Hyperandrogenism in female athletes with functional hypothalamic amenorrhea: a distinct phenotype

Figures & data

Figure 1 Flow diagram depicting selection of FHA-EX+HA cohort.

Abbreviations: FHA, functional hypothalamic amenorrhea; PCOS, polycystic ovary syndrome.

Table 1 Baseline characteristics of all three groups

Characteristic	Group 1 FHA-EX+HA (n=22)	Group 2 FHA-EX (n=22)	Group 3 FHA-AN (n=22)	P-value group 1 and 2	P-value group 1 and 3
Age at diagnosis, in years, median (IQR)	22 (18.7–25)	17.5 (15.7–19)	18 (16–22)	<0.01*	0.01*
BMI (kg/m^2), median (IQR)	21 (19–23)	20.8 (18.5–22.5)	20.3 (19.3–22.3)	0.50	0.72
Ethnicity (Caucasian), n (%)	20 (91%)	18 (82%)	20 (91%)	0.58	0.78
Age at menarche, in years, median (IQR)	13 (13–14)	13.5 (11–14)	14 (12–14)	0.88	0.84
Exercise per week, in hours, median (IQR)	10 (8–14)	10 (8–14)	13 (10–16)	0.60	0.07
Type of physical activity-aerobic, n (%)	16 (73%)	18 (82%)	18 (82%)	0.33	0.38
Weight loss at time of diagnosis (in kg), median (IQR)	2.25 (1.6–3.6)	2.7 (2.3–3.5)	2.25 (1.7–3)	0.17	0.42

Notes: FHA-EX+HA: FHA as well as clinical or biochemical hyperandrogenism; FHA-EX: FHA due to exercise; FHA-AN: FHA due to anorexia nervosa

* P-value significant at <0.05.

Abbreviations: FHA, functional hypothalamic amenorrhea; IQR, interquartile range; BMI, body mass index.

Table 2 Comparison of reproductive, metabolic, and skeletal phenotypes between FHA-EX+HA, FHA-EX, and FHA-AN

Characteristic	FHA-EX+HA (n=22)	FHA-EX (n=22)	FHA-AN (n=22)	P-value FHA-EX+HA vs FHA-EX	P-value FHA-EX+HA vs FHA-AN
Reproductive phenotype
Duration of amenorrhea (months), median (IQR)	6 (6–11.25)	7 (6–12)	6 (6–12)	0.55	0.68
LH/FSH ratio, median (IQR)	1.44 (1.03–1.77)	0.50 (0.20–0.94)	0.67 (0.51–0.87)	<0.01	<0.01
Total testosterone (ng/dL)*, median (IQR)	31.5 (19.8–55.8)	20.5 (18–39.8)	23.5 (15.5–37)	0.12	0.20
Polycystic ovarian morphology (PCOM) (%)	95	17.7	0	<0.01	<0.01
Metabolic phenotype
Systolic blood pressure (mmHg), median (IQR)	109 (94–116.5)	106 (100.8–110.3)	102 (94–108)	0.45	0.03
Diastolic blood pressure (mmHg), median (IQR)	69 (60–74)	62 (54–68.5)	63 (56–68)	0.03	0.04
Fasting glucose (mg/dL), median (IQR)	88.5 (82.8–90)	83.5 (78.8–86.3)	86.5 (83–89)	0.01	0.31
Total cholesterol** (mg/dL), median (IQR)	183 (150.5–232)	157.5 (143.3–221.75)	153 (142–230)	0.44	0.62
Skeletal phenotype
Number of stress fractures, n (%)	1 (4.5)	6 (27)	11 (50)	0.04	0.01
Bone mineral density (z scores) (spine),*** median (IQR)	−0.2 (−0.8–0.8)	−1.5 (−2.2–1.0)	−1.5 (−1.6 – −0.13)	0.02	0.16

Notes: FHA-EX+HA: FHA as well as clinical or biochemical hyperandrogenism; FHA-EX: FHA due to exercise; FHA-AN: FHA due to anorexia nervosa.

* Total testosterone concentrations were available in 20 subjects with FHA-EX+HA, 12 subjects with FHA-EX and eleven subjects with FHA-AN.

** Total cholesterol was available in 13 FHA-EX+HA, ten FHA-EX, and eight FHA-AN subjects.

*** DXA z scores were available in four FHA-EX+HA, 14 FHA-EX, and six FHA-AN subjects. Bold denotes P-value significant at <0.05.

Abbreviations: FHA, functional hypothalamic amenorrhea; IQR, interquartile range; BMI, body mass index; vs, versus; LH/FSH, luteinizing hormone/follicle stimulating hormone; DXA, duel-energy X-ray absorptiometry.

Figure 2 Comparison of LH/FSH ratio between FHA-EX+HA and FHA-EX and FHA-AN.

Notes: (A) Comparison of LH/FSH ratio between FHA-EX+HA and FHA-EX. (B) Comparison of LH/FSH ratio between FHA-EX+HA and FHA-AN. FHA-EX+HA: FHA as well as clinical or biochemical hyperandrogenism; FHA-EX: FHA due to exercise; FHA-AN: FHA due to anorexia nervosa.
Abbreviations: FHA, functional hypothalamic amenorrhea; LH/FSH, luteinizing hormone/follicle stimulating hormone; vs, versus.

Figure 3 Linear regression models depicting relationship between LH/FSH ratio and serum glucose (mg/dL) (A) and relationship between LH/FSH ratio and DXA spine z score (B).

Abbreviations: LH/FSH, luteinizing hormone/follicle stimulating hormone; DXA, duel-energy X-ray absorptiometry.