c-peptide and Ovarian-Diseases

The 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).. Our 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.. We conducted an observational study at an academic hospital that included 148 PCOS women and 22 healthy age-matched normal-weight control women.. A hormone profile was taken at baseline and in response to (1-24)ACTH and to a GnRH agonist, buserelin, administered during dexamethasone suppression.. Based 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).. This 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.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adult; Anthropometry; Blood Glucose; Buserelin; C-Peptide; Cosyntropin; Dexamethasone; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Hormones; Humans; Hyperandrogenism; Insulin; Middle Aged; Ovarian Diseases; Phenotype; Polycystic Ovary Syndrome; Prospective Studies

To assess the oral glucose tolerance test (OGTT)-stimulated insulin secretion and its relation to pulsatile GnRH ovulation induction outcome in patients with multifollicular or polycystic ovaries (PCOs).. Prospective study.. Reproductive Endocrinology Center, University of Bologna, Bologna, Italy.. Eight normal and 29 anovulatory women (8 with multifollicular ovaries and 21 with PCOs).. A standard OGTT was performed in all subjects. In all anovulatory patients, ovulation was induced with pulsatile GnRH (5 micrograms i.v. every 60 minutes). In multifollicular ovary patients, pulsatile GnRH was administered alone, whereas in PCOs it was preceded by GnRH agonist (GnRH-a) suppression.. Glucose, insulin, and C-peptide response to the OGTT, expressed as area under the curve (AUC). Ovulatory rates in response to pulsatile GnRH.. Insulin and C-peptide AUC were greater than controls in both multifollicular ovary and PCO patients. Insulin AUC was positively correlated to ovarian volume. Ovulation was achieved in 88% and 57% of multifollicular ovary and PCO patients, respectively. Body mass index and glucose AUC but not insulin and C-peptide AUC were significantly greater in the anovulatory PCO.. [1] Insulin AUC was increased in both multifollicular ovary and PCO patients; [2] derangements of insulin secretion may be present in a greater variety of anovulatory patients than previously thought; [3] insulin levels during the OGTT did not predict a response to pulsatile GnRH in PCOs, suggesting complex insulin interactions at the ovarian level; [4] given the in vitro stimulatory properties of insulin on granulosa cells synergistic with FSH, we propose that excessive insulin levels may contribute to the ovarian enlargement often found in multifollicular ovary and PCO patients.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Insulin; Insulin Secretion; Ovarian Diseases; Ovarian Follicle; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Prospective Studies; Ultrasonography

Previous studies have shown that hyperinsulinism is associated with hyperandrogenism in patients with the polycystic ovary syndrome, a form of functional ovarian hyperandrogenism (FOH). Although many studies have documented insulin resistance and hyperinsulinemia in polycystic ovary syndrome, the relative roles of insulin secretion and clearance in the pathogenesis of the hyperinsulinism remain uncertain. In this study, using individually derived C-peptide kinetic parameters, insulin secretion rates were calculated directly from plasma C-peptide concentrations in 10 patients with FOH and 7 weight-matched control subjects. All subjects were studied during a 24-h period when they ate a standardized diet consisting of 3 mixed meals. On a separate occasion, insulin sensitivity was calculated during a hyperinsulinemic euglycemic clamp. Although glucose concentrations in both groups were within the normal range, the FOH group had higher basal (P < 0.01) and 24-h insulin (P < 0.04) concentrations. The increased insulin concentrations reflected both a reduced clearance (P < 0.02) and an increased secretion of insulin. Basal insulin secretion rates were significantly increased (P < 0.04) in the FOH patients. By contrast, their incremental insulin secretory response to meals was markedly reduced. This reduction in the postprandial responses resulted from a reduction in the relative amplitude of meal-related (P < 0.007) secretory pulses, rather than from a reduction in the number of pulses present. Insulin sensitivity was also lower in those with FOH. Thus, women with FOH have significantly higher basal insulin secretory rates and attenuated secretory responses to meals. These secretory patterns resemble those of noninsulin-dependent diabetes mellitus more than they do those of simple obesity.

Topics: Adult; Androgens; Blood Glucose; C-Peptide; Female; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Islets of Langerhans; Osmolar Concentration; Ovarian Diseases