title: Hyperandrogenism in female athletes with functional hypothalamic amenorrhea: a distinct phenotype.
abstract: OBJECTIVE
  To compare the reproductive, metabolic, and skeletal profiles of young athletic women with functional hypothalamic amenorrhea (FHA) as well as clinical or biochemical hyperandrogenism (FHA-EX+HA) with body mass index matched women with FHA due to exercise (FHA-EX) or anorexia nervosa (FHA-AN) alone.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Tertiary care teaching hospital.
  
  
  METHODS
  Adolescents and young women, 15-30 years of age, diagnosed with FHA along with concurrent signs of hyperandrogenism (n=22) and body mass index matched control groups consisting of 22 women in each group of FHA-EX and FHA-AN.
  
  
  RESULTS
  1) Reproductive hormone profile: luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone, pelvic ultrasound features. 2) Metabolic function and skeletal health markers: fasting glucose, cholesterol, number of stress fractures and bone mineral density as assessed by spine dual-energy X-ray absorptiometry z scores.
  
  
  RESULTS
  FHA-EX+HA group was older at diagnosis compared to the other groups with a median (interquartile range [IQR]) age of 22 (18.75-25.25) years versus (vs) 17.5 (15.75-19) for FHA-EX; (P<0.01) and 18 (16-22.25) years for FHA-AN (P=0.01). There were no differences among the groups based on number of hours of exercise per week, type of physical activity or duration of amenorrhea. Median (IQR) LH/FSH ratio was higher in FHA-EX+HA than both other groups, 1.44 (1.03-1.77) vs 0.50 (0.20-0.94) for FHA-EX and 0.67 (0.51-0.87) for FHA-AN (P<0.01 for both). Total testosterone concentrations were not different among the groups. Median (IQR) fasting serum glucose concentration was higher in FHA-EX+HA vs FHA-EX, 88.5 mg/dL (82.8-90 mg/dL) vs 83.5 mg/dL (78.8-86.3 mg/dL) (P=0.01) but not different from FHA-AN (P=0.31). Percentage of women with stress fractures was lower in FHA-EX+HA (4.5%) as compared to both FHA-EX (27.3%) and FHA-AN (50%); P=0.04 and 0.01 respectively. The LH/FSH ratio was weakly positively associated with serum glucose (adjusted r (2)=0.102; P=0.01) as well as with dual-energy X-ray absorptiometry spine score (adjusted r (2)=0.191; P=0.04) in the entire cohort.
  
  
  CONCLUSIONS
  In a small cohort of female athletes with hyperandrogenism, a distinct reproductive hormone profile consisting of higher LH to FHS ratio may be associated with adverse metabolic health markers but improved skeletal health.
authors.affiliation: Pediatric and Adolescent Medicine, Division of Pediatric Endocrinology Mayo Clinic, Rochester, MN, USA.
authors.forename: Asma
authors.initials: A
authors.lastname: Javed
authors.affiliation: Department of Anesthesia and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Kashyap
authors.affiliation: Pediatric and Adolescent Medicine, Division of Pediatric Endocrinology Mayo Clinic, Rochester, MN, USA.
authors.forename: Aida N
authors.initials: AN
authors.lastname: Lteif
keywords: functional hypothalamic amenorrhea; hyperandrogenism; polycystic ovary syndrome; young athletes