Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Ultrasensitive DNA-Biomacromolecule Sensor for the Detection Application of Clinical Cancer Samples.

Diagnostic testing of biological macromolecules is of great significance for early warning of disease and cancer. Nevertheless, restricted by limited surface area and large steric hindrance, sensitive detection of macromolecules with interface-based sensing method remains challenging. Here, a "biphasic replacement" electrochemical aptamer-based (BRE-AB) sensing strategy which placed capture reaction of the biomacromolecule in a homogeneous solution phase and replaced with a small diameter of single-stranded DNA to attach to the interface is introduced. Using the BRE-AB sensor, the ultrasensitive detection of luteinizing hormone (LH) with the detection limit of 10 × 10-12 m is demonstrated. Molecular Dynamics simulations are utilized to explore the binding mechanism of aptamer and target LH. Moreover, it is confirmed that the BRE-AB sensor has excellent sensing performance in whole blood and undiluted plasma. Using the BRE-AB sensor, the LH concentrations in 40 clinical samples are successfully quantified and it is found that LH is higher expressed in breast cancer patients. Furthermore, the sensor enables simple, low-cost, and easy to regenerate and reuse, indicating potentially applicable for point-of-care biological macromolecules diagnostics.

Evaluation of fertility and embryo implantation in rats after the oral administration of Salvia officinalis (sage) extract / Evaluación de la fertilidad y la implantación de embriones en ratas después de la administración oral de extracto de Salvia officinalis (salvia)

SUMMARY: In Saudi Arabia, it is widely believed that women with reproductive problems can use the extract of the sage plant as a tea drink. This study was conducted to investigate the effects of this herb on the fertility of female rats and embryo implantation. Forty-eight Wistar virgin female rats were divided into four groups at random, with 12 rats in each group. The control group received distilled water orally. The three treatment groups received different concentrations of sage extract: 15, 60, or 100 mg/kg for 14 days before mating, then mated with a male and sacrificed on the 7th day of gestation, the uterine horns removed, and photographed. The total body weight of mothers, weight of uteri and ovaries and number of fetuses were determined. Ovarian and uteri tissues were cut into 5 µ sections and stained with hematoxylin and eosin. Serum FSH, LH were determined by the ELISA method. The present study showed that low dose of sage (15 mg/kg) have no effects on serum concentration levels of FSH and LH hormones, also has no effect on the number of growing follicles. The present study showed a significant differences (P≤0.05) in body weight, ovary and uterus weight in the groups treated with high doses of Salvia officinalis as compared to control group. Also a significant differences (P≤0.05) found in FSH, LH hormones. Histological study showed overall histomorphological structural configurations including growing and matured graafian follicular countable changes, besides a number of corpora lutea and regressed follicles in the treated groups with high doses of Salvia officinalis as compared to control group. The researchers concluded that the extract of the sage plant with high doses can stimulate the growth graafian follicles and improve fertility in female rats.

RESUMEN: En Arabia Saudita, se cree ampliamente que las mujeres con problemas reproductivos pueden usar el extracto de la planta de salvia como bebida de té. Este estudio se realizó para investigar los efectos de esta hierba sobre la fertilidad de las ratas hembra y la implantación del embrión. Se dividieron cuarenta y ocho ratas hembra vírgenes Wistar en cuatro grupos al azar, con 12 ratas en cada grupo. El grupo control recibió agua destilada por vía oral. Los tres grupos de tratamiento recibieron diferentes concentraciones de extracto de salvia: 15, 60 o 100 mg/kg durante 14 días antes del apareamiento, luego se aparearon con un macho y se sacrificaron el día 7 de gestación, se extrajeron los cuernos uterinos y se fotografiaron. Se determinó el peso corporal total de las madres, el peso del útero y los ovarios y el número de fetos. Los tejidos ováricos y uterinos se cortaron en secciones de 5 µ y se tiñeron con hematoxilina y eosina. FSH sérica, LH se determinaron por el método ELISA. El presente estudio mostró que dosis bajas de salvia (15 mg/kg) no tienen efectos sobre los niveles de concentración sérica de las hormonas FSH y LH, tampoco tienen efecto sobre el número de folículos en crecimiento. El presente estudio mostró diferencias significativas (P≤0,05) en el peso corporal, peso de ovario y útero en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo control. También se encontraron diferencias significativas (P≤0,05) en las hormonas FSH, LH. El estudio histológico mostró configuraciones estructurales histomorfológicas generales que incluyen cambios contables en los folículos maduros (de Graaf) y en crecimiento, además de una cantidad de cuerpos lúteos y folículos en regresión en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo de control. Los investigadores concluyeron que el extracto de la planta de salvia en altas dosis puede estimular el crecimiento de los folículos maduros y mejorar la fertilidad en ratas hembra.

False negative results in testosterone doping in forensic cases: Sensitivity of the urinary detection criteria T/E and T/LH.

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.

Effect of turmeric on adiponectin, sexual function and sexual hormones in stressed mice.

Sexual function is essential for species survival. Melanocortin, progesterone, and estrogen can improve sexual function and they are modulated by adiponectin hormone which can be increased by Turmeric. In various studies shows Turmeric ability that is easily accessible to increase serum adiponectin levels. Therefore, the researchers decided to conduct a study to determine the effect of turmeric on serum adiponectin levels, sexual behavior, and profile of steroid hormones in stressed mice. Thirty female mice, six in each group (1. control group, 2. mice that received stress, 3. stress mice received 100 mg/kg turmeric (extract daily) for 4 weeks, 4. stress mice received turmeric (extract daily) for 4 weeks and also received adiponectin antagonist, and 5. stress groups received adiponectin antagonist), were used in the current study. The mice first underwent blood sampling. Then all mice were subjected to stress testing before the intervention except one group, which considered as a control group. The intervention in this study was done as a 100 mg/kg turmeric extract that was gavaged daily for each mouse. After the intervention, all mice were tested for sexual behavior, and then blood samples were taken to check serum levels of adiponectin, estradiol, progesterone and prolactin. So, the results showed before the intervention there were no significant difference among 5 group in levels of adiponectin (p = 0.145), estradiol (p = 0.148), progesterone (p = 0.166) and prolactin (p = 0.206) but after intervention there were significant difference between 5 group in levels of adiponectin, estradiol and progesterone (p < 0.001). Also there was significant difference among 5 groups in sexual behavior (p < 0.001). Therefore, consumption of turmeric, which increases serum adiponectin in the stressed mice, can improve sexual function and estradiol hormones profiling.

Biochemical predictors of structural hypothalamus-pituitary abnormalities detected by magnetic resonance imaging in men with secondary hypogonadism.

PURPOSE: Organic conditions underlying secondary hypogonadism (SH) may be ascertained by magnetic resonance imaging (MRI) of the hypothalamic-pituitary region that could not be systematically proposed to each patient. Based upon limited evidence, the Endocrine Society (ES) guidelines suggest total testosterone (T) < 5.2 nmol/L to identify patients eligible for MRI. The study aims to identify markers and their best threshold value predicting pathological MRI findings in men with SH. METHODS: A consecutive series of 609 men seeking medical care for sexual dysfunction and with SH (total T < 10.5 nmol/L and LH ≤ 9.4 U/L) was retrospectively evaluated. An independent cohort of 50 men with SH was used as validation sample. 126 men in the exploratory sample and the whole validation sample underwent MRI. RESULTS: In the exploratory sample, patients with pathological MRI findings (n = 46) had significantly lower total T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate specific antigen (PSA) than men with normal MRI (n = 80). Receiver Operating Characteristics analysis showed that total T, LH, FSH and PSA are accurate in identifying men with pathologic MRI (accuracy: 0.62-0.68, all p < 0.05). The Youden index was used to detect the value with the best performance, corresponding to total T 6.1 nmol/L, LH 1.9 U/L, FSH 4.2 U/L and PSA 0.58 ng/mL. In the validation cohort, only total T ≤ 6.1 nmol/L and LH ≤ 1.9 U/L were confirmed as significant predictors of pathologic MRI. CONCLUSION: In men with SH, total T ≤ 6.1 nmol/L or LH ≤ 1.9 U/L should arise the suspect of hypothalamus/pituitary structural abnormalities, deserving MRI evaluation.

Transcription factor immunohistochemistry in the diagnosis of pituitary tumours.

OBJECTIVE: The clinical utility and prognostic value of WHO 2017 lineage-based classification of pituitary tumours have not been assessed. This study aimed to (1) determine the clinical utility of transcription factor analysis for classification of pituitary tumours and (2) determine the prognostic value of improved lineage-based classification of pituitary tumours. METHODS: This was a retrospective evaluation of patients who underwent surgical resection of pituitary tumours at St Vincent's Public and Private Hospitals, Sydney, Australia between 1990 and 2016. Included patients were at least 18 years of age and had complete histopathological data, forming the 'histological cohort'. Patients with at least 12 months of post-surgical follow-up were included in the subgroup 'clinical cohort'. The diagnostic efficacy of transcription factor immunohistochemistry in conjunction with hormone immunohistochemistry was compared with hormone immunohistochemistry alone. The prognostic value of identifying 'higher-risk' histological subtypes was assessed. RESULTS: There were 171 patient tumour samples analyzed in the histological cohort. Of these, there were 95 patients forming the clinical cohort. Subtype diagnosis was changed in 20/171 (12%) of tumours. Within the clinical cohort, there were 21/95 (22%) patients identified with higher-risk histological subtype tumours. These were associated with tumour invasiveness (P = 0.050), early recurrence (12-24 months, P = 0.013), shorter median time to recurrence (49 (IQR: 22.5-73.0) vs 15 (IQR: 12.0-25.0) months, P = 0.005) and reduced recurrence-free survival (P = 0.031). CONCLUSIONS: Application of transcription factor analysis, in addition to hormone immunohistochemistry, allows for refined pituitary tumour classification and may facilitate an improved approach to prognostication.

Buchholzia coriacea (wonderful kola) seeds induce male reproductive toxicity by suppressing the pituitary-gonadal axis in Wistar rats

The methanolic extract of Buchholzia coriacea seeds (MEBC) has been reported to induce male reproductive toxicity by decreasing sperm parameters and fertility index. To elucidate the possible mechanism(s), the effects of graded doses of MEBC on sex hormones and sperm profile were investigated in this study. The MEBC (e.g., 50, 200, 400, and 600 mg/kg) was administered daily (p.o.) to male Wistar rats for 6 weeks, while a concurrent control group received distilled water (vehicle). Then, the animals were sacrificed under sodium pentobarbital anaesthesia. Weights of organs were recorded, and the sperm profile was determined microscopically. Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were assayed from the obtained serum using the ELISA technique. Sperm motility was significantly reduced by MEBC (i.e., 50 and 200 mg/kg), and sperm count reduced in all treated groups in a dose-dependent manner compared with that of the control. Serum testosterone, LH, and FSH decreased in treated rats. A histopathological examination of testes showed a considerable depletion and necrosis of the epithelium of seminiferous tubules. The result suggests that Buchholzia coriacea seeds induce male reproductive toxicity by suppressing the pituitary-gonadal axis.

Pubertat precoç com a síndrome paraneoplàstica / Pubertad precoz como síndrome paraneoplásico / Precocious puberty as paraneoplastic syndrome

INTRODUCCIÓ: L'hepatoblastoma és un tumor hepàtic maligne que destaca per la capacitat de secreció hormonal. Aquestes hormones s'utilitzen en el seguiment (alfa-fetoproteïna) o poden provocar complicacions paraneoplàstiques mimetitzant la funció d'altres hormones. Es presenta un cas clínic d'un nen de 18 mesos amb pubertat precoç. CAS CLÍNIC: Pacient diagnosticat d'hepatoblastoma en tractament quimioteràpic segons el protocol SIOPEL-6, que en la valoració clínica prequirúrgica presenta un estadi de Tanner G3 P2 I un volum testicular de 12 cc bilateral. A nivell analític destaca una elevació de la testosterona I de la gonadotrofina coriònica humana (hCG), sense elevació de la hormona luteoestimulant (LH) ni de la hormona estimulant del fol·licle (FSH), compatible amb una pubertat precoç perifèrica. Després de la resecció tumoral es demostra un descens de la testosterona, de l'hCG I de l'alfa-fetoproteïna, I s'orienta com a síndrome paraneoplàstica del tumor. COMENTARIS: Dins del diagnòstic diferencial de la pubertat precoç, cal distingir entre pubertat precoç central (activació de l'eix hipotàlem-hipofític-gonadal) I perifèrica (producció externa d'hormones sexuals independentment de l'activació central). En el cas descrit s'orienta com a pubertat precoç perifèrica a causa de la secreció d'hCG per l'hepatoblastoma. L'hCG presenta una estructura molecular similar a l'LH I en concentracions elevades promou la secreció de testosterona per les cèl·lules de Leydig. En canvi, l'augment de volum testicular depèn directament de l'FSH, de manera que es planteja la hipòtesi que la producció d'esteroides gonadals en una pubertat precoç perifèrica acabaria sensibilitzant I estimulant l'eix hipotàlem-hipofític

INTRODUCCIÓN: El hepatoblastoma es un tumor hepático maligno que destaca por su capacidad de secreción hormonal. Estas hormonas se utilizan en el seguimiento (alfafetoproteína) o pueden provocar complicaciones paraneoplásicas simulando la función de otras hormonas. Se presenta un caso clínico de un niño de 18 meses con pubertad precoz. CASO CLÍNICO: Paciente diagnosticado de hepatoblastoma en tratamiento quimioterápico según protocolo SIOPEL-6, que en la valoración clínica prequirúrgica presenta un estadio de Tanner G3 P2 y un volumen testicular de 12 cc bilateral. A nivel analítico destaca una elevación de testosterona y gonadotrofina coriónica humana (hCG) sin elevación de la hormona luteinizante (LH) ni de la hormona estimulante del folículo (FSH), compatible con una pubertad precoz periférica. Tras la resección tumoral se demuestra el descenso de testosterona y hCG, orientándose como síndrome paraneoplásico del tumor. COMENTARIOS: Dentro del diagnóstico diferencial de la pubertad precoz, hay que distinguir entre pubertad precoz central (activación del eje hipotálamo-hipofisario-gonadal) y periférica (producción externa de hormonas sexuales independientemente de la activación central). En el caso descrito se orienta como pubertad precoz periférica, debido a la secreción de hCG por el hepatoblastoma. La hCG presenta una estructura molecular similar a la LH y en elevadas concentraciones promueve la secreción de testosterona por las células de Leydig. Dado que el aumento del volumen testicular depende directamente de la FSH, se plantea la hipótesis de que la producción de esteroides gonadales en la pubertad precoz periférica acabaría sensibilizando y estimulando el eje hipotálamo-hipofisario

INTRODUCTION: Hepatoblastoma is a malignant liver tumour characterized by its hormonal secretion. The secreted hormones are used in the follow-up (alpha-fetoprotein) or can cause paraneoplastic complications simulating the function of other hormones. We present a clinical case of an 18-month-old boy with precocious puberty. CASE REPORT: Patient with diagnosis of hepatoblastoma undergoing chemotherapy treatment according to SIOPEL-6 protocol, which presents Tanner G3 P2 stage and testicular volume of 12cc bilateral in the presurgical clinical assessment. In the blood test, there is an elevation of testosterone and human chorionic gonadotropin (hCG) without elevation of luteinising hormone (LH) and follicle-stimulating hormone (FSH), compatible with peripheral precocious puberty. After tumour resection, decrease in testosterone and hCG blood levels are demonstrated, pointing itself as a paraneoplastic tumour syndrome. COMMENTS: In the differential diagnosis of precocious puberty, one must distinguish between central precocious puberty (activation of hypothalamic-pituitary-gonadal axis) and peripheral precocious puberty (external production of sex hormones independently of central activation). The case is an example of peripheral precocious puberty, due to the secretion of hCG by hepatoblastoma. HCG has a molecular structure similar to LH and in high concentrations promotes secretion of testosterone by Leydig cells. However, the increase in testicular volume depends directly on FSH and one hypothesis would be that the production of gonadal steroids in peripheral precocious puberty would end up sensitizing and stimulating the hypothalamic-pituitary axis

Myoglobin-silver reduced graphene oxide nanocomposite stochastic biosensor for the determination of luteinizing hormone and follicle-stimulating hormone from saliva samples.

A silver reduced graphene oxide (Ag-rGO) nanocomposite paste was prepared for the assay of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in children's saliva. The paste was modified with a solution of myoglobin (Myb) to form the stochastic biosensor, to improve the sensitivity of the method. The Ag-rGO powder and Myb-Ag-rGO paste were morphologically and structurally characterized by SEM, TEM and XRD measurements. For the molecular recognition of the hormones, the biosensor based on Myb-Ag-rGO reached determination limits of 8.5 × 10-3 UI L-1 (2.0 × 10-12 g/mL) for luteinizing hormone and 1.4 × 10-2 UI L-1 (1.0 × 10-12 g/mL) for follicle-stimulating hormone. The determination of both hormones in saliva samples collected from children was done with high reliability. Graphical Abstract.

Clinical Implications of Polycystic Ovary Syndrome in Adolescents.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy, affecting as many as 5% to 20% of women of reproductive age, depending on the diagnostic criteria applied. Features of PCOS include physiologic anovulation, hyperandrogenism, elevated luteinizing hormone, and increased gonadotropin-releasing hormone pulse frequency, which often manifest physically as acne and hirsutism. The clinical presentation of PCOS often mimics normal pubertal physiologic development, which may delay diagnosis and treatment of the condition in adolescent girls. A diagnosis of PCOS has life-long implications and is associated with increased risk for infertility, obesity, Type 2 diabetes, endometrial hyperplasia, uterine carcinoma, metabolic disorder, and cardiovascular disease. In this article, we provide an overview of clinical presentation, diagnostic criteria, health consequences, and current evidence-based clinical guidelines for the appropriate diagnosis and management of PCOS in adolescents.

Comparison between semen parameters in specimens collected early in the morning and in the evening.

The majority of facilities in Japan that offer artificial insemination as part of assisted reproduction programs currently perform semen collection in the early morning. The total motile sperm count of the semen used in intrauterine insemination is an important factor in achieving successful fertilization and subsequent childbirth. The present study was initiated to determine whether semen parameters varied with the time of day at which the semen sample was collected. The study subjects were 20 fertile males and 20 infertile males with abnormal seminograms who attended our Reproduction Center. Semen was collected early in the morning (morning collection group) and in the evening (evening collection group) from the same subjects, and total motile sperm count was assessed as the primary outcome measure. As secondary outcome measures, semen volume, sperm concentration, sperm motility and total sperm count were assessed. A sexual abstinence period of 3 days was set for all participants. The semen samples were analyzed using CASA CEROS, a sperm motility analysis system, and the data from the morning and evening collection groups were compared using a Wilcoxon signed rank test. We found that the fertile males had a significantly higher total motile sperm count and total sperm count in the evening collection group than in the morning collection group. In contrast, the male infertility patients showed no significant difference in total sperm count between the two collection times; however, the total motile sperm count was significantly higher in the evening collection group than the morning collection group. Our analyses indicate that total motile sperm count in ejaculated semen is significantly higher after evening collection than after morning collection. From a male side perspective, we suggest that successful intrauterine insemination might be easier to achieve using semen collected in the evening than in the early morning.Abbreviations: IUI: intrauterine insemination; OAT: oligoasthenoteratozoospermia; TSC: total sperm count; TMSC: total motile sperm count.

Comparison of woman-picked, expert-picked, and computer-picked Peak Day of cervical mucus with blinded urine luteinising hormone surge for concurrent identification of ovulation.

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 FertilityCareTM 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.

Salivary luteinizing hormone: An open window to detect oestrous period in buffalo.

Silent oestrus is an unsurmountable problem in the management of buffalo reproduction. In addressing this issue, we have earlier reported variation in the levels of urinary luteinizing hormone (LH) through the different phases of oestrous cycle with an extended window during the mid-oestrous phase. Based on this report, the present study is designed to assess the salivary LH levels in buffalo during the different phases of oestrous cycle. Bovine LH ELISA kit was used to determine the level of salivary LH. We observed a notable variation in salivary LH levels during the different phases of oestrous cycle. The maximum LH level, 39.07 mIU/ml, observed during oestrus, which was significantly (p < .05) higher than other consecutive phases. Altogether, the results showed a significant (p < .05) fold variation during oestrus compared with other phases. Therefore, the study convincingly shows that salivary LH has the potential of application in development of a modality for non-invasive oestrous detection in buffalo.

Age-related presence of spermatogonia in patients with Klinefelter syndrome: a systematic review and meta-analysis.

BACKGROUND: Klinefelter syndrome (KS) has been defined by sex chromosome aneuploidies (classically 47, XXY) in the male patient. The peripubertal timeframe in KS patients has been associated with the initiation of progressive testicular fibrosis, loss of spermatogonial stem cells (SSC), hypogonadism and impaired fertility. Less than half of KS patients are positive for spermatozoa in the ejaculate or testis via semen analysis or testicular sperm extraction, respectively. However, the chance of finding spermatogonia including a sub-population of SSCs in KS testes has not been well defined. Given the recent demonstration of successful cell culture for mouse and human SSCs, it could be feasible to isolate and propagate SSCs and transplant the cells back to the patient or to differentiate them in vitro to haploid cells. OBJECTIVE AND RATIONALE: The main objective of this study was to meta-analyse the currently available data from KS patients to identify the prevalence of KS patients with spermatogonia on testicular biopsy across four age groups (year): fetal/infantile (age ≤ 1), prepubertal (age 1 ≤ x ≤ 10), peripubertal/adolescent (age 10 < x < 18) and adult (age ≥ 18) ages. Additionally, the association of endocrine parameters with presence or absence of spermatogonia was tested to obtain a more powered analysis of whether FSH, LH, testosterone and inhibin B can serve as predictive markers for successful spermatogonia retrieval. SEARCH METHODS: A thorough Medline/PubMed search was conducted using the following search terms: 'Klinefelter, germ cells, spermatogenesis and spermatogonia', yielding results from 1 October 1965 to 3 February 2019. Relevant articles were added from the bibliographies of selected articles. Exclusion criteria included non-English language, abstracts only, non-human data and review papers. OUTCOMES: A total of 751 papers were identified with independent review returning 36 papers with relevant information for meta-analysis on 386 patients. For the most part, articles were case reports, case-controlled series and cohort studies (level IV-VI evidence). Spermatogonial cells were present in all of the fetal/infantile and 83% of the prepubertal patients' testes, and in 42.7% and 48.5% of the peripubertal and adult groups, respectively were positive for spermatogonia. Additionally, 26 of the 56 (46.4%) peripubertal/adolescent and 37 of the 152 (24.3%) adult patients negative for spermatozoa were positive for spermatogonia (P < 0.05). In peripubertal/adolescent patients, the mean ± SEM level for FSH was 12.88 ± 3.13 IU/L for spermatogonia positive patients and 30.42 ± 4.05 IU/L for spermatogonia negative patients (P = 0.001); the mean ± SEM level LH levels were 4.36 ± 1.31 and 11.43 ± 1.68 IU/L for spermatogonia positive and negative, respectively (P < 0.01); the mean ± SEM level for testosterone levels were 5.04 ± 1.37 and 9.05 ± 0.94 nmol/L (equal to 145 ± 40 and 261 ± 27 and ng/dl) for the spermatogonia positive and negative groups, respectively (P < 0.05), while the difference in means for inhibin B was not statistically significant (P > 0.05). A similar analysis in the adult group showed the FSH levels in spermatogonia positive and negative patients to be 25.77 ± 2.78 and 36.12 ± 2.90 IU/L, respectively (mean ± SEM level, P < 0.05). All other hormone measurements were not statistically significantly different between groups. WIDER IMPLICATIONS: While azoospermia is a common finding in the KS patient population, many patients are positive for spermatogonia. Recent advances in SSC in vitro propagation, transplantation and differentiation open new avenues for these patients for fertility preservation. This would offer a new subset of KS patients a chance of biological paternity. Data surrounding the hormonal profiles of KS patients and their relation to fertility should be interpreted with caution as a paucity of adequately powered data exists. Future work is needed to clarify the utility of FSH, LH, testosterone and inhibin B as biomarkers for successful retrieval of spermatogonia.

Hormonal Status and Cognitivo-Emotional Profile in Real-Life Patients With Neuropathic Pain: A Case Control Study.

BACKGROUND: The specific impact of neuropathic pain and recommended neuropathic pain treatments on the hormonal and immune status of patients has been so far poorly explored. This study aimed at studying, in real life, the hypothalamic-pituitary-adrenal axis and the cytokine profile of patients with neuropathic pain. It also explored their links with cognition, emotion, quality of life, and drug treatment. METHODS: This prospective study (clinicaltrials.gov NCT01543425) included 60 patients with neuropathic pain and 60 age- and gender-matched healthy volunteers after obtaining signatures of informed consent. A number of parameters were measured: adrenocorticotropic hormone, cortisol, cortisol awakening response, dehydroepiandrosterone sulphate, sex hormone binding globulin, testosterone, 17-ß-estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, cytokines, brain-derived neurotrophic factor, and vitamin D. Psychological parameters were assessed by questionnaires. RESULTS: Patients with neuropathic pain had lower levels of adrenocorticotropic hormone (P = 0.009) and dehydroepiandrosterone sulphate (P < 0.001) than controls, and the cortisol awakening response was impaired. Patients were more depressed and anxious (P < 0.001) and had a diminished quality of life (P < 0.001), which was influenced by cytokines (P = 0.0067) and testosterone (P = 0.028). Antidepressants and antiepileptics appeared to interfere with testosterone and cognitivo-emotional domains. CONCLUSION: An impairment of the hormonal status and of the immune system was observed in patients. It identified testosterone as a potential pivotal mediator between antidepressants/antiepileptics and quality of life. Further studies must address the exact impact of different types of drugs on central effects, of gender differences, and of the immune system of neuropathic pain.

Pubertal development of estradiol-induced hypothalamic progesterone synthesis.

In females, a hallmark of puberty is the luteinizing hormone (LH) surge that triggers ovulation. Puberty initiates estrogen positive feedback onto hypothalamic circuits, which underlie the stimulation of gonadotropin releasing hormone (GnRH) neurons. In reproductively mature female rodents, both estradiol (E2) and progesterone (P4) signaling are necessary to stimulate the surge release of GnRH and LH. Estradiol membrane-initiated signaling facilitates progesterone (neuroP) synthesis in hypothalamic astrocytes, which act on E2-induced progesterone receptors (PGR) to stimulate kisspeptin release, thereby activating GnRH release. How the brain changes during puberty to allow estrogen positive feedback remains unknown. In the current study, we hypothesized that a critical step in estrogen positive feedback was the ability for estradiol-induced neuroP synthesis. To test this idea, hypothalamic neuroP levels were measured in groups of prepubertal, pubertal and young adult female Long Evans rats. Steroids were measured with liquid chromatography tandem mass spectrometry (LC-MS/MS). Hypothalamic neuroP increases from pre-puberty to young adulthood in both gonad-intact females and ovariectomized rats treated with E2. The pubertal development of hypothalamic E2-facilitated progesterone synthesis appears to be one of the neural switches facilitating reproductive maturation.

Follicular dynamics of glycerophospholipid and sphingolipid metabolisms in polycystic ovary syndrome patients.

Polycystic ovary syndrome (PCOS) is a common heterogeneous disease, affecting up to 5-10% women at reproductive age. Although PCOS patients could produce morphologically normal metaphase II oocytes undergoing assisted reproductive techniques (ART), oocyte developmental competence and embryo development have been impaired in following in-vitro fertilization (IVF) steps. Follicular fluid (FF) provides a variety of information in oocyte environment when oocytes grow. In the present work, based on ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), the metabolic signatures of PCOS FF have been compared with healthy women using untargeted metabolomics approach. Significant abundance differences of a series of glycerolipid, glycerophospholipids, sphingolipids, and carboxylic acids have been discovered. Among them, reduced levels of phosphatidylglycerolphosphate (PGP) and a triglyceride (TG) were highly related to the lower fertilization rate in PCOS; increased abundance of lysoPE and decreased amount of PC were significantly correlated with LH/FSH (ratio of luteinizing hormone to follicle stimulating hormone). Some metabolites, including decreased sphingolipids, glycerophospholipids, and fluctuated fatty acyls, also performed close relationship with other ART and clinical results. We concluded that dysfunctions in the metabolism of glycerolipid, glycerophospholipid, sphingolipid, and glycosphingolipid biosynthesis in PCOS patients' follicles play a non-ignorable role in declining the 2 pronuclei (PN) fertilization rate during IVF procedure.

Prospective evaluation of hypogonadism in male metastatic renal cell carcinoma patients treated with targeted therapies.

OBJECTIVES: To study the prevalence of hypogonadism in male patients with metastatic renal cell carcinoma (mRCC) starting with targeted therapies and the impact of the vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) sunitinib and pazopanib on the luteinizing hormone (LH)/testosterone (TT)-axis. METHODS: Male mRCC patients starting with targeted therapies were prospectively included in this study. TT- and LH-levels were sampled at start as well as during systemic therapy. Endpoints of the study were gonadal status (TT- and LH-levels) at start of targeted therapy and TT- and LH-evolution during targeted therapy. RESULTS: Sixty-three patients were included in this study. At start of targeted therapy, 30% of patients were eugonadal and 48% had secondary hypogonadism. Decreased TT- and increased LH-levels were associated with inflammatory state and poor prognosis. During sunitinib therapy, TT-levels decreased with 32% (p = 0.004) and LH-levels with 14% (p = 0.03). TT-levels were 13% lower (p = 0.007) and LH-levels 15% lower (p = 0.004) on day 28 compared to day 1. In four patients, a dramatic TT decrease was observed shortly after starting sunitinib. In patients treated with pazopanib, no impact on TT- or LH-levels was observed. CONCLUSION: Hypogonadism is a frequent finding in male mRCC-patients at start of targeted therapies. In contrast to pazopanib, during sunitinib therapy, TT- and LH-levels tend to decrease, leading to an increased incidence of secondary hypogonadism.

Evaluation of a Novel General Pituitary Hormone Score to Evaluate the Function of the Residual Anterior Pituitary (Adenohypophysis) in Patients Following Surgery for Pituitary Adenoma.

BACKGROUND The aim was to develop and assess a general pituitary hormone score to evaluate the function of the anterior pituitary (adenohypophysis) in patients following resection of pituitary adenomas. MATERIAL AND METHODS Sixty-six patients with pituitary null cell macroadenoma (1-3 cm diameter) (N=38) and pituitary null cell giant adenoma (≥3 cm diameter) (N=28) had preoperative and postoperative data including magnetic resonance imaging (MRI) and measurement of six pituitary hormones levels, adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone (TSH), prolactin (PRL), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The postoperative general pituitary hormone score, for 57 patients who underwent subtotal resection (>60%) and nine patients who underwent partial resection (≤60%), was 1-5 for each hormone level (score range, 6-30). RESULTS ACTH, GH, TSH, PRL, FSH, and LH levels in 38 patients with pituitary null cell macroadenoma were not statistically different from the 28 patients with pituitary null cell giant adenoma; the general pituitary hormone score in the former group was significantly increased compared with the latter group (P<0.05). ACTH, GH, TSH, PRL, FSH, and LH levels in the 57 patients with subtotal tumor resection were not significantly different from the nine patients with partial tumor resection; the general pituitary hormone score in the former group was significantly reduced compared with the latter group (P<0.05). CONCLUSIONS A general pituitary hormone score was developed that might be relevant to the evaluation of pituitary function following surgical resection of pituitary null cell macroadenoma and giant adenoma.