Human Reproduction, Vol 13, 547-553, Copyright © 1998 by Oxford University Press
F Geisthovel, A Meysing and G Brabant
Hyperleptinaemia is known to be positively associated with obesity in
females. Therefore, circulating leptin concentrations are predicted by body
mass index (BMI). Additional effects of endogenous C19-steroids, sex
hormone binding globulin (SHBG), luteinizing hormone (LH), follicle
stimulating hormone (FSH), C-peptide and insulin on the predictive value of
BMI on serum leptin were investigated in 56 hyperandrogenaemic and/or
hyperinsulinaemic and/or obese premenopausal women. Serum concentrations
(after an overnight 12 h fast) of leptin, total testosterone, free
testosterone, SHBG, dehydroepiandrosterone sulphate (DHEAS), LH, FSH, and
oestradiol as well as serum concentrations of C- peptide and insulin prior
to, and 1 h after, an oral 100 mg glucose load (1 h values) were determined
by immunoassays. Subjects with regular menstrual cycles were studied in the
mid-follicular phase while the remainder were studied at random. Nineteen
normotestosteronaemic, normoinsulinaemic, lean and ovulatory volunteers
served as controls; in order to determine the effect of different stages of
the menstrual cylce, serum concentrations of leptin (and of oestradiol in
12 out of the 19 individuals) were determined at the preovulatory, the
mid-luteal and the following mid-follicular phase. Significant differences
between the patients versus control were not found possibly because of the
heterogeneity in the patient group. Multiple regression indicated a
hyperbolic correlation between BMI and leptin concentrations. As expected,
BMI was the major determinant responsible for >50% (R2=0.51) of the
elevation of leptin concentrations. The combination of BMI with fasting
C-peptide or fasting insulin enhanced the R2 up to 0.59. The multiple
regression with two explaining parameters showed a significant regression
coefficient for BMI at the 0.001 level, and for fasting C- peptide and
fasting insulin at the 0.01 level, which was as statistically significant
as the combination of BMI with the 1 h values of C-peptide and of insulin.
In contrast, total testosterone, free testosterone, SHBG, free
testosterone/SHBG ratio, DHEAS and LH/FSH ratio had no effect. Similarly,
models with more than two variables did not measurably improve the
explained variation. In the control group, leptin concentrations were
significantly higher in preovulatory and mid- luteal phases than the two
mid-follicular phases (P < or = 0.05) and must be considered when
determining sampling time. In conclusion, hyperandrogenaemia does not have
a predictive value on leptin concentrations in premenopausal subjects but
hyperinsulinaemia exerts an effect independent of obesity that is the
strongest predictor for elevation of leptin concentrations.
Hyperinsulinaemia might contribute to the hyperbolic correlation of
circulating leptin in obese patients.
ARTICLES
C-peptide and insulin, but not C19-steroids, support the predictive value of body mass index on leptin in serum of premenopausal women
Institute for Gynaecological Endocrinology and Reproductive Medicine, Freiburg, Germany.
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