Very high frequency of the polymorphism for the insulin receptor substrate 1 (IRS-1) at codon 972 (glycine972arginine) in Southern Italian women with polycystic ovary syndrome.

A major component of the polycystic ovary syndrome (PCOS) is the insulin resistance. Only a few studies have evaluated the IRS-1 polymorphism at codon 972, sometimes in the absence of a control group, and with great variability in frequency (0-23% in PCOS vs. 0-17% in controls), and with no unequivocal relationships between the polymorphism and clinical or biochemical indexes. The aim of the work was to evaluate the frequency of the IRS-1 polymorphism at codon 972 in PCOS, and correlate it to clinical and biochemical indexes. We assessed the rs 1801278 polymorphic variant in the IRS-1 gene (Gly972Gly=wild-type; Gly972Arg=heterozygosity; Arg972Arg=homozygosity) in genomic DNA by restriction fragment length polymorphism. The study was conducted at an academic medical center with the participation of 65 women with PCOS and 27 age-matched healthy women (controls). Compared to controls, Gly972Arg was very frequent in PCOS (77% vs. 18%, p<0.0001); one PCOS woman was homozygous. Compared to wild-type PCOS, heterozygous PCOS women had only three significantly different indexes: higher fasting insulin, insulin resistance index, and lower 120 min OGTT glucose. Moreover, in the correlation analysis between any two clinical or biochemical variables, the Pearson's correlation coefficients were frequently of different magnitude in heterozygous PCOS versus wild-type PCOS. Overall, heterozygous PCOS had a greater number of statistically significant relationships between different clinical, metabolic and hormonal indexes: 44 direct and 9 inverse versus 6 and 3, respectively. The IRS-1 Gly972Arg has the highest frequency reported world-wide for PCOS women. This variant is associated with insulin resistance and higher fasting insulin in PCOS women.

[Low-dose flutamide in the treatment of hyperandrogenism in adolescents]. / La flutamide a basse dosi nell'iperandrogenismo dell'adolescente.

AIM: The aim of the study was to evaluate the results of the use of flutamide at low doses for the therapy of the iperandrogenism in adolescents. METHODS: The study enrolled 35 young women with acne and irsutism; 31 had polycystic ovary syndrome (PCOS) and 4 periferic iperandrogenism. In other 8 young women, sexually active, the flutamide has been associated with the hormonal contraceptive. On the three young women with iperinsulinism it has been decided to associate the flutamide with the metformina. All the young women were checked each month for the liver functional. Before the beginning of the therapy the menstrual situation, the Body Mass Index (BMI), the Ferriman' s and Cremoncini's score, the ovary's ultrasound aspect, and the hormonal order were evaluated. Follow-up was made after three months and after six months after the beginning of the therapy with flutamide 62.5 mg/die. RESULTS: Only in 4 cases the therapy has been suspended due to collateral effects, soon regressed after one week of the treatment interruption. The results have demonstrated a overwhelming improvement of the peripheral symptoms of iperandrogenism in all patients. CONCLUSION: The authors hope that flutamide could enter in the list of medicines normally used to treat the beauty flaws of policistic acne and to restore a hormonal order associated to an effective contraception.