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Aromatase deficiency in men: a clinical perspective

Nature Reviews Endocrinology volume 5, pages 559–568 (2009)Cite this article

Abstract

Human aromatase deficiency is a very rare syndrome characterized by congenital estrogen deprivation that is caused by loss-of-function mutations in CYP19A1, which encodes aromatase. Here, we review the presentation, diagnosis and treatment of aromatase deficiency in men to provide useful advice for clinical management of the condition. At presentation, all men with aromatase deficiency have tall stature, delayed bone maturation, osteopenia or osteoporosis and eunuchoid skeletal proportions. Diagnosis of the condition is supported by the presence of unfused epiphyses and undetectable serum estradiol levels; the condition can be further substantiated by genetic sequencing of CYP19A1. Transdermal estradiol treatment at a daily dose of about 25 µg might be adequate for lifelong replacement therapy. BMD and levels of serum estradiol, luteinizing hormone and testosterone should be monitored carefully and considered powerful biochemical markers of adequate estrogen substitution in clinical practice. Early diagnosis is important to initiate estrogen therapy as soon after puberty as possible to avoid the skeletal complications that are associated with this condition.

Key Points

  • Aromatase deficiency in men often remains undiagnosed until adulthood, which results in delayed and insufficient treatment

  • Aromatase deficiency should be strongly suspected in adult men with continued linear growth of bones, height increases in adulthood and/or documented unfused epiphyses

  • All newborn boys whose mothers exhibited unexplained signs of progressive virilization during pregnancy and all newborn babies with siblings who have documented aromatase deficiency should be screened for aromatase deficiency

  • Hand and wrist radiography and measurement of serum estradiol, testosterone and luteinizing hormone levels help to diagnose aromatase deficiency in men; if the condition is suspected, genetic testing is recommended

  • Adult men with aromatase deficiency should receive estradiol at a high starting dose for a quick completion of bone maturation, followed by a reduced dosage for lifelong replacement therapy

  • An early diagnosis of aromatase deficiency is advocated before irreversible abnormalities develop

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Figure 1: An algorithm of the optimal clinical management of aromatase deficiency.

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Acknowledgements

The authors are grateful to G. Rossi (University of Modena and Reggio Emilia) for providing technical support and help in writing the manuscript; to E. Pignatti (University of Modena and Reggio Emilia) for help with the genetic and biomolecular analyses; and to Y. Ukmar (University of Bologna) for proofreading and editing the manuscript. Part of this study was presented at the 32nd National Congress of the Italian Society of Endocrinology, Verona, Italy, 13–16 June 2007. Some of the underlying concepts and ideas were presented in the PhD thesis of V. Rochira, Fisiopatologia degli estrogeni nel maschio? The work was supported by a grant from the Ministero dell'Università e della Ricerca (MUR ex-40%-2005).

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  1. Department of Medicine, Endocrinology and Metabolism and Geriatrics, University of Modena and Reggio Emilia, Modena, Italy

    Vincenzo Rochira & Cesare Carani

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Correspondence to Vincenzo Rochira.

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Rochira, V., Carani, C. Aromatase deficiency in men: a clinical perspective. Nat Rev Endocrinol 5, 559–568 (2009). https://doi.org/10.1038/nrendo.2009.176

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