Human Reproduction Archives
Human Reproduction Archives
Case Report gynecological endocrinology

Hemochromatosis as a cause of central primary Amenorrhea: A literature review and case report

Gustavo dos Santos Raupp, Vitória Lucietto Piccinini, Marta Ribeiro Hentschke, Mona Lúcia Dall’Agno, Ariane Tieko Frare Kira, Fernanda Braga Seganfredo, Nathalia da Cunha Rossato, Alvaro Petracco, Mariangela Badalotti

Downloads: 1
Views: 330


Introduction: Hereditary hemochromatosis (HH) is a genetic disease that causes systemic iron overload. The excess of iron accumulates in several organs, leading to organ dysfunction. Therefore, the excess of iron deposition might create an endocrine impairment, and can further lead to hypogonadism and, rarely, to amenorrhea. In this study, we aim to report a rare cause of HH and primary amenorrhea, with the help of clinical investigations. Case Description: This study is based on a single patient who was diagnosed with amenorrhea. The patient had a previous history of HH, type I diabetes mellitus, and chronic liver disease. The physical and hormonal investigations were normal, and her karyotype was 46 XX. A magnetic resonance imaging (MRI) demonstrated a diffuse reduction of the pituitary tissue signal, which might resemble HH. Discussion: The diagnosis of HH is based on a biochemical and genetic evaluation. The treatment includes regular phlebotomies and the control of comorbidities. In most of the cases, the hypogonadotropic hypogonadism leads to amenorrhea due to a pituitary impairment. However, a rare appearance of amenorrhea without hypogonadism may also be possible. Hence, the investigation of HH should be suggested incases of primary amenorrhea. The early diagnosis of HH is crucial to prevent the morbidity and mortality in patients with these clinical features.


amenorrhea; diabetes mellitus; hemochromatosis; menstruation disturbances, and pituitary gland.


1. Klein DA, Poth MA. Amenorrhea: an approach to diagnosis and management. Am Fam Physician. 2013;87(11):781-8. PMid:23939500.

2. Deligeoroglou E, Athanasopoulos N, Tsimaris P, Dimopoulos KD, Vrachnis N, Creatsas G. Evaluation and management of adolescent amenorrhea. Ann N Y Acad Sci. 2010;1205(1):23-32. PMid:20840249.

3. Timmreck LS, Reindollar RH. Contemporary issues in primary amenorrhea. Obstet Gynecol Clin North Am. 2003;30(2):287-302. PMid:12836721.

4. Pelusi C, Gasparini DI, Bianchi N, Pasquali R. Endocrine dysfunction in hereditary hemochromatosis. J Endocrinol Invest. 2016;39(8):837-47. PMid:26951056.

5. Porto G, Brissot P, Swinkels D, Zoller H, Kamarainen O, Patton S, et al. EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH). Eur J Hum Genet. 2016;24(4):479-95. PMid:26153218.

6. Goldschmidt H, Spiera H, Schumacher H Jr, Zaroulis CG. Idiopathic hemochromatosis presenting as amenorrhea and arthritis. Am J Med. 1987;82(5):1057-9.

7. McDermott JH, Walsh CH. Hypogonadism in hereditary hemochromatosis. J ClinEndocrinol Metab. 2005;90(4):2451-5.

8. Brissot P, Cavey T, Ropert M, Guggenbuhl P, Loréal O. Genetic hemochromatosis: Pathophysiology, diagnostic and therapeutic management. Presse Med. 2017;46(12):e288-95. PMid:29158016.

9. Bacon BR, Adams P, Kowdley K, Powell L, Tavill A, American Association for the Study of Liver Diseases. Diagnosis and management of hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54(1):328-43. PMid:21452290.

10. Pietrangelo A, Caleffi A, Henrion J, Ferrara F, Corradini E, Kulaksiz H, et al. Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes. Gastroenterology. 2005;128(2):470-9. PMid:15685557.

11. Crownover BK, Covey CJ. Hereditary hemochromatosis. Am Fam Physician. 2013;87(3):183-90.

12. Tweed MJ, Roland JM. Haemochromatosis as an endocrine cause of subfertility. BMJ. 1998;316(7135):915-6. PMid:9552844.

13. Dickerson EH, Raghunath AS, Atkin SL. Initial investigation of amenorrhoea. BMJ. 2009;339:455-7.

14. Schmitt B, Golub RM, Green R. Screening primary care patients for hereditary hemochromatosis with transferrin saturation and serum ferritin level: systematic review for the American College of Physicians. Ann Intern Med. 2005;143(7):522-36. PMid:16204165.

15. Qaseem A, Aronson M, Fitterman N, Snow V, Weiss KB, Owens DK, Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2005;143(7):517-21. PMid:16204164.

16. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for HFE Hemochromatosis. J Hepatol. 2010;53(1):3-22.

17. Powell LW, George D, McDonnell SM, Kowdley KV. Diagnosis of hemochromatosis. Ann Intern Med. 1998. 129(11):925-31.

18. Pietrangelo A. Hereditary Hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology. 2010;139(2):393-408. e2. PMid:20542038.

19. Fujisawa I, Morikawa M, Nakano Y, Konishi J. Hemochromatosis of the pituitary gland: MR imaging. Radiology. 1988;168(1):213-4. PMid:3380960.

20. Sondag MJ, Wattamwar AS, Aleppo G, Nemeth AJ. Case 179: Hereditary hemochromatosis. Radiology. 2012;262(3):1037-41. PMid:22357904.

21. Naredi N, Seth A, Sharma A. Iron Overload: A cause of primary Amenorrhea. Med J Armed Forces India. 2011;67(1):86-7. PMid:27365772.

22. Kelly T, Edwards CQ, Meikle AW, Kushner JP. Hypogonadism in Hemochromatosis: Reversal with Iron Depletion. Ann Intern Med. 1984;101(5):629-32. PMid:6435491.

23. Singer ST, Sweeters N, Vega O, Higa A, Vichinsky E, Cedars M. Fertility potential in thalassemia major women: current findings and future diagnostic tools. Ann N Y Acad Sci. 2010;1202(1):226-30. PMid:20712797.

24. Adams P, Speechley M, Kertesz A. Long-term survival analysis in hereditary hemochromatosis. Gastroenterology. 1991;101(2):368-72. PMid:2065912.

25. Farina G, Pedrotti C, Cerani P, Rovati A, Strada E, Bergamaschi G, et al. Successful pregnancy following gonadotropin therapy in a young female with juvenile idiopathic hemochromatosis and secondary hypogonadotropic hypogonadism. Haematologica. 1955;80(4):335-7. PMid:7590503.

Submitted date:

Accepted date:

5fc004660e88259d5df5cc96 hra Articles
Links & Downloads

Hum Reprod Arch

Share this page
Page Sections