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Physiology and Pathophysiology of Estrogens: Lessons From Pediatric Patients With Complete Aromatase Deficiency

Belgorosky, Alicia MD*; Rivarola, Marco A. MD†

CME Review Article #11

Studies of patients with complete cP450arom deficiency have contributed considerably to the analysis of the importance cP450arom activity on sexual differentiation, the pattern of gonadotropin secretion, reproductive capacity, lipid metabolism and insulin sensitivity, as well as growth and skeletal maturation, in the 2 sexes. In humans, cP450arom appears to be the product of a single gene (CYP19) located on chromosome 15q21.1. In the placenta, the active aromatization of androgens protects the female fetus and the mother from the virilizing actions of fetal androgens. Indeed, 46,XX neonates with complete aromatase deficiency are born with ambiguous external genitalia. Eleven well-documented cases of complete aromatase deficiency secondary to mutations of the CYP19 gene have been reported. The pattern of serum hormones is characterized by very low estrogens and high androgens, follicle-stimulating hormone, and sometimes luteinizing hormone, depending on age and sex. During infancy, a sexual dimorphism of the role of estrogens in the regulation of gonadotropins has been observed. These patients are at risk for developing ovarian cysts, even before puberty. Finally, the study of these patients has been also useful to illustrate the essential role of estrogens in skeletal development, epiphyseal maturation, and in the pubertal growth spurt.

*Research Chairwoman and †Associate Director of Teaching and Research, Garrahan Pediatric Hospital, Buenos Aires, Argentina.

The authors have disclosed that they are recipients of a research grant from Pfizer, the Pharmacia (Pfizer) Endocrine Care International Fund for Research and Education.

Reprints: Alicia Belgorosky, MD, Research Laboratory, Combate de los Pozos 1881, Buenos Aires, Argentina. E-mail:

Chief Editor's Note: This article is the 11th of 36 that will be published in 2004 for which a total of up to 36 Category 1 CME credits can be earned. Instructions for how credits can be earned precede the CME Examination at the back of this issue.

© 2004 Lippincott Williams & Wilkins, Inc.