Dysfunction of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovarian syndrome.

OBJECTIVE: Although a defect in GH regulation has been suggested in women with polycystic ovarian syndrome (PCOS), the data are limited and mechanism obscure. We have assessed the function of the GH/IGF-I axis in women with PCOS by measuring basal IGF-I levels and the ability of the pituitary to secrete GH following dopamine and GHRH. DESIGN: For each woman the complete study lasted 3 days. On the 1st and 2nd days, saline (0.9%, 5 ml/h for 3 h) and dopamine (4 micrograms/kg/min for 3 h) infusion tests were performed, respectively, in all PCOS and control women. Blood samples for GH measurement were obtained before and at 20-minute intervals for 3 hours. On the 3rd day a GHRH test (100 micrograms, i.v. bolus) was performed in 9 of the women with PCOS and in 9 controls. Blood samples for GH measurements were obtained before and at 20-minute intervals for 3 hours. Basal IGF-I levels were measured in the basal blood samples from the saline infusion test in all patients studied. SUBJECTS: Thirteen women with PCOS and 11 normally menstruating women (control group), aged 18-35 years, were studied. All women with PCOS had hirsutism and oligomenorrhoea since menarche, elevated serum values of at least one ovarian androgen and the typical ultrasound appearance of PCOS. RESULTS: Growth hormone releasing hormone (GHRH) induced a significant increase in GH secretion in both control and PCOS groups. However, the GH response to GHRH was found to be significantly lower in women with PCOS. The 3-hour infusion of dopamine induced a significant increase in GH levels only in the control group, while it failed to stimulate GH release in the women with PCOS. Although both dopamine and GHRH failed to induce a normal GH response in women with PCOS, their IGF-I levels did not differ significantly from those observed in control women. CONCLUSIONS: The diminished GH responses to both GHRH and dopamine in women with PCOS, in the presence of normal circulating IGF-I levels, suggests a dysregulation in GH secretion. Although the data are suggestive of a hypothalamic defect, further studies are required to clarify the underlying mechanism and the role, if any, of GH in the pathogenesis of polycyctic ovarian syndrome.

Experimental quantiles of epidemiological indices in case-control studies with non-differential misclassification.

The formulae for some typical epidemiological indices in case-control studies with non-differential misclassification are expressed in terms of two groups (alpha, beta) and (gamma, delta) of misclassification probabilities of exposure E and confounder C, respectively, and the initially estimated frequencies. The parameters alpha and beta denote the probability that subjects exposed to E are classified as non-exposed and the probability that non-exposed ones will be classified as exposed, respectively. Similarly, delta and gamma stand for the probability that those who have been exposed to C will be classified as non-exposed and the probability that non-exposed subjects are classified as exposed, respectively. The non-negativeness of the expressions for the 'true' frequencies in terms of the measured ones and the misclassification probabilities leads to the construction of feasibility regions for alpha, beta, gamma and delta. For a number of 'acceptable' 4-tuples (alpha, beta, gamma, delta), all of which lie inside these feasibility regions, a sequence of feasible values for an epidemiological index is determined, after employing a systematic procedure by means of a 'searching net' with increments delta alpha, delta beta, delta gamma, delta delta. The procedure serves to determine the characteristics of the (experimental) cumulative distribution function for any selected epidemiological index. The final stage in exploiting the structure of feasibility regions for alpha, beta, gamma and delta is to use the cumulative distribution function to calculate quantiles for the index associated with prescribed probabilities.