The Role of 11-Oxygenated Androgens and Endocrine Disruptors in Androgen Excess Disorders in Women.

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.

Steroid Metabolome Analysis in Dichorionic Diamniotic Twin Pregnancy.

Steroid hormones have diverse roles in pregnancy; some help stabilise pregnancy and influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies. To date, only a few studies have performed a very limited steroid analysis in multiple pregnancies. Our teams investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group, and a control singleton pregnancies group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35 + 3 to 39 + 3 weeks, while it was 38 + 1 to 41 + 1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies. Results demonstrate differences in the steroidome between singleton and twin pregnancies. These were based on the presence of two placentae and two foetal adrenal glands, both with separate enzymatic activity. Since every newborn was delivered by caesarean section, analysis was not negatively influenced by changes in the steroid metabolome associated with the spontaneous onset of labour.

COVID-19, Vaccination, and Female Fertility in the Czech Republic.

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.

Altered Steroidome in Women with Gestational Diabetes Mellitus: Focus on Neuroactive and Immunomodulatory Steroids from the 24th Week of Pregnancy to Labor.

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM- women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM- women (n = 33), in weeks 24-28, 30-36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.

Assessment of vitamin D status in Czech children.

OBJECTIVE: Vitamin D deficiency is a global health problem. The aim of this study was to determine the proportion of Czech children with vitamin D deficiency and examine related factors. METHODS: The study subjects were 419 healthy children aged 5 and 9 years. Severe vitamin D deficiency was defined as a serum 25(OH)D level of < 25 nmol/L (3% of children), deficiency as that of 25-50 nmol/L (24% of children), insufficiency as that of 50-75 nmol/L (40% of children) and sufficiency as that of > 75 nmol/L (34% of children). RESULTS: Serum 25(OH)D levels varied mainly with season. The highest levels of 25(OH)D were reached in autumn (median: 79.0 nmol/L), followed by summer (median: 67.8 nmol/L) and winter (median: 56.0 nmol/L). The lowest median value (49.8 nmol/L) was detected in spring. CONCLUSION: Children with sufficiency 25(OH)D levels were more frequently exposed to the sun and exposed a larger part of their body to the sun while spending time outdoors. Levels of 25(OH)D were also associated with using vitamin D supplements within six weeks before sampling.

[Urinary iodine concentration in adult patients with type 1 diabetes mellitus]. / Jodurie u nemocných s diabetes mellitus 1. typu Vztahy k vybraným parametrum charakterizujícím diabetický syndrom.

INTRODUCTION: In patients with type 1 and 2 diabetes mellitus only rare data concerning the status of iodine supplementation and impact of possible iodine deficiency is available. AIM: To get basic information about (a) state of supply with iodine in patients with type 1 diabetes mellitus (DM1T), (b) the difference from non-diabetic population, (c) possible association of iodine saturation with some clinical and laboratory features of the diabetic syndrome, including the state of thyroid gland. SUBJECTS AND METHODS: We examined 54 men and 51 women treated with DM1T in a cross-sectional study. Age: median 42 years (25th quartil 31, 75th quartil 55), DM1T duration: 18 years (13, 23), BMI: 25.9 (23.3, 29.7), HbA1c: 61 mmol/mol (51, 71), creatinine: 71 µmol/l (61, 83), micro-albuminuria 4.3 µg/min (1.9, 11.8), TSH: 1.77 mIU/l (1.12, 2.80). The iodine saturation was evaluated using iodine concentration in a sample of first morning urine. RESULTS: Urinary iodine concentration in the whole group: median 152 µg/l, 25th quartile 117 µg/l, 75th quartile 219 µg/l. More than 50 % of the urinary iodine samples fell within range of optimal saturation (100-200 µg/l), 13 % within insufficient saturation (< 100 µg/l), 35 % of the samples showed increased saturation (> 200 µg/l), in which 2/3 were men. Using multiple regression analysis we found significant positive association of urinary iodine concentration and male gender, body weight, stature, and serum creatinine. No relation between urinary iodine and clinical and laboratory features of the diabetic syndrome was found. CONCLUSIONS: Iodine saturation in examined patients with DM1T was in accordance with ICCIDD (WHO) requirements for optimal/good saturation in non-diabetic population. With respect to the chosen normal urinary iodine concentration, eg. 100, resp. 150 µg/l the features of diabetic syndrome were not different. The question whether other factors than general measures taken in the past for solution of the iodine deficiency in the Czech Republic are involved in good level of iodine saturation in patients with DM1T should be addressed in further investigations comprising larger cohorts of patients.Key words: diabetes mellitus - urinary iodine concentration.

Vitamin D and its metabolites--supply of patients with various endocrine disorders and comparison of analytical methods.

OBJECTIVE: Vitamin D is important not only for its effect on the homeostasis of calcium, but also for its anti-proliferative, pro-differentiation, pro-apoptotic and immuno-modulating effects in the tissues of living organisms. This work describes the results of serum 25(OH)D (n=2175) and 1alpha,25(OH)2D (n=2271) radioimmunoassays (RIA) conducted at the Institute of Endocrinology in Prague (Czech Republic) during the period of 2004-2006. METHODS: Serum concentrations of vitamin D metabolites were determined by RIA kits from IDS Ltd., Boldon, UK. In a group of 20 healthy volunteers, results obtained using the RIA kit were compared with those obtained after serum extraction with acetonitrile, subsequent chromatographic (RP HPLC) separation of 25(OH)D and its detection in collected fractions using the same RIA kit from IDS. RESULTS: The mean concentrations +/- S.D. in the samples studied were 76.4 +/- 45.6 nmol/l for 25(OH)D and 88.9 +/- 45.1 pmol/l for 1alpha,25(OH)2D. The mean concentrations of both metabolites were higher in women than in men, but only the difference for 1alpha,25(OH)2D) was statistically significant (p=0.0000). The lowest concentrations of 25(OH)D or 1alpha,25(OH)2D were found in patients with hyperparathyroidism, the highest concentrations those treated with cholecalciferol for osteoporosis and vitamin D deficiency. The relationship between 25(OH)D and 1alpha,25(OH)2D was expressed by the equation 1alpha,25(OH)2D = 71.0845 + 0.1890 * 25(OH)D (n=1065, p=0.0000, R2=0.0343). Based on the RIA results, only 4 % of individuals were inadequately supplied with 25(OH)D, 79 % were supplied adequately and almost 17 % were supplied more than adequately. Similarly, 1alpha,25(OH)2D shows inadequate concentration in 15 % of the individuals tested, 59 % of these individuals were within the reference range and 26 % had values exceeding the upper limit of the reference range. The mean concentrations of 25(OH)D obtained by HPLC separation were in average by 8 % higher than those obtained using only the RIA kit. CONCLUSION: Interpretation of studies dealing with vitamin D stores must be based on precise and correct analytical procedures. However, only a few information exists about the influence of other vitamin D metabolites and conjugates on the concentration of immunoanalytically measured serum 25(OH)D or 1alpha,25(OH)2D.