Potential REDs health outcomes resulting from problematic LEA
| Spoke | Examples of impairment | Populations with LEA (assessed directly or via surrogates) providing evidence of impairment | Examples of differential diagnoses (issues to be excluded) |
| Impaired reproductive function |
Females
Alteration in LH concentrations or pulsatility Reduced oestrogen and progesterone Reduced testosterone Primary amenorrhoea Oligomenorrhoea/menstrual irregularities Secondary amenorrhoea (FHA) Luteal phase defects/deficiency Anovulatory cycles Males Reduced testosterone Sperm abnormalities Erectile dysfunction Females and males Decreased libido | SF,45 127 173–175 FA176–179
SF,88 FA168 180–184 FA178 FA185 186 SF,88 FA183 187 188 FA181–183 187 189 190 SF,88 174 FA187 SF,88 FA187 MA18 90 98 102 191–193 MA194 MA81 108 111 MA108 111 194 |
Females
Primary amenorrhoea: constitutionally delayed puberty, various genetic syndromes, anatomic abnormalities Secondary amenorrhoea: pregnancy, PCOS, pituitary mass (eg, prolactinoma), thyroid abnormalities Other menstrual dysfunction: use of hormonal birth control methods, physiologic stress Males Primary hypogonadism (gonadal disease), Hypogonadism (eg, hypothalamic/pituitary disease), toxic exposures, infection, psychosomatic neurological dysfunction |
| Impaired bone health | Longitudinal loss of BMD/lack of expected bone accrual or maintenance (younger populations) Lower BMD/low Z-score Impaired bone strength or microarchitecture Bone stress injuries Change/differences in bone remodelling biomarkers | ANF,195 FA,196 MA197
FA49 198–200 MA18 49 200 201 FA202–204 MA205 FA,49 81 206–209 MA49 81 210 SF,125 FA,47 170 179 211 MA53 212 213 |
Low BMD: genetic bone disorders (eg, osteogenesis imperfecta), hyperparathyroidism, poor micronutrient intake (eg, calcium and vitamin D), malabsorption disorders (eg, coeliac disease), malignancies (eg, leukaemia, lymphoma, metastasis), renal diseases, medications (eg, anabolic steroids) Bone stress injury: External reasons (eg, training errors, surface, shoes) or internal issues (eg, body build, medical predispositions as above) |
| Impaired GI function | Abdominal pain/cramps/bloating/alteration in bowel movements | FA,8 81 189 214 MA81 | GI diseases (eg, Coeliac disease, inflammatory bowel disease, Helicobacter pylori, gastro-oesophageal reflux, functional dyspepsia/constipation), medications (eg, antidepressants, iron pills, narcotics, laxative/cathartic use in EDs) |
| Impaired energy metabolism/ regulation | Subclinically or clinically low T3 Low RMR/RMR ratio Reduced leptin Increased cortisol | SF,127 165 215 216 FA,49 168 170 184 188 190 217 218 MA49 192
FA182 189 190 217–222 MA103 191 223 SF,45 160 FA,47 170 179 188 217 MA46 224 SF,127 175 FA,178 179 184 222 225 MA80 102 | Primary or central (secondary and tertiary) hypothyroidism, medications/supplements Increased cortisol: physiologic stress, Cushing disease, steroid use |
| Impaired haematological status | Low iron status Increased hepcidin concentrations/response Reduced iron absorption Lower haemoglobin concentration/mass Reduced response to altitude training | FA226
SF,55 MA171 227 MA227 FA,228 MA73 MA229 | Acute or chronic blood loss (eg, menstrual cycle, GI bleeding), RBC destruction (eg, haemolysis, haemoglobinopathy, splenomegaly), poor micronutrient intake (eg, iron, vitamin B12, folate), bone marrow diseases |
| Urinary incontinence | Urinary incontinence | FA230–232 | Persistent urinary incontinence: trauma (eg, childbirth, surgery, radiation), anatomical abnormalities, neurological diseases Temporary urinary incontinence: pregnancy, urinary tract infection, constipation, certain foods and drugs |
| Impaired glucose and lipid metabolism | Reduced fasting/24-hour glucose Reduced fasting/24-hour insulin Elevated total cholesterol/LDL cholesterol | SF,127 FA,184 214 219 MA233
SF,127 FA,47 MA46 102 233 234 FA,181 235 236 MA72 192 193 | Impaired glucose metabolism: insulinoma, critical illness, medications, adrenal insufficiency Impaired lipid metabolism: familial hyperlipidaemia |
| Mental health issues | Depression Exercise dependence/addiction DE behaviours/EDs | FA,8 78 79 MA79
FA,81 237 MA80 81 FA,81 182 219 MA80 81 | Primary psychologic/mood disorders |
| Impaired neurocognitive function | Reduced/impaired memory Reduced/impaired decision-making Reduced/impaired spatial awareness Poor planning/cognitive flexibility Reduced executive function | FA,238 ANF239
ANF240 FA241 ANF242 FA238 | Dementia (eg, Alzheimer’s disease), vitamin deficiencies, infections, malignancies, ADHD, substance use disorder, primary psychologic/mood disorders, traumatic brain injury |
| Sleep disturbances | Sleep disturbances (self-reported) | FA,76 MA50 | Primary psychologic/mood disorders, shift-work, obstructive sleep apnoea, chronic pain/injury, nocturia, medications/substance use, restless legs syndrome |
| Impaired cardiovascular function | ECG abnormalities (eg, sinus bradycardia, QT prolongation and QT dispersion) Haemodynamic abnormalities (eg, hypotension and orthostatic hypotension, syncope) Impaired endothelial function/reduced blood flow Cardiac abnormalities (eg, MVP, decreased left ventricular mass, decreased left ventricular systolic function, myocardial fibrosis) | FA,189 243 MA,72 244 ANM,245ANF246 247
FA,243 248 ANF,249 MA244 FA,221 235 243 250–254 MA255 ANF,256 ANM245 256 |
Bradycardia: Genetic, ultra-endurance training, hypothyroidism, medications (eg, beta-blockers), toxic exposures, electroconductive disorders, electrolyte abnormalities Hypotension: illness, medications, dehydration |
| Reduced skeletal muscle function | Reduced rate of muscle protein synthesis Reduced rates of muscle glycogen restoration | FA,257–259 SM,260 MA257 258
FA,261 MA48 262 | Inadequate protein intake Inadequate CHO intake |
| Impaired growth and development | Reduced IGF-1 Increased GH/GH resistance Deviation from the expected growth curve | SF,127 215 FA,168 170 MA192 234 263 264
SF,127 FA,178 MA102 264 FA,186ANF,265 266 ANM267 268 | Constitutional delayed puberty, chronic diseases, GH deficiency, congenital or acquired hypogonadotropic hypogonadism, genetic defects, hyperprolactinaemia, long-term drug use (eg, anabolic steroids, opioids, glucocorticosteroids) |
| Reduced immunity | Increased infection/illness susceptibility Change in immune biomarkers | FA,10 269–271 MA10 269 271
FA,272 MA273 | Primary or acquired immune deficiency (eg, chemotherapy, viral infections) Intensive exercise without LEA |
Each of these outcomes can occur in the absence of LEA, therefore the differential diagnosis should be considered in the assessment and diagnosis of REDs severity and/or risk.
Populations providing evidence types: SF: sedentary females; FA: female athletes; ANF: females with anorexia nervosa; MA: male athletes; SM: sedentary males; ANM: males with anorexia nervosa.
ADHD, attention-deficit/hyperactivity disorder; CHO, carbohydrate; ECG, electrocardiogram; EDs, eating disorders; FHA, functional hypothalamic amenorrhoea; GH, growth hormone; GI, gastrointestinal; IGF-1, insulin-like growth factor-1; LDL, low density lipoprotein; LEA, low energy availability; LH, luteinising hormone; MVP, mitral valve prolapse; OCD, obsessive compulsive disorder; PCOS, polycystic ovary syndrome; RMR, resting metabolic rate; T3, triiodothyronine.