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Journal of the International Society of... Dec 2023Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and... (Review)
Review
Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Female athletes have unique and unpredictable hormone profiles, which influence their physiology and nutritional needs across their lifespan. To understand how perturbations in these hormones affect the individual, we recommend that female athletes of reproductive age should track their hormonal status (natural, hormone driven) against training and recovery to determine their individual patterns and needs and peri and post-menopausal athletes should track against training and recovery metrics to determine the individuals' unique patterns. 2. The primary nutritional consideration for all athletes, and in particular, female athletes, should be achieving adequate energy intake to meet their energy requirements and to achieve an optimal energy availability (EA); with a focus on the timing of meals in relation to exercise to improve training adaptations, performance, and athlete health. 3. Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent, therefore we recommend first ensuring athletes meet their carbohydrate needs across all phases of the menstrual cycle. Secondly, tailoring carbohydrate intake to hormonal status with an emphasis on greater carbohydrate intake and availability during the active pill weeks of oral contraceptive users and during the luteal phase of the menstrual cycle where there is a greater effect of sex hormone suppression on gluconogenesis output during exercise. 4. Based upon the limited research available, we recommend that pre-menopausal, eumenorrheic, and oral contraceptives using female athletes should aim to consume a source of high-quality protein as close to beginning and/or after completion of exercise as possible to reduce exercise-induced amino acid oxidative losses and initiate muscle protein remodeling and repair at a dose of 0.32-0.38 g·kg. For eumenorrheic women, ingestion during the luteal phase should aim for the upper end of the range due to the catabolic actions of progesterone and greater need for amino acids. 5. Close to the beginning and/or after completion of exercise, peri- and post-menopausal athletes should aim for a bolus of high EAA-containing (~10 g) intact protein sources or supplements to overcome anabolic resistance. 6. Daily protein intake should fall within the mid- to upper ranges of current sport nutrition guidelines (1.4-2.2 g·kg·day) for women at all stages of menstrual function (pre-, peri-, post-menopausal, and contraceptive users) with protein doses evenly distributed, every 3-4 h, across the day. Eumenorrheic athletes in the luteal phase and peri/post-menopausal athletes, regardless of sport, should aim for the upper end of the range. 7. Female sex hormones affect fluid dynamics and electrolyte handling. A greater predisposition to hyponatremia occurs in times of elevated progesterone, and in menopausal women, who are slower to excrete water. Additionally, females have less absolute and relative fluid available to lose via sweating than males, making the physiological consequences of fluid loss more severe, particularly in the luteal phase. 8. Evidence for sex-specific supplementation is lacking due to the paucity of female-specific research and any differential effects in females. Caffeine, iron, and creatine have the most evidence for use in females. Both iron and creatine are highly efficacious for female athletes. Creatine supplementation of 3 to 5 g per day is recommended for the mechanistic support of creatine supplementation with regard to muscle protein kinetics, growth factors, satellite cells, myogenic transcription factors, glycogen and calcium regulation, oxidative stress, and inflammation. Post-menopausal females benefit from bone health, mental health, and skeletal muscle size and function when consuming higher doses of creatine (0.3 g·kg·d). 9. To foster and promote high-quality research investigations involving female athletes, researchers are first encouraged to stop excluding females unless the primary endpoints are directly influenced by sex-specific mechanisms. In all investigative scenarios, researchers across the globe are encouraged to inquire and report upon more detailed information surrounding the athlete's hormonal status, including menstrual status (days since menses, length of period, duration of cycle, etc.) and/or hormonal contraceptive details and/or menopausal status.
Topics: Female; Humans; Male; Creatine; Progesterone; Athletes; Sports; Amino Acids
PubMed: 37221858
DOI: 10.1080/15502783.2023.2204066 -
Fertility and Sterility May 2023To evaluate the efficacy and safety of acupuncture in the treatment of endometriosis-associated pain. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the efficacy and safety of acupuncture in the treatment of endometriosis-associated pain.
DESIGN
A multicenter, randomized, single-blind, placebo-controlled trial.
INSTITUTIONS
Four tertiary hospitals in Jiangxi and Hainan Provinces.
SUBJECTS
Women with endometriosis-associated pain aged between 20 and 40 years.
INTERVENTION
Subjects were assigned randomly to receive either acupuncture or sham acupuncture treatment for 12 weeks, starting one week before each expected menstruation and administered as a 30-minute session once per day, 3 times a week. During the menstruation period, acupuncture was administered daily when pelvic pain associated with endometriosis occurred. After acupuncture or sham acupuncture treatment, the subjects were followed for another 12 weeks.
MAIN OUTCOME MEASURES
Changes in maximum pain as assessed with the visual analog scale (VAS) for various pelvic pain, duration of dysmenorrhea, and scores on the Multidimensional Pain Inventory, Beck Depression Inventory, Profile of Mood States, and Endometriosis Health Profile from baseline to week 12 and week 24.
RESULTS
A total of 106 women were assigned randomly to the acupuncture and sham groups. In the acupuncture group, the reduction in the dysmenorrhea VAS score was significantly greater after treatment, but not at the end of the trial, compared to the sham group. The duration of pain was significantly shorter in the acupuncture group. All test scores were improved to a significantly greater extent in the acupuncture group than in the sham group at week 12 but not at week 24. Changes in nonmenstrual pelvic pain and dyspareunia VAS scores were not different between the groups. No severe adverse events or differences in adverse events were recorded.
CONCLUSION
Acupuncture is an effective and safe method of relieving dysmenorrhea, shortening the pain duration, and improving wellbeing and quality of life in women with endometriosis-associated pain, although its efficacy fades after treatment is discontinued.
CLINICAL TRIAL REGISTRATION NUMBER
NCT03125304.
Topics: Female; Humans; Young Adult; Adult; Endometriosis; Dysmenorrhea; Quality of Life; Single-Blind Method; Pelvic Pain; Acupuncture Therapy; Treatment Outcome
PubMed: 36716811
DOI: 10.1016/j.fertnstert.2023.01.034 -
Women's Health (London, England) 2022After COVID-19 vaccination, women of reproductive age reported changes in their menstrual cycle.
INTRODUCTION
After COVID-19 vaccination, women of reproductive age reported changes in their menstrual cycle.
MATERIALS AND METHODS
A retrospective study was carried out after a survey on social networks that included women aged 18-41 years with normal cycles according to International Federation of Gynecology and Obstetrics and who were vaccinated (complete schedule for two doses, except J&J/Janssen or incomplete with a single dose). Women with following conditions were excluded: pregnant or lactating women; history of diseases that cause menstrual irregularities or early menopause: anorexia, bulimia, polycystic ovary syndrome, hypothyroidism, obesity, or low weight; hysterectomized or oophorectomized patients; and high performance athletes.
RESULTS
Overall, 950 women completed the survey between July and September 2021. In total, 408 women met the inclusion criteria, and 184 reported the following characteristics: frequency (normal 43.47%, infrequent 25%, and frequent 31.53%), regularity (regular 51.08%, irregular 42.93%, and absent/amenorrhea 5.97%), duration (normal 65.21%, prolonged 26.08%, absent/amenorrhea 8.69%), and volume (heavy 41.84%, light 20.65%, and absent/amenorrhea 6.52%).
CONCLUSIONS
SARS-CoV-2 infection and COVID-19 vaccination can influence the menstrual cycle and cause alterations.
Topics: COVID-19; COVID-19 Vaccines; Female; Humans; Menstrual Cycle; Menstruation Disturbances; Retrospective Studies; SARS-CoV-2; Vaccination
PubMed: 35796571
DOI: 10.1177/17455057221109375 -
Allergologie Select 2023Not available.
Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for...
Not available.
PubMed: 37705676
DOI: 10.5414/ALX02422E -
Fertility and Sterility Oct 2022To synthesize the published literature to better understand the association between cesarean scar defects (CSDs) and abnormal uterine bleeding (AUB). In particular, we... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To synthesize the published literature to better understand the association between cesarean scar defects (CSDs) and abnormal uterine bleeding (AUB). In particular, we aimed to evaluate the risk and pattern(s) of CSD-associated AUB in addition to exploring the relationship between defect morphology with bleeding symptoms.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENTS
Patients with CSD and reports of uterine bleeding as an outcome were identified in 60 studies from database searches.
INTERVENTIONS
Studies that investigated CSD (as defined by investigators) and reported uterine bleeding, menstrual bleeding, or AUB as an outcome were included.
MAIN OUTCOME MEASURES
The prevalence and risk of AUB (intermenstrual, postmenstrual, and unscheduled bleeding) in patients with confirmed CSD.
RESULTS
Nine studies reported on the prevalence of AUB in patients with a confirmed CSD. Patients with CSD were more likely to experience AUB, compared with those without CSD (relative risk, 3.47; 95% confidence interval [CI], 2.02-5.97; 6 studies, 1,385 patients; I = 67%). In a population of patients with at least 1 cesarean delivery, the prevalence of AUB in those with CSD was 25.5% (95% CI, 14.7-40.5; 6 studies, 667 patients, I = 93%). However, symptom prevalence was much higher in patients presenting for imaging for a gynecologic indication where the prevalence of AUB in the presence of a CSD was 76.4% (95% CI, 67.8-83.3; 5 studies, 505 patients; I = 71%). The mean menstrual duration in symptomatic patients with CSD was 13.4 days (95% CI, 12.6-14.2; 19 studies, 2,095 patients; I = 96%), and the mean duration of early-cycle intermenstrual bleeding was 6.8 days (95% CI, 5.7-7.8 days; 9 studies, 759 patients; I = 93%). The most common descriptor of CSD-associated AUB was "brown discharge". Patients with larger CSD experienced more bleeding symptoms.
CONCLUSION
There is a strong and consistent association between patients with CSD and AUB. These patients experience a unique bleeding pattern, namely prolonged menstruation and early-cycle intermenstrual bleeding. These data should provide impetus for including CSD as a distinct entity in AUB classification systems. High heterogeneity in our results calls for standardization of nomenclature and outcome reporting for this condition.
Topics: Cesarean Section; Cicatrix; Female; Humans; Metrorrhagia; Pregnancy; Uterine Diseases; Uterine Hemorrhage
PubMed: 35985862
DOI: 10.1016/j.fertnstert.2022.06.031 -
JAMA May 2022Metformin, a biguanide commonly used to treat type 2 diabetes, has been associated with potential beneficial effects across breast cancer subtypes in observational and... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Metformin, a biguanide commonly used to treat type 2 diabetes, has been associated with potential beneficial effects across breast cancer subtypes in observational and preclinical studies.
OBJECTIVE
To determine whether the administration of adjuvant metformin (vs placebo) to patients with breast cancer without diabetes improves outcomes.
DESIGN, SETTING, AND PARTICIPANTS
MA.32, a phase 3 randomized, placebo-controlled, double-blind trial, conducted in Canada, Switzerland, US, and UK, enrolled 3649 patients with high-risk nonmetastatic breast cancer receiving standard therapy between August 2010 and March 2013, with follow-up to October 2020.
INTERVENTIONS
Patients were randomized (stratified for hormone receptor [estrogen receptor and/or progesterone receptor {ER/PgR}] status, positive vs negative; body mass index, ≤30 vs >30; human epidermal growth factor receptor 2 [ERBB2, formerly HER2 or HER2/neu], positive vs negative; and any vs no chemotherapy) to 850 mg of oral metformin twice a day (n = 1824) or oral placebo twice a day (n = 1825) for 5 years.
MAIN OUTCOMES AND MEASURES
The primary outcome was invasive disease-free survival in hormone receptor-positive breast cancer. Of the 8 secondary outcomes, overall survival, distant relapse-free survival, and breast cancer-free interval were analyzed.
RESULTS
Of the 3649 randomized patients (mean age, 52.4 years; 3643 women [99.8%]), all (100%) were included in analyses. After a second interim analysis, futility was declared for patients who were ER/PgR-, so the primary analysis was conducted for 2533 patients who were ER/PgR+. The median duration of follow-up in the ER/PgR+ group was 96.2 months (range, 0.2-121 months). Invasive disease-free survival events occurred in 465 patients who were ER/PgR+. The incidence rates for invasive disease-free survival events were 2.78 per 100 patient-years in the metformin group vs 2.74 per 100 patient-years in the placebo group (hazard ratio [HR], 1.01; 95% CI, 0.84-1.21; P = .93), and the incidence rates for death were 1.46 per 100 patient-years in the metformin group vs 1.32 per 100 patient-years in the placebo group (HR, 1.10; 95% CI, 0.86-1.41; P = .47). Among patients who were ER/PgR-, followed up for a median of 94.1 months, incidence of invasive disease-free survival events was 3.58 vs 3.60 per 100 patient-years, respectively (HR, 1.01; 95% CI, 0.79-1.30; P = .92). None of the 3 secondary outcomes analyzed in the ER/PgR+ group had statistically significant differences. Grade 3 nonhematological toxic events occurred more frequently in patients taking metformin than in patients taking placebo (21.5% vs 17.5%, respectively, P = .003). The most common grade 3 or higher adverse events in the metformin vs placebo groups were hypertension (2.4% vs 1.9%), irregular menses (1.5% vs 1.4%), and diarrhea (1.9% vs 7.0%).
CONCLUSIONS AND RELEVANCE
Among patients with high-risk operable breast cancer without diabetes, the addition of metformin vs placebo to standard breast cancer treatment did not significantly improve invasive disease-free survival.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01101438.
Topics: Administration, Oral; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Double-Blind Method; Female; Humans; Male; Metformin; Middle Aged; Neoplasm Recurrence, Local; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 35608580
DOI: 10.1001/jama.2022.6147 -
Lancet (London, England) Jun 2022Endometriosis is a common cause of pelvic pain in women, for which current treatment options are suboptimal. Relugolix, an oral gonadotropin-releasing hormone receptor... (Randomized Controlled Trial)
Randomized Controlled Trial
Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2).
BACKGROUND
Endometriosis is a common cause of pelvic pain in women, for which current treatment options are suboptimal. Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, combined with estradiol and a progestin, was evaluated for treatment of endometriosis-associated pain.
METHODS
In these two replicate, phase 3, multicentre, randomised, double-blind, placebo-controlled trials at 219 community and hospital research centres in Africa, Australasia, Europe, North America, and South America, we randomly assigned women aged 18-50 years with surgically or directly visualised endometriosis with or without histological confirmation, or with histological diagnosis alone. Participants were eligible if they had moderate to severe endometriosis-associated pain and, during the 35-day run-in period, a dysmenorrhoea Numerical Rating Scale (NRS) score of 4·0 or higher on two or more days and a mean non-menstrual pelvic pain NRS score of 2·5 or higher, or a mean score of 1·25 or higher that included a score of 5 or more on 4 or more days. Women received (1:1:1) once-daily oral placebo, relugolix combination therapy (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0·5 mg), or delayed relugolix combination therapy (relugolix 40 mg monotherapy followed by relugolix combination therapy, each for 12 weeks) for 24 weeks. During the double-blind randomised treatment and follow-up period, all patients, investigators, and sponsor staff or representatives involved in the conduct of the study were masked to treatment assignment. The co-primary endpoints were responder rates at week 24 for dysmenorrhoea and non-menstrual pelvic pain, both based on NRS scores and analgesic use. Efficacy and safety were analysed in the modified intent-to-treat population (randomised patients who received ≥1 study drug dose). The studies are registered at ClinicalTrials.gov (SPIRIT 1 [NCT03204318] and SPIRIT 2 [NCT03204331]) and EudraCT (SPIRIT 1 [2017-001588-19] and SPIRIT 2 [2017-001632-19]). Eligible patients who completed the SPIRIT studies could enrol in a currently ongoing 80-week open-label extension study (SPIRIT EXTENSION [NCT03654274, EudraCT 2017-004066-10]). Database lock for the on-treatment duration has occurred, and post-treatment follow-up for safety, specificially for bone mineral density and menses recovery, is ongoing at the time of publication.
FINDINGS
638 patients were enrolled into SPIRIT 1 and randomly assigned between Dec 7, 2017, and Dec 4, 2019, to receive relugolix combination therapy (212 [33%]), placebo (213 [33%]), or relugolix delayed combination therapy (213 [33%]). 623 patients were enrolled into SPIRIT 2 and were randomly assigned between Nov 1, 2017 and Oct 4, 2019, to receive relugolix combination therapy (208 [33%]), placebo (208 [33%]), or relugolix delayed combination therapy (207 [33%]). 98 (15%) patients terminated study participation early in SPIRIT 1 and 115 (18%) in SPIRIT 2. In SPIRIT 1, 158 (75%) of 212 patients in the relugolix combination therapy group met the dysmenorrhoea responder criteria compared with 57 (27%) of 212 patients in the placebo group (treatment difference 47·6% [95% CI 39·3-56·0]; p<0·0001). In SPIRIT 2, 155 (75%) of 206 patients in the relugolix combination therapy group were dysmenorrhoea responders compared with 62 (30%) of 204 patients in the placebo group (treatment difference 44·9% [95% CI 36·2-53·5]; p<0·0001). In SPIRIT 1, 124 (58%) of 212 patients in the relugolix combination therapy group met the non-menstrual pelvic pain responder criteria versus 84 (40%) patients in the placebo group (treatment difference 18·9% [9·5-28·2]; p<0·0001). In SPIRIT 2, 136 (66%) of 206 patients were non-menstrual pelvic pain responders in the relugolix combination therapy group compared with 87 (43%) of 204 patients in the placebo group (treatment difference 23·4% [95% CI 13·9-32·8]; p<0·0001). The most common adverse events were headache, nasopharyngitis, and hot flushes. There were nine reports of suicidal ideation across both studies (two in the placebo run-in, two in the placebo group, two in the relugolix combination therapy group, and three in the delayed relugolix combination therapy group). No deaths were reported. Least squares mean percentage change in lumbar spine bone mineral density in the relugolix combination therapy versus placebo groups was -0·70% versus 0·21% in SPIRIT 1 and -0·78% versus 0·02% in SPIRIT 2, and in the delayed relugolix combination group was -2·0% in SPIRIT 1 and -1·9% in SPIRIT 2. Decreases in opioid use were seen in treated patients as compared with placebo.
INTERPRETATION
Once-daily relugolix combination therapy significantly improved endometriosis-associated pain and was well tolerated. This oral therapy has the potential to address the unmet clinical need for long-term medical treatment for endometriosis, reducing the need for opioid use or repeated surgical treatment.
FUNDING
Myovant Sciences.
Topics: Analgesics, Opioid; Double-Blind Method; Dysmenorrhea; Endometriosis; Estradiol; Female; Humans; Pelvic Pain; Phenylurea Compounds; Pyrimidinones; Treatment Outcome
PubMed: 35717987
DOI: 10.1016/S0140-6736(22)00622-5 -
Current Opinion in Obstetrics &... Aug 2019Sleep disturbances are increasing in prevalence in North America. There is growing evidence that poor sleep quality and short sleep duration may adversely affect... (Review)
Review
PURPOSE OF REVIEW
Sleep disturbances are increasing in prevalence in North America. There is growing evidence that poor sleep quality and short sleep duration may adversely affect circadian rhythms, which in turn may affect female reproduction. The objective of this review is to evaluate recent literature on the association between sleep disturbances and female reproduction.
RECENT FINDINGS
There is accumulating evidence that sleep quality and duration are important for female reproduction, but epidemiologic research is limited. Recent studies provide suggestive evidence that sleep disorders are associated with increased menstrual irregularity, subfertility/infertility, and poor pregnancy and birth outcomes. Mechanisms underlying these associations are likely to be multifactorial and complex. In addition to genetics, circadian disruption may impact reproductive outcomes through dysregulation of the hypothalamic-pituitary-adrenal axis, insulin resistance, oxidative stress, and systemic inflammation. Recommendations for future studies include: use of prospective study designs; assessment of populations not already experiencing reproductive disorders; more detailed and accurate assessments of sleep such as validated self-reported measures or objective sleep measures (e.g. actigraphy); comprehensive assessment of potential confounders and mediators; and elucidation of biologic mechanisms.
SUMMARY
There is a growing body of literature showing evidence that sleep disturbances influence female reproduction, although further epidemiologic research is needed.
Topics: Abortion, Spontaneous; Circadian Rhythm; Female; Fertility; Humans; Hypothalamo-Hypophyseal System; Infertility, Female; Male; Menstrual Cycle; Menstruation Disturbances; Pituitary-Adrenal System; Pregnancy; Pregnancy Outcome; Reproduction; Sleep; Sleep Wake Disorders
PubMed: 31082843
DOI: 10.1097/GCO.0000000000000554