DIURNAL-VARIATION OF SEX-HORMONE BINDING GLOBULIN AND INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROME

OBJECTIVES The aim of this study was to examine (1) the diurnal variat ion in SHBG and (2) the inter-relationships of insulin, IGF-I, SHBG an d IGFBP-1 over 24 hours in 10 women with anovulatory PCOS and compare them with weight-matched ovulatory controls. PATIENTS AND METHODS The two groups comprised 10 anovulatory women with PCOS (as defined by cli nical, ultrasound and biochemical criteria) and 10 weight matched cont rols, Serum samples were taken at two-hourly intervals for 24 hours an d stored for measurement of SHBG, IGFBP-1, insulin and IGF-I. Differen ces between the groups were compared using the Wilcoxon ranked paired tests of the individual peak and trough concentrations in each group. The variation in insulin, IGFBP-1 and SHBG concentrations over 24 hour s was tested using two-way analysis of variance with the factors time and subject, Spearman's correlation coefficient was calculated from th e subjects' median value over 24 hours. RESULTS The median (interquart ile range) body mass index (BMI) was 25.2 (22.2-29.3) in the PCOS grou p and 24.3 (23.2-25.7) kg/m(2) in the control group. Serum testosteron e (T) and LH levels were significantly raised in the PCOS group compar ed to the control group; T 3.8 (2.9-5.6) vs 1.9 (1.9-2.5) nmol/l (P < 0.007) and LH 12 (10-15) vs 4.1 (3.6-4.5) lull (P < 0.005) respectivel y. There was no diurnal variation in SHBG. The median (interquartile r anges) of the peak SHBG concentrations was lower in the PCOS group: 29 .4 (14.9-39.4) vs 52.1 (39.4-61) nmol/l in the control group (P < 0.01 ). The fasting levels of insulin at 0600 h (median (interquartile rang es)) were not significantly different between the groups; 6.6 (5.4-9.8 ) and 6.2 (1.9-7.6) mU/l, respectively, although the peak median conce ntrations were significantly different; PCOS 66.1 (50.9-129.2) vs 40 ( 36.1-74.2) mull (P<0.05). Two-way analysis of variance showed a diurna l variation in insulin concentrations in the control group (P = 0.001) but not in the PCOS group (P = 0.1). The diurnal variation in IGFBP-1 was similar in the two groups but the peak median levels were lower i n the women with PCOS 54.9 (22.3-79.2) vs 71.5 (60.5-99.3) mu g/l (P<0 .03). The decline in IGFBP-1 concentrations correlated with the increa se in insulin concentrations. The IGF-I concentrations were similar in the two groups. There was a significant negative correlation between SHBG and insulin (P < 0.05) and between insulin and IGFBP-1 (P < 0.01) . CONCLUSION This study demonstrates that there is no diurnal variatio n in SHBG concentrations and confirms the finding of a marked diurnal variation in the concentration of IGFBP-1. Women with PCOS who are ano vulatory have an abnormal pattern of insulin secretion with an absence of diurnal variation compared to weight matched controls. This provid es further evidence of the relative insulin resistance which Is indepe ndent of weight found in women with anovulatory PCOS. The inverse corr elations of insulin concentrations with SHBG and IGFBP-1 support the r ole of insulin as a possible regulator of the circulating levels of th ese binding proteins although the difference in the time course of the ir response makes it unlikely that they are co-regulated.