GH responsiveness varies during the menstrual cycle

Abstract

Objective: The GH -IGF-1 axis is affected by oestrogen. Both endogenous and exogenous oestrogen facilitates the central drive of pulsatile GH secretion. However, the effect on IGF-1 levels is more subtle, and a reduction in GH sensitivity has been proposed. The IGF generation test has confirmed reduced GH sensitivity with high doses of exogenous oestrogen. It is not known, however, whether fluctuant levels of endogenous oestrogen modify GH sensitivity. To investigate this further, women were challenged with the IGF-1 generation test at different stages of the menstrual cycle. Methods: Nine women (age 38(6) years (mean (S.D.)) with regular menstrual cycles were recruited. An IGF-1 generation test, s.c. injection of 7 mg GH, was performed in the early-follicular (EF), periovulatory (PO) and midluteal (ML) phases. IGF-1, insulin-like growth factor binding protein (IGFBP)-3 and acid-labile subunit (ALS) levels were measured at baseline and 24 h after GH administration. Results: Oestradiol levels were lower in the EF than PO or ML phases (32.6(7.8) vs 69.6(16.2) vs 66.6(23.6) pg/ml respectively (repeated measures ANOVA, P , 0.001)). Baseline IGF-1 was lower, but increment IGF-1 (peak minus baseline) was higher in the EF than PO or ML phases (baseline: 291.8(56.6) vs 335.0(55.2) vs 346.6(78.2) ng/ml (P ¼ 0.008); increment IGF-1: 234.6(59.2) vs 194.7(37.8) vs 185.2(37.3) ng/ml (P ¼ 0.008)). Conclusions: Increased endogenous oestrogen levels are associated with only a modestly elevated baseline IGF-1 from midcycle onward despite a previously reported twofold increase in GH secretion. In parallel with this apparent GH insensitivity, increased endogenous oestrogen levels are associated with reduction in GH sensitivity evidenced by reduction in increment IGF-1. This may have clinical implications for women with isolated GH deficiency with regular menstrual cycles on a fixed dose of GH. This possibility requires further study. European Journal of Endocrinology 153 775-779

Endogenous estradiol may influence IGF-I levels in acromegalic women treated with pegvisomant

“…GH levels are higher in women than in men and lower in postmenopausal women compared to young women [2,3]. During menstrual cycle, GH levels vary in strong correlation to estrogen levels, showing higher GH and IGF-I levels after midcycle [4] and during the periovulatory phase than during the early follicular phase [5]. Furthermore, oral exogenous estrogens reduce IGF-I levels [6] and increase GH levels which is suggested to be caused by a decrease in GH sensitivity [4] or a loss of negative feedback by IGF-I [7].…”

“…During menstrual cycle, GH levels vary in strong correlation to estrogen levels, showing higher GH and IGF-I levels after midcycle [4] and during the periovulatory phase than during the early follicular phase [5]. Furthermore, oral exogenous estrogens reduce IGF-I levels [6] and increase GH levels which is suggested to be caused by a decrease in GH sensitivity [4] or a loss of negative feedback by IGF-I [7]. Transdermal application of estrogen seems to have less influence on IGF-I levels [7], although at high doses it may also have a suppressive effect on IGF-I [8].…”

Does IGF-1 play a role in the biology of ovarian cancer?

“…Furthermore, after the menopause, a decrease not only in total serum IGF-1 but also in the concentration of its biologically active form, i.e. free IGF-1, have been observed [10,11,[19][20][21]. On the other hand, some sources reported no changes in serum IGF-1 levels depending on different phases of the menstrual cycle, and found no correlation between IGF-1 levels and endogenous serum estrogen concentrations [22][23][24].…”

Lumbar Bone Mineral Density and Insulin-like Growth Factor Binding Protein-3 in Japanese Collegiate Women

“…In addition, physical exercise was not allowed 48 hr prior to the blood sampling to avoid the acute effects of exercise, and beverages other than water could not be consumed 24 hr prior to the blood sampling. Furthermore, because GH, IGF-1, and estrogen levels change throughout the menstrual cycle, 29,30) blood samples were obtained between days 7 and 9 of the menstrual cycle when estrogen levels were relatively low. 25) Physical activity, [17][18][19] and dietary and nutrient intakes, such as Ca, phosphorus, protein, vitamin D, fruit, vegetables, and milk intakes, [17][18][19][20] have been reported to influence BMD.…”

“…Each food item was coded according to the Tables of Japanese Foodstuff Composition. 28) Blood Analysis --Because GH and IGF-1 levels change throughout the menstrual cycle, 29,30) blood samples were obtained between days 7 and 9 of the menstrual cycle when estrogen levels were relatively low. 25) Physical exercise was not allowed 48 hr prior to the blood sampling, and beverages other than water could not be consumed 24 hr prior to the blood sampling.…”