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1294006 
Journal Article 
Preadipocyte factor-1 levels are higher in women with hypothalamic amenorrhea and are associated with bone mineral content and bone mineral density through a mechanism independent of leptin 
Aronis, KN; Kilim, H; Chamberland, JP; Breggia, A; Rosen, C; Mantzoros, CS 
2011 
Yes 
Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
EISSN: 1945-7197 
96 
10 
E1634-E1639 
English 
21795455 
CONTEXT: Preadipocyte factor 1 (pref-1) is increased in anorexia nervosa and is associated negatively with bone mineral density (BMD). No previous studies exist on pref-1 in women with exercise-induced hypothalamic amenorrhea (HA), which similar to anorexia nervosa, is an energy-deficiency state associated with hypoleptinemia.

OBJECTIVE: Our objective was to evaluate whether pref-1 levels are also elevated and associated with low BMD and to assess whether leptin regulates pref-1 levels in women with HA.

DESIGN: Study 1 was a double-blinded, placebo-controlled randomized clinical trial of metreleptin administration in women with HA. Study 2 was an open-label study of metreleptin administration in low physiological, supraphysiological, and pharmacological doses in healthy women volunteers.

SETTING AND PATIENTS: At Beth Israel Deaconess Medical Center, 20 women with HA and leptin levels higher than 5 ng/ml and nine healthy control women participated in study 1, and five healthy women participated in study 2.

INTERVENTION: For study 1, 20 HA subjects were randomized to receive either 0.08 mg/kg metreleptin (n = 11) or placebo (n = 9). For study 2, five healthy subjects received 0.01, 0.1, and 0.3 mg/kg metreleptin in both fed and fasting conditions for 1 and 3 d, respectively.

MAIN OUTCOME MEASURES: Circulating pref-1 and leptin levels were measured.

RESULTS: Pref-1 was significantly higher in HA subjects vs. controls (P = 0.035) and negatively associated with BMD (ρ = -0.38; P < 0.01) and bone mineral content (ρ = -0.32; P < 0.05). Metreleptin administration did not alter pref-1 levels in any study reported herein.

CONCLUSIONS: Pref-1 is higher in HA subjects than controls. Metreleptin administration at low physiological, supraphysiological, and pharmacological doses does not affect pref-1 levels, suggesting that hypoleptinemia is not responsible for higher pref-1 levels and that leptin does not regulate pref-1.