Most cited article - PubMed ID 28738570
Determination of selected bisphenols, parabens and estrogens in human plasma using LC-MS/MS
The gradual phaseout of dental amalgam has contributed to a significant increase in the use of resin-based materials. While these materials offer several desirable properties, concerns persist regarding their biocompatibility, particularly the release of bisphenol A (BPA). BPA is an endocrine-disrupting chemical linked to adverse effects on human health, including reproductive, developmental, and metabolic disorders. Although food contact materials are the primary source of human BPA exposure and the contribution of dental materials is minor, the associated risks cannot be dismissed due to BPA's nonmonotonic dose-response relationship. In 2023, the European Food Safety Authority proposed a 20,000-fold reduction in the tolerable daily intake of BPA to 0.2 ng/kg body weight, citing immune system effects at extremely low doses. This proposal has sparked regulatory and scientific debate, as adopting such a stringent limit would effectively ban the use of BPA in food contact materials and many other products. Given this context, it is essential to assess the release of BPA from dental materials both in vitro and in vivo. However, data interpretation is complicated by methodological inconsistencies, including variations in material composition, specimen preparation, choice of extraction media, experimental duration, and analytical methods. In addition, pivotal differences in reporting results make it difficult to synthesize findings and draw reliable conclusions. This review examines the controversy surrounding BPA, critically evaluates evidence on its release from dental materials, and explores mitigation strategies. By highlighting gaps in knowledge and proposing future research directions, this review aims to provide clinicians, researchers, and policymakers with a clearer understanding of BPA-related complexities, ultimately contributing to patient safety and material innovation.
- Keywords
- biocompatibility, composite materials, endocrinology, resin(s), sealants, toxicology,
- MeSH
- Benzhydryl Compounds * adverse effects analysis MeSH
- Endocrine Disruptors * adverse effects analysis MeSH
- Phenols * adverse effects analysis MeSH
- Risk Assessment MeSH
- Humans MeSH
- Dental Materials * chemistry adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Benzhydryl Compounds * MeSH
- bisphenol A MeSH Browser
- Endocrine Disruptors * MeSH
- Phenols * MeSH
- Bisphenol A Compounds MeSH
- Dental Materials * MeSH
Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis.
- Keywords
- 11-hydroxytestosterone, 11-ketotestosterone, 11-oxygenated androgen, bisphenol A, bisphenol S, endocrine disruptor, idiopathic hirsutism, polycystic ovary syndrome,
- MeSH
- Androgens * blood metabolism MeSH
- Benzhydryl Compounds blood MeSH
- Cytokines blood metabolism MeSH
- Adult MeSH
- Endocrine Disruptors * blood MeSH
- Phenols MeSH
- Hirsutism * blood etiology chemically induced MeSH
- Hyperandrogenism blood MeSH
- Humans MeSH
- Young Adult MeSH
- Obesity blood metabolism MeSH
- Polycystic Ovary Syndrome * blood metabolism MeSH
- Tandem Mass Spectrometry MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Androgens * MeSH
- Benzhydryl Compounds MeSH
- bisphenol A MeSH Browser
- Cytokines MeSH
- Endocrine Disruptors * MeSH
- Phenols MeSH
The fast-track process to approve vaccines against COVID-19 has raised questions about their safety, especially in relation to fertility. Over the last 2 years, studies have appeared monitoring female fertility, especially from assisted reproduction centers or in animal experiments. However, studies monitoring healthy populations are still limited. The aim of our study was to monitor the relevant parameters of female fertility (sex and other steroids, LH, FSH, SHBG, Antimüllerian hormone and antral follicle count) before and then 2-4 months after the third dose of vaccination against COVID-19 in a group of 25 healthy fertile woman. In addition, anti-SARS-CoV-2 and anti-SARS-CoV-2S antibodies were determined. We did not observe significant changes in the measured parameters before and after the third dose of vaccination. By comparing levels of the analytes with antibodies indicating a prior COVID-19 infection, we found that women who had experienced the disease had statistically lower levels of estrone, estradiol, SHBG and 5α-dihydroprogesterone, and conversely, higher levels of androgen active dehydroepiandrosterone and dihydrotestosterone. Our results confirm that vaccination does not affect female fertility, and that what fertile women should be worried about is not vaccination, but rather COVID-19 infection itself.
- Keywords
- AMH, COVID-19, antral follicle count, infection, safety, steroids, vaccination, woman fertility,
- MeSH
- 20-alpha-Dihydroprogesterone MeSH
- Androgens MeSH
- Anti-Mullerian Hormone * MeSH
- COVID-19 * prevention & control MeSH
- Dehydroepiandrosterone MeSH
- Dihydrotestosterone MeSH
- Estradiol MeSH
- Estrone MeSH
- Fertility MeSH
- Follicle Stimulating Hormone MeSH
- Humans MeSH
- COVID-19 Vaccines MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- 20-alpha-Dihydroprogesterone MeSH
- Androgens MeSH
- Anti-Mullerian Hormone * MeSH
- Dehydroepiandrosterone MeSH
- Dihydrotestosterone MeSH
- Estradiol MeSH
- Estrone MeSH
- Follicle Stimulating Hormone MeSH
- COVID-19 Vaccines MeSH
Bisphenol A (BPA)-based monomers are commonly contained in dental resin-based materials. As BPA is an endocrine disruptor, its long-term release from restorative composites and resin-modified glass ionomers (RM-GICs) under two polymerization conditions was measured in this study. Specimens of two conventional composites containing BPA-based monomers, two "BPA-free" composites, and two RM-GICs were polymerized from one side for 20 s at 1300 mW/cm2 or for 5 s at 3000 mW/cm2. The amounts of BPA released in artificial saliva and methanol after 1, 4, 9, 16, 35, 65, 130, and 260 days were measured using liquid chromatography-tandem mass spectrometry. The highest amounts of BPA were released from conventional composites, followed by RM-GICs, while the least was released from "BPA-free" composites. Amounts of released BPA were significantly higher in methanol and decreased gradually after the first day. Fast polymerization (5 s at 3000 mW/cm2) resulted in a significantly higher release of BPA after 1 day, but the effect of polymerization conditions was not significant overall. In conclusion, fast polymerization increased the initial release of BPA, but the released amounts were significantly lower than the current tolerable daily intake (4 μg/kg body weight/day) even in methanol, representing the worst-case scenario of BPA release.
- Keywords
- Bis-GMA, bisphenol A, glass ionomer cements, light-curing, liquid chromatography, mass spectrometry, resin composite,
- Publication type
- Journal Article MeSH
Polycarbonates are polymers of bisphenol A (BPA), a well-known endocrine disruptor. This study evaluated the release of BPA from polycarbonate crowns that were (1) milled from Temp Premium Flexible (ZPF, Zirkonzahn, Italy) or Tizian Blank Polycarbonate (TBP, Schütz Dental, Germany), or (2) 3D-printed (Makrolon 2805, Covestro, Germany). Commercial prefabricated polycarbonate crowns (3M, USA) and milled poly(methyl methacrylate) (PMMA) crowns (Temp Basic, Zirkonzahn, Italy) were included for comparison. The crowns were stored at 37 °C in artificial saliva (AS) or methanol, which represented the worst-case scenario of BPA release. Extracts were collected after 1 day, 1 week, 1 month and 3 months. BPA concentrations were measured using liquid chromatography-tandem mass spectrometry. The amounts of released BPA were expressed in micrograms per gram of material (μg/g). After 1 day, the highest amounts of BPA were measured from milled polycarbonates, TBP (methanol: 32.2 ± 3.8 μg/g, AS: 7.1 ± 0.9 μg/g) and ZPF (methanol 22.8 ± 7.7 μg/g, AS: 0.3 ± 0.03 μg/g), followed by 3D-printed crowns (methanol: 11.1 ± 2.3 μg/g, AS: 0.1 ± 0.1 μg/g) and prefabricated crowns (methanol: 8.0 ± 1.6 μg/g, AS: 0.07 ± 0.02 μg/g). Between 1 week and 3 months, the average daily release of BPA in methanol and AS decreased below 2 μg/g and 0.6 μg/g, respectively. No BPA was released from PMMA in AS, and the cumulative amount released in methanol was 0.2 ± 0.06 μg/g. In conclusion, polycarbonates could be a relevant source of BPA, but the current tolerable daily intake of BPA (4 μg/kg body weight) should not be exceeded.
- Keywords
- 3D-printing, bisphenol A, chromatography, dental prosthesis, mass spectrometry, milling, polycarbonate, splint,
- Publication type
- Journal Article MeSH
Androgens represent the main hormones responsible for maintaining hormonal balance and function in the prostate and testis. As they are involved in prostate and testicular carcinogenesis, more detailed information of their active concentration at the site of action is required. Since the introduction of the term intracrinology as the local formation of active steroid hormones from inactive precursors of the adrenal gland, mainly dehydroepiandrosterone (DHEA) and DHEA-S, it is evident that blood circulating levels of sex steroid hormones need not reflect their actual concentrations in the tissue. Here, we review and critically evaluate available methods for the analysis of human intraprostatic and intratesticular steroid concentrations. Since analytical approaches have much in common in both tissues, we discuss them together. Preanalytical steps, including various techniques for separation of the analytes, are compared, followed by the end-point measurement. Advantages and disadvantages of chromatography-mass spectrometry (LC-MS, GC-MS), immunoanalytical methods (IA), and hybrid (LC-IA) are discussed. Finally, the clinical information value of the determined steroid hormones is evaluated concerning differentiating between patients with cancer or benign hyperplasia and between patients with different degrees of infertility. Adrenal-derived 11-oxygenated androgens are mentioned as perspective prognostic markers for these purposes.
- Keywords
- androgens, biomarkers, cancer, determination, disease prediction, methods, prostate, testes,
- MeSH
- Androgens metabolism MeSH
- Humans MeSH
- Adrenal Glands metabolism MeSH
- Gonadal Steroid Hormones metabolism MeSH
- Prostate metabolism MeSH
- Steroids metabolism MeSH
- Testis metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Androgens MeSH
- Gonadal Steroid Hormones MeSH
- Steroids MeSH
Dental composite materials often contain monomers with bisphenol A (BPA) structure in their molecules, e.g. bisphenol-A glycidyl dimethacrylate (Bis-GMA). In this study, it was examined whether dental restorative composites could be a low-dose source of BPA or alternative bisphenols, which are known to have endocrine-disrupting effects. Bis-GMA-containing composites Charisma Classic (CC) and Filtek Ultimate Universal Restorative (FU) and "BPA-free" Charisma Diamond (CD) and Admira Fusion (AF) were examined. Specimens (diameter 6 mm, height 2 mm, n=5) were light-cured from one side for 20 s and stored at 37 °C in methanol which was periodically changed over 130 days to determine the kinetics of BPA release. BPA concentrations were measured using a dansyl chloride derivatization method with liquid chromatography - tandem mass spectrometry detection. The amounts of BPA were expressed in nanograms per gram of composite (ng/g). BPA release from Bis-GMA-containing CC and FU was significantly higher compared to "BPA-free" CD and AF. The highest 1-day release was detected with FU (15.4+/-0.8 ng/g), followed by CC (9.1+/-1.1 ng/g), AF (2.1+/-1.3 ng/g), and CD (1.6+/-0.8 ng/g), and the release gradually decreased over the examined period. Detected values were several orders of magnitude below the tolerable daily intake (4 microg/kg body weight/day). Alternative bisphenols were not detected. BPA was released even from "BPA-free" composites, although in significantly lower amounts than from Bis-GMA-containing composites. Despite incubation in methanol, detected amounts of BPA were substantially lower than current limits suggesting that dental composites should not pose a health risk if adequately polymerized.
- MeSH
- Benzhydryl Compounds analysis MeSH
- Bisphenol A-Glycidyl Methacrylate chemistry MeSH
- Phenols analysis MeSH
- Humans MeSH
- Methacrylates chemistry MeSH
- Siloxanes chemistry MeSH
- Composite Resins chemistry MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Dental Materials chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- admira MeSH Browser
- Benzhydryl Compounds MeSH
- Bisphenol A-Glycidyl Methacrylate MeSH
- bisphenol A MeSH Browser
- Charisma composite resin MeSH Browser
- Phenols MeSH
- Methacrylates MeSH
- Siloxanes MeSH
- Composite Resins MeSH
- Dental Materials MeSH
As environmental and genetic components contribute to the PCOS expression, we compared levels of endocrine disruptors, steroid hormones, cytokines, and metabolic parameters in twenty healthy, nine normal-weight PCOS women, and ten obese PCOS women. Steroid hormones, bisphenols (BPA, BPS, BPF, BPAF) and parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-parabens) were measured by liquid chromatography-tandem mass spectrometry. Differences between the groups were assessed using the Mann-Whitney U test. Spearman correlation coefficients were calculated for the individual parameters relationship. Significantly higher levels of BPA, anti-Müllerain hormone, lutropine, lutropine/folitropine ratio, testosterone, androstenedione, 7beta-OH-epiandrosterone, and cytokines (IL-6, VEGF, PDGF-bb), were found in normal-weight PCOS women compared to controls. Between normal-weight and obese PCOS women, there were no differences in hormonal, but in metabolic parameters. Obese PCOS women had significantly higher insulin resistance, fatty-liver index, triglycerides, cytokines (IL-2, IL-13, IFN-gamma). In healthy, but not in PCOS, women, there was a positive correlation of BPA with testosterone, SHBG with lutropine, and folitropine, while testosterone negatively correlated with SHBG. In obese women with PCOS, insulin resistance negatively correlated with SHBG and estradiol. No differences were observed in the paraben exposure. Levels of BPA were higher in PCOS women, indicating its role in the etiology. Obesity significantly worsens the symptoms.
- MeSH
- Cytokines blood MeSH
- Adult MeSH
- Endocrine Disruptors blood MeSH
- Estrogens blood MeSH
- Body Mass Index MeSH
- Insulin Resistance MeSH
- Humans MeSH
- Obesity blood epidemiology pathology MeSH
- Case-Control Studies MeSH
- Polycystic Ovary Syndrome blood epidemiology pathology MeSH
- Testosterone blood MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- Cytokines MeSH
- Endocrine Disruptors MeSH
- Estrogens MeSH
- Testosterone MeSH