Sex Steroids and the Growth Hormone/Insulin-Like Growth Factor-I Axis in Adults

Abstract

In healthy adults insulin-like growth factor (IGF)-I levels do not differ between males and females, whereas spontaneous growth hormone (GH) secretion is approximately twofold higher in females. Untreated GH-deficient (GHD) women exhibit lower IGF-I levels compared with men and the increase in serum IGF-I during GH replacement is also significantly less. These data suggest a resistance to GH in women, which in healthy subjects is compensated for by increased GH secretion. Administration of oral oestrogen in healthy postmenopausal women suppresses hepatic IGF-I production and increases pituitary GH release, and oral oestrogen replacement in women with GHD lowers IGF-I concentrations and increases the amount of GH necessary to achieve IGF-I target levels during treatment. These data clearly suggest that hepatic suppression of IGF-I production by oestrogen subserves the gender difference in GH sensitivity, but it is also likely that sex steroids may interact with the GH/IGF axis at other levels. There is also circumstantial evidence to indicate that testosterone stimulates IGF-I production and it is speculated that a certain threshold level of androgens is essential to ensure hepatic IGF-I production. Whether these data should translate into earlier discontinuation of oestrogen replacement therapy in women with hypopituitarism merits consideration.

Is there a relationship between spontaneous GH secretion, anthropometric parameters and exercise capacity in healthy men over 50 years?

“…Among women with GH deficiency, the estrogen use leads to an increase in the necessary dose of GH to reach the same target level of IGF-I during the treatment. These data confirm a difference concerning gender in regards to sensitivity to GH, although other data suggest that sexual steroids might interact in other levels with the IGF-I/GH [22,23].…”

Gender differences in serum GH and IGF-I levels and the GH response to dynamic tests in patients with acromegaly

“…Administration of oral estrogen in healthy postmenopausal female induces a 30% decrease in serum IGF-I levels and increases pituitary GH secretion, indicating that estrogen antagonizes GH-induced hepatic IGF-I production [15]. Recently, Leung et al described the mechanism of this phenomenon.…”

IGF-I measurements in the diagnosis of adult growth hormone deficiency

“…Women with GH deficiency have lower IGF-I levels compared with GH-deficient men [21][22][23]. Administration of oral estrogen in women with GH deficiency lowers IGF-I concentrations and increases the amount of GH necessary to achieve IGF-I target levels during GH replacement therapy [24]. However, there is less of an effect on serum IGF-I levels when low doses of transdermal estrogen are used [25].…”