Metformin, estrogen replacement therapy and gonadotropin inhibition fail to improve insulin sensitivity in a girl with aromatase deficiency.

Abstract

BACKGROUND:

Insulin resistance (IR), abnormal lipid profile, and other features of the metabolic syndrome have been described in CYP19 gene knockout mice and in aromatase-deficient adult men but not in prepubertal affected girls.

AIMS:

To study insulin sensitivity, as well as the effects of estrogen, metformin and GnRHa treatment on glucose homeostasis, in an aromatase-deficient girl.

METHODS:

Clinical, metabolic and hormonal follow-up data, from 8 to 12 years of age, is presented.

RESULTS:

At 9 years of age, IR (HOMA 5.6) and glucose intolerance was detected, along with high serum testosterone (2.28 nmol/l), androstenedione (4.92 nmol/l) and FSH (13.4 mIU/ml) levels. Estrogen replacement was ineffective to suppress gonadotropin and androgen levels, as well as IR. Under metformin therapy, she developed type 2 diabetes and acanthosis nigricans. GnRHa administration for 1 year resulted in marked decreases in gonadotropin and serum androgens, but severe IR persisted.

CONCLUSION:

Postnatal estrogen replacement and a marked decrease of endogenous androgens failed to improve IR and glucose tolerance. We propose that, in females, the increment of androgens and/or lack of estrogens during fetal life might alter the mechanism of fetal programming of insulin sensitivity.

• Authors: Gabriela Guercio, Maria Isabel Di Palma, Carolina Pepe, Nora I Saraco, Mariana Prieto, Carola Saure, Carmen Mazza, Marco A Rivarola, Alicia Belgorosky
• Journal: Hormone research (Horm Res) Vol. 72 Issue 6 Pg. 370-6 ( 2009) ISSN: 1423-0046 [Electronic] Switzerland
• PMID: 19844126 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgen Antagonists
• Androgens
• Gonadotropin-Releasing Hormone
• Metformin
• Aromatase

Topics

• Androgen Antagonists (therapeutic use)
• Androgens (metabolism)
• Aromatase (deficiency)
• Child
• Diabetes Mellitus, Type 2 (etiology)
• Estrogen Replacement Therapy
• Feedback, Physiological
• Female
• Fetus (physiopathology)
• Gonadotropin-Releasing Hormone (antagonists & inhibitors)
• Humans
• Insulin Resistance (physiology)
• Male
• Metabolic Syndrome (drug therapy, etiology, physiopathology)
• Metformin (therapeutic use)
• Pregnancy