Urinary Hormone Research Articles

Utility of First-Morning-Voided Urinary Total Luteinizing Hormone in Detecting the Onset of Central Puberty

Introduction: Early morning basal serum luteinizing hormone (S-LH) ≥0.3 IU/L is a specific marker for the onset of central puberty. In this study, we aimed to investigate the sensitivity and specificity of the first-morning-voided (FMV) total urinary LH (U-LH) to replace this marker. Methods: We re-analyzed our previously published data set of 297 children (145 boys and 152 girls, aged 5–15 years, across Tanner stages 1 through 5) using receiver operating characteristic (ROC) analysis and determined cutoff values for FMV total U-LH in predicting early morning S-LH concentration at or above 0.3 IU/L. We also determined S-LH and serum follicle-stimulating hormone (S-FSH) concentrations in girls at different stages of sexual maturation. Results: ROC analysis showed that FMV total U-LH levels of 0.60 and 0.63 IU/L in girls and boys, respectively, predicted early morning S-LH levels of 0.3 IU/L or higher with 97.4% sensitivity and 90.6% specificity. Higher cutoff levels for U-LH (0.78 IU/L for boys and 0.79 IU/L for girls) yielded 94.7% specificity at the expense of a relatively lower level of sensitivity (94.1%). The areas under the curve were 0.98 in boys and 0.99 in girls, respectively. Additionally, the increase in FMV total U-LH (or S-LH) levels identified the activation of central pubertal development at the mean age of 10.3 (10.3) in boys and 10.5 (10.6) in girls. The S-FSH concentrations of the six biochemically prepubertal girls with thelarche, ranging between 2.3 and 2.7 IU/L, were significantly higher than those measured in biochemically and clinically prepubertal girls of the same 10–12-year-old age group and significantly lower than those measured in both biochemically and clinically pubertal girls (p = 0.039 and p = 0.018, respectively). Conclusions: A FMV total U-LH concentration of 0.6 IU/L or above reliably reflects pubertal morning S-LH levels and is effective in detecting the onset of central puberty, which occurs at similar ages in both sexes. Concurrent S-FSH or noninvasive FMV U-FSH determinations may be useful in the differential diagnosis of isolated thelarche.

The assessment of urinary sexual hormones within minipuberty and correlations with anthropometrics in a cohort of healthy term children.

Minipuberty follows different trends in boys and girls. Aim of our study was to explore timing and dynamics of minipuberty in healthy infants, analyzing urinary levels of sexual hormones. Moreover, we analyzed the association among HPG axis activity and linear growth, ano-genital distances (AGDs) in both sexes, and penile length in males. Longitudinal cohort study in healthy term infants from birth to 6 months of life. Clinical evaluation (anthropometrics and AGDs) and urine sampling were performed at 0 (T0), 3 (T3), and 6 (T6) months. Urine samples were analyzed for gonadotropins and sex hormones. 165 participants were involved. The growth trend of our population was regular, as were the AGDs. Urinary hormones were correlated each other's. Specifically, in boys, the correlation coefficient between urinary FSH (uFSH) and urinary LH (uLH) decreased from T0 to T6, while between urinary Testosterone (uT) and uFSH increased. In girls, correlations between uFSH and urinary Estradiol (uE) were observed at each time point. Notably, several correlations between hormones and anthropometrics and AGDs were found; the most interesting correlation was found in males within uLH and PL (at T0 ρ: 0.323, p < 0.05 and at T3 ρ: 0.371, p < 0.01), whereas in females uFSH at T0 showed negative correlations with both length and body weight percentile at T3 (ρ: -0.505, p < 0.01 and ρ: -0.478, p < 0.01, respectively). Urinary matrix has proved to be a valuable, practical, non-invasive and cheaper method for sexual hormone assessment.

N-acetylcysteine supplementation improves endocrine-metabolism profiles and ovulation induction efficacy in polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) affects 6–20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS.MethodsFemale C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups.ResultsSimilar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p < 0.005) and significantly greater clinical pregnancy rates per OI cycle and cumulative clinical pregnancy rates per patient (p < 0.005).ConclusionNAC supplementation improved endocrine-metabolic parameters in PCOS mice and significantly enhanced OI efficacy with sequential LE and uFSH in women with PCOS. Therefore, NAC could be a valuable adjuvant in OI for women with PCOS.

Helping Patients to Predict and Confirm Ovulation with the Use of Combined Urinary Hormonal and Smartphone Technology: A Proof-of-Concept Retrospective Descriptive Case Series.

Smartphone-based fertility awareness methods with home-based urinary hormonal testing are gaining popularity for fertility tracking. In our university-affiliated family practice, we integrated a previously developed ovulation tracking application into a protocol for monitoring urinary sex hormones and cervical secretions. Serum progesterone was used to confirm the luteal phase, with levels ≥ 15.9 nmol/L ensuring confirmation. Data from 110 women seen for infertility treatment (n = 95) or family planning advice (n = 15) and using our ovulation prediction protocol showed that most opted for a combination of cervical mucus and luteinizing hormone testing (n = 86). Among those using it for family planning, the median usage among women spanned 56 cycles, and 13 cycles per woman required progesterone testing for confirmation. Thirteen patients are still using the method without unintended pregnancies. No unintended pregnancies occurred. Confidence in tests based on serum progesterone was high (93%). For infertility, the method helped in the identification of anovulation, evaluating treatment response, and in diagnosing subfertility causes. This proof-of-concept retrospective descriptive case series suggests the potential for smartphone-based monitoring in fertility management, urging further studies for application enhancements and prospective validation.

7269 Interim Analysis of Gonadotropin-Releasing Hormone Agonist (GnRHa) Treatment in Children with Central Precocious Puberty: Focus on FMV Urinary LH Levels and Clinical Outcomes

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) refers to early activation of the hypothalamic–pituitary–gonadal (HPG) axis in children. There is an urgent need to understand the treatment pattern and clinical outcomes among children suffering from CPP. Studies have reported that first morning voided (FMV) urinary Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) have substantial association with CPP tested in GnRH stimulation test and can be useful in diagnosis and management of CPP in children. Gonadotropin-releasing hormone agonists (GnRHa) such as Leuprolide acetate (LA) are the recommended treatment for children suffering from CPP. The current study aimed to provide the information on level of LH and FSH in FMV urine when CPP diagnosis at baseline and the present results may also revealed trend of FMV-LH and FMV-FSH change during LA intervention in children with CPP. Here we present interim results from this study. Methods: This is an open-label, multicentre, single arm, prospective study that enrolled 31 subjects with CPP. Individuals were administered LA depot 11.25 mg, subcutaneously every 12 weeks. The study comprises a screening period; a 6-month treatment period: 24 weeks; and a post-treatment follow-up period: 12 weeks. The FMV urinary LH and FSH were diagnosed by Clopper-Pearson method with a 95% confidence interval. Results: Due to the data collection time point for the interim analysis, only 8 female subjects reached the 12-week visit time point and had a 12-week visit for FMV urinary Gn testing. Therefore, for this interim analysis, only FMV Gn decline at week 12 of the 8 subjects who had a 12-week visit will be presented. At baseline, the mean value of FMV urinary LH and FSH is 0.58 IU/L and 2.27 IU/L respectively. The FMV Gn urinary LH was demonstrated a decrease in 87.5% (95% CI: 47.35,99.68) of the children after LA intervention. Additionally, urinary FSH value of FMV urinary Gn was found to decrease in 75.00% of the children (95% CI: 34.91,96.81) compared to baseline FSH value. Conclusion: The present study reveals a decreasing trend in FMV Gn urinary LH and FSH levels in CPP children treated with LA during interim analysis. LA was shown to be safe and effective in ameliorating the level of LH and FSH in children suffering from CPP. From the study, it can be concluded that urinary LH and FSH may act as a potential biomarker for diagnosis and management of CPP. Presentation: 6/3/2024

6485 Unilateral Adrenal Metastasis From Unknown Primary Carcinoma Mimicking Primary Adrenocortical Carcinoma

Abstract Disclosure: S. Watanabe: None. S. Suzuki: None. K. Ishiwata: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None. Background: Adrenal metastasis from carcinomas of the lung, breast, and melanoma are observed. However, isolated adrenal metastasis with unknown primary carcinoma origin has been rare, and the diagnosis is challenging. We encountered a case of unilateral adrenal tumor clinically diagnosed as non-functional primary adrenocortical carcinoma, but found to be a metastatic tumor on postoperative pathology. Clinical Case: A 68-year-old man was referred to our hospital for examination of an 8mm right adrenal incidentaloma. He underwent hormone therapy for prostate cancer four years ago, and the condition is in remission with no recurrence signs. Follow-up CT revealed that the adrenal tumor rapidly enlarged from 8 mm to 36 mm within six months, and its mean attenuation value was 38 HU. MRI showed that the adrenal tumor had a low signal intensity on T1 and a high signal on T2. At the same time, there is mediastinal lymphadenopathy and a 9-mm nodule in the lower lobe of the right lung, which was considered benign from the stable condition. FDG-PET/CT showed FDG uptake only in the right adrenal tumor (maximum standardized uptake value of 21.39). [1]23I-MIBG scintigraphy did not show any accumulations. The serum and urinary adrenal hormones were all within normal limits. Notably, tumor markers such as prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and cancer antigen 19-9 (CA 19-9) were all within normal ranges. Therefore, we clinically suspected non-functional primary adrenocortical carcinoma, and the laparoscopic right adrenalectomy was performed. The resected right adrenal lesion was encapsulated and measured 79×54×22 mm. On histological analysis, the nodule comprised tumor cells with eosinophilic cytoplasm, and abundant tissue infiltrating lymphocytes. Immunohistochemical studies revealed that the tumor was not of adrenal origin due to negative steroidogenic factor-1 (SF-1) and inhibin alpha staining. From these results, the adrenal tumor was diagnosed as adrenal metastasis from unknown primary carcinoma. The tumor cells were positive for cytokeratin19, CEA, and thyroid transcription factor-1 but negative for PSA, p63, cytokeratin 5/6, insulinoma-associated protein-1, and synaptophysin. Genetically, the adrenal tumor harbored genomic abnormalities in CDKN2A, TP53, NF1, PBRM1, and KEAP1 genes. Conclusion: Isolated adrenal metastasis without a detectable primary tumor is rare but should be considered a differential diagnosis in the case of an enlarged, non-functioning adrenal tumor. Adrenalectomy or tumor biopsy may be actively considered to diagnose and determine the optimal course of treatment. Presentation: 6/3/2024

Influence of Menstrual Phase and Symptoms on Match Running in Professional Footballers.

This study examined the effects of menstrual cycle phases and symptoms on match running performance in football (soccer) players. Twenty-one nonhormonal contraceptive using football players from four professional teams were monitored for up to four menstrual cycles during a domestic league season. Menstrual phases, classified as early-follicular phase (EFP), mid-late follicular phase (MFP), and luteal phase (LP), were determined by self-reporting of menstruation and urinary hormone tests (luteinizing hormone and pregnanediol-3-glucuronide). On match day, players completed a menstrual symptom severity questionnaire. In repeated matches, players wore 10 Hz Global Positioning Satellite (GPS) devices to measure relative (/min) total distance, high-speed running distance, very high-speed distance, peak speed, acceleration count, and deceleration count. Linear mixed models were performed for each GPS measure to determine the relationship with phase or symptoms. Data for 7 and 10 players were included for menstrual phase and menstrual symptoms analyses, respectively. A significantly higher total distance was reported during MFP compared to EFP (Δ 5.1 m min-1; p = 0.04) and LP (Δ 5.8 m min-1; p = 0.007). Significantly greater high-speed running was reported during MFP compared to EFP (Δ 1.2 m min-1; p = 0.012) and LP (Δ 1.1 m min-1; p = 0.007). No significant effect of menstrual phase was found for any other GPS measures (p > 0.05). Accelerations declined with increasing symptom severity (p = 0.021, estimate = -0.01count.min-1). Menstrual symptom severity did not affect any other GPS measures (p > 0.05). In conclusion, greater total distance and high-speed running occurred during the MFP. Additionally, accelerations minimally decreased with increasing menstrual symptom severity. Large intra- and inter-variability existed, suggesting individualized monitoring and management of menstrual effects on performance would be beneficial.

Current Ovulation and Luteal Phase Tracking Methods and Technologies for Fertility and Family Planning: A Review

AbstractOvulation is critical for both conception and overall health, but many people who may ovulate are not tracking ovulation or any other part of their menstrual cycle. Failure to track ovulation, especially in those trying to conceive, can lead to fertility challenges due to absent ovulation, mistiming intercourse, or an undetected luteal phase defect. Ovulatory disorders and mistiming intercourse are both primary causes of infertility, and tracking ovulation is shown to decrease the average time to conception. While there are many tracking methods and apps available, the majority are predictive apps or ovulation predictor kits and do not test or track both successful ovulation and the health of the luteal phase, leading to missing information that could contribute to diagnosis or successful conception. Here, we review why ovulation tracking and a healthy luteal phase are important for those trying to conceive. We present currently available ovulation tracking methods that detect both ovulation and the luteal phase, including cervical mucus, urinary hormone testing, and basal body temperature, and discuss the use, advantages, and disadvantages of each. Finally, we consider the role of digital applications and tracking technologies in ovulation tracking.

Comparative Analysis of Commercial Immunoassays for the Determination of Total, Intact, and Nonintact Luteinizing Hormone in Urine.

In our recent publications, we reported the identification of three different molecular forms of total luteinizing hormone (LH) in urine, the intact LH, the free beta-subunit (LHβ), and its core fragment of LHβ (LHβcf), the latter two establishing the nonintact portion of LH. Following the discontinuation of the Delfia immunofluorometric assay (IFMA) (Wallac, PerkinElmer Finland, Finland), a leading method for detecting urinary LH for 30 years, this study seeks to assess the efficacy of three alternative commercial immunoassays in identifying various forms of U-LH. Diluted urine samples underwent gel filtration to separate them into fractions, each containing different forms of LH. These were then assayed using Delfia IFMA, Architect LH (Abbott, USA), Elecsys LH Cobas (Roche, Switzerland), and Immulite 2000 LH (Siemens, Germany) immunoassays. Both Delfia and Immulite assays detected total U-LH, that is, all three forms of U-LH, including intact LH, LHβ, and LHβcf. Cobas detected only intact LH and LHβ, whereas Architect detected solely the intact LH. Immulite assay can be an alternative tool to detect all forms of urinary LH, a feature likely to be instrumental in developing noninvasive, practical, and scalable solutions for evaluating total U-LH changes during minipuberty in neonates, during the onset of central puberty in peripubertal children, puberty-associated disorders in adolescents, and the fertility window in women, with a special focus on postpeak changes.

Hypothalamic-pituitary-ovarian axis suppression is common among women during US Army Basic Combat Training

ObjectiveLess than half of servicewomen report loss of menses during initial military training. However, self-reported menstrual status may not accurately reflect hypothalamic-pituitary-ovarian (HPO) axis suppression and may underestimate reproductive health...

Characterization of the thyroid hormones level in urine by liquid chromatography coupled to mass spectrometry focus in the antidoping field.

This paper aims to study the metabolism of thyroid hormones (TH) in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was applied to samples collected before and after the administration of sodium triiodothyronine (T3) and sodium levothyroxine (T4) to a euthyroid volunteer and to samples of athletes declaring and not declaring thyroid supplementation. Samples were analyzed by LC-MS/MS after enzymatic hydrolysis, liquid-liquid, and solid-phase extractions. Ratios between T3/thyronine and T4/3,3'-T2 may be used for the detection of the administration of exogenous T3 in urine. Meanwhile, 3-T1 concentrations may be used to detect exogenous T4 administration. Nevertheless, these markers may not work properly in hypothyroid population, as athletes seem to be. The levels of T3 and T4 of athletes were lower than those of a euthyroid state even when they are under administration of TH supplements. The HTP axis high efficiency does not allow observing differences between athletes who do not declare and those who declare having used TH supplementation by direct measurements of T3 and T4 in urine. The detection of TH administration in urine (triiodothyronine and levothyroxine) may work when dealing with euthyroid individuals. Nevertheless, in individuals with hypothyroidism where the tendency is toward the maintenance of homeostasis, and it may be not possible to detect their consumption by applying cut-off values.

At What Point in the Menstrual Cycle Are the Pelvic Floor Muscles at Their Weakest?

Pelvic floor muscle (PFM) strength is a critical factor for optimal pelvic floor function. Fluctuations in strength values based on different phases of the menstrual cycle (MC) could signify a need for a paradigm shift in evaluating, approaching, and planning training. This research aims to examine and contrast the pelvic floor muscle strength during different phases of the menstrual cycle. A prospective observational study employing digital assessment with the modified Oxford scale and vaginal dynamometry measurements was performed, in order to assess the baseline strength and the contraction strength of the PFMs in eumenorrheic females at three different phases of the MC: the early follicular phase (EFP), the late follicular phase (LFP), and the mid-luteal phase (MLP). During two complete cycles, tympanic temperature and body weight were measured and the urinary luteinizing hormone concentration was tested to determine the time of ovulation. In total, 216 dynamometric measurements of PFM strength were obtained from eighteen nulliparous women (25.72 ± 5.03 years). There were no differences between the baseline strength (p = 0.886) and the contraction strength (p = 0.756) with the dynamometric speculum. In the post hoc analysis, the baseline strength, contraction strength, and strength showed no significant differences between MC phases. As no differences in PFM strength in women were found, the PFMs do not seem to be weaker at any time during the menstrual cycle. It appears that the assessment, establishment, and monitoring of a PFM training program could be initiated at any point in the cycle.

Comparison of Day-Specific Serum LH, Estradiol, and Progesterone with MiraTM Monitor Urinary LH, Estrone-3-glucuronide, and Pregnanediol-3-glucuronide Levels in Ovulatory Cycles.

Background and Objectives: Fertility tracking apps and devices are now currently available, but urinary hormone levels lack accuracy and sensitivity in timing the start of the 6-day fertile window and the precise 24 h interval of transition from ovulation to the luteal phase. We hypothesized the serum hormones estradiol (E2) and progesterone (P) might be better biomarkers for these major ovulatory cycle events, using appropriate mathematical tools. Materials and Methods: Four women provided daily blood samples for serum E2, P, and LH (luteinizing hormone) levels throughout their entire ovulatory cycles, which were indexed to the first day of dominant follicle (DF) collapse (defined as Day 0) determined by transvaginal sonography; therefore, ovulation occurred in the 24 h interval of Day -1 (last day of maximum diameter DF) to Day 0. For comparison, a MiraTM fertility monitor was used to measure daily morning urinary LH (ULH), estrone-3-glucuronide (E3G), and pregnanediol-3-glucuronide (PDG) levels in three of these cycles. Results: There were more fluctuations in the MiraTM hormone levels compared to the serum levels. Previously described methods, the Fertility Indicator Equation (FIE) and Area Under the Curve (AUC) algorithm, were tested for identifying the start of the fertile window and the ovulation/luteal transition point using the day-specific hormone levels. The FIE with E2 levels predicted the start of the 6-day fertile window on Day -7 (two cycles) and Day -5 (two cycles), whereas no identifying signal was found with E3G. However, both pairs of (E2, P) and (E3G, PDG) levels with the AUC algorithm signaled the Day -1 to Day 0 ovulation/luteal transition interval in all cycles. Conclusions: serum E2 and (E2, P) were better biomarkers for signaling the start of the 6-day fertile window, but both MiraTM and serum hormone levels were successful in timing the [Day -1, Day 0] ovulatory/luteal transition interval. These results can presently be applied to urinary hormone monitors for fertility tracking and have implications for the direction of future fertility tracking technology.

Detection of thyroid hormones in urine by liquid chromatography coupled to tandem mass spectrometry.

Recently, the trend of thyroid hormones (TH) consumption in the sports community has been published. It is known the capacity of the exogenously administered TH to enhance metabolism, being an attractive feature for athletes, who search for weight control and increased caloric expenditure. This paper aimed the validation of a method to measure TH and related compounds in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was applied to urine samples collected before and after the administration of a diiodothyronine (3,5-T2) supplement. A method to detect nine TH included an enzymatic hydrolysis, liquid-liquid extraction, and solid-phase extraction. The extracts were analyzed by LC-MS/MS. Validated parameters showed good results for accuracy (85%-104%), precision (3%-16%), LOD (10-40 pg/mL, except for thyronacetic acids that was 200 pg/mL), and the combined uncertainty (2.2%-22%). Maximum concentration of 3,5-T2 in pre-administration samples was 0.71 ng/mL, and after 30 h of the last administration, concentrations returned to pre-administration values. Maximum values of ratios between the analyte and thyronine, T3, and T4 were 0.09, 0.19, and 0.12, respectively, and after 30 h of the last administration, the ratios reached back the basal values. Acidic or basic metabolites were not found in urine at least at the method LOD. A proposed method to assess TH in urine was validated, and as a proof of concept, its efficacy was demonstrated with an excretion study of 3,5-diiodothyronine. The consumption of 3,5-T2 was detected in urine measuring the analyte concentration and ratios between the analyte and thyronine, T3, and T4.

P-601 Monitoring reproductive hormones during ovarian stimulation: performance and usability of a self-operated at-home urine test

Abstract Study question How effective and user-friendly is a non-invasive, patient-operated urine test (Kinder) in tracking reproductive hormone levels during ovarian stimulation (OS) treatment in an IVF cycle? Summary answer Urinary E1-3G correlates well with blood E2 levels and ovarian follicle development. Patients found it easy and stress-free to perform the urine test at home. What is known already Monitoring blood reproductive hormone levels during OS is a widely accepted practice to ensure the optimal ovarian response to gonadotropin treatment, timing of oocyte maturation triggering and mitigating hyperstimulation risk. However, conventional blood testing is invasive, necessitating patients to travel to clinics for blood sampling, adding to their overall burden. Previous studies have revealed a robust correlation between blood E2 levels, and its corresponding urinary metabolites E1-3G. Kinder is a portable device designed for quantifying urinary E1-3G, allowing patients to conduct tests in the privacy of their homes, and for many obviating the need to travel substantial distances for monitoring. Study design, size, duration This is a prospective, single-cohort, study of Caucasian patients (28-34 years), conducted at Fertility Specialists of Western Australia in Perth, Australia, where patients may travel vast distances for treatment. Twenty-five patients were enrolled from Aug 2022-Aug 2023, and performed home urine tests utilizing the Kinder device in parallel with clinic scheduled blood (ELISA) and ultrasound tests. The primary end point of the study was the correlation between urinary and blood reproductive hormone concentrations (E1-3G). Participants/materials, setting, methods Spearman and Pearson correlation coefficients (CC) and 95% confidence intervals were calculated for E1-3G and E2, and E1-3G/E2 and follicle development (total volume of ovarian follicles by ultrasound). To assess patient acceptability patient-reported outcomes (PRO) were assessed using the State Trait Anxiety Inventory (STAI) questionnaire. Further, patient-reported experiences (PRE) were evaluated through the System Usability Scale (SUS) questionnaire, along with assessing their likelihood to recommend Kinder to their friends or family undergoing IVF treatment. Main results and the role of chance Upon analysing 100 concurrent urine and blood samples from 25 patients, a robust correlation was found between E1-3G and E2 levels (Spearman CC: 0.818, 95% CI: 0.680-0.904; Pearson CC: 0.847, 95% CI: 0.712-0.939). Additionally, we observed a moderate correlation between E1-3G levels and ovarian volume (Spearman CC: 0.701, 95% CI: 0.556-0.805; Pearson CC: 0.670, 95% CI: 0.519-0.781, n = 72), resembled the correlation between E2 levels and ovarian volume (Spearman CC: 0.874, 95% CI: 0.804-0.920; Pearson CC: 0.849, 95% CI: 0.770-0.902, n = 75). PRE: 22 out of 23 patients who completed the survey confirmed that they would definitely, or probably, recommend Kinder. The mean SUS score (91.4) signified an excellent user experience. PRO: Anxiety levels were not affected by use of Kinder (STAI score below threshold of 42.38) in 18/20 patients who completed three STAI surveys (first one before and second one after the initial Kinder test; third one after the third/fourth Kinder test). Although 2/20 patients reported a STAI score of 49 in the final survey, suggesting increased anxiety, both affirmed in the PRE survey that they “will definitely recommend Kinder”, suggesting that the elevated STAI score can be attributed to the overall IVF treatment rather than the use of Kinder itself. Limitations, reasons for caution The sample size is relatively small, necessitating further multi-centre studies with a larger sample size to validate the findings. Wider implications of the findings The results suggest an acceptable interchangeability between at-home urine E1-3G and at-clinic blood E2 monitoring hormone levels during OS treatment. A digital health approach, combining tele-counselling, remote at-home hormone monitoring, and follicle tracking, could reduce patient burden and save many patients the inconvenience of travelling large distances for cycle monitoring. Trial registration number ACTRN12622000488707

Solvent Bar Microextraction Method Based on a Natural Deep Eutectic Solvent and Multivariate Optimization for Determination of Steroid Hormones in Urine and Water

Steroid hormones may pose potential risks to both human health and wildlife, primarily through the consumption of medication or polluted food and water; efforts are being made to monitor their levels in the human body and regulate and minimize their releases to the environment. In this study, a simple and environmentally friendly sample preparation method was developed to simultaneously determine three steroid hormones in urine and water samples. A monoterpene (menthol) and a fatty acid (lauric acid) were combined in various ratios to form a hydrophobic deep eutectic (HDE) solvent as an extraction solvent in solvent bar microextraction (SBME). Using a univariate strategy, a menthol-to-lauric acid HDE ratio of 4:1 and a pH 7 of the sample solution resulted in the highest extraction efficiency (EE%) of the selected steroids. The computational methods have been employed to predict a 4:1 HDE interaction with chosen steroids. Additionally, chemometric approaches suggested that the optimal extraction conditions involved HDEs as extract solvent confined within three SBME devices directly immersed into a 20 mL sample solution with a 30 min extraction time, followed by ultrasonication within 200 μL of elution solvent for a 5 min elution time. Under optimized conditions, the method calibration graph for the spiked selected steroids in the water and urine samples showed good linearity with R2 ≥ 0.994 with limits of detection/quantification lower than 0.40/1.35 μg L−1 and repeatability/reproducibility (RSD%, n = 5) lower than 5.09/7.11. The developed method allows a safe, rapid, and reliable analysis of three steroid hormones in human urine and water samples without using toxic volatile organic solvents.

Consumer wearables and personal devices for tracking the fertile window

The market for technology that tracks ovulation to promote conception is rapidly expanding in the United States, targeting the growing audience of technologically proficient, reproductive-age female consumers. In this narrative review, twenty-three different, non-prescription wearables and devices designed to help women track their fertile window were identified as currently, commercially available in the United States. The majority of these utilize measurements of basal body temperature or combinations of various urinary hormones. This clinical opinion characterizes the scant available research validating the accuracy of these technologies. It further examines research oversight, discusses the utility of these wearables and devices to consumers, and considers these technologies through an equity lens. The discussion concludes with a call for innovation, describing promising new technologies that not only harness unique physiologic parameters to predict ovulation, but also focus on cost-effectiveness with the hope of increasing access to these currently costly devices and wearables.

A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.

Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol andadrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068). Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.

Associations of pentachlorophenol exposure during pregnancy with maternal and infant reproductive hormones based on a birth cohort

Pentachlorophenol (PCP), a typical environmental endocrine disruptor and a new persistent organic pollutant, has been extensively used as a pesticide worldwide. Although its use has been restricted for decades, PCP remains prevalent in both the environment and human bodies. Despite the known endocrine-disrupting and exogenous hormonal effects of PCP, few epidemiological studies examined such impact, especially among sensitive populations and during critical periods. Based on a prospective birth cohort in Wuhan, China, we collected maternal (first trimester; 13.0 ± 1.02 gestational weeks) and infant urine samples (1.16 ± 0.22 months postpartum) from 720 mother-infant pairs. We aimed to examine the association of PCP exposure during early pregnancy with maternal and infant urinary sex steroid hormones, including estrogens (estrone, E1; estradiol, E2; estriol, E3), progestogens (progesterone, P4; pregnenolone, P5; 17α-OH-Progesterone, 17OHP4; 17α-OH-Pregnenolone, 17OHP5), and androgens (testosterone, Testo; dihydrotestosterone, DHT; dehydroepiandrosterone, DHEA; androstenedione, A4). Additionally, gonadotropins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were measured in infant urine. Detection frequencies of all the sex steroid hormones in the maternal urine samples (>99 %) were higher than those in the infants' [most ≥80 %, except for E1 (3.36 %) and E2 (21.4 %)]. Maternal urinary PCP concentration was found to be significantly related with increased maternal sex steroid hormone concentrations; each interquartile increase in PCP concentration was positively related with percent change of the hormones (%Δ) ranging from 26.6 % to 48.5 %. On the other hand, maternal PCP exposure was associated with significantly increased P4 in male infants [%Δ (95 % confidence interval): 10.5 (0.56, 21.4)] but slightly decreased P4 in female infants [−11.9 (−21.8, 0.68)]. In addition, maternal PCP exposure was significantly associated with decreased FSH [%Δ (95 % CI): −9.90 (−17.0, −2.18)] and LH [−8.44 (−16.0, −0.19)] in the female infants, but not in the male infants. Sensitivity analyses, excluding infertility related treatment, pregnancy complications, preterm birth, or low birth weight, showed generally consistent results. Our findings implied that maternal/prenatal PCP exposure might disrupt the homeostasis of maternal and infant reproductive hormones. However, further studies are needed to confirm the findings.

Attachment-like behavioral expressions to humans in puppies are related to oxytocin and cortisol: A comparative study of Akitas and Labrador Retrievers

This study investigated the relationship between urinary hormone concentrations and attachment-related behaviors in two dog breeds, the Akitas and Labrador Retrievers, to elucidate the hormonal and behavioral mechanisms underlying domestication and interspecies attachment to humans. By measuring cortisol and oxytocin concentrations, and conducting the Strange Situation Test (SST), we aimed to investigate breed differences in endocrine secretions associated with domestication and how these differences influence dog behavior toward humans. Our results showed significant breed differences in urinary cortisol concentrations, with Akitas exhibiting higher levels than Labrador Retrievers. This suggests a breed-specific stress response related to genetic proximity to wolves. However, oxytocin concentrations did not differ significantly, which suggests a complex interplay between factors influencing the domestication process and the formation of attachment behaviors. Behavioral observations during the SST revealed breed-specific patterns, with Labrador Retrievers showing more playful and attachment-like behaviors and Akitas showing more exploratory and passive behaviors. The study found correlations between hormones and behaviors within breeds, particularly in Labrador Retrievers, where oxytocin concentrations were associated with attachment-like behaviors, and cortisol concentrations reflected individual differences in physical activity rather than stress responses to social situations. These findings contribute to the understanding of the evolutionary and adaptive processes underlying the ability of domestic dogs to form close relationships with humans while highlighting the role of hormonal mechanisms in mediating attachment behaviors and the influence of breed-specific genetic backgrounds on these processes.