High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception.
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/m(2)), 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 (x 1000/mm(3)) 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.
Ibáñez
Lourdes
L
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Spain. libanez@hsjdbcn.org
Jaramillo
Adriana Maria
AM
Ferrer
Angela
A
de Zegher
Francis
F
D000293:Adolescent; D000328:Adult; D000726:Androgen Antagonists / Q000008:administration & dosage*; D002648:Child; D003276:Contraceptives, Oral / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005485:Flutamide / Q000008:administration & dosage*; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy* / Q000276:immunology; D006946:Hyperinsulinism / Q000188:drug therapy* / Q000276:immunology; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007958:Leukocyte Count; D008572:Menarche; D008687:Metformin / Q000008:administration & dosage*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects
D000726:Androgen Antagonists; D003276:Contraceptives, Oral; D007004:Hypoglycemic Agents; D005485:Flutamide; D008687:Metformin