Modification of plasma insulin-like growth factors and binding proteins during oral contraceptive use and the normal menstrual cycle

OBJECTIVE: Sex steroid regulation of the insulin-like growth factor axis is a subject of contention. We examined the effect of combined oral contraceptives and investigated the cyclic variations in the insulin-like growth factor axis. STUDY DESIGN: Fasting blood samples were taken from 9 women receiving oral contraceptives, 10 women receiving no medication, and 10 male subjects. RESULTS: in women receiving oral contraceptives, insulin-like growth factor binding protein 1 remained highly phosphorylated and levels were acutely increased by sex steroid treatment (305 ± 110 μg/L on day 14 of the cycle [medication phase] vs 118 ± 70 μg/L during the medication- free period, P <.03). In women receiving no medication, insulin-like growth factor binding protein 1 levels were significantly lower (69 ± 50 μg/L on day 14 of the menstrual cycle, P <.001) and varied cyclically, with a rise in the late-secretory phase that coincided with the appearance of nonphosphorylated and less phosphorylated insulin-like growth factor binding protein 1 isoforms. Compared with those in untreated women and in men. insulin-like growth factor I levels were decreased in women receiving oral contraceptives (405 ± 104 ng/mL in untreated women and 330 ± 28 ng/mL in men vs 287 ± 73 ng/mL in women receiving oral contraceptives, P <.004). Oral contraceptive use had no effect on insulin-like growth factor II levels, and neither insulin-like growth factor I nor insulin-like growth factor II showed cyclic variation. CONCLUSION: The bioavailability of insulin-like growth factor I is reduced in users of oral contraceptives. This may contribute to the metabolic changes observed in such subjects.