not only to patients with type 2 diabetes, but also to those with PCOS who are at increased risk of miscarriage, preterm delivery and the diagnosis of GDM in subsequent stages of pregnancy. Conclusive and uniform recommendations for the use of metformin at each stage of pregnancy have not been established yet due to the doubts about the mechanisms of action of the drug, particularly at the cellular level. This review paper presents the current state of knowledge on the use of metformin during pregnancy.

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.

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.

Background Autoimmune thyroid disease is often accompanied by celiac disease. Objective The purpose of this study was to investigate whether a gluten-free diet affects thyroid autoimmunity, hypothalamic-pituitary-thyroid axis activity and thyroid function tests in women with Hashimoto’s thyroiditis and incidentally found positive anti-tissue transglutaminase antibodies. Methods The study included 34 women with autoimmune thyroiditis divided into two group. The patients belonging to the first one (group A, n=16) complied with the gluten-free diet for 6 months, while the remaining patients (group B, n=18) remained without any dietary treatment. Serum titers of thyroid peroxidase and thyroglobulin antibodies, as well as serum levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D were measured at the beginning of the study and 6 months later. Based on thyrotropin and free thyroid hormone levels, Jostel’s thyrotropin index, the SPINA-GT index and the SPINA-GD index were calculated. Results All patients completed the study protocol. In group B, serum thyrotropin and free thyroid hormones levels, serum 25-hydroxyvitamin D levels as well as the calculated indices remained at the similar levels. The gluten-free diet reduced thyroid antibody titers, as well as slightly increased 25-hydroxyvitamin D levels and the SPINA-GT index. In group A, the impact on TPOAb and TgAb titers correlated with the changes in the SPINA-GT index, whereas the impact on TPOAb with the changes in 25-hydroxyvitamin D levels. Conclusions The obtained results suggest that the gluten-free diet may bring clinical benefits to women with autoimmune thyroid disease.

Background Elevated prolactin levels are associated with sexual dysfunction in women. No previous study has investigated the effect of dopamine agonists on sexual functioning in women. Methods The study enrolled 30 young women with mild hyperprolactinemia (serum prolactin levels in the range between 25 and 50 ng/mL), 15 of whom were later treated with bromocriptine (5–10 mg daily), as well as 14 age- and weight-matched healthy women. All women completed a questionnaire evaluating female sexual function (Female Sexual Function Index – FSFI) and a questionnaire evaluating the presence and severity of depressive symptoms (Beck Depression Inventory Second Edition – BDI-II). Results Women with mild hyperprolactinemia had a lower total FSFI score, lower scores in all domains of sexual functioning (desire, arousal, lubrication, and dyspareunia), as well as a lower total BDI-II score than control women. Bromocriptine increased the FSFI score and tended to reduce BDI-II score. Moreover, the drug normalized desire, arousal, lubrication and dyspareunia, as well as improved orgasm and sexual satisfaction and this action correlated with changes in prolactin levels and an improvement in insulin sensitivity. No changes in sexual functioning and depressive symptoms were observed in untreated women with mild hyperprolactinemia and healthy controls. Conclusions Bromocriptine treatment improves female sexual functioning and slightly affects depressive symptoms in women with elevated prolactin levels and this effect is related to its prolactin-lowering and metabolic effects.

Objective Even mild hypothyroidism in pre-menopausal women is accompanied by impaired sexual functioning. The study was aimed at comparing the effect of levothyroxine, administered alone or in combination with liothyronine, on sexual function and depressive symptoms in pre-menopausal women treated because of hypothyroidism. Methods This quasi-randomized, single-blind study included 39 young women receiving levothyroxine treatment who, despite thyrotropin and thyroid hormone levels within normal limits, still experienced clinical symptoms of hypothyroidism. These patients were divided into two groups: group A (n = 20) continued levothyroxine treatment, while group B (n = 19) received levothyroxine/liothyronine combination therapy. At the beginning of the study, and 6 months later, all participants of the study filled in questionnaires evaluating female sexual functioning (Female Sexual Function Index; FSFI) and the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition; BDI-II). Results The study was completed by 37 women. Baseline sexual functioning and depressive symptoms did not differ between the study groups. Neither the total FSFI score nor the domain scores changed throughout the study in women who continued levothyroxine treatment. Compared to levothyroxine administered alone, levothyroxine/liothyronine combination therapy increased scores for two domains: sexual desire and arousal, tended to increase the total FSFI score, as well as tended to decrease the overall BDI-II score. The effect of the combination therapy on sexual function correlated with a treatment-induced increase in serum levels of free triiodothyronine and testosterone. Conclusions The obtained results suggest that levothyroxine administered together with liothyronine is superior to levothyroxine administered alone in affecting female sexual functioning.

Introduction: No previous study has investigated sexual functioning in prediabetic women. Aim: This study was aimed at investigating sexual function in young women with various types of prediabetes. Methods: The study included four groups of women: women with isolated impaired fasting glucose (Group A; n=19), isolated impaired glucose tolerance (Group B; n=18), presence of both impaired fasting glucose and impaired glucose tolerance (Group C; n=18), as well as matched healthy controls (Group D; n=19). All participants completed questionnaires evaluating sexual function (Female Sexual Function Index - FSFI) and the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition – BDI-II). Results: The total FSFI and BDI-II scores were lower in Group C than in the remaining groups of women, while the total FSFI score was lower in Groups A and B than in Group D. Patients with both impaired fasting glucose and impaired glucose tolerance had lower scores in all domains (sexual desire, arousal, lubrication, orgasm, sexual satisfaction and dyspareunia). Compared to Group D, Group A was characterized by lower domain scores for sexual desire and sexual satisfaction, while Group B by lower domain scores for desire, arousal and orgasm. In all groups of prediabetic women, the overall FSFI score correlated negatively with the degree of insulin resistance and weakly with the total BDI-II score. Conclusions: Impaired fasting glucose and impaired glucose tolerance may disturb sexual functioning and induce depressive symptoms.

Background/Aims: Oxidative stress is one of the leading factors contributing to increased mortality in patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT). Cinacalcet is now commonly used in the treatment of sHPT in patients with CKD. The aim of this study was to assess the influence of treatment with cinacalcet on the oxidative stress markers in patients on hemodialysis with sHPT. Methods: In 58 hemodialysed patients with sHPT (parathyroid hormone [PTH] > 300 pg/mL) plasma Advanced Oxidation Protein Products (AOPP), serum total antioxidant capacity – ImAnOx (TAS/TAC), serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 6 months of treatment. Results: Serum PTH concentration decreased significantly from 895 (748–1,070) to 384 (289–510) pg/mL after 6 months of treatment; p < 0.0001. Mean serum concentrations of ­calcium and phosphate remained stable. Plasma AOPP concentration decreased significantly from 152 (126–185) to 49 ­(43–57) µmol/L after 6 months of treatment; p < 0.0001. ImAnOx significantly increased from 260 (251–270) to 272 (264–280) µmol/L; p = 0.04. After 6 months of treatment, a significant, positive correlation was found between ImAnOx and the daily dose of cinacalcet (r = 0.30; p = 0.02). Also, the change of serum ImAnOx during treatment with cinacalcet significantly correlated with the daily dose of cinacalcet r = 0.35; p = 0.01. No significant correlations were found between plasma AOPP concentration or ImAnOx and PTH, or their changes in time. Conclusions: (1) Six-month treatment based on cinacalcet seems to reduce oxidative stress markers in maintenance hemodialysis patients with sHPT. (2) This benefit may be related rather to the direct action of cinacalcet than to the serum PTH concentration decrease.

Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on hypothalamic-pituitary-thyroid axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2.55-3 g daily). Glucose homeostasis markers as well as serum levels of thyrotropin, free thyroid hormones and prolactin were measured at the beginning of the study and 6 months later. Thirty women completed the study. With the exception of prolactin, baseline serum levels of the assessed hormones were comparable in both study groups. Although metformin reduced serum thyrotropin levels in both groups, this effect was more pronounced in the antipsychotic-treated than in the antipsychotic-naive patients. The effect on serum prolactin was observed only in antipsychotic-treated patients. The impact on serum thyrotropin levels correlated with improvement in insulin sensitivity and with a reduction in prolactin levels. Free thyroxine and free triiodothyronine remained at a similar level throughout the study. The obtained results indicate that metformin reduces serum thyrotropin levels in elderly women, and this effect is particularly pronounced in women with diminished dopaminergic transmission.

Background Metformin was found to reduce circulating levels of pituitary hormones. Objective The purpose of this study was to assess whether sex determines the effect of metformin on lactotroph secretory function. Methods The study population included 25 women and 12 men with mildly elevated serum prolactin levels (25–75 ng/mL). Because of concomitant type 2 diabetes, all participants were treated with metformin (3 g daily). Plasma levels of glucose and lipids, HOMA1-IR, serum levels of prolactin, thyrotropin and free thyroid hormones, as well as Jostel’s, SPINA-GT and SPINA-GD indices were assessed at baseline and at the end of metformin treatment. Results The study completed 24 women and 11 men. At baseline, there were no significant differences in circulating levels of glucose and lipids, insulin sensitivity, hormones, Jostel’s, SPINA-GT and SPINA-GD indices between women and men. In both men and women, metformin reduced fasting glucose levels and HOMA1-IR. However, only in women metformin decreased elevated prolactin levels and this effect correlated with an improvement insulin sensitivity, as well as with the impact on SPINA-GT. Conclusions The results of the study suggest that the effect of metformin on serum prolactin levels is sex-dependent.

Background: No previous study has investigated cardiometabolic risk factors in untreated patients with congenital adrenal hyperplasia (CAH).Methods: The study population consisted of 14 premenopausal women with previously untreated non-classic congenital adrenal hyperplasia (NC-CAH) and 20 matched healthy women. Apart from 17-hydroxyprogesterone and androgen levels, the outcomes of interest were glucose homeostasis markers, plasma lipids, plasma levels of uric acid, C-reactive protein, fibrinogen, homocysteine and 25-hydroxyvitamin D, as well as urinary albumin-to-creatinine ratio (UACR).Results: As expected, women with NC-CAH were characterised by higher levels of 17-hydroxyprogesterone and were more insulin-resistant than control women. The mean values of C-reactive protein, fibrinogen, homocysteine and UACR were higher while 25-hydroxyvitamin D levels were lower in subjects with NC-CAH. The investigated cardiometabolic risk factors correlated with androgen levels and insulin sensitivity.Conclusions: The obtained results suggest that the occurrence of NC-CAH in premenopausal women may increase cardiometabolic risk.

WHAT IS KNOWN AND OBJECTIVE 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. METHODS 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 12 months before the beginning of the study. Over the entire study period (4 months), all participants received oral metformin (1.7-3 g 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. RESULTS AND DISCUSSION 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. WHAT IS NEW AND CONCLUSION This study is the first one to have shown that oral oestrogens potentiate the effect of metformin on hypothalamic-pituitary-thyroid axis activity.