Weight loss and functional hypothalamic amenorrhea in a young female athlete: A case of relative energy deficiency in sport mimicking anorexia nervosa

BACKGROUND Relative energy deficiency in sport (RED-S) is a clinical condition characterized by low energy availability (LEA) and/or excessive energy expenditure with serious long-term consequences on health and sporting performance [1]. Energy availability can be defined as the amount of dietary energy remaining for normal physiological functioning after exercise, like cell maintenance, thermoregulation, growth and reproduction. For this reason, low energy availability affects many physiological systems, such as energy metabolism, protein synthesis, bone health, immunity, cardiovascular and psychological health [2]. RED-S derives from a previous syndrome, the female athlete triad, which combines LEA, menstrual dysfunction and low bone mineral density in active women, while in male undernourished athletes can cause a parallel syndrome with hypogonadotropic hypogonadism [1]. Eating disorders represent a major cause of LEA, however energy deficit can also result by involuntary decrease in energy intake or failure to increase caloric consumption because of exercise. Prolonged exercise, unawareness of caloric needs during exercise, high-carbohydrate diets and suppression of appetite are potential pathophysiologic mechanisms [2]. Lastly, it is important to calculate Energy Availability in order to detect LEA and make a differential diagnosis with other pathological conditions like ED (eating disorders), that are very recurring in professional athletes. 40 5° Congresso Nazionale SINuC SINuC 2022 CASE A 19-year-old female was admitted to our outpatient service for weight loss, functional hypothalamic amenorrhea, and depressed mood. She was a synchronized swimming athlete and she trained 3 hours a day for 6 days a week, alternating training in gym and in pool. During the first visit, body weight was 45.7 Kg, height equal to 1.65 m, BMI (Body Mass Index) 16.78 Kg/m2. A 7-day dietary record was administered, and the patient underwent a psychological counseling leading to suspicion of ED. Blood and instrumental tests were also prescribed, as follows: • Blood tests: FT3:3.07 pMoli/L (n.r. 3.08-6.16), suggesting metabolic adaptation, , MCV 73 fL (n.r. 78-92 fL); LH was significantly reduced ( n.r. 0.38 mIU/ mL, follicular phase 1.80-11.78, ovulation phase 7.59-89.08, luteal phase 0.56-14), E2 (17 beta-estradiol) was <10pg /mL, (n.r. follicular phase 21-251, ovulation phase 38-649, luteal phase 21-312), plasma cortisol tended to be close to the upper limit (17.9 ug/dL, n.r. 3.7-19.4 ). • DXA: at the level of the lumbar spine BMD values were equal to 0.913 (BMD Z- score: -2.1) • EKG: electrocardiogram showed sinus rhythm at HR (Heart Rhythm) 68 bpm, normal-oriented electrical axis, AV and IV conduction within normal limits, absence of alterations in the ventricular repolarization phase. • Echocardiogram: normal, EF (Ejection Fraction) 65%. • Bioimpedance analysis: at the first assessment body weight was 45.7 kg, FFM was 42.5 kg and body fat was 7%; at the last follow-up visit, after 1 year: body weight was 52 kg, FFM was 43.4 kg and body fat was 16.5%. MANAGEMENT The patient underwent a multidisciplinary treatment provided by different healthcare professionals: a physician nutrition specialist, a psychologist and a psychiatrist. On the basis of the multidimensional assessment, the RED-S was diagnosed. 5° Congresso Nazionale SINuC 41 SINuC 2022 Based on the dietary record the energy availability was calculated, in terms of calories per kilogram of fat-free mass per day (kcal/kg FFM/day). An optimal nutritional status is characterized by energy levels > 45 kcal/kg FFM/day. In this case, the energy availability at the admission was < 30 kcal/kg FFM/day and this condition underpinned the functional hypothalamic amenorrhea and the reduced BMD. The patient underwent nutritional rehabilitation, the dietary intervention targeted adequate EA (45 kcal/kg/day), starting from an energy intake equal to BMR + 20% (due to the presence of metabolic adaptation) and progressively increasing to meet the TDEE requirements. In addition the following dietary supplements were prescribed because the patients kept training at the same volume and intensity: oral phosphatidylserine (600 mg/day) [3] and maltodextrin 0.6 g/ kg/day) during the training sessions [4]. The patient is still under treatment, with the final aim to have body weight restored and menstrual cycle resumed to improve BMD. PRACTICAL TIPS • In the differential diagnosis for weight loss in athletes, the RED-S should be taken into account and disentangled from eating disorders such as anorexia nervosa. • RED-S affects both female and male athletes. • RED-S causes alterations in various functions of the body such as bone metabolism, menstrual cycle, cardiovascular performance and mental health, overlapping with functional hypothalamic amenorrhea. • It is important to make a correct diagnosis in order to be able to intervene with the most correct therapy as possible. • The clinical approach must be multidisciplinary in order to target the clinical and psychological features of the syndrome. • After diagnosis of RED-S, the treatment consists in increasing the caloric intake or reducing the energy expenditure to achieve an adequate energy balance and to provide sufficient energy availability. • Changes in serum LH can be a used as an indirect marker of energy availability restoration. 42 5° Congresso Nazionale SINuC SINuC 2022 REFERENCES [1] Statuta SM, Asif IM, Drezner JA. Relative energy deficiency in sport (RED-S). Br J Sports Med. 2017 Nov;51(21):1570-1571. doi: 10.1136/bjsports-2017-097700. Epub 2017 Jul 6. PMID: 28684389. [2] Skarakis NS, Mastorakos G, Georgopoulos N, Goulis DG. Energy deficiency, menstrual disorders, and low bone mineral density in female athletes: a systematic review. Hormones (Athens). 2021 Sep;20(3):439-448. doi: 10.1007/s42000-021-00288-0. Epub 2021 Apr 22. PMID: 33884586. [3] Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr. 2008 Jul 28; 5:11. doi: 10.1186/1550-2783-5-11. PMID: 18662395; PMCID: PMC2503954. [4] Martínez-Olcina M, Miralles-Amorós L, Asencio-Mas N, Vicente-Martínez M, Yáñez-Sepúlveda R, Martínez-Rodríguez A. Ingestion of Carbohydrate Solutions and Mouth Rinse on Mood and Perceptual Responses during Exercise in Triathletes. Gels. 2022 Jan 9;8(1):50. doi: 10.3390/ gels8010050. PMID: 35049585 [5] Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, Meyer N, Sherman R, Steffen K, Budgett R, Ljungqvist A. The IOC consensus statement: beyond the Female Athlete Triad - Relative Energy Deficiency in Sport (RED-S). Br J Sports Med. 2014 Apr;48(7):491-7. doi: 10.1136/bjsports-2014-093502. PMID: 24620037.