RESUMO
Minipuberty is a term describing transient postnatal activation of the hypothalamic-pituitary-gonadal axis, likely playing an important role in the postnatal growth of female genital organs and breasts. Unlike infant boys, there are no data concerning the impact of gestational hypothyroidism on the course of minipuberty in infant girls. Therefore, the aim of the current study was to investigate the reproductive axis and genital organs in daughters of women with thyroid hypofunction during pregnancy. The study population included three matched groups of infant girls: offspring of women with thyroid hypofunction non-substituted or inadequately treated during gestation (group 1), descendants of women adequately substituted throughout pregnancy (group 2), and daughters of healthy women (group 3). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone, and androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate) and urine levels of gonadotropins were measured monthly from month 1 to month 6, once every two months between postnatal months 6 and 12, and once every three months between postnatal months 12 and 18. During each visit, we also determined ovarian volume, uterine length, and breast diameter. Concentrations of FSH, LH, and estradiol were lowest in group 1, and this group was also characterized by the shortest detection period for gonadotropins and estradiol. These differences were paralleled by differences in ovarian volume, uterine length, and breast diameter. There were no differences between groups 2 and 3 in levels of both hormones and in the size of the measured structures. The obtained results seem to indicate that non-substituted or inadequately substituted hypothyroidism during pregnancy may impair the course of minipuberty in the female offspring.
Assuntos
Hipotireoidismo , Humanos , Feminino , Hipotireoidismo/metabolismo , Gravidez , Adulto , Complicações na Gravidez/metabolismo , Puberdade , Ovário/metabolismo , Adolescente , Lactente , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
OBJECTIVES: Global antimicrobial resistance (AMR) surveillance in Neisseria gonorrhoeae is essential. In 2017-18, only five (10.6%) countries in the WHO African Region reported to the WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP). Genomics enhances our understanding of gonococcal populations nationally and internationally, including AMR strain transmission; however, genomic studies from Africa are extremely scarce. We describe the gonococcal genomic lineages/sublineages, including AMR determinants, and baseline genomic diversity among strains in Uganda, Malawi and South Africa, 2015-20, and compare with sequences from Kenya and Burkina Faso. METHODS: Gonococcal isolates cultured in Uganda (nâ=â433), Malawi (nâ=â154) and South Africa (nâ=â99) in 2015-20 were genome-sequenced. MICs were determined using ETEST. Sequences of isolates from Kenya (nâ=â159), Burkina Faso (nâ=â52) and the 2016 WHO reference strains (nâ=â14) were included in the analysis. RESULTS: Resistance to ciprofloxacin was high in all countries (57.1%-100%). All isolates were susceptible to ceftriaxone, cefixime and spectinomycin, and 99.9% were susceptible to azithromycin. AMR determinants for ciprofloxacin, benzylpenicillin and tetracycline were common, but rare for cephalosporins and azithromycin. Most isolates belonged to the more antimicrobial-susceptible lineage B (nâ=â780) compared with the AMR lineage A (nâ=â141), and limited geographical phylogenomic signal was observed. CONCLUSIONS: We report the first multi-country gonococcal genomic comparison from Africa, which will support the WHO GASP and WHO enhanced GASP (EGASP). The high prevalence of resistance to ciprofloxacin (and empirical use continues), tetracycline and benzylpenicillin, and the emerging resistance determinants for azithromycin show it is imperative to strengthen the gonococcal AMR surveillance, ideally including genomics, in African countries.
Assuntos
Antibacterianos , Gonorreia , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Neisseria gonorrhoeae , Azitromicina/farmacologia , Malaui , África do Sul , Uganda/epidemiologia , Farmacorresistência Bacteriana , Gonorreia/epidemiologia , Gonorreia/tratamento farmacológico , Ciprofloxacina/farmacologia , Testes de Sensibilidade Microbiana , Tetraciclina/farmacologia , GenômicaRESUMO
BACKGROUND: Genital ulcer diseases (GUDs) are a common syndrome associated with sexually transmitted infections. Genital ulcer diseases increase the risk of HIV transmission, necessitating appropriate diagnosis and treatment. We provide an updated GUD etiology assessment in Malawi to guide diagnostic development and treatment algorithms. METHODS: We enrolled patients 18 years or older presenting with GUD at a sexually transmitted infection clinic in Lilongwe, Malawi, between May and October 2021. We purposively sampled by HIV status. Swabs of ulcers were tested for Treponema pallidum, herpes simplex virus (HSV)-1 and HSV-2, Haemophilus ducreyi, and Chlamydia trachomatis using polymerase chain reaction. Blood was collected for syphilis and HSV-2 serologies and acute HIV testing. Participants were treated per Malawi guidelines. Ulcer resolution (size reduced by >50%) was evaluated 14 days later. RESULTS: Fifty participants enrolled (30 without HIV, 2 with acute HIV infection, 18 with HIV seropositivity; 32 men, 18 women). Forty-six (92%) had an etiology identified. Syphilis was more common among those without HIV (22 of 30 [73%]) than participants with HIV (PWH; 8 of 20 [40%]; P = 0.04). Herpes simplex virus was more common among PWH (11 of 20 [55%]) than participants without (2 of 30 [7%]; P = 0.0002). One-fifth (9 of 50 [18%]) had H. ducreyi. Among those who returned for follow-up (n = 45), 9 (20%) had unresolved ulcers; persistent GUD was slightly more common in PWH (6 of 19 [32%]) than participants without (3 of 26 [12%]; P = 0.14). CONCLUSIONS: We observed a dramatic increase in syphilis ulcer proportion in a population whose GUDs were previously HSV predominant. Observed differences in etiology and resolution by HIV status could play an important role in the ongoing transmission and treatment evaluation of GUD.
Assuntos
Doenças dos Genitais Masculinos , Infecções por HIV , Herpes Genital , Herpesvirus Humano 1 , Infecções Sexualmente Transmissíveis , Sífilis , Masculino , Humanos , Feminino , Úlcera/epidemiologia , Úlcera/etiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Sífilis/complicações , Sífilis/epidemiologia , Sífilis/diagnóstico , Malaui/epidemiologia , Infecções Sexualmente Transmissíveis/epidemiologia , Herpesvirus Humano 2 , Genitália , Herpes Genital/complicações , Herpes Genital/epidemiologia , Doenças dos Genitais Masculinos/etiologiaRESUMO
INTRODUCTION: Metformin reduces elevated levels of FSH and LH. In some studies, gonadotroph secretory function was inhibited by statins. The aim of the present study was to investigate whether statin therapy modulates the impact of metformin on hypothalamic-pituitary-gonadal axis activity in postmenopausal women. METHODS: The study population included 60 postmenopausal women with prediabetes, 40 of whom, because of high cardiovascular risk, received rosuvastatin (20-40 mg daily). One group of rosuvastatin-treated women (group A, n = 23) and all statin-naïve patients (group B, n = 20) were matched for age, glucose homeostasis markers, and gonadotropin levels. Over the entire study period (6 months), these women received metformin. The third group (group C) included 17 rosuvastatin-treated women refusing metformin treatment. We assessed baseline and follow-up plasma lipids, glucose homeostasis markers, and concentrations of FSH, LH, thyrotropin, prolactin, adrenocorticotropic hormone (ACTH), insulin-like growth factor-1, estradiol, progesterone, and anti-Müllerian hormone (in selected patients). RESULTS: Fifty-three women (18 in groups A and B and 17 in group C) completed the study. At study entry, rosuvastatin-treated and statin-naïve women differed in levels of total cholesterol, LDL-cholesterol, and ACTH. In statin-naïve women, metformin reduced FSH levels and tended to reduce LH levels. In rosuvastatin-treated women, metformin decreased FSH and LH levels, and both effects were stronger than in statin-naïve women. Although observed in both groups, the impact on glucose homeostasis markers was more pronounced in individuals not receiving statin therapy. Metformin treatment did not affect circulating levels of lipids, thyrotropin, prolactin, ACTH, insulin-like growth factor-1, estradiol, and anti-Müllerian hormone. In group C, plasma lipids, glucose homeostasis markers, and hormone levels remained at a similar level throughout the study period. CONCLUSION: The obtained results indicate that statin therapy may enhance gonadotropin-lowering effects of metformin.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Metformina , Humanos , Feminino , Metformina/farmacologia , Metformina/uso terapêutico , Rosuvastatina Cálcica/farmacologia , Rosuvastatina Cálcica/uso terapêutico , Prolactina , Projetos Piloto , Fator de Crescimento Insulin-Like I , Pós-Menopausa , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hormônio Antimülleriano , Gonadotropinas , Estradiol , Tireotropina , Hormônio Foliculoestimulante , Hormônio Adrenocorticotrópico , Glucose , LipídeosRESUMO
INTRODUCTION: Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to reduce thyroid antibody titers. The aim of this study was to investigate plasma markers of cardiometabolic risk in statin-treated women with thyroid autoimmunity. METHODS: We compared two matched groups of euthyroid women with hypercholesterolemia receiving atorvastatin treatment: subjects with autoimmune (Hashimoto's) thyroiditis (group A, n = 29) and subjects without thyroid pathology (group B, n = 29). Plasma lipids, glucose homeostasis markers, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before atorvastatin treatment and 6 months later. RESULTS: At entry, both groups differed in antibody titers, insulin sensitivity, and plasma levels of uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. Atorvastatin-induced reduction in hsCRP and homocysteine, but not in total cholesterol and LDL-cholesterol, was more pronounced in group B than in group A. Only in group B, the drug decreased uric acid and fibrinogen and increased 25-hydroxyvitamin D. In group A, atorvastatin reduced insulin responsiveness. CONCLUSION: The obtained results indicate that euthyroid women with Hashimoto's thyroiditis may benefit to a lesser degree from atorvastatin treatment than other populations of women with hypercholesterolemia.
Assuntos
Doenças Cardiovasculares , Doença de Hashimoto , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Tireoidite Autoimune , Humanos , Feminino , Atorvastatina/uso terapêutico , Atorvastatina/farmacologia , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Tireoidite Autoimune/complicações , Tireoidite Autoimune/tratamento farmacológico , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Proteína C-Reativa/uso terapêutico , Fatores de Risco Cardiometabólico , Ácido Úrico , Fatores de Risco , Doença de Hashimoto/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Colesterol , Fibrinogênio/análise , Fibrinogênio/uso terapêutico , Doenças Cardiovasculares/prevenção & controleRESUMO
INTRODUCTION: Polycystic ovary syndrome (PCOS) is a frequent endocrinopathy in young women with significantly increased cardiometabolic risk. Siblings of women with this disorder are at increased risk of insulin resistance and androgen excess. The current study was aimed at investigating cardiometabolic effects of atorvastatin in sisters of women with PCOS. METHODS: This prospective observational study compared two age-, body mass index-, blood pressure-, and plasma lipid-matched groups of women with hypercholesterolemia: sisters of PCOS probands (group A) and unrelated control subjects (group B), receiving atorvastatin (40 mg daily). Plasma lipids, glucose homeostasis markers, concentrations of sex hormones, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen and uric acid, and the urinary albumin-to-creatinine ratio (UACR) were measured before entering the study and 6 months later. RESULTS: Both groups differed in the degree of insulin resistance, testosterone, free androgen index (FAI), circulating levels of hsCRP and homocysteine, and UACR. There were no between-group differences in the impact of atorvastatin on plasma lipids. Despite reducing hsCRP and homocysteine in both groups of women, the effect on these biomarkers was stronger in group B than in group A. Only in group B, atorvastatin did reduce fibrinogen, uric acid, and UACR. Only in group A, atorvastatin did worsen insulin sensitivity and tended to reduce testosterone and FAI. The impact of atorvastatin on hsCRP, homocysteine, fibrinogen, uric acid, and UACR inversely correlated with testosterone and FAI. CONCLUSION: The obtained results suggest that sisters of women with PCOS may benefit to a lesser degree from atorvastatin treatment than other women.
Assuntos
Doenças Cardiovasculares , Resistência à Insulina , Síndrome do Ovário Policístico , Humanos , Feminino , Atorvastatina/uso terapêutico , Atorvastatina/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/complicações , Androgênios , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Ácido Úrico , Fatores de Risco Cardiometabólico , Irmãos , Fatores de Risco , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Testosterona , Fibrinogênio/análiseRESUMO
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.
Assuntos
Hiperprolactinemia , Resistência à Insulina , Metformina , Humanos , Feminino , Metformina/farmacologia , Prolactina , Fator de Crescimento Insulin-Like I , Glicemia , Hemoglobinas Glicadas , Tireotropina , Inositol/farmacologia , Hormônio AdrenocorticotrópicoRESUMO
Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of atherosclerotic plaque instability (MRI). Cytokines such as osteopontin, osteoprotegerin, and metalloproteinase 9 could be used as the most recent markers to identify and track the efficacy of anti-atherosclerotic therapy. Patients with USG and MRI-verified unstable atherosclerotic plaque were included in the study. Biomarker concentrations were measured and compared before and after PCSK9 inhibitor therapy. Additionally, concentrations prior to treatment were correlated with MRI images of the carotid artery. After treatment with alirocumab, the concentrations of MMP-9 (p < 0.01) and OPN, OPG (p < 0.05) decreased significantly. Furthermore, the results of OPN, OPG, and MMP 9 varied significantly depending on the type of atherosclerotic plaque in the MRI assay. In stable atherosclerotic plaques, the concentrations of OPN and OPG were greater (p < 0.01), whereas the concentration of MMP9 correlated with the instability of the plaque (p < 0.05). We demonstrated, probably for the first time, that alirocumab therapy significantly decreased the serum concentration of atherosclerotic plaque markers. In addition, we demonstrated the relationship between the type of atherosclerotic plaque as determined by carotid MRI and the concentration of these markers.
Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Pró-Proteína Convertase 9 , UltrassonografiaRESUMO
BACKGROUND: Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. METHODS: Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. RESULTS: Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 µg/mL; 111 (78.7%), MIC = 4 µg/mL; and 28 (19.9%), MIC = 8 µg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 µg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). CONCLUSIONS: Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.
Assuntos
Gonorreia , Neisseria gonorrhoeae , Feminino , Humanos , Masculino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Cefixima/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Malaui/epidemiologia , Testes de Sensibilidade Microbiana , Espectinomicina/farmacologia , Espectinomicina/uso terapêutico , Tetraciclina/farmacologia , Tetraciclina/uso terapêutico , Resultado do Tratamento , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: Hypoprolactinemia, which is usually a consequence of treatment with inadequate high doses of dopaminergic agents, is a poorly understood clinical condition. The aim of the current study was to investigate whether the cardiometabolic effects of statin therapy differ between patients with low prolactin production and patients with normal levels of this hormone. METHODS: We studied two groups of cabergoline-treated premenopausal women with hypercholesterolemia matched for age, plasma lipids, cabergoline dose, and treatment duration: 11 women with hypoprolactinemia (group A) and 15 women with plasma levels of this hormone within the reference range (group B). The control group (C) included 25 dopaminergic-naïve normoprolactinemic women, matched for age and lipid levels. Plasma lipids, insulin sensitivity, and levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before and after 14-week treatment with atorvastatin (20 mg daily). RESULTS: Patients with hypoprolactinemia were more insulin-resistant, had lower values of total testosterone and free androgen index, and had higher levels of hsCRP and fibrinogen than individuals with normal prolactin levels. Although atorvastatin reduced total and LDL cholesterol and hsCRP in all study groups, this effect was stronger in groups B and C than in group A. Only in groups B and C, the drug decreased uric acid, fibrinogen, and homocysteine and increased 25-hydroxyvitamin D. In turn, only in group A, atorvastatin worsened insulin sensitivity and reduced free androgen index. CONCLUSION: Coexisting hypoprolactinemia may have an unfavorable impact on the pleiotropic effects of statins.
Assuntos
Doenças Cardiovasculares , Resistência à Insulina , Humanos , Feminino , Atorvastatina/efeitos adversos , Prolactina , Cabergolina , Projetos Piloto , Proteína C-Reativa/análise , Ácido Úrico , Androgênios/farmacologia , Fatores de Risco , Fibrinogênio , HomocisteínaRESUMO
Although both exogenous vitamin D and a gluten-free diet were found to reduce thyroid antibody titers, no study investigated interactions between gluten intake and vitamin D status in patients with autoimmune thyroid disorders. The aim of the present study was to assess whether the gluten-free diet determines the effect of vitamin D treatment on thyroid autoimmunity and thyroid function in young women with autoimmune (Hashimoto's) thyroiditis. The study compared two groups of euthyroid premenopausal women with this disorder, matched for thyroid antibody titers: 31 women with non-celiac gluten sensitivity complying for at least 12 months with the gluten-free diet and 31 unaffected sisters of women with non-celiac gluten sensitivity remaining without any dietary intervention. Plasma titers of thyroid peroxidase and thyroglobulin antibodies, as well as plasma concentrations of thyrotropin, free thyroid hormones, prolactin, 25-hydroxyvitamin D and high-sensitive C-reactive protein were measured at entry and after a six-month follow-up. Moreover, at both time points, the structure parameters of thyroid homeostasis were assessed. Although exogenous vitamin D decreased titers of thyroid peroxidase and thyroglobulin antibodies and increased 25-hydroxyvitamin D levels in each treatment group, this effect was less pronounced in patients on the gluten-free diet than in patients not following any dietary recommendations. Only in the latter group of patients, vitamin D increased SPINA-GT. Treatment-induced changes in thyroid peroxidase and thyroglobulin antibodies correlated with the impact of treatment on 25-hydroxyvitamin D levels. The obtained results suggest that gluten-free diet may impair beneficial effects of exogenous vitamin D in individuals with Hashimoto's thyroiditis.
Assuntos
Doença de Hashimoto , Tireoidite Autoimune , Humanos , Feminino , Autoimunidade , Iodeto Peroxidase , Projetos Piloto , Tireoidite Autoimune/tratamento farmacológico , Tireoglobulina/farmacologia , Dieta Livre de Glúten , Doença de Hashimoto/tratamento farmacológico , Vitamina D , Vitaminas , CalcifediolRESUMO
WHAT IS KNOWN AND OBJECTIVE: Metformin treatment decreases thyrotropin levels in individuals with hypothyroidism and this effect seems to be mediated by the 5'-adenosine monophosphate-activated protein kinase pathway in the pituitary. The activity of this pathway is also stimulated by statins. The current study was aimed at investigating whether the impact of metformin on hypothalamic-pituitary-thyroid axis activity is affected by statin use. METHODS: The study included three matched groups of men with non-autoimmune hypothyroidism and prediabetes: patients treated for at least 6 months with high-intensity rosuvastatin therapy (20-40 mg daily) [groups A (n = 24) and C (n = 19)] and men not receiving statin therapy [group B (n = 24)]. Over the entire study period (6 months), groups A and B received metformin (2.55-3 g daily). Moreover, groups A and C continued rosuvastatin therapy. The lipid profile, glucose homeostasis markers, and plasma concentrations of thyrotropin, total and free thyroid hormones, prolactin, FSH, LH, ACTH and insulin-like growth factor-1 were determined at baseline and 6 months later. RESULTS AND DISCUSSION: Fifty-nine patients completed the study. There were differences between groups A and C and group B in baseline values of total cholesterol, LDL-cholesterol, gonadotropins and ACTH. Although observed in both groups of metformin-treated patients, the effect on thyrotropin levels was more pronounced in group A than in group B. The impact on fasting glucose and insulin sensitivity was stronger in group B than group A. In turn, only in group A metformin tended to reduce gonadotropin levels. There were no differences between follow-up and baseline values of lipids, total and free thyroid hormones, prolactin, ACTH and insulin-like growth factor-1 in both these groups. In group C, all assessed variables remained at a similar level. WHAT IS NEW AND CONCLUSION: The results of the current study suggest that rosuvastatin potentiates the inhibitory effect of metformin on thyrotrope secretory function.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hipotireoidismo , Metformina , Estado Pré-Diabético , Masculino , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Tireotropina , Rosuvastatina Cálcica/farmacologia , Rosuvastatina Cálcica/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Prolactina , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipotireoidismo/tratamento farmacológico , Hormônios Tireóideos , Glucose/uso terapêutico , Hormônio Adrenocorticotrópico/uso terapêuticoRESUMO
WHAT IS KNOWN AND OBJECTIVE: Insulin resistance impairs the impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity. Both metformin and myo-inositol were found to improve insulin sensitivity and to reduce thyrotropin levels in individuals with hypothyroidism. The aim of the present study was to compare the effect of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity between women receiving metformin and myo-inositol. METHODS: The study included two groups of women with autoimmune hypothyroidism, treated for at least 6 months with either metformin (group A; n = 25) or myo-inositol (group B; n = 25). Both groups were matched for age, insulin sensitivity, hormone levels and antibody titers. For the following 6 months, all women received levothyroxine. Plasma levels of glucose, insulin, thyrotropin, free thyroid hormones, prolactin, 25-hydroxyvitamin D and high-sensitivity C-reactive protein (hsCRP), as well as titers of thyroid peroxidase and thyroglobulin antibodies were assessed at the beginning and at the end of the study. RESULTS AND DISCUSSION: At baseline there were not differences between the study groups. Although levothyroxine reduced thyrotropin levels, increased free thyroid hormone levels and decreased antibody titers in both study groups, these effects were more pronounced in group A than group B. Only in group A, levothyroxine increased 25-hydroxyvitamin D, decreased hsCRP and improved insulin sensitivity. The impact of levothyroxine on thyrotropin and free thyroid hormones correlated with treatment-induced changes in insulin sensitivity, antibody titers, 25-hydroxyvitamin D and hsCRP. WHAT IS NEW AND CONCLUSION: The present study suggests that the impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity is stronger in women receiving metformin than in women treated with myo-inositol.
Assuntos
Hipotireoidismo , Resistência à Insulina , Metformina , Autoimunidade , Proteína C-Reativa/efeitos adversos , Feminino , Glucose/efeitos adversos , Doença de Hashimoto , Humanos , Hipotireoidismo/tratamento farmacológico , Inositol/efeitos adversos , Insulina , Iodeto Peroxidase , Metformina/efeitos adversos , Prolactina , Tireoglobulina , Hormônios Tireóideos , Tireoidite Autoimune , Tireotropina , Tiroxina/farmacologiaRESUMO
WHAT IS KNOWN AND OBJECTIVE: Vitamin D and myo-inositol reduce thyroid antibody titers in subjects with autoimmune thyroiditis. No previous study has investigated interactions between these agents. The aim of the current study was to determine whether the impact of exogenous vitamin D on thyroid autoimmunity and thyroid function in women with Hashimoto's thyroiditis depends on myo-inositol supplementation. METHODS: The study population consisted of three thyroid antibody- and insulin sensitivity-matched groups of women with autoimmune thyroiditis and high-normal or slightly elevated TSH levels. Forty-one women (21 in group A and 20 in group C) had been treated for at least 6 months with myo-inositol (group A), while 21 women (group B) had not received myo-inositol preparations. Over the entire study period (6 months), groups A and C continued treatment with myo-inositol (2 g daily), while groups A and B received exogenous vitamin D (4000 IU daily). Plasma titers of thyroid peroxidase and thyroglobulin antibodies, as well as plasma concentrations of glucose, insulin, TSH, free thyroid hormones, prolactin, and 25-hydroxyvitamin D (25-OH-D) were assessed at entry and 6 months later. Moreover, baseline and follow-up values of the structure parameters of thyroid homeostasis were calculated RESULTS AND DISCUSSION: In groups A and B, vitamin D improved insulin sensitivity and increased 25-OH-D levels. Although follow-up antibody titers in both these groups were lower than baseline ones, the impact of vitamin D on thyroid peroxidase and thyroglobulin antibodies was stronger in group A than in group B. Only in group A, vitamin D decreased TSH levels and increased SPINA-GT. There were no differences between baseline and follow-up free values of glucose, thyroid hormones, prolactin, Jostel's index, and SPINA-GD. The impact of vitamin D treatment on antibody titers correlated with treatment-induced changes in 25-OH-D levels and the degree of improvement in insulin sensitivity. In group C, glucose homeostasis markers, antibody titers and hormone levels remained at a similar level throughout the study period. WHAT IS NEW AND CONCLUSION: The obtained results suggest that the impact of vitamin D on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in subjects with autoimmune thyroiditis is more pronounced if they receive myo-inositol.
Assuntos
Doença de Hashimoto , Resistência à Insulina , Tireoidite Autoimune , Humanos , Feminino , Iodeto Peroxidase , Autoimunidade , Projetos Piloto , Tireoidite Autoimune/tratamento farmacológico , Tireoglobulina , Prolactina , Vitamina D , Hormônios Tireóideos , Tireotropina , Inositol/farmacologia , GlucoseRESUMO
OBJECTIVES: Metformin decreased circulating levels of anterior pituitary hormones and its effect on thyrotropin concentration was found to be stronger in individuals receiving myo-inositol. Phospholipids containing inositols are precursors of second messengers of several hormones, including gonadotropins and insulin. The aim of the current study was to investigate whether the concomitant use of myo-inositol changes the effect of metformin on gonadotropin levels. DESIGN: A prospective observational study. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: This study, conducted at a university-affiliated medical center, included two groups of postmenopausal women with prediabetes, matched for age, FSH and LH levels, and insulin sensitivity: women taking myo-inositol preparations for at least 6 months (group A, n = 23) and women not receiving inositol preparations (group B, n = 23). All participants were treated with metformin (850 mg twice daily) for the following 6 months. At the beginning and at the end of the study, we assessed plasma glucose, insulin, FSH, LH, thyrotropin, prolactin, adrenocorticotropic hormone, insulin-like growth factor-1, estradiol, and glycated hemoglobin. RESULTS: The impact of metformin on glucose levels, the homeostatic model assessment 1 of insulin resistance ratio, and glycated hemoglobin was more pronounced in group A than in group B. Metformin administered with myo-inositol reduced both FSH and LH. No significant changes in gonadotropin levels were observed in women receiving only metformin. The impact on FSH and LH levels correlated with their baseline concentrations and with the degree of improvement in insulin sensitivity. Levels of the remaining hormones did not change throughout the study. LIMITATIONS: The most important limitation of the study is a relatively small number of participants. Moreover, the study protocol does not allow to conclude whether similar effects are observed in premenopausal women. CONCLUSIONS: Myo-inositol may enhance the inhibitory effect of metformin on gonadotropin production in postmenopausal women.
Assuntos
Resistência à Insulina , Metformina , Feminino , Humanos , Hormônio Foliculoestimulante , Hemoglobinas Glicadas , Gonadotropinas , Inositol/farmacologia , Insulina , Metformina/farmacologia , Metformina/uso terapêutico , Pós-Menopausa , Tireotropina , Pessoa de Meia-IdadeRESUMO
ABSTRACT: 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.
Assuntos
Alopecia/complicações , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Lisinopril/uso terapêutico , Adulto , Alopecia/sangue , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Biomarcadores/sangue , Fatores de Risco Cardiometabólico , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/fisiopatologia , Lisinopril/efeitos adversos , Masculino , Projetos Piloto , Medição de Risco , Fatores Sexuais , Resultado do TratamentoRESUMO
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.
Assuntos
MetforminaRESUMO
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.
Assuntos
TiroxinaRESUMO
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-naïve women with vitamin D insufficiency (group A), women receiving vitamin D preparations because of vitamin D deficiency (group B), as well as vitamin D-naïve 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.
Assuntos
Dislipidemias , Adulto , Feminino , Fenofibrato , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.