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 contracep tives and investigated the cyclic variations in the insulin-like growth fac tor 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 i ncreased by sex steroid treatment (305 +/- 110 mu g/L on day 14 of the cycl e [medication phase] vs 118 +/- 70 mu g/L during the medication-free period , P <.03). In women receiving no medication, insulin-like growth factor bin ding protein 1 levels were significantly lower (69 +/- 50 mu g/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 nonphosphorylate d and less phosphorylated insulin-like growth factor binding protein 1 isof orms. Compared with those in untreated women and in men, insulin-like growt h factor I levels were decreased in women receiving oral contraceptives (40 5 +/- 104 ng/mL in untreated women and 330 +/- 28 ng/mL in men vs 287 +/- 7 3 ng/mL in women receiving oral contraceptives, P<.004). Oral contraceptive use had no effect on insulin-like growth factor II levels, and neither ins ulin-like growth factor I nor insulin-like growth factor II showed cyclic v ariation. CONCLUSION: The bioavailability of insulin-like growth factor I is reduced in users of oral contraceptives. This may contribute to the metabolic chang es observed in such subjects.