• Renato Pasquali, Laura Patton, Patrizia Pocognoli, Graciela Estela Cognigni, and Alessandra Gambineri.
• Division of Endocrinology, Department of Internal Medicine, Sant'Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, Italy. renato.pasquali@unibo.it
• J. Clin. Endocrinol. Metab. 2007 Nov 1; 92 (11): 4208-17.

ContextThe exaggerated 17-hydroxyprogesterone response to GnRH agonists, which reflects functional ovarian hyperandrogenism (FOH), is believed to be the prominent abnormality in women with polycystic ovary syndrome (PCOS).ObjectiveOur objectives were to quantify the prevalence of PCOS with FOH and to evaluate whether the presence of FOH may distinguish different clinical and biochemical phenotypes.Design, Setting, And ParticipantsWe conducted an observational study at an academic hospital that included 148 PCOS women and 22 healthy age-matched normal-weight control women.Main Outcome MeasuresA hormone profile was taken at baseline and in response to (1-24)ACTH and to a GnRH agonist, buserelin, administered during dexamethasone suppression.ResultsBased on the data obtained in the control subjects, the PCOS patients were divided into two groups, one with a normal (NR-PCOS, n = 78) and one with a high 17-hydroxyprogesterone response (HR-PCOS, n = 70) to buserelin. The two groups of PCOS subjects had similar anthropometric parameters and clinical signs of hyperandrogenism. Age and body weight at menarche were significantly lower and higher, respectively, in the HR-PCOS group than the NR-PCOS group. Moreover, the HR-PCOS group had higher basal testosterone (P < 0.001), free androgen index (P < 0.01), 17-hydroxyprogesterone (P < 0.05), estrogens (P < 0.05), area under the curve for insulin (insulin(AUC)) (P < 0.05), and C-peptide(AUC) (P < 0.01) and lower insulin sensitivity (as composite insulin sensitivity index) (P < 0.05) than the NR-PCOS group. The response of 17-hydroxyprogesterone to (1-24)ACTH (as percent variation) was lower in the HR-PCOS group with respect to the NR-PCOS group (P < 0.05), whereas the response of cortisol, androstenedione, and dehydroepiandrosterone was similar. Finally, the HR-PCOS group had lower percent suppression of androstenedione (P < 0.001) and 17-hydoxyprogesterone (P < 0.05) to dexamethasone. In a multiple regression model applied in all PCOS women, insulin(AUC) but not androgens or markers of insulin resistance predicted the 17-hydroxyprogesterone response to buserelin to a highly significant extent (t = 3.269; P < 0.01).ConclusionsThis study indicates that the paradigm that FOH is a specific feature of the PCOS status can no longer be sustained. We have shown that women with an exaggerated 17-hydroxyprogesterone response to a GnRH agonist, buserelin, are characterized by more severe hyperandrogenemia, glucose-stimulated beta-cell insulin secretion, and worse insulin resistance than those without evidence of FOH. Our data may be consistent with the hypothesis that excess insulin may represent a candidate factor responsible for FOH in these women, through the overactivation of the cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) enzyme pathway.

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