Hum. Reprod. Advance Access originally published online on May 19, 2005
Human Reproduction 2005 20(9):2457-2462; doi:10.1093/humrep/dei072
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High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception
1 Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Spain and 2 Department of Pediatrics, University of Leuven, Belgium
3 To whom correspondence should be addressed at: Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain. Email: libanez{at}hsjdbcn.org
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.
Key words: flutamide/leukocytosis/metformin/oral contraception/ovarian hyperandrogenism
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