20 YEARS OF LEPTIN: Role of leptin in human reproductive disorders

    1. Christos Mantzoros1,2
    1. Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, 5841 South Maryland Avenue, MC 1027, Chicago, Illinois 60637, USA
      1Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, FD-876, Boston, Massachusetts 02215, USA
      2Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, Massachusetts, USA
    1. Correspondence should be addressed to C Mantzoros; Email: cmantzor{at}bidmc.harvard.edu


    Leptin, as a key hormone in energy homeostasis, regulates neuroendocrine function, including reproduction. It has a permissive role in the initiation of puberty and maintenance of the hypothalamic–pituitary–gonadal axis. This is notable in patients with either congenital or acquired leptin deficiency from a state of chronic energy insufficiency. Hypothalamic amenorrhea is the best-studied, with clinical trials confirming a causative role of leptin in hypogonadotropic hypogonadism. Implications of leptin deficiency have also emerged in the pathophysiology of hypogonadism in type 1 diabetes. At the other end of the spectrum, hyperleptinemia may play a role in hypogonadism associated with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these conditions of energy excess, mechanisms of reproductive dysfunction include central leptin resistance as well as direct effects at the gonadal level. Thus, reproductive dysfunction due to energy imbalance at both ends can be linked to leptin.

    • Received in final form 8 July 2014
    • Accepted 23 July 2014
    • Made available online as an Accepted Preprint 23 July 2014
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