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Hum. Reprod. Advance Access published online on May 19, 2005
Human Reproduction, doi:10.1093/humrep/dei072
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received February 21, 2005
Revised March 28, 2005
Accepted April 15, 2005

Article

High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception

Lourdes Ibáñez 1*, Adriana Maria Jaramillo 1, Angela Ferrer 1, and Francis de Zegher 2

1 Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Spain
2 Department of Pediatrics, University of Leuven, Belgium

* To whom correspondence should be addressed.
Lourdes Ibáñez, E-mail: libanez{at}hsjdbcn.org


  Abstract

BACKGROUND: The endocrine hallmark of polycystic ovary syndrome (PCOS) is hyperinsulinaemic hyperandrogenism; another facet of PCOS is low-grade inflammation. METHODS: In adolescents and young women with hyperinsulinaemic hyperandrogenism (n=118; mean age 16 years, body mass index 22 kg/m2), we analysed whether the PCOS-associated rise in leukocyte count is already detectable at young age and, if so, whether such elevation is lowered by metformin, flutamide-metformin, oral contraception (OC), or their combination. RESULTS: Leukocyte count (x1000/mm3) in patients was high versus controls (7.5 ± 0.1 versus 6.4 ± 0.1; P < 0.001) due to a rise in neutrophils (4.2 ± 0.1 versus 3.0 ± 0.1; P < 0.001). Randomized studies at mean ages of 12.5 years (n=24) and 15.2 years (n=33) demonstrated normalizing effects of metformin (850 mg/day; P < 0.001) and, respectively, metformin plus flutamide (62.5 mg/day) on neutrophil counts; in young women (18.3 years; n=41), the neutrophil count rose further on OC monotherapy (P=0.003), but normalized on the same OC plus flutamide-metformin (P < 0.001 versus OC alone). CONCLUSIONS: (i) A high leukocyte count is already present in girls with hyperinsulinaemic hyperandrogenism, and this is due to a raised neutrophil count; (ii) this hyperneutrophilia is attenuated by metformin or flutamide-metformin, and is amplified by OC monotherapy; (iii) if these treatments are combined, the normalizing effect of flutamide-metformin overcomes the OC effect on neutrophil count.

Keywords: flutamide; leukocytosis; metformin; oral contraception; ovarian hyperandrogenism.
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