Functional hypothalamic amenorrhea: Evaluation and management
- Kathryn E Ackerman, MD, MPH
Kathryn E Ackerman, MD, MPH
- Assistant Professor of Medicine
- Harvard Medical School
- Madhusmita Misra, MD, MPH
Madhusmita Misra, MD, MPH
- Fritz Bradley Talbot and Nathan Bill Talbot Professor of Pediatrics
- Harvard Medical School
- Section Editors
- Robert L Barbieri, MD
Robert L Barbieri, MD
- Editor-in-Chief — Obstetrics, Gynecology and Women's Health
- Section Editor — General Gynecology and Female Reproductive Endocrinology
- Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
- William F Crowley, Jr, MD
William F Crowley, Jr, MD
- Section Editor — Female Reproductive Endocrinology
- Daniel K Podolsky Professor of Medicine
- Harvard Medical School
Low energy availability (from decreased caloric intake, excessive energy expenditure, or both) and stress are common causes of hypogonadotropic hypogonadism in women. Functional hypothalamic amenorrhea (FHA) is the term used to describe amenorrhea that results from such causes and is diagnosed after excluding other etiologies of amenorrhea. The terms functional hypothalamic amenorrhea and hypothalamic amenorrhea (HA) are often used interchangeably.
FHA is presumed to be a functional disruption of pulsatile, hypothalamic gonadotropin-releasing hormone (GnRH) secretion. The abnormal GnRH secretion characteristic of FHA leads to decreased pulses of gonadotropins, absent midcycle surges in luteinizing hormone (LH) secretion, absence of normal follicular development, anovulation, and low serum estradiol (E2) concentrations. Variable neuroendocrine patterns of LH secretion can be seen. Serum concentrations of follicle-stimulating hormone (FSH) are low or normal and often exceed those of LH, similar to the pattern in prepubertal girls.
This topic will review the evaluation and management of FHA. The pathophysiology and clinical manifestations of FHA, as well as the approach to women with primary and secondary amenorrhea, are presented separately. (See "Functional hypothalamic amenorrhea: Pathophysiology and clinical manifestations" and "Evaluation and management of primary amenorrhea" and "Evaluation and management of secondary amenorrhea".)
Diagnosis — FHA is a disorder that, by definition, excludes organic disease. The diagnosis of FHA is based upon the findings of amenorrhea, low serum gonadotropins and estradiol (E2), and, usually, evidence of a precipitating factor (exercise, low weight, stress). As in every woman with new-onset amenorrhea, other causes should first be excluded before diagnosing this condition. Our approach is consistent with the Endocrine Society's 2017 Clinical Practice Guideline for the diagnosis and treatment of FHA . (See "Functional hypothalamic amenorrhea: Pathophysiology and clinical manifestations" and "Evaluation and management of primary amenorrhea" and "Evaluation and management of secondary amenorrhea".)
Exclude other disorders — Women with FHA usually present with secondary amenorrhea, although some present with primary amenorrhea. The evaluation of both types of amenorrhea includes a thorough history and physical examination, biochemical testing, assessment of estrogen status, and, in some cases, imaging. These are reviewed in detail separately (algorithm 1 and algorithm 2). (See "Evaluation and management of primary amenorrhea" and "Evaluation and management of secondary amenorrhea".)
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- Exclude other disorders
- - History and physical examination
- - Biochemical testing
- - Evaluation of estrogen status
- - Imaging
- Bone density testing
- Screening for anxiety and mood disorders
- Reproductive issues
- - Amenorrhea
- Weight gain/lifestyle changes
- - Anovulatory infertility
- - Sexual function
- Cognition and anxiety
- Low bone density
- - Initial nonpharmacologic therapy
- - Calcium and vitamin D supplementation
- - Pharmacologic therapy
- Expert guidelines
- Estrogen replacement
- - Experimental
- Addition of androgens
- Other therapies
- - Other therapies to optimize bone density
- Antiresorptive therapies
- - Bisphosphonates
- Bone-anabolic therapies
- - Teriparatide
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS