Clinically Relevant Laboratory Monitoring of Gender-Affirming Hormone Therapy in Transgender People-Experiences from a Teaching Hospital in the Netherlands.

BACKGROUND: Transgender care is shifting from academic to nonacademic settings leading to use of common (immunoassay) compared to sophisticated (mass spectrometry) methods to monitor estradiol and testosterone during gender-affirming hormone therapy (GAHT). The type of assay can influence results and have significant implications for clinical decision making. An evidence gap is present in recommendations regarding the assay needed to monitor GAHT. The present study aimed to summarize current evidence and evaluate immunoassay estradiol and testosterone concentrations in transgender people visiting a nonacademic hospital for GAHT. METHODS: Clinical practice guidelines on GAHT and scientific literature on assay methodologies were screened and summarized. Laboratory and medical data from 252 patients who visited the transgender outpatient clinic of the Maasstad Hospital for GAHT between 2020 and 2022 were retrospectively analyzed. RESULTS: Our research showed that the most used clinical practice guidelines for GAHT provide hormonal target values without recommending a preferred method. A comprehensive literature search on agreement between immunoassay and mass spectrometry showed substantial heterogeneity in results. Retrospective analysis of our immunoassay measured data in transgender people showed hormonal changes during GAHT that are to be expected from the medication used. CONCLUSIONS: We demonstrate that laboratory monitoring of GAHT in a nonacademic hospital can be done safely by immunoassay in most cases. Only in cases where clinical observation is discordant with the hormonal results do more sophisticated methods need to be deployed. A best practice model was proposed for transgender care in nonacademic hospitals.

Hormonal residues in chicken and cattle meat: A risk threat the present and future consumer health.

The study was designated to determine some hormonal residues (estradiol, progesterone, and testosterone) in chicken and cattle meat as well as assess the risk of these residues for adult and child consumer health. A total of 92 chicken meat samples were collected from four different chicken farm sales outlets, and 56 cattle meat samples from two brands were collected from markets through 2022 in Assiut City, Egypt. An enzyme-linked immunosorbant assay (ELISA) was used to measure the hormonal residues. Results showed that the estimated daily intake (EDI) of estradiol exceeded acceptable daily intakes (ADIs) in all analyzed samples except four chicken farm meat samples for adults only, which were below 0.05 µg/kg bw, and the hazard index (HI) of estradiol and testosterone residues for adults and children exceeded 1 in all examined samples of the study. The U.S. Food and Drug Administration (FDA) set safe limits for these anabolic hormones to ensure high food quality and quantity for humans, but in Egypt, monitoring and assessment of hormonal residues in food became very urgent as no safe limits have been set till now.

Idiopathic hypogonadotropic hypogonadism caused by compound heterozygosity for two novel mutations in the GNRH1 gene: a case report.

BACKGROUND: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare congenital or acquired genetic disorder caused by gonadotropin-releasing hormone (GnRH) deficiency. IHH patients are divided into two major groups, hyposmic or anosmic IHH (Kallmann syndrome) and normosmic IHH (nIHH), according to whether their sense of smell is intact. Here we report a case of novel compound heterozygous mutations in the GNRH1 gene in a 15-year-old male with nIHH. CASE PRESENTATION: The patient presented typical clinical symptoms of delayed testicular development, with testosterone < 3.5 mmol/L and reduced gonadotropin (follicle-stimulating hormone, luteinizing hormone) levels. Two heterozygous variants of the GNRH1 gene were detected, nonsense variant 1: c.85G > T:p.G29* and variant 2: c.1A > G:p.M1V, which disrupted the start codon. CONCLUSIONS: Two GNRH1 mutations responsible for nIHH are identified in this study. Our findings extend the mutational spectrum of GNRH1 by revealing novel causative mutations of nIHH.

The association of prenatal amniotic sex hormones and digit ratio (2D:4D) in children aged 5 to 70 months: A longitudinal study.

The sex difference of the 2D:4D digit ratio (female > male)-a proposed marker for prenatal testosterone exposure-is well established. Studies suggest it already exists in utero and is of moderate effect size in adulthood. However, evidence for the claim that 2D:4D reflects prenatal androgen action is limited, and the sex difference may exhibit lability during childhood. In the present study, 244 mothers were recruited in the course of an amniocentesis examination (performed between gestational weeks 14 and 18). Prenatal testosterone (T) and estradiol (E) levels were determined from amniotic fluid for boys and girls. The majority (97.4%, n = 114) of available female T levels (n = 117) were found below the level of quantification. Therefore, only male amniotic fluid data (n = 117) could be included for the analysis of associations between amniotic sex hormones (T levels and T to E ratio (T/E)) and 2D:4D. The families were then invited to each of the five consecutive follow-ups (ages: 5, 9, 20, 40, and 70 months) where children's 2D:4D was measured for both hands. The alternative marker D[r-l] reflects the directional asymmetry of 2D:4D (right subtracted by left 2D:4D) and was subsequently calculated as an additional measure for prenatal T exposure. No significant correlations between amniotic T or the T/E ratio (measured between week 14 and 18 of gestation) with 2D:4D respectively D[r-l] were observed for any time point. There was a significant sex difference (females > males) and a significant age effect with moderate correlations of 2D:4D between time points. 2D:4D increased between 20 and 40 months and between 40 and 70 months of age. The findings raise questions regarding the applicability of 2D:4D as a marker for prenatal androgen action and are discussed in terms of the reliability of obtained digit ratio data as well as in terms of the developmental timing of amniocentesis.

Gonadal Function in Male Patients With Metastatic Renal Cell Cancer Treated With Sunitinib.

BACKGROUND/AIM: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. PATIENTS AND METHODS: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. RESULTS: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. CONCLUSION: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib.

Influence of smoking status on acute biomarker responses to successive days of arduous military training.

INTRODUCTION: Habitual smoking is highly prevalent in military populations despite its association with poorer training outcomes. Smoking imposes challenges on the immune and endocrine systems which could alter how smokers acutely respond to, and recover from, intensive exercise particularly over multiple days of training. METHODS: Over a two-day period, 35 male British Army recruits (age 22±3 years; mass 76.9±8.0 kg; height 1.78±0.06 m; 15 smokers) completed a 16.1 km loaded march (19.1 kg additional mass) on the first morning and a best-effort 3.2 km 'log race' (carrying a 60 kg log between six and eight people) on the subsequent morning. Blood samples were obtained on waking and immediately postexercise on both days and analysed for C reactive protein (CRP), interleukin 6 (IL-6), testosterone to cortisol ratio and insulin-like growth factor 1 (IGF-1). RESULTS: Independent of smoking group, the exercise bouts on both days evoked significant increases in IL-6 (p<0.001) and decreases in testosterone to cortisol ratio (p<0.05). CRP concentrations on day 2 were significantly higher than both time points on day 1 (p<0.001), and a 9% decline in IGF-1 occurred over the two-day period, but was not significant (p=0.063). No significant differences were observed between smokers and non-smokers (p>0.05). CONCLUSIONS: Military-specific tasks elicited inflammatory and endocrine responses, with systemic CRP and IGF-1 indicating that the physiological stress generated during the first training day was still evident on the second day. Despite the well-established impacts of smoking on resting levels of the markers examined, responses to two days of arduous military-specific training did not differ by smoking status.

Evaluation of thumbnail clipping as a specimen for retrospectively assessing average production of testosterone.

BACKGROUND: The chronic abnormal production of testosterone (T) is associated with many disorders in men. Fingernail clippings might be more suited for the diagnosis and medium-to-long term therapeutic monitoring for the T-related chronic disorders than the blood-derived specimens. The objective of this study was to characterize a thumbnail clipping as the specimen for assessing the several months-old T status. METHODS: Thumbnail clippings from various subjects were analyzed by liquid chromatography/electrospray ionization-tandem mass spectrometry to evaluate the gender difference, and changes caused by aging and androgen deprivation therapy (ADT) in the thumbnail T concentration. RESULTS: There was an evident gender difference in the thumbnail T concentrations [male; 2.55 ± 0.85 ng/g and female; 0.48 ± 0.29 ng/g, mean ± SD (n = 25 each), Welch t-test]. The thumbnail T concentrations significantly decreased with age in men (n = 268, Scheffé F-test), which was similar to those of the free or bioavailable T in serum/plasma. The thumbnail T concentrations sharply decreased by a 6-months ADT (especially the effect of the luteinizing hormone-releasing hormone agonist/antagonist) for patients with prostate cancer (n = 10). CONCLUSIONS: The thumbnail clipping can be a specimen to retrospectively assess the average T production.

Involvement of Hypoxia-Inducible Factor 1-α in Experimental Testicular Ischemia and Reperfusion: Effects of Polydeoxyribonucleotide and Selenium.

Polydeoxyribonucleotide (PDRN) is an agonist of the A2A adenosine receptor derived from salmon trout sperm. Selenium (Se) is a trace element normally present in the diet. We aimed to investigate the long-term role of PDRN and Se, alone or in association, after ischemia-reperfusion (I/R) in rats. The animals underwent 1 h testicular ischemia followed by 30 days of reperfusion or a sham I/R and were treated with PDRN or Se alone or in association for 30 days. I/R significantly increased hypoxia-inducible factor 1-α (HIF-1α) in Leydig cells, malondialdehyde (MDA), phosphorylated extracellular signal-regulated kinases 1/2 (pErk 1/2), and apoptosis decreased testis weight, glutathione (GSH), testosterone, nuclear factor erythroid 2-related factor 2 (Nrf2), induced testicular structural changes, and eliminated HIF-1α spermatozoa positivity. The treatment with either PDRN or Se significantly decreased MDA, apoptosis, and HIF-1α positivity of Leydig cells, increased testis weight, GSH, testosterone, and Nrf2, and improved the structural organization of the testes. PDRN and Se association showed a higher protective effect on all biochemical, structural, and immunohistochemical parameters. Our data suggest that HIF-1α could play important roles in late testis I/R and that this transcriptional factor could be modulated by PDRN and Se association, which, together with surgery, could be considered a tool to improve varicocele-induced damages.

Digit ratio (2D:4D) and maternal testosterone-to-estradiol ratio measured in early pregnancy.

The ratio of index to ring finger (2D:4D) has been hypothesised to indicate prenatal androgen exposure, yet evidence for its validity is lacking. We report the first pre-registered study to investigate mothers' early pregnancy sex hormone concentrations in relation to their children's digit ratios measured at 18-22-month follow-up. Although the testosterone (T) to estradiol (E) ratio correlated negatively with right hand digit ratio (R2D:4D) and directional asymmetry (right-minus-left) in digit ratio (D[R-L]), neither effect remained statistically significant once demographic and obstetric covariates were controlled for. Nevertheless, the multivariate level of analysis did reveal that T correlated positively with left hand digit ratio (L2D:4D) and negatively with D[R-L]. However, the first of these effects is in the opposite direction to that predicted by theory. Taken together, the results of our study suggest research with larger samples is required to determine whether digit ratios are valid proxies for maternal sex hormone exposure.

Age-associated reductions in cardiovagal baroreflex sensitivity are exaggerated in middle-aged and older men with low testosterone.

Aging is associated with reductions in cardiovagal baroreflex sensitivity (cBRS), which increases cardiovascular disease risk. Preclinical data indicate that low testosterone reduces cBRS. We determined whether low testosterone is associated with greater age-associated reductions in cBRS in healthy men. Twenty-six men categorized as young (N = 6; age = 31 ± 4 yr; testosterone = 535 ± 60 ng/dL), middle-aged/older with normal (N = 10; aged 56 ± 3 yr; testosterone = 493 ± 85 ng/dL) or low (N = 10; age = 57 ± 6 yr; testosterone = 262 ± 31 ng/dL) testosterone underwent recordings of beat-by-beat blood pressure and R-R interval during rest and two Valsalva maneuvers, and measures of carotid artery compliance. IL-6, C-reactive protein (CRP), oxidized LDL cholesterol, and total antioxidant status (TAS) were also measured in blood. Middle-aged/older men had lower cBRS compared with young men (17.0 ± 6.5 ms/mmHg; P = 0.028); middle-age/older men with low testosterone had lower cBRS (5.5 ± 3.2 ms/mmHg; P = 0.039) compared with age-matched men with normal testosterone (10.7 ± 4.0 ms/mmHg). No differences existed between groups during Phase II of the Valsalva maneuver; middle-aged/older men with low testosterone had reduced cBRS (4.7 ± 2.6 ms/mmHg) compared with both young (12.8 ± 2.8 ms/mmHg; P < 0.001) and middle-aged/older men with normal testosterone (8.6 ± 4.4 ms/mmHg; P = 0.046). There were no differences in oxidized LDL (P = 0.882) or TAS across groups (P = 0.633). IL-6 was significantly higher in middle-aged/older men with low testosterone compared with the other groups (P < 0.05 for all) and inversely correlated with cBRS (r = -0.594, P = 0.007). Middle-aged/older men had reduced carotid artery compliance compared with young, regardless of testosterone status (P < 0.001). These observations indicate that low testosterone in middle-aged/older men may contribute to reductions in cBRS. These data suggest that increased inflammation may contribute to reductions in cBRS.NEW & NOTEWORTHY Middle-aged/older men with low testosterone have accelerated reductions in cardiovagal BRS compared with middle-aged/older men with normal testosterone. Increased concentrations of the proinflammatory cytokine IL-6 appear to contribute to the reductions in cardiovagal BRS in men with low testosterone.

Evaluating suitability of saliva to measure steroid concentrations in grey seal pups.

Measurement of steroids in wild pinnipeds can facilitate assessment of breeding, nutritional and stress status, and is useful in understanding behavioral responses. Even in young animals, sex steroids may be important in behavioral interactions and immune modulation. Use of saliva can avoid the large fluctuations seen in some steroids in plasma, and can negate the need for venipuncture, making it a potentially useful matrix in the wildlife. However, its utility in estimating steroid levels in wild young pinnipeds has not been evaluated. Here, we investigated the suitability of saliva for steroid hormone analysis in wild grey seal pups during their suckling and post-weaning fast periods. We collected saliva (n = 38) and plasma (n = 71) samples during the breeding season on the Isle of May, Scotland, 2012. We investigated success of sample collection, ease of preparation, accuracy and precision of analysis, and, where possible, comparability of measurements (n = 27) from saliva and plasma. Plasma sampling was rapid, whereas sampling saliva took up to five times longer. Analytical performance criteria (parallelism, accuracy, and precision (intra and inter assay co-efficient of variation (% CV)) of commercial ELISA kits to measure estradiol, testosterone and cortisol in both matrices were assessed. Estradiol and cortisol assays performed well and can be used in plasma and saliva. However, we could not confidently validate testosterone for either matrix. Saliva estradiol correlated with levels in plasma. Saliva sample preparation was faster and simpler than plasma preparation because it did not require extraction. However, given the additional time taken to obtain saliva in the wild, the possibility of blood contamination from oral damage and the lower success rate in obtaining sufficient sample for analysis, we recommend that this matrix only be used as an alternative to plasma sampling measurement in pinnipeds when animals are anaesthetized, tolerate mouth swabbing, or have been trained to accept saliva sampling in captivity.

Alterations of gut microbiota diversity, composition and metabonomics in testosterone-induced benign prostatic hyperplasia rats.

BACKGROUND: Studies had shown many diseases affect the stability of human microbiota, but how this relates to benign prostatic hyperplasia (BPH) has not been well understood. Hence, this study aimed to investigate the regulation of BPH on gut microbiota composition and metabonomics. METHODS: We analyzed gut samples from rats with BPH and healthy control rats, the gut microbiota composition and metabonomics were detected by 16S rDNA sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: High-throughput sequencing results showed that gut microbiota beta-diversity increased (P < 0.01) in the BPH group vs. control group. Muribaculaceae (P < 0.01), Turicibacteraceae (P < 0.05), Turicibacter (P < 0.01) and Coprococcus (P < 0.01) were significantly decreased in the BPH group, whereas that of Mollicutes (P < 0.05) and Prevotella (P < 0.05) were significantly increased compared with the control group. Despite profound interindividual variability, the levels of several predominant genera were different. In addition, there were no statistically significant differences in several bacteria. BPH group vs. control group: Firmicutes (52.30% vs. 57.29%, P > 0.05), Bacteroidetes (46.54% vs. 41.64%, P > 0.05), Clostridia (50.89% vs. 54.66%, P > 0.05), Ruminococcaceae (25.67% vs. 20.56%, P > 0.05). LC-MS/MS of intestinal contents revealed that differential metabolites were mainly involved in cellular processes, environmental information processing, metabolism and organismal systems. The most important pathways were global and overview maps, lipid metabolism, amino acid metabolism, digestive system and endocrine system. Through enrichment analysis, we found that the differential metabolites were significantly enriched in metabolic pathways, steroid hormone biosynthesis, ovarian steroidogenesis, biosynthesis of unsaturated fatty acids and bile secretion. Pearson correlation analysis (R = 0.94) showed that there was a strong correlation between Prevotellaceae, Corynebacteriaceae, Turicibacteraceae, Bifidobacteriaceae and differential metabolites. CONCLUSION: Our findings suggested an association between the gut microbiota and BPH, but the causal relationship between the two groups is unclear. Thus, further studies are warranted to elucidate the potential mechanisms and causal relationships between BPH and gut microbiota.

Simultaneous detection of 93 anabolic androgenic steroids in dietary supplements using gas chromatography tandem mass spectrometry.

In recent years, anabolic androgenic steroids (AASs) have been frequently detected as undeclared ingredients in dietary supplements, where the adverse analytical findings (AAFs) were obtained from analysis of athletes' urine samples after ingestion. In our present study, a GC-MS/MS method for simultaneous detection of 93 anabolic steroids was developed. The chromatographic and mass spectrometric conditions were optimized, and selective reaction monitoring (SRM) mode was adopted to obtain the necessary sensitivity. The whole sample analysis process was completed within 23 min, and the limit of detection (LOD) was 0.5-4 ng.g-1 for solid samples and 0.1-0.8 ng.mL-1 for liquid samples. This method was verified according to World Anti-Doping Agency (WADA) regulations. In addition, the method was found to be specific, accurate. The developed method was then applied to a routine analysis of more than 300 liquid and solid dietary supplements, and one testosterone-positive sample was found. Three suspected drugs, (4-hydroxyandrostenedione, DHEA, and 6-Br androstenedione) were found in three dietary supplements obtained from the Internet through the pretreatment method of this study. This study provides a high-throughput method for screening and monitoring the ingredients of supplements and their subsequent harm to public health.

Do women's natural hormonal fluctuations modulate prosociality? A within-subject analysis.

Prosocial behavior is central to functional societies. While studies have shown that the administration of exogenous hormones modulates prosocial propensities, it remains unclear whether natural hormonal fluctuations track women's prosocial behavior. In this study, we investigated the relationships between women's natural salivary steroid hormone levels (estradiol, progesterone, and testosterone) and their prosociality in a variety of contexts, as measured by three behavioral tasks (Charitable Donation, Social Value Orientation, and Social Discounting tasks) and one self-reported questionnaire (the Prosocial Tendencies Measure). Participants completed five weekly laboratory tests to obtain within-subject hormonal fluctuation data and prosociality measurements. In a pre-registered analysis, we found little evidence supporting the hypotheses that women's prosociality tracked natural changes in salivary estradiol, progesterone, estradiol-to-progesterone ratio, or testosterone. Our results demonstrate the importance of performing within-subject analyses when examining the relationships between hormonal levels and social behavior.

Comprehensive Sex Steroid Profiling in Multiple Tissues Reveals Novel Insights in Sex Steroid Distribution in Male Mice.

A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.

Dose dependent effect of cilostazol in induced testicular ischemia reperfusion via modulation of HIF/VEGF and cAMP/SIRT1 pathways.

Twisting of the spermatic cord is a common dangerous health problem that may be accompanied with testicular necrosis and infertility. Cilostazol (CLZ) is a selective phosphodiesterase (PDE) 3A inhibitor used for treatment of intermittent claudication. It has a great role in myocardial, spinal cord and hepatic ischaemia/reperfusion. However, till now, there are no researches evaluating its role in testicular ischaemia/reperfusion (TIR). The current work studies its capability to improve TIR induced injury with more concentration on the mechanisms involved in such effect. Four groups of animals were included: sham, TIR induced group, TIR plus CLZ low dose (10 mg/kg), TIR plus CLZ high dose (30 mg/kg). Our results proved that TIR had significant decrease of the serum ELISA of testosterone, marked disturbances in oxidative stress evaluated parameters as malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), ELISA measurement of tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL1ß) inflammatory mediators, apoptotic marker (caspase3) using western blotting, immunohistochemistry of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). TIR reduced the protective agents as cyclic adenosine monophosphate (cAMP) and sirtuin-1 (SIRT1) by ELISA method with marked germinal cell apoptosis. The biochemical results were confirmed by the histopathological findings that showed marked decrease in both Johnsen's score and Cosentino's score. However, treatment with CLZ significantly reversed the profound TIR damaging effects, on the basis of its anti-inflammatory, anti-oxidant, and anti-apoptotic activities with recuperation of the testicular vascularity. Modulation of HIF/VEGF and cAMP/SIRT1 pathways showed a great role in mediating such effect.

Comparison of Estradiol, Testostosterone, and CYP19 Methylation Levels between Full-Term and Preterm Newborns.

Estradiol (E), testosterone (T), and their ratio are crucial axis in life. Especially during intrauterine growth, they orchestrate the complex development of organs and their interaction, which have lifelong impact on health and an organism's capacity to respond to environmental stressors. The aim of this study was to compare for the first time E, T, and their ratio levels with aromatase (CYP19) gene methylation levels between preterm newborns (PN) and full-term newborns (FN) with respect to their mother's environmental exposure and diet. In this study, 56 FN of 37-42 weeks of gestation age (GA) and 46 PN at GA 27-36 weeks were analysed for E and T levels and CYP19A1 gene pI.3/II promoter region methylation. Results showed there was no difference in E levels between PN and FN, but there were significantly lower levels of T in PN than in FN (2.81 nmol vs. 3.76 nmol, respectively) and consequently a significantly higher E/T ratio in PN than in FN (5278.04 vs. 2891.23, respectively). CYP19A1 methylation was significantly lower in PN than in FN (86.04% vs. 90.04%, respectively). CYP19A1 methylation was significantly reduced in newborns whose mothers reported daily milk consumption. Our study is the first to provide referent values for CYP19A1 methylation levels in FN and PN and shows that PN and FN significantly differ in CYP19A1 methylation levels, T levels, and E/T ratio. Future research should further investigate the mechanisms involved in GA-dependent CYP19A1 methylation levels and mechanisms of sex hormone disturbances which may contribute to preterm birth.

Quantification of androgens and their precursors in full-term human placenta.

INTRODUCTION: The two major androgens in humans are testosterone (T) and dihydrotestosterone (DHT). DHT is produced via the classical, backdoor, and alternative steroidogenic pathways. In addition, recent studies have identified C11-oxy C19 steroids as novel human androgens. Although the placenta is known to be involved in steroid metabolism, androgen levels in full-term placentas have poorly been investigated. SUBJECTS AND METHODS: Ten placentas of healthy full-term neonates (five males and five females) were examined. We quantified progesterone, androstenedione (A4), T, allopregnanolone, androsterone, and estradiol, as well as four C11-oxy androgens (11ß-hydroxyandrostenedione, 11ß-hydroxytestosterone, 11-ketoandrostenedione (11KA4), and 11-ketotestosterone (11KT)), using liquid chromatography-tandem mass spectrometry. RESULTS: In all samples, levels of the ten steroids were above the detection limit. Progesterone was by far most abundant, while levels of T and androsterone were relatively low. Levels of 11KT and 11KA4 were higher than those of T and A4, respectively. There were no differences in steroid levels between male and female samples. DISCUSSION: This study demonstrates that full-term placentas contain several steroids in the classical, backdoor, and alternative pathways. Placentas are likely to function as the supplier of progesterone to other steroidogenic tissues. More importantly, we found that placentas comprise relatively large amounts of 11KA4 and 11KT, which may be produced through steroid transfer from the adrenal gland or from the maternal circulation. These results indicate that the placenta participates in a feto-maternal multi-organ network for androgen biosynthesis.

Evaluation of sex hormone profile and semen parameters in acromegalic male patients.

OBJECTIVE: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). METHODS: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. RESULTS: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. CONCLUSION: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

The impact of regular sperm donation on bulls' seminal plasma hormonal profile and phantom response.

The aim of this study was to analyze the relationship between the concentration of hormones in the seminal plasma, the bull maintenance system in the insemination station, and the regularity of sperm donation and the response to the phantom (libido level). An additional goal was to determine whether there is a relationship between the hormonal profile in the blood, the sperm plasma, the oxidative and antioxidant profile in the blood of bulls and the biometry of their testicles and scrotum, as well as the quality of their sperm in both different seasons and intensities of reproductive use. For the study, 220 healthy and sexually mature Polish Holstein-Friesian bulls were used. They all had normal libido and were fed equally. The animals were grouped according to the scheme: young (16-20 month/n = 60) and old (26-30 month/n = 60) including: individually housed (n = 30) and group housed (n = 30) young, old individually housed (n = 30) and group housed (n = 30) (n total animals = 120); young animals donating semen once a week (every Thursday) (n = 25) and sporadically (once every two months on a random day of the week) (n = 25), old animals donating semen once a week (every Thursday) (n = 25 ) and sporadic donors (once every two months on a random day of the week) (n = 25) (n total animals = 100). When analyzing the results of this study, it should be stated that regular use has a positive effect on the secretion of sex hormones in bulls. Higher levels of testosterone and lower levels of estradiol and prostaglandins resulted in higher sexual performance, expressed by a stronger response to the phantom. The differences in favor of regular use were independent of the bull's age. The results of our research illustrate that the quality of semen and its freezing potential may depend on the season and frequency of its collection, as well as on the age of the males.