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Will leptin become the treatment of choice for functional hypothalamic amenorrhea?

Nature Clinical Practice Endocrinology & Metabolism volume 3, pages 556–557 (2007)Cite this article

Functional hypothalamic amenorrhea (FHA)—a disorder that results in low estradiol levels in the setting of normal to low gonadotropin levels—affects 3% of reproductive-aged women and accounts for 20% of all cases of amenorrhea. Common causes of FHA include eating disorders, weight loss, excessive exercise, and psychogenic stress.1 These stressors are thought to lead to low energy availability (i.e. the difference between dietary energy intake and energy output),2 which disrupts hypothalamic gonadotropin-releasing hormone (GnRH) secretion and reproductive function. Low energy availability also leads to suppression of the hypothalamic–pituitary–thyroid axis, activation of the hypothalamic–pituitary–adrenal axis, and growth hormone resistance, which is characterized by increased growth hormone levels but decreased levels of insulin-like growth factor 1 (IGF-I).

The signals that indicate sufficiency of energy stores from the periphery to the hypothalamus have been the focus of years of investigation. Leptin is a hormone secreted by adipocytes that has an important role in the regulation of both energy homeostasis and reproduction in humans.3 Leptin levels rapidly decrease in states of acute energy deprivation (e.g. fasting), which results in suppression of luteinizing hormone (LH) pulse secretion and reduced thyroid function. These changes can be reversed by exogenous leptin administration. Leptin replacement in leptin-deficient patients who are both obese and hypogonadal results in decreased food intake, weight reduction, increased physical activity, and increased levels of T4 and TSH. Leptin replacement also promotes pubertal development in patients who have reached the normal pubertal age, although the requirement for leptin might not be absolute,4 which suggests that leptin has a permissive, rather than causal, role in reproductive development.

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  1. Reproductive Endocrine Unit, BHX 511, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA cwelt@partners.org

Authors and Affiliations

  1. CK Welt is an Assistant Professor of Medicine at Harvard Medical School and an Assistant in Medicine in the Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.,

    Corrine K Welt

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  1. Corrine K Welt
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Welt, C. Will leptin become the treatment of choice for functional hypothalamic amenorrhea?. Nat Rev Endocrinol 3, 556–557 (2007). https://doi.org/10.1038/ncpendmet0561

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