In research settings, EA below 45Kcal/Kg of fat free mass (FFM) and certainly of 30 Kcal/Kg/FFM has been shown to disrupt endocrine function. However, to calculate EA this requires detailed analysis of energy intake and expenditure, which are laborious and prone to inaccuracies. Additionally FFM needs to be assessed through DXA. Therefore it is not practical in clinical settings to quantify EA in every individual suspected of having RED-S. In any case an absolute threshold of EA is not applicable to every individual and there is far less research in male athletes. Furthermore calculation of EA is only valid at that particular time point and does not provide information on temporal aspect: whether acute or chronic. Therefore clinical assessment, taking into account sport/dance specific factors is the most valuable method of assessing RED-S backed up with objective measures of low energy availability such as blood markers and menstrual status in females.
- RED-S involves multiple systems and hence bone stress injury may not necessarily be the presentation; particularly in acute low EA and/or in non-weight bearing sports. So taking a detailed history, including specific sport/dance related questions for example regarding training load, nutrition and recovery is important. Background information from the athlete’s coach and parents, where appropriate, can be very helpful.
- Recurrent illness, fatigue, athletic underperformance and psychological issues rather than injury can be presenting features of RED-S. In the case of female athletes there are validated questionnaires such as LEAF-Q. For male athletes SEAQ-I (sports specific energy available questionnaire) was recently trialled in male cyclists. See references.
- In young athletes, RED-S may present as delayed puberty, fall off growth centiles for height and/or weight
- In any woman of reproductive age in the absence of pregnancy, whether exercising or not, if menstrual cycles are not regular then this requires medical investigation, as RED-S is a diagnosis of exclusion. The Royal College of Obstetrics and Gynaecology (RCOG) defines primary amenorrhoea as no menarche by 16 years of age, secondary amenorrhoea as cessation of periods for >6 months in a previously regular menstruating woman and oligomenorrhoea is defined as less than 9 cycles per calendar year.
- The equivalent of menstrual cycles indicating normal hypothalamic-pituitary-gonad axis function, in men is morning erections indicating reproductive endocrine axis function with adequate testosterone levels.
- Athletes/dancers with RED-S may first present with injury to a Physiotherapist. In the case of weight bearing training, this could be a bone stress response, including stress fracture typically of the lower limb/pelvis. Bear in mind that stress fractures occur after chronic low EA and often with increased training loads, as when moving junior to senior ranks. Accumulation of peak bone mass (PBM) mass have been impaired with early age onset of low EA. In the case of female athletes/dancers asking about menstruation (not withdrawal bleeds on hormonal contraception) is vital for medical referral as necessary.
- Recurrent soft tissue injury could also be a presenting feature of RED-S.
Directed at excluding medical causes of the presenting symptoms outlined in the RED-S model.
- In female dancers/athletes exclude other causes of menstrual disruption, before diagnosing functional hypothalamic amenorrhoea
- In all athletes/dancers exclude systemic and localised medical conditions that could be causing presenting symptoms eg infective, endocrine/metabolic, inflammatory and autoimmune conditions
- Consider DXA scan to assess bone health where appropriate (eg amenorrhoea >6 months or in presence of stress fracture). Z score of lumbar spine < -1 supports diagnosis of RED-S
Considering investigation of amenorrhoea, the algorithm below is based on the WHO categorisation of hypogonadism where the level of follicle stimulating hormone (FSH) and lutenising hormone (LH) being supressed, normal or elevated will correspond to clinical situations of hypogonadotrophic hypogonadism, polycystic cystic syndrome (PCOS) or mild hypothalamic amenorrhoea and premature ovarian failure respectively. It is important to distinguish between the causes of amenorrhoea, as apart from PCOS (and the physiological amenorrhoea of pregnancy), all other endocrine causes of amenorrhoea result in oestrogen deficiency. Therefore the cause of amenorrhoea will determine the management: to prevent endometrial hyperplasia in PCOS, or directed at preventing sequaelae of low oestrogen such as impaired bone and cardiovascular health in all other cases of amenorrhoea.
Ovarian conditions, in particular PCOS, account for the majority of all cases of secondary amenorrhoea. PCOS is diagnosed according to the Rotterdam criteria 2003, where at least 2 of the 3 factors are confirmed: oligo or amenorrhoea, clinical or biochemical evidence of hyperadrongenism, multiple follicles on pelvic ultrasound and exclusion of other causes of PCOS such as congenital adrenal hyperplasia (CAH), Cushings’ syndrome, acromegaly and testosterone secreting tumours. In the case of hypothalamic/pituitary causes of amenorrhoea, presenting with supressed FSH and LH, although mild elevation of prolactin can be associated with primary hypothyroidism and PCOS, marked elevation suggests a pituitary adenoma. A small number of cases of secondary amenorrhoea are due to endocrine disorders of thyroid and adrenal glands.
In the clinical setting, the most frequent differential diagnosis is mild PCOS and FHA. Although PCOS can present with a range of phenotypes, not restricted to the text book appearance originally described in the Stein-Leventhal syndrome, nevertheless there are some differentiating features between PCOS and FHA in terms of endometrial thickness, multiple follicles in ovaries, androgen and LH levels. Why it is crucial to distinguish between these 2 clinical situations is that these present diametrically opposed conditions of oestrogen sufficiently (potentially unopposed) and oestrogen insufficiency.
Hence functional hypothalamic amenorrhoea (FHA) RED-S, is a diagnosis of exclusion.
- Treat any medical condition
- Consider referral to NHS Sports/Dance Endocrine and RED-S clinic at Dr Roger Wolman, RNOH London
- If RED-S is diagnosed as result of exclusion work up above, based on results of history, examination and investigations. These results can be used in risk stratification according to RED-S Clinical Assessment Tool 2015
- Facilitation of integrated periodisation of training/nutrition/recovery. This will involve discussion with athlete/dancer, coach/teacher, parent and multi-disciplinary team (MDT) for input on nutrition and psychological strategies.
- In the case of functional hypothalamic amenorrhoea of RED-S in female athletes/dancers pharmacological treatment is not recommended, unless in the situation of primary amenorrhoea with delayed puberty or secondary amenorrhoea with significant bone health issue from DXA. Any replacement hormonal treatment must always be combination of transdermal oestrogen and cyclic progesterone and in conjunction with nutritional support. Note that the oral contraceptive pill (OCP) is not appropriate in treatment of RED-S (see IOC BJSM 2018 update on RED-S)
- In male athletes, testosterone is a WADA banned substance and Therapeutic Use Exemptions (TUE) not justified if low testosterone is a result of an imbalance of training/nutrition/recovery, rather than a medical condition per se.
- RED-S is a diagnosis of exclusion
- Over training syndrome and RED-S are examples of imbalances in nutrition, training load and recovery
Download the Clinical Assessment Tool for Risk Stratification of RED-S
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