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Many hirsute women may present a form of functional ovarian hyperandrogenism (FOH), since they show an exaggerated 17-hydroxyprogesterone (17-OHP) response to GnRH agonists administration. As the failure of dexamethasone to reduce testosterone levels may be indicative of an ovarian source of androgen secretion, we evaluated the usefulness of dexamethasone suppression test, in comparison with buserelin challenge, in the assessment of hirsutism. Twenty-seven hirsute women (aged 15-42 yr) underwent ACTH and buserelin tests: 4 patients were heterozygotes for 21-OH deficiency and 8 patients were affected with FOH: 2 of the patients with hyperresponse to buserelin also had 21-hydroxylase deficiency. The results of the dexamethasone suppression test (2 mg/day for 7 days) were compared to those obtained after buserelin test. Basal T and delta4 levels (mean+/-SE) were higher than in controls (4.2+/-0.5 vs 2.2+/-0.2 nmol/l and 10.9+/-0.9 vs 5.9+/-0.6 nmol/l, p<0.02), while no differences were found in 17-OHP and DHEAS levels. A significant reduction (p<0.001) in T (1.8+/-0.4 nmol/l), delta4 (3.2+/-0.5 nmol/l) and DHEAS levels (2.4+/-0.3 micromol/l) was observed at the 3rd day of dexamethasone administration and no differences between sampling at 3rd, 5th and 7th day were found. Serum T was not suppressed in 6 cases, delta4 and DHEAS levels in 3 and 1 of them, respectively. Buserelin injection caused an excessive 17-OHP response in 8 patients, only 4 of them did not reduce T levels during dexamethasone. The sensitivity and specificity of the dexamethasone suppression test, with respect to the buserelin test, were 50% and 89%, respectively. In conclusion, 37% of hirsute patients had an abnormal responsiveness to buserelin and/or ACTH tests, indicating that hormonal investigations are mandatory. An ovarian origin of hirsutism was identified by buserelin test in 30% of patients and by dexamethasone in 22% of cases; only 4 of 8 patients showed concordant results to both tests. Therefore, buserelin challenge seems a more useful, cost-effective and less time consuming tool than dexamethasone administration in order to recognize the possible ovarian origin of hyperandrogenism.
Many hirsute women may present a form of functional ovarian hyperandrogenism (FOH), since they show an exaggerated 17-hydroxyprogesterone (17-OHP) response to GnRH agonists administration. As the failure of dexamethasone to reduce testosterone levels may be indicative of an ovarian source of androgen secretion, we evaluated the usefulness of dexamethasone suppression test, in comparison with buserelin challenge, in the assessment of hirsutism. Twenty-seven hirsute women (aged 15-42 yr) underwent ACTH and buserelin tests: 4 patients were heterozygotes for 21-OH deficiency and 8 patients were affected with FOH: 2 of the patients with hyperresponse to buserelin also had 21-hydroxylase deficiency. The results of the dexamethasone suppression test (2 mg/day for 7 days) were compared to those obtained after buserelin test. Basal T and delta4 levels (mean+/-SE) were higher than in controls (4.2+/-0.5 vs 2.2+/-0.2 nmol/l and 10.9+/-0.9 vs 5.9+/-0.6 nmol/l, p<0.02), while no differences were found in 17-OHP and DHEAS levels. A significant reduction (p<0.001) in T (1.8+/-0.4 nmol/l), delta4 (3.2+/-0.5 nmol/l) and DHEAS levels (2.4+/-0.3 micromol/l) was observed at the 3rd day of dexamethasone administration and no differences between sampling at 3rd, 5th and 7th day were found. Serum T was not suppressed in 6 cases, delta4 and DHEAS levels in 3 and 1 of them, respectively. Buserelin injection caused an excessive 17-OHP response in 8 patients, only 4 of them did not reduce T levels during dexamethasone. The sensitivity and specificity of the dexamethasone suppression test, with respect to the buserelin test, were 50% and 89%, respectively. In conclusion, 37% of hirsute patients had an abnormal responsiveness to buserelin and/or ACTH tests, indicating that hormonal investigations are mandatory. An ovarian origin of hirsutism was identified by buserelin test in 30% of patients and by dexamethasone in 22% of cases; only 4 of 8 patients showed concordant results to both tests. Therefore, buserelin challenge seems a more useful, cost-effective and less time consuming tool than dexamethasone administration in order to recognize the possible ovarian origin of hyperandrogenism.
Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome determined in most patients by the association of two main factors: hyperandrogenism and insulin resistance. These characters are probably independent of each other and seem to be inherited by several different mechanisms. In some patients homozygous gene alteration has been found but in most patients PCOS seems to be determined by the association of gene polymorphisms that are common in the general population but alone are unable to determine phenotypic consequences. Alteration of genes that regulate the initial steps of ovarian steroidogenesis is probably the main causal factor of hyperandrogenism. Insulin resistance may be the result of many different gene alterations including insulin receptor substrate (IRS)-1 and 2, calpain-10 and peroxisome proliferator-activated receptor gamma(PPARgamma). Some polymorphisms may be protective against other gene alterations. Insulin sensitivity is also modified by socioeconomic and cultural factors that influence quantity and quality of food and energy expenditure. However, even eating behavior and weight response to food intake may be under genetic regulation. Different combinations of multiple gene polymorphisms and of environmental factors explain the heterogeneity of PCOS.
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