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Study Question: What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window?, Summary Answer: Both oestrogen and progesterone contribute to a delay in the onset of the fertile window., What Is Known Already: Oestrogen enhances cervical mucus secretion while progesterone inhibits it., Study Design, Size, Duration: Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder., Participants/materials, Setting, Methods: Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva., Main Results and the Role of Chance: Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4 µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle., Limitations, Reasons for Caution: This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings., Wider Implications of the Findings: This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction., Study Funding/competing Interest(s): The authors declare no conflicts of interest. No funding was provided for this secondary data analysis., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Identifying the time of ovulation is an important process for women seeking and avoiding pregnancy. Luteinizing hormone (LH) plays an important role in ovulation, which is very important in the reproductive mechanism. Therefore, detecting the LH level is of great importance in monitoring ovulation. In this study, sensitive, rapid and selective electrochemical biosensors were developed to detect LH quantitatively from human urine samples and to monitor the ovulation period. Isopotential region and current density optimization studies revealed that sensors with an electrode width and spacing of 1 mm had the optimum performance. Electrochemical impedance spectra evidenced immobilization of DSP self-assembled monolayers and anti-LH-beta antibody on the surface. While the mobile phone vibrator led to a 3.5-fold enhancement in response signals, the agitation system developed resulted in a 10-fold improvement. The sensors displayed detection limits of 1.02 and 1.53 mIU/ml in the range of 0-40 mIU/ml LH concentration obtained using two statistical approaches. Additionally, the sensors showed no cross-reactivity to hCG, which is very similar in structure and is widely reported to have high cross-reactivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the level of first morning voided (FMV) urinary luteinizing hormone (LH) in girls with breast development, and to determine the value of FMV urine LH in the evaluation of central precocious puberty (CPP)., Methods: From September 2018 to April 2021, among the patients who were admitted to the Department of Pediatrics of Peking University Third Hospital for "precocious puberty" and underwent gonadotropin-releasing hormone (GnRH) stimulation test, a total of 108 girls were enrolled. According to CPP diagnostic criteria, they were divided into CPP group ( n =45) and non-CPP group ( n =63). The clinical characteristics and hormone levels of the two groups were compared. Receiver operating characteristic (ROC) curve was used to analyze the cut-off value of FMV urinary LH in the diagnosis of CPP in girls. Further analyses were done to evaluate the value of FMV urinary LH in the diagnosis of CPP using correlation analysis between urinary LH level and common clinical cha-racteristics., Results: ROC curve analysis showed that FMV urine LH level was significant for the diagnosis of CPP. The cut-off value of FMV urine LH was 0.69 IU/L (specificity 56.9%, sensitivity 85.0%, area under curve 0.804, P < 0.001). The basic clinical characteristics without GnRH stimulation test were analyzed by binary Logistic regression analysis, indicating that the level of FMV urine LH, uterine volume, ovarian volume and advanced T-bone age had predictive significance for CPP diagnosis in girls ( OR values were 2.125, 1.961, 1.564 and 2.672, respectively). The prediction model was established and the area under the ROC curve was 0.904, P < 0.001. The level of FMV urine LH was positively correlated with the levels of serum LH, FSH and estrogen before GnRH stimulation test, the peak value of blood LH after GnRH stimulation test, T bone age and uterine volume, with r values of 0.462, 0.373, 0.242, 0.360, 0.373 and 0.263, respectively, and P values were < 0.001, < 0.001, 0.013, < 0.001, < 0.001 and 0.007, respectively., Conclusion: FMV urine LH can provide a good indication for the diagnosis of CPP. Combining with bone age advanced level and pelvic ultrasound measurement, the predictive value of FMV urine LH can be further improved for the diagnosis of CPP in girls.

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., (© 2024 The Author(s). Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: We examined different molecular forms of luteinizing hormone (LH) in urine samples taken during periovulatory days with the aim of revealing different forms of LH immunoreactivity (LH-ir) in normally menstruating women., Methods: Serum and first-morning-voided urine serum samples were obtained from six healthy, 22 to 38 years old, regularly menstruating women during their periovulatory days based on their previous menstrual cycles. The day of the LH surge was determined on the basis of serum LH concentrations and confirmed by an at least two-fold increase in urinary concentrations of intact LH on consecutive days. Different molecular forms of LH-ir were identified by gel filtration of first-morning-voided urine samples obtained from regularly menstruating women on periovulatory days., Results: Different forms of LH immunoreactivity (LH-ir) were distinguished as intact LH, its free beta-subunit (LHβ), and the core fragment of LHβ (LHβcf) according to their molecular sizes. The latter two are also called non-intact LH. Intact LH was the dominating form on the day before and on the day of LH surge while LHβcf was the major form of LH immunoreactivity after the LH surge for the following 5-7 days. LHβ was detected on the day of the LH surge as well as on the following day., Conclusions: These results indicate that LH is degraded in the kidneys and excreted as LHβ, and mainly as LHβcf for 7 days following the LH peak.

Highly purified human menopausal gonadotropin (HP-hMG [Menopur ® , Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur ® and two of Menogon ® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid ® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel ® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid ® ) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.

Objective: The aim of this study was to investigate the feasibility of different gonadotropin assays for determining total and intact luteinizing hormone (LH), and follicle-stimulating hormone (FSH) immunoreactivity in urine (U-LH-ir and U-FSH-ir, respectively) during early infancy., Design, Patients and Measurements: Morning urine samples were obtained from 31 infants, aged between 0 and 6 months, to study the age-related course of urinary gonadotropins. Additionally, we investigated bi-hourly urine samples of a 5-day-old male neonate for 24 h to observe the course of urinary gonadotropins during a daily cycle. We employed different immunofluorometric assays for measuring total and intact U-LH-ir, and U-FSH-ir., Results: In neonates up to 21 days of age, the U-LH-ir levels measured by the regular LH assay (also detecting hCG) were significantly higher than those determined by the total (specific) LH assays (p = .004). U-FSH-ir was higher in girls than boys during both the first and the next 5 months (p = .02 and p < .001, respectively), whereas total U-LH-ir was higher in boys until 6 months of age (p < .001). Total U-LH-ir/U-FSH-ir ratio was significantly higher in boys than girls across the first half-year (p < .001)., Conclusions: The assessment of total U-LH-ir and U-FSH-ir, and their respective ratio constitutes a noninvasive, practical and scalable tool to investigate sex-specific changes during early infancy, with the ratio being significantly higher in boys than girls. Only highly specific LH assays detecting beta-subunit and its core fragment in addition to intact LH should be used for determining U-LH-ir in the neonatal period to avoid potential cross-reactivity with hCG of placental origin., (© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

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 Mira TM 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 Mira TM 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 Mira TM 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.

Objective: To investigate the diagnostic value of urine luteinizing hormone (ULH) after the triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP)., Methods: The girls with precocious puberty were included. The triptorelin stimulation test at 8:30 a.m. was performed. Two consecutive 12-hour urine samples were collected after the test, defined as the first 12-hour and second 12-hour urine, respectively. ICMA measured ULH. Urine creatinine (Cr) concentration was measured. CPP and peripheral precocious puberty (PPP) were diagnosed by the same pediatric endocrinologist based on clinical symptoms, signs, and progression of clinical development., Results: A total of 97 cases (CPP n=69; PPP n=28) were included, with 12 cases not meeting the receiver operating characteristic analysis criteria. The first and second 12-hour ULH/Cr in the CPP group were higher than those in the PPP group. When the first 12-hour ULH/Cr was≥287.252 IU/mol, the sensitivity and specificity for diagnosing CPP were 87.3% and 90.9%, respectively. When the second 12-hour ULH/Cr was≥152.769 IU/mol, the sensitivity and specificity for diagnosing CPP were 92.1% and 90.9%, respectively. The area under the curve of the first and second 12-hour ULH/Cr were 0.933 and 0.954, respectively., Conclusion: The ULH detection method after the triptorelin stimulation test has clinical significance for diagnosing CPP in girls. When blood sampling compliance in girls with precocious puberty is poor, the first 12-hour ULH/Cr≥288 IU/mol (or second 12-hour≥153 IU/mol) after the triptorelin stimulation test can serve as a laboratory indicator for diagnosis of CPP., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: Human choriogonadotrophin (hCG) treatment of gonadotrophin-deficient infertile men uses hCG of urinary (uhCG) or recombinant (rhCG) origin, but these treatments have not been compared nor are there studies defining rhCG dosing in men., Design: hCG products were studied in randomized cross-over single-dose studies of standard (Study 1, 1500 IU and 62.5 µg, respectively) or high (Study 2, 5000 IU and 250 µg) dose and a multi-dose population pharmacology study of hCG use., Participants: Eight (Study 1) and seven (Study 2) volunteers in cross-over and 52 gonadotrophin-deficient men in the multi-dose study MEASUREMENTS: In cross-over studies, serum testosterone (T), dihydrotestosterone (DHT) and estradiol by liquid chromatography-mass spectrometry (LCMS) and serum hCG, LH, FSH, SHBG and T (observational study) by immunoassays., Results: After standard and high-dose injection, serum hCG and testosterone responses had similar timing and peak concentrations except for a mildly lower early (<48 h) serum testosterone with uhCG. In the multi-dosing study, both hCGs had similar pharmacokinetics (pooled half-life 5.8 days, p < .001), while serum testosterone concentrations were stable after injection and did not differ between hCG products. Bench testing verified that 20% of pens from 4/10 individuals were used inappropriately., Conclusions: Although hCG pharmacokinetics are not formally bioequivalent, the similar pharmacodynamic effects on serum testosterone indicate that at the doses tested both hCGs provide comparable clinical effects. The starting dose of rhCG for treating gonadotrophin-deficient men should be 62.5 µg (6 clicks) of the rhCG pen., (© 2024 Commonwealth of Australia. Clinical Endocrinology published by John Wiley & Sons Ltd.)

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., Competing Interests: We do not report any conflicts of interest and we are responsible for the writing of this article. This article is being submitted as a special issue invitation by the journal and the cost for open publication was provided by PreMom, but they had no role in any data gathering, analysis, and writing of this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Study Question: Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls?, Summary Answer: This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP., What Is Known Already: Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool., Study Design, Size, Duration: This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed., Participants/materials, Setting, Methods: This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA., Main Results and the Role of Chance: The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort., Limitations, Reasons for Caution: This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity., Wider Implications of the Findings: The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity., Study Funding/competing Interest(s): No specific funding was used. All authors declared no conflict of interest., Trial Registration Number: In-house #23-5214 registered study., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

This study aims to determine the variability of the components of fitness along the menstrual cycle (MC) of physically active eumenorrheic women. Fifteen subjects were monitored along two consecutive MCs through the calendar-based counting method in combination with a urine luteinizing hormone surge kit. Subjects were tested at the early follicular phase (EFP), pre-ovulatory or late follicular phase (LFP), and post-ovulatory or mid-luteal phase (MLP). In each session, the back squat one-repetition maximum (1-RM), maximum fat oxidation (MFO), maximum oxygen uptake (VO 2max ) and acute recovery capacity were determined. The results revealed a wide variability among components of fitness and a low to high variability among subjects (acute recovery: 3.6% [range 1.5 to 9.5%]; back squat 1-RM: 6.1% [range 2.2 to 11%]; VO 2max : 6.6% [range 1.1 to 15%]; MFO: 23% [range 4.6 to 35%]). Despite the individual nature, considering the number and magnitude of the responses in each MC phase, VO 2max and acute recovery capacity tended to be enhanced at the LFP, the MFO at the MLP, and the back squat 1-RM remained stable along the MC. Thus, practitioners are aware of which components are susceptible to change along the MC phase, but an individual monitoring is recommended., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: We designed a longitudinal study to investigate the association between the ages of central pubertal activation and the appearance of clinical signs of puberty and determined total luteinizing hormone (LH) immunoreactivity in daytime- and nocturnal sleeptime-excreted urine samples., Patients and Measurements: Thirty healthy volunteers (17 boys and 13 girls, aged 3.4-15.2 years and 4.3-14.3 years, respectively, at the beginning of the study) were included. Male and female subjects were followed for an average of 15 visits during 5.5 and 5.8 years on average, respectively. At each visit, subjects provided 24-h urine samples divided into nocturnal sleeptime and waketime portions according to the participant's sleep-and-wake rhythm. Total urinary LH (U-LH) concentrations were measured in duplicate by Delfia® IFMA (Wallac), which has been designed specifically to detect intact LH as well as the beta subunit and its core fragment, but not the human chorionic gonadotropin., Results: The initial increases in nocturnal sleeptime total U-LH concentrations over the cutoff value of 0.7 IU/L occurred at around the same time (around 9-10 years of age) in both sexes, which could not be detected in waketime urine samples. The mean first age for the nocturnal sleeptime total U-LH concentrations to reach or surpass the cutoff was 10.7 years (range: 10.2-11.6 years) in boys and 11.8 years (range: 10.7-13.4 years) in girls, showing no statistically significant difference between the sexes (p = .15). The mean time span from the age at which sleeptime total U-LH concentration first exceeded the 0.7 IU/L level to observing pubertal stage 2 was 1.5 years in boys and 0.1 years in girls., Conclusions: Findings in our population with a limited sample size suggest that the timing of central pubertal activation is a sex-independent phenomenon, which can be observed by monitoring the nocturnal sleeptime total LH concentrations in urine. The lag time from central pubertal activation of gonadotropin secretion to the clinical onset of puberty is significantly longer in boys., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

The Athlete Biological Passport (ABP) is a longitudinal tool used in anti-doping to monitor biological parameters known to change with performance-enhancing drug use. The ABP consists of multiple modules, including two aimed at detecting the use of endogenous anabolic androgenic steroids: the urinary and serum steroid modules. Human chorionic gonadotropin (hCG) is a protein hormone potentially abused by male athletes to increase the production of endogenous testosterone. To date, no studies have investigated the impact of extended hCG administration on the urinary and serum steroid modules of the ABP. The goal of this study was to identify the impact of multiple hCG administrations on the parameters tracked as part of the urinary and serum steroid modules of the ABP. Ten recreationally active, healthy male individuals self-administered seven 250 μg hCG injections over 3 weeks. Serum and urine samples were collected before, during, and 2 weeks following the final injection. All ABP parameters were quantified in the respective matrix, and steroid profiles were created with Anti-Doping Administration and Management System adaptive model upper and lower limits for both matrices. In both serum and urine profiles, testosterone increased; however, the testosterone/epitestosterone ratio in urine and the testosterone/androstenedione ratio in serum showed minimal changes. Additionally, serum luteinizing hormone (LH) was quantified using an immunoassay, and a serum testosterone/LH ratio was generated. Serum LH values decreased during administration causing large increases in the serum T/LH ratio, indicating this ratio may be a more sensitive parameter for detecting hCG abuse than urinary testosterone/epitestosterone or serum testosterone/androstenedione., (© 2023 John Wiley & Sons Ltd.)

Home use tests to monitor hormone trends during the menstrual cycle have been available over-the-counter for a long time. However, these tests often depend upon manual readouts and hence may lead to false analysis. Furthermore, a lot of these tests are also not quantitative. The aim of this study was to evaluate the accuracy of the quantitative home-based fertility monitor, Inito Fertility Monitor (IFM) and to use it to identify novel hormone trends in natural menstrual cycles. There were two aspects to our analysis: (i) Evaluating the efficacy of Inito Fertility Monitor in the measurement of urinary Estrone-3-glucuronide (E3G), Pregnanediol glucuronide (PdG) and Luteinizing hormone (LH), and (ii) A retrospective study of patients' hormone profiles using IFM. To evaluate the efficacy, the recovery percentage of the three hormones from IFM was evaluated using standard spiked solutions, the accuracy of measurement was calculated and the correlation between reproducible values from IFM and ELISA was established. During the validation of IFM, novel hormone trends were also observed. In order to reinforce the observations, a second group of 52 women was recruited. Assessment of the accuracy of IFM and evaluation of the volunteer urine samples was performed in a laboratory. Home assessment of hormone analysis was carried out using IFM. For the validation study, 100 women aged 21-45 years with cycle lengths ranging from 21 to 42 days were recruited. The participants had no previously diagnosed infertility conditions and their cycle lengths did not vary for more than 3 days from the expected cycle length. Daily first morning urine samples were collected from these 100 women. For the second group, 52 women were selected meeting the same criteria set for the validation study and IFM was provided to these women for testing at home. Coefficient of variation and recovery percentage of IFM with respect to laboratory based ELISA. Percentage occurrence of novel hormone trends and AUC analysis of a novel criteria identified for confirming ovulation. We observed that with all three hormones, IFM had an accurate recovery percentage. We found that the assay has an average CV of 5.05% in PdG measurement, 4.95% in E3G measurement and 5.57% in LH measurement. Furthermore, in predicting the concentration of E3G, PdG and LH in urine samples, we show that IFM has a high correlation with ELISA. In this study, we could also reproduce hormones trends across the menstrual cycle that have been observed by previous studies. We also identified a novel criterion for earlier confirmation of ovulation which could accurately distinguish ovulatory from anovulatory cycles with 100% specificity and had an area under the ROC curve of 0.98. In addition, we identified a new hormone trend which could be observed in 94.5% of the ovulatory cycles. The Inito Fertility Monitor is an effective tool for calculating the urinary concentrations of E3G, PdG and LH and can also be used to provide accurate fertility scores and confirm ovulation. We show that certain hormone trends associated with urinary E3G, PdG and LH could be accurately captured using IFM. In addition, we report a novel criterion for earlier confirmation of ovulation compared to existing criteria. Finally, we present a novel hormone pattern associated with most of the menstrual cycles by examining hormone profiles from the volunteers recruited for the clinical trial.Trial registration: The trial is registered at the current controlled trials ISRCTN registry #ISRCTN15534557., (© 2023. The Author(s).)

Background: A new fertility monitor is now available that provides quantitative measurement of urinary hormones, but clinical use requires validation against an established fertility monitor that provides only qualitative results., Research Design and Methods: Two fertility monitors were compared using daily first morning urine samples over 3 cycles of use in 21 women users with experience using a fertility monitor with the Marquette Method of Natural Family Planning., Results: Women were aged 33.4 ± 5.5 years and had menstrual cycles ranging between 23 and 41 days. The quantitative Mira Monitor estimates of ovulation were highly correlated with the qualitative ClearBlue Fertility Monitor (CBFM) estimates of ovulation. Both monitors provided an accurate estimate of the fertile window., Conclusions: In this preliminary trial, the Mira monitor was shown to be effective at delineating the fertile window and ovulation. We demonstrated the feasibility of applying the Marquette Method algorithm with the use of the Mira monitor. Satisfaction differences between the two monitors did not reach statistical significance. We anticipate that quantitative fertility monitoring will give couples and health-care providers new and unprecedented insights into the menstrual cycle and fertility.

Context: Although gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP), it is invasive, expensive, and time-consuming, requiring multiple blood samples to measure gonadotropin levels., Objective: We evaluated whether urinary hormones could be potential biomarkers for prepuberty or postpuberty, aiming to simplify the current diagnosis and prognosis procedure., Methods: We performed a cross-sectional study of a total of 355 girls with CPP in National Clinical Research Center for Child Health in China, including 258 girls with positive and 97 girls with negative results from GnRHST. Twenty patients received GnRH analogue (GnRHa) treatment and completed a 6-month follow up. We measured luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, prolactin, progesterone, testosterone, and human chorionic gonadotropin in the first morning voided urine samples., Results: Their urinary LH levels and the ratios of LH to FSH increased significantly with the advancement in Tanner stages. uLH levels were positively associated with basal and peak LH levels in the serum after GnRH stimulation. A cutoff value of 1.74 IU/L for uLH reached a sensitivity of 69.4% and a specificity of 75.3% in predicting a positive GnRHST result. For the combined threshold (uLH ≥ 1.74 + uLH-to-uFSH ratio > 0.4), the specificity reached 86.6%. After 3 months of GnRHa therapy, the uLH and uFSH levels decreased accordingly., Conclusion: uLH could be a reliable biomarker for initial CPP diagnosis and screening; uLH could also be an effective marker for evaluating the efficacy of clinical treatment., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

At the Swedish national forensic toxicology laboratory, a measured testosterone/epitestosterone (T/E) ratio ≥ 12 together with testosterone/luteinizing hormone (T/LH) in urine > 400 nmol/IU is considered as a proof of exogenous testosterone administration. However, according to the rules of the World Anti-Doping Agency (WADA), samples with T/E ratio > 4 are considered suspicious and shall be further analysed by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) to confirm the origin of testosterone and its metabolites. The aim of this study was to investigate the possibility of false negative results and to estimate the frequency of negative results using the current criteria for detection of abuse of testosterone in forensic investigations. Urine and serum samples were collected by the police at suspected infringement of the doping law in Sweden. Fifty-eight male subjects were included in the study. Urinary testosterone was determined by gas chromatography-mass spectrometry (GC-MS), serum testosterone and LH-by immunoassay. The origin of testosterone and its metabolites was confirmed by means of GC-C-IRMS. Twenty-six of the 57 analysed subjects tested positive for exogenous testosterone using the criteria T/E ≥ 12 combined with T/LH > 400 nmol/IU. The IRMS analyses confirmed 47 positives; thus, 21 were considered false negatives. Negative predictive value was 32% (95% confidence interval [CI]: 16%-50%) and sensitivity 55%. No false positive subjects were found. The number of false negative cases using the current criteria for the detection of testosterone abuse and hence the low sensitivity indicates a need to discuss introduction of new strategies in forensic doping investigations., (© 2021 John Wiley & Sons, Ltd.)

In this work we have investigated the influence of the intake of two synthetic isoflavones, methoxyisoflavone and ipriflavone, on the urinary concentration of endogenous steroids, and on their relative ratios, of doping relevance. Specifically, the concentrations of testosterone (T), epitestosterone (E), androsterone (A), etiocholanolone (Etio), 5α-androstan-3α,17α-diol (5αAdiol), 5β-androstan-3α,17α-diol (5βAdiol), and the ratios T/E, A/T, A/Etio, 5αAdiol/5βAdiol, 5αAdiol/E, were considered, in the framework of the Steroidal Module of the Athlete Biological Passport (ABP). The above set of parameters were complemented by the urinary levels of luteinizing hormone (total LH) and the ratio between T and LH (T/total LH), to assess the possible effects on the biosynthesis of the mentioned steroids. Five healthy Caucasian male volunteers were selected for the study. Urine samples were collected before and during the administration of (i) methoxyisoflavone (Methoxyisoflavone, MyProtein) and (ii) ipriflavone (Osteofix ®, Chiesi Farmaceutici). For the analysis of the urinary steroid profile, after enzymatic hydrolysis with β-glucuronidase from Escherichia Coli (E. Coli) and liquid-liquid extraction with tert-buthylmethyl ether, all samples were analyzed by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS), while for the determination of total LH all urine samples were directly analyzed by a chemiluminescent immunometric assay technique (Siemens Immulite 2000 LH). Our results show that the administration of either methoxyisoflavone or ipriflavone causes an alteration of the urinary concentrations and concentration ratios of the investigated steroids, in the range 55-80% from the baseline values. Furthermore, an oversecretion of LH after the daily intake of methoxyisoflavone or ipriflavone was also recorded in all volunteers, corresponding to an increase in the biosynthesis and excretion of T and some of its metabolites. These changes trigger a disregulation in the pattern of urinary excretion of the steroids included in the Steroidal Module of the ABP, which makes more difficult the interpretation of the longitudinal steroid profile based on the definition of individual normality ranges for each athlete. Our data are also consistent with previous evidence regarding the in vitro effects of natural and synthetic isoflavones, suggesting that their monitoring in doping control routine analysis would be very beneficial for the result management activities., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development., Objective: Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage., Methods: Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007-2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis., Results: Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3., Conclusions: Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset., Competing Interests: MG, LMK, JWM, JSK, MM, CM and DPS declare no competing interests exist. AJCJ, JAM, CB-C and DSC are employed by a commercial company, Social & Scientific Systems, Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: The menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition., Study Design: SWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy., Outcome Measures: We measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C)., Results: A variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood., Conclusion: Fluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Determination of LH in urine has proved to be a reliable method for evaluation of pubertal development. The human LH assay based on time-resolved immunofluorometric (IFMA) technology (AutoDELFIA, PerkinElmer, Wallac) has been found to be suitable for this purpose thanks to its high sensitivity but other assays have not been evaluated. We have analyzed our data obtained by another potentially sensitive detection technique, enhanced luminometric assay (LIA) with the objective of finding a viable alternative to IFMA since these may not be available in the future., Methods: LIA was used to measure LH and FSH in serum and urine samples from 100 healthy subjects of each Tanner stage and both genders, whose pubertal development has been determined., Results: Urinary gonodotropin concentrations measured by LIA correlated well with Tanner stage [(r=0.93 for girls, r=0.81 for boys; p<0.01 for LH) and (r=0.81 for girls, r=0.73 for boys; p<0.01 for FSH)]. LIA determinations revealed the increase in U-LH concentrations during the transition from Tanner stage 1-2 in both girls and boys (p<0.001), whereas U-FSH and S-LH were able to detect the increase from Tanner stage 1-2 only in boys or girls, respectively (both p<0.001)., Conclusions: Measurement of urinary gonadotropin concentrations by LIA may be useful for the evaluation of overall pubertal development and also in the detection of transition from prepuberty to puberty., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Lutenising hormone (LH) and human chorionic gonadotropin (hCG) hormone are useful biochemical markers to indicate ovulation and embryonic implantation, respectively. We explored "point-of-care" LH and hCG testing using a digital home-testing device in a cohort trying to conceive., Objective: To determine conception and spontaneous pregnancy loss rates, and to assess whether trends in LH-hCG interval which are known to be associated with pregnancy viability could be identified with point-of-care testing., Methods: We recruited healthy women aged 18-44 planning a pregnancy. Participants used a home monitor to track LH and hCG levels for 12 menstrual cycles or until pregnancy was conceived. Pregnancy outcomes (viable, clinical miscarriage, or biochemical pregnancy loss) were recorded. Monitor data were analysed by a statistician blinded to pregnancy outcome., Results: From 387 recruits, there were 290 pregnancies with known outcomes within study timeline. Adequate monitor data for analysis were available for 150 conceptive cycles. Overall spontaneous first-trimester pregnancy loss rate was 30% with clinically recognised miscarriage rate of 17%. The difference to LH-hCG interval median had wider spread for biochemical losses (0.5-8.5 days) compared with clinical miscarriage (0-5 days) and viable pregnancies (0-6 days). Fixed effect hCG profile change distinguished between pregnancy outcomes from as early as day-2 post-hCG rise from baseline., Conclusions: The risk of first-trimester spontaneous pregnancy loss in our prospective cohort is comparable to studies utilising daily urinary hCG collection and laboratory assays. A wider LH-hCG interval range is associated with biochemical pregnancy loss and may relate to late or early implantation. Although early hCG changes discriminate between pregnancies that will miscarry from viable pregnancies, this point-of-care testing model is not sufficiently developed to be predictive., (© 2020 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

To elucidate the fluid regulation in different menstrual cycle phases during e xercise. Sex hormones affect fluid regulation in different ways. Moreover, the renin angiotensin-aldosterone system is activated in the luteal phase in rest. However, there are limited studies on fluid regulation affected by such hormone excretion in the menstrual cycle during exercise, especially during a light walking exercise. A non-invasive method using urine samples to determine menstrual cycle phases was used, and the follicular and luteal phases were successfully confirmed in 10 participants (age, 21 ± 1 years; body mass index, 20.5 ± 2.1 kg/m 2 ). The experimental exercise sessions consisted of 5-min standing and 15-min walking at 2 km/h on 15% slope (approximately 8.3°) on a treadmill. Each participant carried a backpack weighing 5% of her own weight, and performed three sessions of walking exercise. Urine aldosterone excretion was significantly higher in the luteal than in the follicular phase before and after walking ( p < 0.05). Urinary excretion of aldosterone was five times higher in the luteal than in the follicular phase before and after walking exercise. Heart rates during walking, after rest, and after recovery were all significantly higher in the luteal than in the follicular phase (p < 0.05). The participants' ratings of perceived exertion during the first and third session of walking in the luteal phase was not higher than that at the follicular phase. The results of our study suggested that increased activity of the renin-angiotensin-aldosterone system in the luteal phase of the menstrual cycle might be further activated during exercise. This may increase the circulatory load, which is reflected as increased heart rate. These results suggested that premenopausal women may better take into account a possibility of an increased circulatory load in the luteal phase even when they perform light exercise., (© Journal of Sports Science and Medicine.)

Research question: Urine LH testing may be useful to confirm an LH surge after the GnRH agonist (GnRHa) trigger prior to oocyte retrieval in IVF. Design: A prospective cohort study, including oocyte donors undergoing ovarian stimulation, treated with a GnRHa trigger for final oocyte maturation. Urine LH testing was performed at home, 12 h after the GnRHa trigger. In the case of a negative result, serum LH and progesterone measurements were done that same day. Donors with no serum LH peak after trigger were re-scheduled using a dual trigger, with GnRHa and hCG. Results: Three hundred and fifty nine oocyte donors were included in the analysis. Three hundred and fifty six donors had positive urine LH tests, followed by oocyte retrieval. In one case, the LH test was positive, however, no oocytes were retrieved (false positive 1/356). Three LH tests were negative in urine: in one of these three cases, LH was tested again in blood, confirming an LH rise, consistent with an optimal response to the GnRHa trigger; in the other two cases, serum LH was <15 mUI/mL, after which the oocyte retrieval was re-scheduled for 36 h after an being re-triggered, resulting in the retrieval of 19 and 22 MII oocytes, respectively. Considering the cost analysis, it would be a significantly cost-saving strategy, as blood testing would have costed 14,840€ vs. only 185.5€ in urine LH kits. Conclusions: Urinary testing of the LH surge after GnRHa trigger is easy, safe, reliable, and convenient. In addition, LH urine testing allows identifying donors and patients who could benefit from a rescue hCG trigger after an unsuccessful GnRHa trigger., (Copyright © 2020 Cozzolino, Matey, Alvarez, Toribio, López, Perona, Henzenn, Piró, Humaidan and Garcia-Velasco.)

Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Background: Previous research has demonstrated that women instructed in fertility awareness methods can identify the Peak Day of cervical mucus discharge for each menstrual cycle, and the Peak Day has high agreement with other indicators of the day of ovulation. However, previous studies enrolled experienced users of fertility awareness methods or were not fully blinded., Objective: To assess the agreement between cervical mucus Peak Day identified by fertile women without prior experience on assessing cervical mucus discharge with the estimated day of ovulation (1 day after urine luteinising hormone surge)., Methods: This study is a secondary analysis of data from a randomised trial of the Creighton Model FertilityCare TM System (CrM), conducted 2003-2006, for women trying to conceive. Women who had no prior experience tracking cervical mucus recorded vulvar observations daily using a standardised assessment of mucus characteristics for up to seven menstrual cycles. Four approaches were used to identify the Peak Day. The referent day was defined as one day after the first identified day of luteinising hormone (LH) surge in the urine, assessed blindly. The percentage of agreement between the Peak Day and the referent day of ovulation was calculated., Results: Fifty-seven women with 187 complete cycles were included. A Peak Day was identified in 117 (63%) cycles by women, 185 (99%) cycles by experts, and 187 (100%) by computer algorithm. The woman-picked Peak Day was the same as the referent day in 25% of 117 cycles, within ±1 day in 58% of cycles, ±2 days in 84%, ±3 days in 87%, and ±4 days in 92%. The ±1 day and ± 4 days' agreement was 50% and 90% for the expert-picked and 47% and 87% for the computer-picked Peak Day, respectively., Conclusions: Women's daily tracking of cervical mucus is a low-cost alternative for identifying the estimated day of ovulation., (© 2020 John Wiley & Sons Ltd.)

Objective: To further characterize the endocrinology of the menopause transition, we sought to determine: whether relationships between urine and serum hormones are maintained as women enter their sixth decade; whether a single luteal phase serum progesterone (P) is reflective of integrated-luteal urinary pregnanediol glucuronide (uPdg); and whether serum P, like luteal uPdg, declines as women approach their final menses (FMP)., Methods: The Study of Women's Health Across the Nation (SWAN) Daily Hormone Study's (DHS) is a community-based observational study. A subset of participants underwent a timed, luteal blood draw planned for cycle days 16 to 24 during the same month of DHS collection. Serum-luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and P, and urine LH, FSH, estrone conjugates (E1c), and daily and integrated luteal uPdg were measured in 268 samples from 170 women. Serum/urine hormone associations were determined using Pearson's correlation and linear regression, adjusted for concurrent age, body mass index, smoking status, and race/ethnicity., Results: Pearson's r ranged from 0.573 (for LH) to 0.843 (for FSH) for serum/urine correlations. Integrated luteal uPdg weakly correlated with serum P (Pearson's r = 0.26, P = 0.004) and explained 7% of the variability in serum P in adjusted linear regression (total R 0.09, P = 0.002). Serum P demonstrated a marginally significant decline with approaching FMP in adjusted analysis (P = 0.04)., Conclusions: Urine and serum hormones maintain a close relationship in women into their sixth decade of life. Serum luteal P was weakly reflective of luteal Pdg excretion.

Luteinizing hormone (LH) is a dimeric glycoprotein produced and secreted by the pituitary gland, with a molecular weight of approximately 30 000 Da. The main clinical use for exogenous LH-administration is typically linked to the treatment of infertility, in both men and women. The desired effect of LH misuse in sport is due to the enhancement of testicular production of testosterone. Elevated LH levels may also indicate the usage of gonadotropin-releasing factors or estrogen blockers. Therefore, LH is listed by the World Anti-Doping Agency (WADA) as a prohibited substance in male athletes, and according to the WADA technical document, laboratories should determine the the total LH concentrations in urine. The TD lists two different assays that are suitable for measuring total LH in urine, Delfia and Siemens Immulite. Other fit-for-purpose assays can be used, as long as they are capable of detecting total LH in urine. In case an assay not listed in the TD will be used, population-based reference values have to be determined in the validation procedure. In this study a new immunoassay was validated for the measurement of LH in urine. The assay (AccuBind ELISA Microwells, Luteinizing Hormone, Monobind Inc.), originally intended for serum, showed adequate sensitivity and was proven fit-for-purpose in routine doping control. Population-based distribution of the assay was in good agreement with the results of Delfia and Immulite assays, for which the method-specific cut-off-values are 40 IU/L (Delfia) and 60 IU/L (Siemens Immulite)., (© 2019 John Wiley & Sons, Ltd.)

Introduction: The aim of this review is to provide methodological recommendations for menstrual cycle research in exercise science and sports medicine based on a review of recent literature. Research in this area is growing but often reports conflicting results, and it is proposed that some of this may be explained by methodological issues., Methods: This review examined the menstrual cycle verification methods used in recent literature on exercise performance over the menstrual cycle identified through a literature search of PubMed and SportDiscus from 2008 until 2018., Results: Potential changes over the menstrual cycle are likely related to hormone fluctuations; however, only 44% of the selected studies measured the actual concentrations of the female steroid hormones estrogen and progesterone. It was shown that the likely inclusion of participants with anovulatory or luteal phase-deficient cycles in combination with small participant numbers has affected results in recent menstrual cycle research and, consequently, our understanding of this area., Conclusion: To improve the quality of future menstrual cycle research, it is recommended that a combination of three methods is used to verify menstrual cycle phase: the calendar-based counting method combined with urinary luteinizing hormone surge testing and the measurement of serum estrogen and progesterone concentrations at the time of testing. A strict luteal phase verification limit of >16 nmol·L for progesterone should be set. It is also recommended that future research should focus on the inclusion of the late follicular estrogen peak. It is envisaged that these methodological recommendations will assist in clarifying some of the disagreement around the effects of the menstrual cycle on exercise performance and other aspects of exercise science and sports medicine.

Purpose: This study aims to compare the accuracy of fertile window identification with the contraceptive app Natural Cycles against the Rhythm Method and Standard Days Method (SDM). Materials and methods: Menstruation dates, basal body temperature (BBT), and luteinising hormone (LH) test results were collected anonymously from Natural Cycles app users. The fraction of green days (GDs) and wrong green days (WGDs) allocated by the various algorithms was determined over 12 cycles. For comparison of Natural Cycles and the Rhythm Method, 26,626 cycles were analysed. Results: Natural Cycles' algorithms allocated 59% GDs (LH, BBT) in cycle 12, while the fraction of WGDs averaged 0.08%. The Rhythm Method requires monitoring of six cycles, resulting in no GDs or WGDs in cycle 1-6. In cycle 7, 49% GDs and 0.26% WGDs were allocated. GDs and WGDs decreased to 43% and 0.08% in cycle 12. The probabilities of WGDs on the day before ovulation with Natural Cycles were 0.31% (BBT) and 0% (LH, BBT), and 0.80% with the Rhythm Method. The probability of WGDs on the day before ovulation was 6.90% with the SDM. Conclusions: This study highlights that individualised algorithms are advantageous for accurate determination of the fertile window and that static algorithms are more likely to fail during the most fertile days.

Background: Women who experience pregnancy loss are especially prone to high stress, though the effects of stress on reproductive outcomes in this vulnerable population are unknown. We assessed relationships between perceived stress and hormones, anovulation, and fecundability among women with prior loss., Methods: One thousand two hundred fourteen women with 1-2 prior losses were followed for ≤6 cycles while attempting pregnancy and completed end-of-cycle stress assessments. For cycles 1 and 2, women also collected daily urine and completed daily perceived stress assessments. We assessed anovulation via. an algorithm based on human chorionic gonadotropin (hCG), pregnanediol-3-glucuronide (PdG), luteinizing hormone (LH), and fertility monitor readings. Pregnancy was determined via. hCG. Adjusted weighted linear mixed models estimated the effect of prospective phase-varying (menses, follicular, periovulatory, and luteal) perceived stress quartiles on estrone-1-glucuronide (E1G), PdG, and LH concentrations. Marginal structural models accounted for time-varying confounding by hormones and lifestyle factors affected by prior stress. Poisson and Cox regression estimated risk ratios and fecundability odds ratios of cycle-varying stress quartiles on anovulation and fecundability. Models were adjusted for age, race, body mass index (BMI), parity, and time-varying caffeine, alcohol, smoking, intercourse, and pelvic pain., Results: Women in the highest versus lowest stress quartile had lower E1G and PdG concentrations, a marginally higher risk of anovulation [1.28; 95% confidence interval (CI) = 1.00, 1.63], and lower fecundability (0.71; 95% CI = 0.55, 0.90)., Conclusion: Preconception perceived stress appears to adversely affect sex steroid synthesis and time to pregnancy. Mechanisms likely include the effects of stress on ovulatory function, but additional mechanisms, potentially during implantation, may also exist.

Recent evidence indicates that urinary gonadotropins may be an alternative method for detecting pubertal disorders. The aim of this study was to evaluate the associations of first morning voided (FMV) and random urinary gonadotropins with the pubertal response to a gonadotropin-releasing hormone (GnRH) stimulation test to determine whether random urinary gonadotropins can be used as an alternative method for evaluating central precocious puberty (CPP). In total, 100 girls aged 6.0-8.9 years were enrolled. The subjects were divided into two groups according to their pubertal response to the GnRH stimulation test: a positive group (n = 68) and a negative group (n = 32). Random urinary luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the LH:FSH ratio were significantly positively correlated with FMV urinary LH (r = 0.411, p < 0.001), FMV urinary FSH (r = 0.494, p < 0.001), and the FMV urinary LH:FSH ratio (r = 0.519, p < 0.001). The optimal cutoff values from receiver operating characteristic (ROC) curve analyses were determined to be 0.20 IU/L for random urinary LH (area under the curve (AUC) of 0.812, p < 0.001), 3.03 IU/L for random urinary FSH (AUC of 0.670, p = 0.004) and 0.08 for the random urinary LH:FSH ratio (AUC of 0.784, p < 0.001). No differences were observed between FMV and random urinary LH (p = 0.827), between FMV and random urinary FSH (p = 0.650), or between the FMV and random urinary LH:FSH ratio (p = 0.688) in ROC curve analyses with DeLong's test. Based on our findings, random urinary gonadotropins may be applicable in clinical practice as a useful initial test for girls with CPP.

Dietary fish oil restores ovarian function in subfertile rats, which is thought to be associated with decreased transcription of follicle-stimulating hormone (FSH) β-subunit. We have previously demonstrated a reduction in early follicular serum FSH levels in normal weight but not obese women after treatment with omega-3 polyunsaturated fatty acids (PUFA). Herein, we report the effect of supplementation with omega-3 PUFA on urinary reproductive hormones across the whole menstrual cycle. This interventional study included 17 eumenorrheic women, aged 24-41 years. One month of daily morning urine was collected before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. Measurements included urinary FSH, luteinizing hormone (LH) and estrogen and progesterone metabolites, plasma fatty acid composition, and markers of endoplasmic reticulum stress. Compliance with dietary supplementation was verified by significantly reduced ratios of omega-6 to omega-3 PUFA for all subjects after treatment ( P < .01). After 1 month of omega-3 PUFA supplementation, urinary FSH was significantly decreased in normal weight, but not obese women, in both follicular and luteal phases (-28.4% and -12.6%, respectively, both P = .04). No significant changes were seen in LH or sex steroids for either weight group. The selective and specific decrease in FSH suggests that omega-3 PUFA supplementation merits further investigation in normal weight women with decreased fertility and/or diminished ovarian reserve.

Objective: To compare effectiveness of spontaneous ovulation monitored by urinary luteinising hormone (LH) versus induced ovulation by administration of human chorionic gonadotrophin (hCG) in couples undergoing gonadotrophin-stimulated intrauterine insemination (IUI)., Design: Randomised controlled trial., Setting: University-level infertility unit., Population: Couples with unexplained infertility, mild endometriosis, mild male factor infertility and polycystic ovarian syndrome., Methods: Couples were randomised to an LH group (Group A), in which urinary LH was measured daily to detect spontaneous ovulation, or an hCG group (Group B), in which urinary hCG was administered as a trigger., Main Outcome Measures: Clinical pregnancy rate. Secondary outcomes - ongoing pregnancy, live birth, multiple pregnancy and miscarriage rates., Results: A total of 392 couples were randomised with 196 in each arm. The clinical pregnancy rate per woman randomised was 14/196 (7.1%) in the LH arm versus 15/196 (7.6%) in the hCG arm (P = 0.847, which was not statistically significant). Similarly, the ongoing pregnancy rates [13/196 (6.6%) versus 14/196 (7.1%); P = 0.84] and the live birth rates [13/196 (6.6%) versus 14/196 (7.1%); P = 0.84] between the two groups did not show any significant difference. The duration of stimulation and gonadotrophin dosage also did not differ significantly between the two methods., Conclusion: There was no significant difference in clinical pregnancy rates when urinary LH and hCG trigger were compared as methods to time insemination in women undergoing gonadotropin-stimulated IUI., Tweetable Abstract: A randomised controlled study showing similar effectiveness between two different methods of timing IUI., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Low urinary luteinizing hormone (LH) values have been discussed as a marker to detect steroid abuse. However, suppressed LH concentrations related to highly diluted urine samples could be a misleading indication of anabolic steroid abuse. One aim of the present study was to examine the effect of hyperhydration on the interpretation of LH findings during doping control analysis and to investigate different possibilities to correct volume-related changes in urinary LH concentrations. Seven healthy, physically active, nonsmoking White males were examined for a 72-hr period, using water and a commercial sports drink as hyperhydration agents (20 ml/kg body weight). Urine samples were collected and analyzed according to the World Anti-Doping Agency's technical documents. Baseline urinary LH concentrations, expressed as the mean ± SD for each individual, were within the acceptable physiological range (7.11 ± 5.42 IU/L). A comparison of the measured LH values for both hyperhydration phases (Phase A: 4.24 ± 5.60 IU/L and Phase B: 4.74 ± 4.72 IU/L) with the baseline ("normal") values showed significant differences (Phase A: p < .001 and Phase B: p < .001), suggesting the clear effect of urine dilution due to hyperhydration. However, an adjustment of urinary LH concentrations by specific gravity based on a reference value of 1.020 seems to adequately correct the hyperhydration-induced decrease on the LH levels.

Objective: The aim of this study was to assess whether luteinising hormone (LH) surge characteristics influenced the likelihood of conceiving naturally., Methods: This was a single-cycle, home-based, observational, case-controlled study. Volunteers collected daily urine samples for one menstrual cycle. LH was measured and the basal levels, surge day, peak day, peak concentration and magnitude of LH surges were examined. Predictive models using sociodemographic data, LH surge characteristics, and sociodemographic data combined with LH profile properties, were evaluated., Results: The surge profile did not differ between cycles with early or late ovulation and was not affected by age or body mass index (BMI). The mean LH surge day was day 16 for both groups. Mean LH surge and concentrations did not differ between groups (surge concentration 54.8 IU/l vs. 58.2 IU/l and peak concentration 82.0 IU/l vs. 81.6 IU/l for pregnant vs. non-pregnant volunteers, respectively). Non-pregnant volunteers were more likely, however, to have a raised or a reduced basal LH on day 6 or have an atypical LH profile. Sociodemographic characteristics were significant predictors of pregnancy, and sociodemographic variable-based models had the greatest predictive ability for conception, providing up to 65% predictive accuracy., Conclusions: Sociodemographic variables can be used to predict the likelihood of a woman conceiving naturally. Provided an LH surge is present, its profile does not relate to the likelihood of spontaneous pregnancy. The conception rate was significantly lower, however, in women with elevated or reduced basal levels of LH, suggesting that follicular maturation needs an optimal basal level of LH in natural conception cycles.

Background: Gonadotropin-releasing hormone stimulation test is a gold standard for evaluating the function of the hypothalamic-pituitary-gonadal axis (HPGA) in children. These tests are usually uncomfortable because of multi-venipunctures. A urine specimen is a good alternative because it is noninvasive and convenient. More studies have shown the correlation between sera and urine LH and FSH levels under different physiological and pathological conditions., Methods: The study investigated the dynamic trends of urine LH (uLH) and FSH (uFSH) assayed by immunochemiluminometric assays (ICMA) during triptorelin stimulation tests in girls. The triptorelin stimulation tests were performed in 52 girls with disorders of puberty. The time 0 hour was regarded as the start time of the test (8:30 am). The day before the tests, urine samples were collected at 12 hours diurnal (-24 hours ~ -12 hours) and nocturnal (-12 hours ~ 0 hour) time points. On the day of the testing, the first 12 hours (0 hour ~ 12 hours), the second 12 hours (12 hours ~ 24 hours), the third 12 hours (24 hours ~ 36 hours), the fourth 12 hours (36 hours ~ 48 hours), the third and fourth overnight urine samples were also collected. The LH and FSH levels were assayed by ICMA, and uLH and uFSH were corrected for creatinine (Cr)., Results: The HPGA in 41 girls was activated but it was nonactivated in 11 girls. In girls with HPGA activated, uLH/Cr or uFSH/Cr was significantly elevated within 24 hours, and gradually dropped to baseline after 48 hours. When HPGA was nonactivated in girls, there were the same dynamic trends but much lower amplitude of uLH/Cr or uFSH/Cr, which dropped to baseline after 24 hours., Conclusions: The stimulated uLH and uFSH assayed by ICMA are valuable for evaluating the function of HPGA in girls, and the valuable time window is within 24 hours.

There is a growing concern over the timing of pubertal breast development and its possible association with exposure to endocrine disrupting chemicals (EDCs), such as bisphenol A (BPA). BPA is abundantly used to harden plastics. The aim of this study was to investigate the relation between premature thelarche (PT) and BPA by comparing the urinary BPA levels of PT girls with those of healthy subjects. Twenty-five newly diagnosed nonobese PT subjects (aged 4-8 years) who were admitted to the Pediatric Endocrinology Department at Akdeniz University were recruited. The control group composed of 25 age-matched girls without PT and other endocrine disorders. Urinary BPA levels were measured by high pressure liquid chromatography. The median urinary concentrations of BPA were found to be significantly higher in the PT group compared to the healthy control group (3.2 vs. 1.62 μg/g creatinine, p < 0.05). We observed a weak positive correlation between uterus volume and urinary BPA levels. There was a weak correlation between estradiol and urinary BPA levels ( r = 0.166; p = 0.37); and luteinizing hormone and urinary BPA levels ( r = 0.291; p = 0.08) of PT girls. Our results suggest that exposure to BPA might be one of the underlying factors of early breast development in prepubertal girls and EDCs may be considered as one of the etiological factors in the development of PT.

Background: The postnatal gonadotrophin surge is sexually dimorphic: FSH levels predominate in girls and LH levels in boys. However, in preterm (PT) girls, both gonadotrophin levels are higher than in PT boys., Objective: To evaluate how gonadal maturation contributes to the sex differences in FSH and LH., Design: Monthly follow-up of 58 full-term (FT, 29 boys) and 67 PT (33 boys) infants from 1 week (D7) to 6 months of age (M1-M6). Analyses were also carried out according to postmenstrual (PM) age in PT infants., Methods: Urinary LH, FSH, oestradiol (E2), testosterone (T) and serum inhibin B (InhB) levels., Results: High gonadotrophin levels in PT girls abruptly decreased (P < .001) by M2, corresponding to a PM age of 38-42 weeks, and LH levels fell below the levels found in boys. This decrease was parallel to a steep increase in E2 levels (P < .001), and, from M4 to M6, LH and E2 correlated positively in PT girls (P < .01). T levels in PT boys increased earlier than E2 levels in PT girls. In addition, InhB levels were high in PT boys already at D7, in contrast to low InhB in PT girls. InhB and FSH correlated negatively in the whole group (P < .001)., Conclusions: Ovarian hormone synthesis is immature and incapable of responding to gonadotrophin stimulus before 38-42 PM weeks in PT girls, which may explain their highly elevated FSH and LH levels. The higher InhB levels in boys compared to girls may explain sexual dimorphism in FSH levels., (© 2018 John Wiley & Sons Ltd.)

Background: The impact of testosterone (T) treatment on antidoping detection tests in female-to-male (F2M) transgender men is unknown. We investigated urine and serum sex steroid and luteinizing hormone (LH) profiles in T-treated F2M men to determine whether and, if so, how they differed from hypogonadal and healthy control men., Method: Healthy transgender (n = 23) and hypogonadal (n = 24) men aged 18 to 50 years treated with 1000 mg injectable T undecanoate provided trough urine and blood samples and an additional earlier postinjection sample (n = 21). Healthy control men (n = 20) provided a single blood and urine sample. Steroids were measured by mass spectrometry-based methods in urine and serum, LH by immunoassay, and uridine 5'-diphospho-glucuronosyltransferase 2B17 genotype by polymerase chain reaction., Results: Urine LH, human chorionic gonadotropin, T, epitestosterone (EpiT), androsterone (A), etiocholanolone (Etio), A/Etio ratio, dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and 5α,3α- and 5β,3α-androstanediols did not differ between groups or by time since last T injection. Urine T/EpiT ratio was <4 in all controls and 12/68 (18%) samples from T-treated men, but there was no difference between T-treated groups. Serum estradiol, estrone, and DHEA were higher in transgender men, and serum T and DHT were higher in earlier compared with trough blood samples, but serum LH, follicle-stimulating hormone, and 3α- and 3β,5α-diols did not differ between groups., Conclusion: Urine antidoping detection tests in T-treated transgender men can be interpreted like those of T-treated hypogonadal men and are unaffected by time since last T dose. Serum steroids are more sensitive to detect exogenous T administration early but not later after the last T dose.

Purpose: To investigate if generic Wondfo ovulation sticks (WLH) are sufficiently sensitive to the luteinizing hormone (LH) surge in urine when used with the Marquette Fertility Algorithm. The electronic hormonal fertility monitor (EHFM) is highly accurate in detecting the LH surge but cost of the monitor and the accompanying test sticks has increased over the last several years. The EHFM is sensitive to detect the LH surge at 20 milli-international units per milliliter (mIU/mL); the WLH sticks are slightly less sensitive at 25 mIU/mL., Study Design and Methods: A convenience sample of women using the Marquette Method of Natural Family Planning with the EHFM to avoid pregnancy were recruited (N = 54). Each participant used the EHFM every morning after cycle day 6 and tested morning and evening urine with the WLH stick until the day following detection of the LH surge on the EHFM., Results: Forty-two women provided 219 cycles. Frequency of LH surge detection was 182/219 (83.1%) for EHFM and 203/219 (92.7%) for WLH sticks. Agreement between the EHFM and the WLH on the day of the LH surge was 97.7%. High fertility readings providing a warning of peak fertility at least 5 days before peak was 67% for the WLH; the EHFM was 47.7%. Paired sample correlations for high fertility was .174 (p = .014) and paired sample differences t was -4.729 (p = .000)., Clinical Implications: The WLH stick is sufficiently sensitive to use in place of the EFHM for determining peak fertility and with the Marquette Fertility algorithm. Even with minimal use, WLH sticks cost about half the price of the monitor strips and provide more flexibility of use. Cost differences increase with the number of sticks used per cycle. Further research with a larger sample is needed to verify results.

Background: Urine is a good alternative body fluid for gonadotropin studies. There was limited information about the effects of different storage conditions on urinary gonadotropin measurement by using immunochemiluminometric assay (ICMA)., Methods: ICMA was used to determine gonadotropin in urine stored under different conditions, such as different pH, storage time, and cycles of freeze-thaw., Results: Luteinizing hormone (LH) level was not significantly affected at pH 2.5 to 10.5 or being stored at 4°C for 3 days. Follicular stimulating hormone (FSH) level was not significantly changed at pH 3.5 to 10.5 or throughout 49-day storage at 4°C in the absence of glycerol. LH was significantly decreased after freeze-thawing twice, while FSH was resistant to freeze-thaw procedures., Conclusions: LH and FSH can be determined by ICMA in normal urine pH range (4.6 ~ 8.0). Urine LH is more sensitive to long-term storage and multiple freeze-thaw procedures than FSH.

Although under investigation for more than two decades, a common agreement on the occurrence of cyclical shifts in women's masculinity and symmetry preferences is still missing. Such shifts are considered to be an important feature of sexual selection as they supposedly direct women's attention towards cues for "good genes" (e.g. masculinity and symmetry) during times when probability of conception is the highest. Multiple studies have, however, failed to find these shifts. We attempt to address this lack of agreement analysing a sample of 110 healthy women, using intra-participant design and repeated measurements of oestradiol and LH during the cycle. To ensure the reliable detection of increased conception probability, both LH- based ovulation tests and multiple oestradiol measurements were used. We found no significant differences between women's preferences during different cycle phases for either body or facial masculinity, or for facial symmetry. Differences remained non-significant after controlling for participants' sexual openness, relationship status, and self-judged attractiveness. We suggest that putative cyclical shifts in preferences for cues for good genes are either very small (impossible to be tracked even with a relatively large sample) or they are far more complex than previously assumed, and further studies accounting for more confounding variables should be undertaken., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To determine whether premenarchal girls exhibit positive estradiol feedback similar to regularly cycling adult women when given exogenous estradiol., Methods: This was a prospective clinical cohort study at 2 institutions. Nine girls and 6 women received a 7-day course of transdermal estradiol designed to produce physiologic, mid-cycle circulating estradiol levels. Participants collected daily morning urine for luteinizing hormone (LH), estradiol metabolites (E1c), and progesterone metabolites (Pdg), corrected for creatinine. Main outcomes were percentage increase in LH from nadir to peak and the absolute value of peak LH between the 2 groups, using t testing and linear mixed-effects modeling., Results: All participants exhibited a positive feedback response to estradiol. Adult women had a 532.8% (95% confidence interval [CI]: 253.7-1119) increase in LH after estradiol exposure; premenarchal girls had a 497.9% increase (95% CI: 274.5-903.2; P = .86). The absolute value of the LH surge in women was 9.50 mLU/mgCr (95% CI: 2.59- 43 34.90) and in premenarchal girls was 2.57 mLU/mgCr (95% CI: 0.53-12.49; P = .15)., Conclusions: Premenarchal girls can mount an LH surge proportionally similar to regularly cycling adults. This occurs earlier in puberty than previously believed, in contrast to current dogma that maturation of the hypothalamic-pituitary-ovarian axis occurs after menarche and is the rate-limiting step for the establishment of regular, ovulatory cycles. Failure to achieve regular cycles may instead be due to nutritional or ovarian factors. Young girls who fail to ovulate shortly after menarche may warrant further evaluation for endocrinopathies.

Background: Many surveys have shown that older children are ubiquitously exposed to bisphenol A (BPA), and many laboratory studies have shown that BPA exposure has adverse effects related to estrogenic disruption, whereas the evidence in infants has not yet been observed., Methods: Women in early pregnancy were recruited by the Maternal and Child Health and Family Planning Service Center, Daishan, China, from March 2012 to December 2014. After delivery, urine samples were collected from the diapers of 59 infants (0 to 6months of age). Urinary BPA, estradiol (E 2 ), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and creatinine were analyzed. The partial correlation and multivariable linear regression were applied to assess the associations of BPA with E 2 , T, FSH, and LH for each of the development stages: at birth, 14days, 28days, 42days, 3months, and 6months., Results: For both genders from birth to 6months, infants showed randomly changed urinary BPA but regularly changed hormones, i.e., the monotonic decreasing E 2 and T, the "U" shaping E 2 /T and upside down "U" shaping FSH and LH with extreme values at approximately the 14-day stage, respectively. However, the creatinine-adjusted FSH for all stages and E 2 from 6months were genders different. After adjustment for creatinine, gender, and infant body mass index, BPA was positively associated with E 2 both in male (for 14-, 28-, and 42-day stages) and female (for 14-, 28-, 42-day, and 3-month stages) infants; positively associated with E 2 /T ratio in both male (for 14- and 28-day stages) and female (for 14-day stage) infants; and positively associated with T in female (for 3-month stage) infants., Conclusions: To the best of our knowledge, this is the first time that associations of BPA with E 2 , E 2 /T, and T in infant urine were observed. The results suggested that the infants first demonstrate a surge of steroids after leaving the maternal uterus's steroidogenic environment (i.e., mini-puberty) and may be affected by BPA; this pollution may disrupt the premature gonad function at some important developmental windows., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Context: Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels., Objective: We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty., Design: Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients., Setting: Population-based and outpatient clinic., Patients or Other Participants: Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP)., Main Outcome Measures: Clinical pubertal staging, including serum and urinary gonadotropin levels., Results: Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P < 0.001) and gonadotropin-releasing hormone (GnRH)-stimulated serum LH (r = 0.82, P < 0.001). Urinary LH was superior to urinary FSH in differentiating the pubertal stage. Receiver operating curve analysis revealed that a cut-off standard deviation (SD) score of 2 for urinary LH (IU/L) gave a sensitivity of 75% and a specificity of 92% in predicting a positive GnRH stimulation test (LHmax > 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs., Conclusions: Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty., (Copyright © 2017 Endocrine Society)

Estrus detection in buffaloes has been a major concern for decades, and lack of reliable methods affects their effective reproductive management. Luteinizing hormone (LH) detection in urine is in practice for several mammals for timed insemination, whereas very few reports are available on buffalo urinary LH. The focus of this study is to detect the presence of LH in buffalo urine, quantitate variation in urinary LH during different estrous cycle phases and examine the duration of mid-cycle LH window. Nearly hundred buffaloes were examined, longitudinal urine samples (n=42) were collected from seventeen animals and classified into respective phases based on several estrus detection parameters. The urinary LH was detected using bovine LH ELISA kit validated for serum/plasma/tissue homogenate. Detection of buffalo LH in the neat urine convincingly proved the competence of the bovine LH kit. Variation in the LH range was observed between different phases of estrous cycle and significant fold variation (P<0.05) was noticed during estrus phase (1.01±0.23) with average baseline value of 46.73±3.36mIU/mL. Interestingly, an extended window (A1-A3) of mid-cycle LH surge was observed due to its lingering excretion in urine. The results, altogether, revealed that LH can be detected in buffalo urine with noticeable fold variation during estrus phase and the extended LH window intensifies the chance of ovulation prediction for timed insemination., (Copyright © 2016 Elsevier Inc. All rights reserved.)