FMUP - Nov 2021 (summary and comments of paper)

Summary of: The Effects of Menstrual Cycle Phase on Elite Athlete Performance: A Critical and Systematic Review

Menstrual Cycle Phase, Hormonal Contraception, and Alcohol Consumption in Premenopausal Females: A Systematic Review

Women may be particularly vulnerable to alcohol harm, but many current theories fail to acknowledge the unique factors that influence female alcohol use. The biological mechanisms underlying female alcohol consumption have largely been unexplored, although recently the menstrual cycle has been highlighted as a potentially important factor. This systematic review, using a narrative synthesis, examined the association between the menstrual cycle phases on alcohol consumption and aimed to determine whether hormonal contraception influences this association. The review follows PRISMA and SWiM guidelines, registration number: CRD42018112744. Electronic searches were conducted in the relevant databases with keyword (e.g., “menstrua*”; “alcohol”). Thousand six hundred and sixty-two titles were identified, 16 of which were included in the review. Results were inconsistent regarding whether an association between menstrual cycle phase and alcohol consumption was found. Furthermore, there was inconsistency regarding which phase was associated with higher consumption, and different factors were reported to have moderated the direction, e.g., family history of alcohol use disorder (AUD), premenstrual syndrome (PMS). These conflicting results may be partly explained by variability in both study quality and design, and differences in measurement of cycle phase and alcohol consumption. More robust research is needed before conclusions can be drawn with regard to the role of the menstrual cycle and hormonal contraception on female drinking behavior. This review provides recommendations to strengthen research in this area.

A Pilot Study on the Impact of Menstrual Cycle Phase on Elite Australian Football Athletes

The effect of the menstrual cycle on athlete performance, wellbeing and perceived exertion and fatigue is not well understood. Furthermore, it has not been investigated specifically in Australian Football athletes. This pilot study aimed to explore how naturally menstruating Australian Football athletes may be affected by menstrual cycle phase. The data collected from the routine monitoring of five naturally menstruating athletes (average menstrual cycle length of 28 ± 3 [SD] days) in one team (athlete age range 18–35 years) competing in the Women’s Australian Football League during the 2019 season were retrospectively analysed to compare performance (countermovement jump parameters and adductor squeeze pressure), perceived exertion, perceived fatigue and wellbeing (perceived sleep quality, stress and soreness) outcomes between the follicular and luteal phases. Performance, perceived exertion, stress and soreness did not appear to be affected by menstrual cycle phase (p > 0.17). However, perceived fatigue appeared to be significantly greater (p = 0.042) and sleep quality worse (p = 0.005) in the luteal phase. This pilot study suggests further research focusing on the effect of menstrual cycle phase on subjective fatigue and wellbeing is warranted.

THE EFFECT OF THE MENSTRUAL CYCLE PHASE ON THE OUTCOME OF AUGMENTATION MAMMOPLASTY

To determine the optimal timing for augmentation mammoplasty (AM) relative to the menstrual cycle phase.

P–290 Time-course analysis of endometrial miR/isomiR expression dynamics during hCG-primed menstrual-cycle phase transitions

Study question What is the qualitative and quantitative profile of microRNAs (miR) and their sequence variants - isomiRs, and how it changes during the menstrual-cycle phase transitions? Summary answer Time-course analysis of endometrial miR/isomiR profiles has shown that menstrual-phase transitions cause widespread and complex changes in miR gene expression and processing. What is known already Embryo implantation depends on the receptivity of the endometrium during the window of implantation, when ovarian hormones and genetic factors coordinate the development of the uterine lining and prepare it for embryo implantation. The most important factors for successful implantation studied so far are the embryo itself, the histological dating of the endometrium and its molecular genetic characteristics, including miRs. With the rapid development of next-generation sequencing technologies, it has become clear that miR genes have the potential to produce not only miR but also variants (isomiRs) thereof, which can differ in sequence and length and can be functionally significant. Study design, size, duration miR/isomiR landscape was assessed by small RNA sequencing of endometrial biopsy samples at 4 time points of endometrial cycle covering the proliferative and secretory phases. Healthy, fertile, female volunteers took part in the study lasting one and a half years. For accurate phase dating, human chorionic gonadotropin (hCG) was administrated, and ultrasonic, histological and hormonal assessments were done at each time point. Statistically significant data of miR/isomiR identification and expression dynamics was considered for analysis. Participants/materials, setting, methods Participant choice criteria - at least one child born, problem-free pregnancies, no diseases or allergies; hCG application time determined according follicle and endometrium ultrasound scanning, and ovarian hormone levels; endometrial biopsies taken at hGC (before hormone application), hGC+2, hGC+7, hGC+9 time points; small RNAseq completed by Karolinska Institute, Sweden; miR/isomiR identified using local Galaxy instance with an in-built workflow and tools developed by our laboratory; differential expression and target prediction evaluated with DESeq2 and miRDB,resp. Main results and the role of chance Within the cohort of patients, across the four study time points, the small RNAseq data revealed numbers of miRs and isomiRs to be changed. The largest statistically significant changes in their expression were found at LH + 9. The miR families that showed the largest number of members with altered expression were miR125a, miR30d, miR449c, miR92a/b and miR99a. The expression levels tended to decrease in the miR125a and miR92a families and to increase in the miR10a and miR449c families during the three studied time points of the cycle compared to the proliferative phase. Among those affected, the number of isomiRs, including templated and non-templated isomiRs, was much higher than that of miRs. For example, the ratio of the significantly altered miRs/templated isomiRs/non-templated isomiRs was 6/16/11 at LH + 9. Templated isomiRs of hsa-miR–148a–3p, hsa-miR–30d–5p and hsa-miR–449c–5p were among the most upregulated, while several templated and non-templated isomiRs of hsa-miR–125–5p were the most downregulated at LH + 9. Of particular interest are those isomiRs, in which the seed site is shifted compared to the reference miRs and results in altered target transcripts. Target prediction of the most affected isomiR of hsa-miR–449c–5p identified new targets of target scores much higher than of the reference miR. Limitations, reasons for caution IsomiRs are a source of novel biomarkers for clinical diagnosis. An important next step is the validation of the in-silico predicted miRs/isomiRs and their target transcripts by RT-qPCR in larger number of individuals. Expression profiles should be associated with the dominant cell type in the endometrial biopsy preparation. Wider implications of the findings: MiR/isomiR signatures, together with those of their target mRNAs, can be applied to distinguish the endometrial phases, especially the implantation window, as well as for diagnosing endometrial dysfunction. It is worth investigating the possibility of miRs/isomiRs being used as biomarkers not only in endometrial biopsy but also in liquid biopsy. Trial registration number The Bulgarian National Science Fund КП–06 Н31/2

The Effects of Menstrual Cycle Phase on Elite Athlete Performance: A Critical and Systematic Review

Background: In elite athletes, training individualization is widely recommended to optimize competitive performance. Previous studies have evidenced the impact of hormonal fluctuations on different performance parameters among female athletes. While consideration of menstrual cycle (MC) phases as a parameter in training individualization strategies is necessary, systematic evidence identifying such impacts in elite athletes should be evaluated.Objective: Systematically review publications that have investigated the link between MC phases and performance in elite female athletes. The overarching aim is to identify whether a consensus across studies exists enabling evidence-based recommendations for training individualization depending on menstrual cycle phases.Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three major scientific publication databases were searched from inception until November 3, 2020. Studies included focused on the influence of physiological or psychological parameters throughout at least one phase of the menstrual cycle of elite athletes.Results: A total of 780 search results were yielded and 26 references from a past bibliography were added manually. About 662 papers were reviewed of which 218 studies were assessed for eligibility. Of these, only seven (1%) precisely investigated the influence of a performance or physical parameter during at least one menstrual cycle phase. These seven studies included a total of 314 elite female participants (20.58 ± 1.91 years). Three used interviews, questionnaires or prospective analyses of reports. Four conducted several performance tests or included physical measures although only two performed tests during training or before/during competition. Among the seven studies, five performed hormonal testing through sampling of blood, saliva, or urine. The remaining relied on athletes’ menstruation diaries. The current evidence suggests a variable association between menstrual cycle and a few performance-related outcomes, such as endurance or power resistance, ligament stiffness, decision making skills, psychology, or competitiveness.Conclusion: Different sports performance-related parameters are affected during the menstrual cycle among elite athletes, but the parameters themselves and the magnitude and the direction of the effects are inconclusive. Additional longitudinal and prospective studies to systematically monitor on-field performance parameters are urgently required in order to enable recommendations and training individualization in female elite athletes.

Adjuvant Surgical Oophorectomy Efficacy According to Hormonally-Determined Menstrual Cycle Phase

Purpose: While there is now considered to be no significant outcome impact of the timing of breast surgery in the menstrual cycle of premenopausal women with breast cancer, the data with respect to adjuvant surgical oophorectomy in women with breast cancer have received limited exposition and attention. In a trial investigating the timing of surgical oophorectomy in women with metastatic disease, we observed a trend for poorer overall survival in women in women in prolonged follicular phases of the menstrual cycle, with low progesterone levels. Methods: The data from a previously reported adjuvant randomized clinical trial addressing the timing of surgical oophorectomy in the menstrual cycle have been examined in detail, presenting here new data from pre-planned secondary analyses. Multivariable Cox models were used.

Ferritin status impact on hepcidin response to endurance exercise in physically active women along different phases of the menstrual cycle

Serum ferritin has been proposed as a predictor of hepcidin concentrations in response to exercise. However, this fact has not been studied in physically-active women. Therefore, the main objective of this study was to analyse the hepcidin response at different ferritin status before and after running exercise in physically active females. Fifteen eumenorrheic women performed a 40-min running protocol at 75% of VO2peak speed in different menstrual cycle phases (early-follicular phase, mid-follicular phase and luteal phase). Blood samples were collected pre-exercise, 0h post-exercise and 3h post-exercise. For statistics, participants were divided into two groups according to their pre-exercise ferritin levels (<20 and ≥20 μg/L). Through menstrual cycle, hepcidin was lower in both early follicular phase (p=0.024; 64.81±22.48 ng/ml) and mid-follicular phase (p=0.007; 64.68±23.91 ng/ml) for <20 μg/L ferritin group, in comparison with ≥20 μg/L group (81.17±27.89 and 79.54±22.72 ng/ml, respectively). Hepcidin showed no differences between both ferritin groups in either pre-exercise, 0h post-exercise and 3h post-exercise. Additionally, no association between pre-exercise ferritin and hepcidin levels 3h post-exercise (r=-0.091; p=0.554) was found. Menstrual cycle phase appears to influence hepcidin levels depending on ferritin reserves. In particular, physically-active females with depleted ferritin reserves seems to present lower hepcidin levels during the early-follicular phase and mid-follicular phase. However, no association between ferritin and hepcidin levels was found in this study. Hence, ferritin levels alone may not be a good predictor of hepcidin response to exercise in this population. Multiple factors such as sexual hormones, training loads and menstrual bleeding must be taken into account.

The Impact of Menstrual Cycle Phase on Athletes’ Performance: A Narrative Review

The effect of the menstrual cycle on physical performance is being increasingly recognised as a key consideration for women’s sport and a critical field for further research. This narrative review explores the findings of studies investigating the effects of menstrual cycle phase on perceived and objectively measured performance in an athletic population. Studies examining perceived performance consistently report that female athletes identify their performance to be relatively worse during the early follicular and late luteal phases. Studies examining objective performance (using anaerobic, aerobic or strength-related tests) do not report clear, consistent effects of the impact of menstrual cycle phase on physical performance. Overall sport performance can be influenced by both perceived and physical factors. Hence, to optimise performance and management of eumenorrheic female athletes, there is a need for further research to quantify the impact of menstrual cycle phase on perceived and physical performance outcomes and to identify factors affecting variability in objective performance outcomes between studies.