D. Hamiltonfairley et al., DIURNAL-VARIATION OF SEX-HORMONE BINDING GLOBULIN AND INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 IN WOMEN WITH POLYCYSTIC-OVARY-SYNDROME, Clinical endocrinology, 43(2), 1995, pp. 159-165
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.