BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.
- MeSH
- Androstenes MeSH
- Androgen Receptor Antagonists * adverse effects therapeutic use MeSH
- Benzamides adverse effects MeSH
- Phenylthiohydantoin MeSH
- Cardiovascular Diseases * chemically induced epidemiology MeSH
- Humans MeSH
- Prostatic Neoplasms * drug therapy pathology MeSH
- Nitriles adverse effects MeSH
- Randomized Controlled Trials as Topic MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Network Meta-Analysis MeSH
- Systematic Review MeSH
- Keywords
- olaparib,
- MeSH
- Abiraterone Acetate administration & dosage pharmacology therapeutic use MeSH
- Androgen Receptor Antagonists * pharmacology therapeutic use MeSH
- Remission Induction MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Prostatic Neoplasms, Castration-Resistant * diagnosis drug therapy MeSH
- Poly(ADP-ribose) Polymerase Inhibitors * pharmacology therapeutic use MeSH
- Prostate-Specific Antigen analysis blood MeSH
- Aged MeSH
- Insurance, Health MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
Androgenní alopecie je nejčastější příčinou vypadávání vlasů u mužů i žen. Tento stav je způsoben genetickými predispozicemi a vlivem androgenů, zejména dihydrotestosteronu (DHT), který negativně ovlivňuje vlasové folikuly a vede k jejich postupné miniaturizaci. Mezi běžné léčebné možnosti patří farmakologická terapie (např. finasterid nebo minoxidil) a chirurgické metody, jako je transplantace vlasů. Novou a slibnou metodou je autologní transplantace progenitorových buněk, která představuje miniinvazivní zákrok využívající regenerační schopnosti vlastních buněk pacienta. Tento přístup může významně podpořit obnovu vlasových folikulů, zlepšit kvalitu vlasů a oddálit další progresi onemocnění, a to s minimálním rizikem vedlejších účinků.
Androgenetic alopecia is the most common cause of hair loss in both men and women. This condition results from genetic predispositions and the influence of androgens, particularly dihydrotestosterone (DHT), which adversely affects hair follicles and leads to their gradual miniaturization. Conventional treatment options include pharmacological therapy (e.g., finasteride or minoxidil) and surgical methods such as hair transplantation. A novel and promising approach is autologous progenitor cell transplantation, a minimally invasive procedure that utilizes the regenerative potential of the patient's own cells. This method has the potential to significantly enhance hair follicle regeneration, improve hair quality, and delay further progression of the condition, all while minimizing the risk of adverse effects.
- MeSH
- Alopecia * diagnosis etiology drug therapy MeSH
- Transplantation, Autologous methods MeSH
- Dihydrotestosterone metabolism MeSH
- Adult MeSH
- Case Reports as Topic MeSH
- Humans MeSH
- Stem Cell Transplantation * methods MeSH
- Hair Follicle pathology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Review MeSH
V kohortových studiích měli muži s diabetes mellitus 2. typu (DM2) konzistentně 2krát vyšší frekvenci nízké hladiny testosteronu než muži bez diabetu. Metabolický syndrom a diabetes mellitus 2. typu vedou k nižší hladině testosteronu u mužů zejména útlumem hypotalamické sekrece gonadoliberinu a zvýšenou konverzí testosteronu na estrogen. Hypogonadismus potom sám o sobě zhoršuje obezitu a inzulinovou rezistenci. Za hypogonadismus je podle současných doporučení považován stav, kdy jsou zároveň přítomny typické příznaky hypogonadismu a současně snížená hladina testosteronu (pod 12 nmol/l). Dle doporučených postupů je vhodné aktivně pátrat po hypogonadismu u mužů s DM2 a v případě jeho potvrzení zahájit vhodnou léčbu. Ke screeningu příznaků hypogonadismu se mezinárodně používá Aging Males’ Symptoms (AMS) dotazník, který je cenným nástrojem pro hodnocení kvality života a symptomů souvisejících se zdravím u stárnoucích mužů. Na základě výsledků a hladiny testosteronu se rozhodujeme o léčbě, která při nízkých hladinách testosteronu je substituční. Dotazník nám také pomáhá prolomit komunikační bariéru na téma sexuálního života pacienta a případné erektilní dysfunkce, kterou lze v řadě případů úspěšně léčit.
In cohort studies, men with type 2 diabetes mellitus (T2DM) consistently had twice the frequency of low testosterone levels compared to men without diabetes. Metabolic syndrome and type 2 diabetes mellitus lead to lower testosterone levels primarily by suppressing hypothalamic gonadoliberin secretion and by increasing the conversion of testosterone to oestrogen. Hypogonadism itself then worsens obesity and insulin resistance. According to current recommendations, hypogonadism is defined as the presence of typical hypogonadal symptoms together with a reduced testosterone level (below 12 nmol/l). It is advisable to actively screen for hypogonadism in men with T2DM and, if confirmed, initiate appropriate treatment. The Aging Males’ Symptoms (AMS) questionnaire is used internationally to screen for symptoms of hypogonadism; it is a valuable tool for assessing quality of life and health-related symptoms in aging men. Based on the questionnaire results and testosterone levels, treatment decisions are made; in cases of low testosterone levels, testosterone replacement therapy is indicated. The questionnaire also helps break down communication barriers regarding the patient’s sexual life and potential erectile dysfunction, which can often be successfully treated.
There is increasing pressure on meat producers worldwide due to the need for higher yields and improved meat quality. This is why anabolic androgenic steroids (AAS) have been widely used in most countries, due to their ability to accelerate animal muscle growth. However, out of concern for their side effects, EU states have banned their use and implemented control mechanisms. But they are reaching their limits, and therefore, it is necessary to look for new ways and investigate the mechanism of action of AAS on muscle tissue. This study replicated the administration of banned AAS (testosterone, nandrolone and their combination) and observed their effect on pig muscle. The pig model was purposely chosen for the study, as no such research has been carried out on this species. At the same time, pork is one of the most consumed meats in Europe. It focused on histological changes in muscle structure, specifically the size of muscle fibres and the number of satellite cells per muscle fibre. Furthermore, ultrastructural changes in muscle fibres, the diameter of myofibrils, the number of myofibrils per area, the distance between myofibrils and the size of sarcomeres were examined. The results using the techniques of histology, fluorescent labelling and transmission electron microscopy showed that, after the application of AAS, there is an increase in the diameter of muscle fibres, an increase in the diameter of myofibrils, a decrease in the number of myofibrils per surface area and, in the case of testosterone, an increase in the distance between myofibrils and an increase in the length of sarcomeres. There was also a significant increase in the number of satellite cells per muscle fibre. The detected statistically significant differences between control and experimental groups provide evidence that selected histological parameters could be additional mechanisms for detecting the presence of AAS in pork meat in the future.
- MeSH
- Anabolic Agents * pharmacology MeSH
- Muscle Fibers, Skeletal * drug effects ultrastructure MeSH
- Muscle, Skeletal drug effects anatomy & histology ultrastructure MeSH
- Myofibrils * drug effects ultrastructure MeSH
- Nandrolone * pharmacology MeSH
- Swine anatomy & histology MeSH
- Sarcomeres drug effects ultrastructure MeSH
- Satellite Cells, Skeletal Muscle drug effects ultrastructure MeSH
- Testosterone * pharmacology MeSH
- Microscopy, Electron, Transmission veterinary MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND/AIM: New generation androgen receptor-targeting agents (ARTA) have been in the spotlight for their efficacy in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific antigen (PSA) represents one of the most commonly used serum cancer biomarkers worldwide. The present retrospective study focused on the prognostic role of serum PSA isoforms and their early dynamics in mCRPC patients treated with abiraterone acetate (ABI) or enzalutamide (ENZ). PATIENTS AND METHODS: The association between outcomes of 334 mCRPC patients treated with ABI or ENZ and the levels of serum total PSA (tPSA), free PSA (fPSA), [-2]proPSA and the Prostate Health Index (PHI) at baseline and one month after treatment initiation was analyzed retrospectively. RESULTS: In the multivariable Cox proportional hazards models, baseline tPSA>50 μg/l (p<0.001), and [-2]proPSA>300 ng/l (p=0.017) remained independent significant factors associated with inferior OS, while baseline fPSA>1.75 μg/l (p=0.050) and Δ [-2]proPSA >-50% approached statistical significance (p=0.062). The results of ROC analyses assessing the ability of baseline tPSA, fPSA, and [-2]proPSA to predict mortality within two years showed area under the curve (AUC) values of 0.709, 0.685, and 0.740, respectively. Among the subgroup with baseline tPSA≤20.0 μg/l, the results of ROC analyses for baseline tPSA, fPSA and [-2]proPSA showed AUC values of 0.441, 0.682, and 0.688, respectively. CONCLUSION: Our results suggest a significant correlation between pretreatment serum levels of tPSA and [-2]proPSA with OS in mCRPC patients receiving ARTA.
- MeSH
- Abiraterone Acetate therapeutic use administration & dosage MeSH
- Receptors, Androgen * blood metabolism MeSH
- Androgen Receptor Antagonists therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Biomarkers, Tumor blood MeSH
- Prostatic Neoplasms, Castration-Resistant * drug therapy blood pathology mortality MeSH
- Prognosis MeSH
- Prostate-Specific Antigen * blood MeSH
- Protein Isoforms * blood MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
Vitamin D hraje velice významnou roli pro lidské zdraví. Jeho nedostatek je spojen s mnoha zdravotními komplikacemi. Obecně je ale méně známý jeho vliv na reprodukci a sexuální funkce mužů i žen. V článku přinášíme přehledné informace o této problematice a informujeme i o možnostech suplementace vitaminu D. Suplementace vitaminu D je pro zdraví a kvalitu života přínosná téměř ve všech oblastech. Nejúčinnější je léčba přípravky na lékařský předpis. Nová možnost léčby kalcifediolem je ještě efektivnější a bezpečnější volbou.
Vitamin D plays a very significant role in human health. Its deficiency is associated with many health complications. However, its influence on reproduction and sexual function in both men and women is generally less known. This article provides an overview of this issue and informs about the possibilities of vitamin D supplementation. Vitamin D supplementation is beneficial for health and quality of life in almost all areas. The most effective treatment is with prescription drugs. A new treatment option with calcifediol is an even more effective and safer choice.
- MeSH
- Avitaminosis etiology drug therapy MeSH
- Erectile Dysfunction drug therapy prevention & control MeSH
- Fertility drug effects MeSH
- Humans MeSH
- Menstrual Cycle metabolism drug effects MeSH
- Premature Ejaculation drug therapy prevention & control MeSH
- Reproductive Health * MeSH
- Polycystic Ovary Syndrome drug therapy MeSH
- Testosterone physiology MeSH
- Vitamin D * physiology metabolism MeSH
- Check Tag
- Humans MeSH
The objective of our in vitro study was to quantify the biochemical profile where the total polyphenol, flavonoid and phenolic acid content was determined. The antioxidant potential of microgreen extract from Trigonella foenum-graecum L., was measured molybdenum reducing power assay. Specifically, the study assessed parameters such as metabolic activity (AlamarBlueTM assay), membrane integrity (CFDA-AM assay), mitochondrial potential (JC-1 assay), as well as reactive oxygen species generation (NBT assay). In addition, the steroid hormone release in TM3 murine Leydig cells after 12 h and 24 h exposures were quantified by enzyme-linked immunosorbent assay. The gained results indicate the highest value in total flavonoid content (182.59+/-2.13 mg QE) determination, supported by a significant (108.25+/-1.27 mg TE) antioxidant activity. The effects on metabolic activity, cell membrane integrity, and mitochondrial membrane potential were found to be both time- and dose-dependent. Notably, a significant suppression in reactive oxygen species generation was confirmed at 150, 200 and 250 microg/ml after 24 h exposure. In addition, progesterone and testosterone release was stimulated up to 250 microg/ml dose of Trigonella, followed by a decline in both steroid production at 300 and 1000 microg/ml. Our results indicate, that Trigonella at lower experimental doses (up to 250 microg/ml) may positively affect majority of monitored cell parameters in TM3 Leydig cells. Overleaf, increasing experimental doses may negatively affect the intracellular parameters already after 12 h of in vitro exposure. Key words Microgreens, Trigonella foenum-graecum L., Fenugreek, Leydig cells, Male reproduction.
- MeSH
- Antioxidants pharmacology MeSH
- Cell Line MeSH
- Phytochemicals pharmacology MeSH
- Leydig Cells * drug effects metabolism MeSH
- Membrane Potential, Mitochondrial drug effects MeSH
- Mice MeSH
- Reactive Oxygen Species metabolism MeSH
- Plant Extracts * pharmacology MeSH
- Testosterone metabolism MeSH
- Trigonella * chemistry MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Adherence to rhinitis treatment has been insufficiently assessed. We aimed to use data from the MASK-air mHealth app to assess adherence to oral antihistamines (OAH), intra-nasal corticosteroids (INCS) or azelastine-fluticasone in patients with allergic rhinitis. METHODS: We included regular European MASK-air users with self-reported allergic rhinitis and reporting at least 1 day of OAH, INCS or azelastine-fluticasone. We assessed weeks during which patients answered the MASK-air questionnaire on all days. We restricted our analyses to data provided between January and June, to encompass the pollen seasons across the different assessed countries. We analysed symptoms using visual analogue scales (VASs) and the combined symptom-medication score (CSMS), performing stratified analyses by weekly adherence levels. Medication adherence was computed as the proportion of days in which patients reported rhinitis medication use. Sensitivity analyses were performed considering all weeks with at most 1 day of missing data and all months with at most 4 days of missing data. RESULTS: We assessed 8212 complete weeks (1361 users). Adherence (use of medication > 80% days) to specific drug classes ranged from 31.7% weeks for azelastine-fluticasone to 38.5% weeks for OAH. Similar adherence to rhinitis medication was found in users with or without self-reported asthma, except for INCS (better adherence in asthma patients). VAS and CSMS levels increased from no adherence to full adherence, except for INCS. A higher proportion of days with uncontrolled symptoms was observed in weeks with higher adherence. In full adherence weeks, 41.2% days reported rhinitis co-medication. The sensitivity analyses displayed similar results. CONCLUSIONS: A high adherence was found in patients reporting regular use of MASK-air. Different adherence patterns were found for INCS compared to OAH or azelastine-fluticasone that are likely to impact guidelines.
- MeSH
- Medication Adherence * MeSH
- Anti-Allergic Agents therapeutic use MeSH
- Histamine Antagonists therapeutic use MeSH
- Adult MeSH
- Fluticasone therapeutic use administration & dosage MeSH
- Phthalazines therapeutic use MeSH
- Adrenal Cortex Hormones therapeutic use administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Surveys and Questionnaires MeSH
- Pollen immunology MeSH
- Seasons * MeSH
- Rhinitis, Allergic, Seasonal * drug therapy epidemiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent. Four IBU-based combinations were studied: 1:4 M ratio with octanoic acid (OctA), 1:5 with nonanoic acid (NonA), 1:3 with decanoic acid (DeA) or 1:2 with dodecanoic acid (DoA). Fatty acids of different chain lengths were analyzed and discussed considering surface charge densities obtained via quantum chemistry. The THEDESs listed could apparently dissolve AbAc amounts up to 1311.0 ± 125.4 mg/g in IBU:OctA THEDES, 1151.7 ± 22.2 mg/g in IBU:NonA, 1160.4 ± 33.5 mg/g in IBU:DeA, and 231.3 ± 10.7 mg/g in IBU:DoA. In vitro dissolution of the simultaneously released drugs reached 37.8 ± 9.0 % to 64.2 ± 1.0 % for IBU and 5.0 ± 3.3 % to 19.4 ± 0.1 % for AbAc. This increased to between 60.4 ± 2.8 % and 79.4 ± 5.0 % of released IBU, and 23.6 ± 1.0 % to 57.3 ± 5.8 % of released AbAc, with 20 % (w/w) Tween 80 added to the formulations. This showed the significant potential of drug-containing THEDESs as solubilizing agents for poorly soluble drugs, in the form of fixed-dose combinations of synergistic APIs.
- MeSH
- Abiraterone Acetate * chemistry administration & dosage MeSH
- Chemistry, Pharmaceutical methods MeSH
- Drug Combinations MeSH
- Ibuprofen * chemistry administration & dosage MeSH
- Fatty Acids chemistry MeSH
- Drug Compounding methods MeSH
- Antineoplastic Agents chemistry administration & dosage MeSH
- Solvents * chemistry MeSH
- Solubility * MeSH
- Drug Liberation MeSH
- Publication type
- Journal Article MeSH
