BACKGROUND: Identifying biological alterations in patients with depression, particularly those that differ between responders and non-responders, is of interest to clinical practice. Biomarker candidates involve neuroactive steroids, including pregnenolone (PREG) and allopregnanolone (ALLO). However, alterations in PREG and ALLO associated with treatment response are understudied. This study's main aim was to evaluate the effects of antidepressant treatment, clinical response, and treatment duration on PREG and ALLO in depression. MATERIALS AND METHODS: In a 4-week, open-label trial, participants were allocated randomly to the venlafaxine (n = 27) or mirtazapine (n = 30) group. Urine concentrations of PREG and ALLO were assessed through gas chromatography-mass spectrometry. Participants collected night urine between 10:30 p.m. and 8:00 a.m. Two primary outcomes were analyzed. Firstly, the effect of treatment (mirtazapine or venlafaxine), clinical response (operationalized through the Hamilton Depression Rating Scale), and time (baseline compared to 28 days) on the urine concentrations of PREG or ALLO in depression. Finally, the effect of clinical response and time on the urine concentration of PREG or ALLO, independently of the antidepressant given (mirtazapine or venlafaxine). Linear mixed models were carried out. RESULTS: There was no significant difference in PREG and ALLO concentrations between baseline and 28 days in responders and non-responders when investigating the venlafaxine or the mirtazapine group. However, we found a significant reduction of urine PREG concentration after 28 days of treatment in responders who received either venlafaxine or mirtazapine (estimate = -0.56; p = 0.016; 95CI [-1.003; -0.115]; Cohen's d = -0.61). CONCLUSIONS: Our main results indicate that responders in depression show reduced urinary PREG concentrations after 4-weeks of therapy, independently of the antidepressant used. More studies are needed to confirm these findings.
- Klíčová slova
- Allopregnanolone, Biomarker, Depression, Neurosteroids, Pregnenolone, Treatment outcome,
- Publikační typ
- časopisecké články MeSH
The hypothesis that the most common female endocrine disease, the polycystic ovarian syndrome (PCOS), has a male equivalent, has recently become more widely accepted. The male form of PCOS is marked by alterations in the secretion of gonadotropins, increased insulin resistance, and changes of the levels of several steroid hormones, with clinical manifestations including premature androgenic alopecia (AGA). Because these symptoms are not always found in men with genetic predispositions, knowledge of the male equivalent of PCOS needs to be supplemented by measurements of adrenal 11-oxygenated C19 steroids, particularly 11-keto-, and 11β-hydroxy-derivatives of testosterone and dihydrotestosterone, by focusing on the newly-realized role of skin as an endocrine organ, and by confirming any age-related factors in glucose metabolism disorders in such predisposed men.
- Klíčová slova
- Androgens, Insulin resistance, Polycystic ovarian syndrome, Premature androgenic alopecia, SHBG,
- MeSH
- alopecie etiologie MeSH
- androgeny MeSH
- inzulinová rezistence * MeSH
- lidé MeSH
- syndrom polycystických ovarií * MeSH
- testosteron MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- androgeny MeSH
- testosteron MeSH
Male hypogonadism associated with obesity by yet not fully understood mechanisms promote fat depositions and on contrary obesity induces decrease of androgen production. It is necessary to diagnose hypogonadism correctly and to treat it. The definition of hypogonadism is based on subnormal levels of circulating testosterone and on the occurrence of symptoms, which, however, are not much specific. As obesity decreases substantially the concentrations of sex hormone binding globulin SHBG it is recommended in these men to check not only the level of total testosterone but also the concentration of free testosterone or the value of the index of free androgens. Proven hypogonadism in obese men should be treated as well as by testosterone substitution as the body mass reduction. The most effective treatment in this respect is considered bariatric surgery.
- Klíčová slova
- SHBG, male hypogonadism, obesity, testosterone.,
- MeSH
- androgeny MeSH
- bariatrická chirurgie * MeSH
- globulin vázající pohlavní hormony MeSH
- hypogonadismus * MeSH
- lidé MeSH
- testosteron MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- androgeny MeSH
- globulin vázající pohlavní hormony MeSH
- testosteron MeSH
The cytokine erythropoietin is the main hemopoietic factor synthesized mainly by the kidney. However, erythro-poietin and its receptors are expressed in several tissues and exert pleiotropic activities also in nonhemopoietic tissues. Erythropoietin has an antiapoptotic activity and plays a potential neuroprotective, nefroprotective and cardioprotective role against ischemia and other type of injury. Erythropoietin is also involved in angiogenesis, neurogenesis, and the immune response. It can prevent metabolic alterations, vascular and neuronal degeneration, and inflammatory cell activation. Erythropoietin reduces hyperglycaemia and retards proliferative retinopathy in diabetic patients. Consequently, erythropoietin may be of therapeutic value for a variety of disorders. This short review provides an insight into the nonhemopoietic role of erythropoietin and its mechanisms of action. For elimination of polycythaemia after erythropoietin administration analogues without haematopoietic activity were prepared and tested in animals and in some cases also evaluated in clinical trials.
- Klíčová slova
- diabetes, energetic metabolism, erythropoietin, pleitropic action, proliferative retinopathy, tissue protective effect,
- MeSH
- apoptóza MeSH
- erythropoetin * farmakologie fyziologie MeSH
- ischemie MeSH
- ledviny MeSH
- lidé MeSH
- patologická angiogeneze MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- erythropoetin * MeSH
Spa treatment can effectively reestablish mood balance in patients with psychiatric disorders. In light of the adrenal gland's role as a crossroad of psychosomatic medicine, this study evaluated changes in 88 circulating steroids and their relationships with a consolidation of somatic, psychosomatic and psychiatric components from a modified N-5 neurotic questionnaire in 46 postmenopausal 50+ women with anxiety-depressive complaints. The patients underwent a standardized one-month intervention therapy with physical activity and an optimized daily regimen in a spa in the Czech Republic. All participants were on medication with selective serotonin reuptake inhibitors. An increase of adrenal steroidogenesis after intervention indicated a reinstatement of the hypothalamic-pituitary-adrenal axis. The increases of many of these steroids were likely beneficial to patients, including immunoprotective adrenal androgens and their metabolites, neuroactive steroids that stimulate mental activity but protect from excitotoxicity, steroids that suppress pain perception and fear, steroids that consolidate insulin secretion, and steroids that improve xenobiotic clearance. The positive associations between the initial values of neurotic symptoms and their declines after the intervention, as well as between initial adrenal activity and the decline of neurotic symptoms, indicate that neurotic impairment may be alleviated by such therapy provided that the initial adrenal activity is not seriously disrupted.
- Klíčová slova
- adrenal, mood balance, postmenopausal females, spa treatment, steroid metabolome,
- MeSH
- afekt * MeSH
- cvičení * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nadledviny metabolismus MeSH
- postmenopauza * MeSH
- projektivní techniky MeSH
- psychoterapie * MeSH
- senioři MeSH
- steroidy biosyntéza MeSH
- určení symptomu MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- steroidy MeSH
Testing of the adrenal function with ACTH 1-24 (Synacthen test) or insulin (insulin tolerance test-ITT) is commonly used. The question of ongoing debate is the dose of Synacthen. Moreover, it may be important from the physiological point of view besides measurement of cortisol levels and 17α-hydroxy-progesterone to know also the response of other steroids to these test. The plasma levels of 24 free steroids and their polar conjugates were followed after stimulation of 1 μg, 10 μg and 250 μg of ACTH 1-24 and after insulin administration in thirteen healthy subjects. The study aimed to describe a response of steroid metabolome to various doses of ACTH 1-24 and to find the equivalency of these tests. The additional ambition was to contribute to understanding of physiology of these stimulation tests and suggest an additional marker for HPA axis evaluation. No increase of most conjugated steroids and even decrease of some of them during all of the Synacthen tests and ITT at 60th min were observed. The levels of steroid conjugates decreased in ITT but did not during all of the Synacthen tests by 20 min of each test. Testosterone and estradiol did not increase during the Synacthen tests or ITT as expected. The results suggest that the conjugated steroids in the circulation can serve as reserve stock for rapid conversion into free steroids in the first minutes of the stress situation. Various doses of ACTH 1-24 used in the Synacthen tests implicate earlier or later occurrence of maximal response of stimulated steroids. The equivalent dose to ITT and standard 250 μg of ACTH 1-24 seemed to be dose of 10 μg ACTH 1-24 producing the similar response in all of the steroids in the 60th min of the test.
- Klíčová slova
- Conjugated steroids, GC–MS, HPA axis, Hypoglycaemia, Steroid metabolome, Synacthen,
- MeSH
- dospělí MeSH
- estradiol krev MeSH
- hydrokortison krev MeSH
- inzulin aplikace a dávkování MeSH
- kosyntropin aplikace a dávkování MeSH
- lidé MeSH
- metabolom MeSH
- nadledviny metabolismus patologie MeSH
- steroidy metabolismus MeSH
- systém hypofýza - nadledviny účinky léků patologie MeSH
- systém hypotalamus-hypofýza metabolismus patologie MeSH
- testosteron krev MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- estradiol MeSH
- hydrokortison MeSH
- inzulin MeSH
- kosyntropin MeSH
- steroidy MeSH
- testosteron MeSH
Androst-5-ene-triols are metabolites of dehydroepiandrosterone, the most abundant steroid hormone in human circulation. Many observations in rodents have demonstrated the anti-inflammatory and immune modulating activity of 7β-hydroxy-androst-5-enes, and on the basis of these experiments androst-5-ene-3β,7β,17β-triol is considered as a potential agent in the treatment of autoimmune diseases. In contrast to the fairly abundant information on the levels and effects of androst-5-ene-triols in experimental animals and of their the pharmacological perspective, little is known about androst-5-ene-3β,7α/β,17β-triols circulating in human blood, their regulation by the hypothalamo-pituitary-adrenal axis, or their daily concentration variability. Here we provide some data on androst-5-ene-3β,7α/β,17β-triol concentrations under various conditions in men and women.
- Klíčová slova
- 5-Androstene-3β,7β,17β-triol, ACTH test, Androst-5-ene-3β,7α,17β-triol, Daily profile, Insulin tolerance test, β-AET,
- MeSH
- androsteron krev MeSH
- dospělí MeSH
- hypothalamus metabolismus MeSH
- lidé MeSH
- systém hypofýza - nadledviny metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- androsteron MeSH
BACKGROUND: The harmful effects of endocrine disrupting compounds (EDCs) on human health are generally well-known, and exposure during fetal development may have lasting effects. Fetal exposure to bisphenol A (BPA) has been recently relatively well-studied; however, less is known about alternatives such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF), which have started to appear in consumer products. Parabens are another widespread group of EDCs, with confirmed transplacental passage. The usage of many cosmetic, pharmaceutical and consumer products during the pregnancy that may contain parabens and bisphenols has led to the need for investigation. OBJECTIVES: To shed more light into the transplacental transport of BPA, its alternatives, and parabens, and to study their relation to fetal steroidogenesis. METHODS: BPA, BPS, BPF, BPAF, methylparaben, ethylparaben, propylparaben, butylparaben, benzylparaben and 15 steroids including estrogens, corticoids, androgens and immunomodulatory ones were determined in 27 maternal (37th week of pregnancy) and cord plasma samples using liquid chromatography - tandem mass spectrometry methods. RESULTS: In cord blood, significantly higher BPA levels (p=0.0455) were observed compared to maternal plasma. The results from multiple regression models showed that in cord blood, methylparaben (β=-0.027, p=0.027), propylparaben (β=-0.025, p=0.03) and the sum of all measured parabens (β=-0.037, p=0.015) were inversely associated with testosterone levels. CONCLUSION: To the best of our knowledge, this is the first study reporting the simultaneous detection of BPA, alternative bisphenols, parabens and steroids in maternal and cord plasma. Our study confirmed the transplacental transport of BPA, with likely accumulation in the fetal compartment. The negative association of cord blood parabens and testosterone levels points to possible risks with respect to importance of testosterone for prenatal male development.
- Klíčová slova
- Bisphenol, Endocrine disruptor, Paraben, Pregnancy, Steroid,
- MeSH
- benzhydrylové sloučeniny farmakokinetika farmakologie MeSH
- chromatografie kapalinová MeSH
- dospělí MeSH
- endokrinní disruptory * farmakokinetika MeSH
- estrogeny fyziologie MeSH
- fenoly farmakokinetika MeSH
- fetální krev * chemie MeSH
- lidé MeSH
- matka - expozice noxám MeSH
- novorozenec MeSH
- parabeny * farmakokinetika MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- bisphenol A MeSH Prohlížeč
- endokrinní disruptory * MeSH
- estrogeny MeSH
- fenoly MeSH
- parabeny * MeSH
An important potential consequence of the anabolic steroid misuse is hypogonadotropic hypogonadism due to the inhibition of pituitary secretion of gonadotropins. By the symptoms as testicular atrophy, spermatogenic and fertility disturbances or dysfunction in sexual life, the anabolic steroids induced hypogonadism (ASIH) could be differentiated from organic hypogonadotropic hypogonadism only with difficulty unless the misuse is reported by the user. When diagnosed, the crucial step in the therapy is the stop of anabolic use. Convalescence lasts usually several months or even more than one year. First could be seen the retreat of testicular atrophy followed by the rearrangement of spermatogenesis. The users mainly well informed from internet use for amelioration of the symptoms injections of human choriogonadotropin (hCG), selective estrogen receptor modulators (SERM) or aromatase inhibitors.Key words: anabolic steroids - doping - hypogonadotropic hypogonadism - side effects.
- MeSH
- doping ve sportu MeSH
- dospělí MeSH
- hypogonadismus chemicky indukované MeSH
- kongenery testosteronu škodlivé účinky MeSH
- lidé MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- kongenery testosteronu MeSH
In this study, a novel liquid chromatography - tandem mass spectrometry method for the simultaneous determination of bisphenols (BPA, BPS, BPF, BPAF), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-paraben) and estrogens (estrone, estradiol, estriol) in human plasma is presented. Since all analytes possess the phenolic group, dansyl chloride derivatization was applied in order to gain high sensitivity. The method was validated according to FDA guidelines, and all validation requirements were satisfactory. The lower limits of quantifications were 41.6, 54.9, 43.5 and 150.8pg/mL for BPA, BPS, BPF and BPAF; 172, 149, 171, 134 and 202pg/mL for methyl-, ethyl-, propyl-, butyl- and benzyl-paraben; 10.5, 6.7 and 9.4pg/mL for estrone, estradiol and estriol, respectively. This is the first method allowing the determination of plasma bisphenols, parabens and estrogens in one run, and also the first determination of BPF levels in human plasma. The method was used to examine the plasma levels of healthy normospermic men, where three times higher plasma levels of BPF than BPA were found.
- Klíčová slova
- Alternative bisphenol, Bisphenol A, Bisphenol F, Endocrine disruptor, LC-MS/MS, Paraben,
- MeSH
- biochemická analýza krve metody MeSH
- chromatografie kapalinová MeSH
- estrogeny krev MeSH
- fenoly krev MeSH
- lidé MeSH
- limita detekce MeSH
- parabeny analýza MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- estrogeny MeSH
- fenoly MeSH
- parabeny MeSH