Evidence that the woman's ovarian cycle is driven by an internal circamonthly timing system.

The ovarian cycle has a well-established circa-monthly rhythm, but the mechanisms involved in its regularity are unknown. Is the rhythmicity driven by an endogenous clock-like timer or by other internal or external processes? Here, using two large epidemiological datasets (26,912 cycles from 2303 European women and 4786 cycles from 721 North American women), analyzed with time series and circular statistics, we find evidence that the rhythmic characteristics of the menstrual cycle are more likely to be explained by an endogenous clock-like driving mechanism than by any other internal or external process. We also show that the menstrual cycle is weakly but significantly influenced by the 29.5-day lunar cycle and that the phase alignment between the two cycles differs between the European and the North American populations. Given the need to find efficient treatments of subfertility in women, our results should be confirmed in larger populations, and chronobiological approaches to optimize the ovulatory cycle should be evaluated.

Urinary gonadotropin assay on 24-h collections as a tool to detect early central puberty onset in girls: determination of predictive thresholds.

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 menstrual cycle is influenced by weekly and lunar rhythms.

OBJECTIVE: To study whether the menstrual cycle has a circaseptan (7 days) rhythm and whether it is associated with the lunar cycle (also defined as the synodic month, it is the cycle of the phases of the Moon as seen from Earth, averaging 29.5 days in length). DESIGN: Cross-sectional study. SUBJECTS: A total of 35,940 European and North American women aged 18-40 years. EXPOSURE: Data were collected in real-life conditions. INTERVENTION: No intervention was performed. MAIN OUTCOME MEASURE: The onset of menstruation was assessed in prospectively measured menstrual cycles (311,064 cycles) over 3 full years (2019-2021). Associations were calculated between the onset of menstruation and the day of the week, and between the onset of menstruation and the lunar phase. RESULTS: In this large data set, a circaseptan (7-day) rhythmicity of menstruation was observed, with a peak (acrophase) of menstrual onset on Thursdays and Fridays. This circaseptan rhythm was observed in every age group, in every phase of the lunar cycle, and in all seasons. This feature was most pronounced for cycle durations between 27 and 29 days. In winter, the circaseptan rhythm was found in cycles of 27-29 days, but not in other cycle lengths. A circalunar rhythm was also statistically significant, but not as clearly defined as the circaseptan rhythm. The peak (acrophase) of the circalunar rhythm of menstrual onset varied according to the season. In addition, there was a small but statistically significant interaction between the circaseptan rhythm and the lunar cycle. CONCLUSION: Although relatively small in amplitude, the weekly rhythm of menstruation was statistically significant. Menstruation occurs more often on Thursdays and Fridays than on other days of the week. This is particularly true for women whose cycles last between 27 and 29 days. Circalunar rhythmicity was also statistically significant. However, it is less pronounced than the weekly rhythm.

Principios de lectura crítica de la literatura médica-relación con los diferentes modelos en investigación clínica

La literatura y la investigación en medicina han tenido un desarrollo importante en los últimos tiempos. El profesional de la salud cada día dispone de menos tiempo para poder vivir actualizado. Esto ha llevado a crear una metodología que permita evaluar las diferentes publicaciones y la influencia que esta tuviera en la práctica diaria. El lector tiene un doble objetivo: valorar la credibilidad y definir su aplicabilidad. Gracias al método de lectura en ocho etapas, se estará capacitando para eliminar rápidamente lo que no es válido y poder dar una mirada ágil y objetiva sobre la calidad de los resultados propuestos por los autores. Estas ocho etapas son: análisis de los objetivos del estudio, tipo de estudio, factores estudiados, criterio de juicio, resultados y su significado clínico y estadístico, como también el poder del estudio y por supuesto el juicio de lector. Este método tiene la ventaja que puede adaptarse a todos los tipos de publicaciones, pero la última palabra la tendrá, por supuesto, el médico frente a su paciente