Recovery of menses after functional hypothalamic amenorrhoea: if, when and why

BACKGROUND Prolonged amenorrhoea occurs as a consequence of functional hypothalamic amenorrhoea (FHA) which is most often induced by weight loss, vigorous exercise or emotional stress. Unfortunately, removal of these triggers does not always result in the return of menses. The prevalence and conditions underlying the timing of return of menses vary strongly and some women report amenorrhoea several years after having achieved and maintained normal weight and/or energy balance. A better understanding of these factors would also allow improved counselling in the context of infertility. Although BMI, percentage body fat and hormonal parameters are known to be involved in the initiation of the menstrual cycle, their role in the physiology of return of menses is currently poorly understood. We summarise here the current knowledge on the epidemiology and physiology of return of menses. OBJECTIVE AND RATIONALE The aim of this review was to provide an overview of (i) factors determining the recovery of menses and its timing, (ii) how such factors may exert their physiological effects and (iii) whether there are useful therapeutic options to induce recovery. SEARCH METHODS We searched articles published in English, French or German language containing keywords related to return of menses after FHA published in PubMed between 1966 and February 2020. Manuscripts reporting data on either the epidemiology or the physiology of recovery of menses were included and bibliographies were reviewed for further relevant literature. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria served to assess quality of observational studies. OUTCOMES Few studies investigate return of menses and most of them have serious qualitative and methodological limitations. These include (i) the lack of precise definitions for FHA or resumption of menses, (ii) the use of short observation periods with unsatisfactory descriptions and (iii) the inclusion of poorly characterised small study groups. The comparison of studies is further hampered by very inhomogeneous study designs. Consequently, the exact prevalence of resumption of menses after FHA is unknown. Also, the timepoint of return of menses varies strongly and reliable prediction models are lacking. While weight, body fat and energy availability are associated with the return of menses, psychological factors also have a strong impact on the menstrual cycle and on behaviour known to increase the risk of FHA. Drug therapies with metreleptin or naltrexone might represent further opportunities to increase the chances of return of menses, but these require further evaluation

Dietary iron and the elite dancer

Dancers are an athlete population at high risk of developing iron deficiency (ID). The aesthetic nature of the discipline means dancers potentially utilise dietary restriction to meet physique goals. In combination with high training demands, this means dancers are susceptible to problems related to low energy availability (LEA), which impacts nutrient intake. In the presence of LEA, ID is common because of a reduced mineral content within the low energy diet. Left untreated, ID becomes an issue that results in fatigue, reduced aerobic work capacity, and ultimately, iron deficient anaemia (IDA). Such progression can be detrimental to a dancer’s capacity given the physically demanding nature of training, rehearsal, and performances. Previous literature has focused on the manifestation and treatment of ID primarily in the context of endurance athletes; however, a dance-specific context addressing the interplay between dance training and performance, LEA and ID is essential for practitioners working in this space. By consolidating findings from identified studies of dancers and other relevant athlete groups, this review explores causal factors of ID and potential treatment strategies for dancers to optimise absorption from an oral iron supplementation regime to adequately support health and performance

Dietary iron and the elite dancer

Dancers are an athlete population at high risk of developing iron deficiency (ID). The aesthetic nature of the discipline means dancers potentially utilise dietary restriction to meet physique goals. In combination with high training demands, this means dancers are susceptible to problems related to low energy availability (LEA), which impacts nutrient intake. In the presence of LEA, ID is common because of a reduced mineral content within the low energy diet. Left untreated, ID becomes an issue that results in fatigue, reduced aerobic work capacity, and ultimately, iron deficient anaemia (IDA). Such progression can be detrimental to a dancer’s capacity given the physically demanding nature of training, rehearsal, and performances. Previous literature has focused on the manifestation and treatment of ID primarily in the context of endurance athletes; however, a dance-specific context addressing the interplay between dance training and performance, LEA and ID is essential for practitioners working in this space. By consolidating findings from identified studies of dancers and other relevant athlete groups, this review explores causal factors of ID and potential treatment strategies for dancers to optimise absorption from an oral iron supplementation regime to adequately support health and performance

The Relationship between Within-Day Energy Balance and Menstruation in Active Females

Background: Past studies suggest that inadequate energy intake (EI) is directly related to menstrual dysfunction (MD) in active females. Inadequate EI causes activation of the hypothalamic-pituitary-adrenal axis, disrupting the normal hormonal signaling of reproductive cycling and resulting in MD. However, studies have also demonstrated similar EI in athletes, but with different menstrual function. Traditionally, energy balance has been evaluated in 24-hour time periods. Recent research suggests there is benefit to analyzing energy balance at smaller intervals to better address physiologic response in real time. It is possible that women who meet their daily EI needs could still, therefore, experience MD if the majority of the day is spent in energy deficit. Objective: The purpose of this study is to determine whether within-day energy balance is a factor in menstrual status in active adult females. Methods: Twenty active females tracked hourly EI and energy expenditure over three days. A two-page survey was utilized to obtain information on training, health, and menstrual status. Participants were also asked to respond to several questions regarding eating habits and attitude towards food. Within-day energy balance was calculated and evaluated using NutriTimingTM software. Collected energy balance data were analyzed for associations with menstrual status. Results: Participants spent more hours in a catabolic state (energy balance less than zero) than in an anabolic state (20.5 hrs vs 3.5 hrs) and averaged a caloric deficit of -504 kcal over 24-hours. Nine subjects (45%) had experienced loss of menses for greater than 3 months (LoM\u3e3mos), indicative of amenorrhea. Hours spent in energy surplus \u3e400 kcal was inversely correlated with LoM\u3e3mos (r = -0.463; P = 0.04). The impact of number of miles run per week and menstrual dysfunction, based on a quartile stratification of miles run, were analyzed using an ANOVA with Tamhane non-parametric post hoc test. Significant differences were found between the upper two quartiles of distance run per week and LoM\u3e3mos (P = 0.048). There was no relationship between end-of-day energy balance and Lom\u3e3mos. Conclusion: Researchers and healthcare professionals would do well to examine energy balance in an hour-by-hour manner as it is has implications for MD. This would help to clarify whether within-day energy balance is a factor in MD, and allow for the development of appropriate intervention strategies to improve health and athletic outcomes for active women

The potential treatments of osteoporosis and hormone dysregulation caused by female athlete triad syndrome

Female Athlete Triad Syndrome (FAT) is a metabolic disorder that presents as a dysregulation of energy availability, menstrual functioning, and bone health. This condition impacts a growing number of female athletes. The triad of physiological and endocrine disruption can develop into conditions of low energy availability, functional hypothalamic amenorrhea, and osteoporosis. This state of interwoven dysfunction occurs in females who participate in endurance sports, excessive exercise, restrictive eating behaviors, or additional stressful situations. The focus of this review is to highlight the physiological implications of each aspect of the triad, delineate diagnostic tools, and analyze potential treatment options for those in need. Long term health consequences caused by FAT include cardiovascular disease, impaired reproductive capabilities, decreased bone mineral density, and mounting endocrine hormone dysregulation. Additional research is required to improve nonpharmaceutical and pharmaceutical interventions for FAT

The Cardiometabolic and Skeletal Profile of Female Endurance Athletes with Amenorrhea and Oligomenorrhea

Background Menstrual disturbances, namely amenorrhea and oligomenorrhea are relatively common disorders in female endurance athletes as a result of low energy availability (LEA). LEA is characterised by the perturbation of several hormones of which are involved in the regulation of bone (re)modelling and also those with cardio-protective properties. The impact on bone health is relatively well understood, but the extent of cardiometabolic risk factors ranging along a scale of both time and severity of menstrual disturbances is yet to be determined. Methods In this observational study, 4 amenorrheic athletes (AA), 3 oligomenorrheic athletes (OA) and 5 eumenorrheic athletes (EA) completed the LEAF-Q and received measurements of stature, mass, resting heart rate, resting blood pressure, waist circumference, body composition using bioelectrical impedance analysis and dual energy X-ray absorptiometry (DXA). Bone Mineral Density was measured by DXA at the total body, total hip, femoral neck, and anteriorposterior lumbar spine (L1-L4). Results There were statistically significant differences in the total body and lumbar spine BMD Zscores between amenorrheic and eumenorrheic athletes. Mean BMD Z-scores (-1.13 - 1.33) for the amenorrheic group were not outside of the normal range (>-0.2). Total body water (TBW) was at the top end of the normal range for the amenorrheic group, but not statistically significant from the eumenorrheic group. TBW was, negatively associated with waist:height ratio (R=-.874, p=<.001). Waist:height ratio was positively associated with total body BMD Zscore (R=.741, P=.006). BMD total body (Z-score) was positively associated with percentage body fat (PBF) (R=.682, p=0.015). Conclusions This study confirms the findings of previous work, that exemplify the differences in bone density between amenorrheic and eumenorrheic endurance athletes. Further studies need to be undertaken to confirm bone loss and better understand the time-course for any bone loss from onset of menstrual disturbance. Due to COVID-19 restrictions, the study sample size was limited and biochemical markers of cardiometabolic status were possible

Recreational Female CrossFit Athletes and Low Energy Availability

CrossFit is a demanding sport in which athletes perform constantly varied, functional movements at a high intensity, therefore requiring an adequate energy availability to avoid negative health and performance consequences. The purpose of this study was to assess risk of low energy availability (low EA) (phase 1) among recreational, female CrossFit athletes and measure and calculate energy availability using a 7-day dietary to measure energy intake (EI) and exercise energy expenditure (ExEE) (phase 2). In phase 1, using the LEAF-Q (Low Energy Availability in Females Questionnaire), 49% of survey respondents (n=149) were found to be at risk of low EA. Of the 167 participants interested in phase 2 per the survey in phase 1, 83 completed at least one day of the EI and ExEE record, and 67 completed all 7 days. The athletes in phase 2 did not meet EI recommendations set forth by the International Society of Sports Nutrition (ISSN), 30% of participants were below 30 kcals.kgFFM-1.d-1, and the average energy availability among participants was 34.1 ± 12.3 kcals.kgFFM-1.d-1. EA was correlated to ExEE, EI, and carbohydrate and fat intake. Currently, CrossFit nutrition recommendations fall short when compared to those of the ISSN. CrossFit athletes and coaches should become familiar with the signs, symptoms, and implications of low EA and its resulting syndrome, RED-S (Relative Energy Deficiency in Sport)

Reproductive dysfunction and associated pathology in women undergoing military training

Evidence from civilian athletes raises the question of whether reproductive dysfunction may be seen in female soldiers as a result of military training. Such reproductive dysfunction consists of impaired ovulation with or without long term subfertility. We critically review pertinent evidence, which points towards reduced energy availability as the most likely explanation for exercise-induced reproductive dysfunction. Evidence also suggests reproductive dysfunction is mediated by activation of the hypothalamic-pituitary-adrenal axis and suppression of the hypothalamic-pituitary-gonadal axis, with elevated ghrelin and reduced leptin likely to play an important role. The observed reproductive dysfunction exists as part of a female athletic triad, together with osteopenia and disordered eating. If this phenomenon was shown to exist with UK military training this would be of significant concern. We hypothesise that the nature of military training and possibly field exercises may contribute to greater risk of reproductive dysfunction among female military trainees compared with exercising civilian controls. We discuss the features of military training and its participants, such as energy availability, age at recruitment, body phenotype, type of physical training, psychogenic stressors, altered sleep pattern and elemental exposure as contributors to reproductive dysfunction. We identify lines of future research to more fully characterise reproductive dysfunction in military women, and suggest possible interventions which, if indicated, could improve their future wellbeing

The influence of the female athlete triad on bone quality in endurance athletes

The female athlete triad was defined in 1997 by the American College of Sports Medicine (ACSM) consisting of three components: Disordered Eating, Amenorrhea and Osteoporosis (Waldrop, 2005). Previous literature has identified a reduced bone health in athletes with altered menstrual cycles and/or those with eating disorders. For this masters, athletes were recruited from elite athletic databases then grouped according to their menstrual cycle irregularities and physical activity levels identified from a questionnaire completed prior to participation. The three groups identified were controls, eumonrrheic athletes or amenorrheic athletes. Each participant was subject to dual energy X-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT) scanning, a blood test, if willing, to assess hormonal status. A three day food diary was completed prior to testing. Significant differences between both eumenorrehic and amenorheic athletes and controls were identified for total calorie, proteins, carbohydrate, potassium and phosphorous intake per day. pQCT scanning showed significantly lower cortical thickness in the amenorrheic athletes compared with eumenorrheic athletes (P=0.025). The amenorrehic athletes had a greater endochondrol circumference than both control and eumenorrheic athletes, indicating that the amenorrehic athletes had a diaphysis much wider and thinner than the control and eumenorrheic athletes (P=0.011). There was a significant difference at the tibia cortical area of the diaphysis between the control and amenorrheic athletes (P=0.017). DEXA results highlighted significant differences between control and amenorrheic athletes, with controls having a greater bone mineral density, at non weight bearing sites of the head (P=0.038), trunk (p=0.004), ribs (p=0.027), pelvis (p=0.015), spine (p=0.008) and L1-L4 (p=0.025). With further significant differences found between the amenorrehic and eumenorrheic group of athletes at the trunk (p=0.020) and pelvis (p=0.016), in this case the bone mineral density of the eumenorrheic athletes was higher than the amenorrheic athletes. Blood tests demonstrated a significantly higher level of the bone resoprtion marker Tartrate resistant- acid phosphatase (TRAP) in amenorrheic athletes than in the eumenorrheic and control groups (p=0.026). Overall results demonstrate that elite level endurance athletes with amenorrhea have lower bone mineral density in the radius and tibia compared with other eumenorrheic athletes and controls which was associated with increased circulating levels of TRAP