Modulation by progestogens of the effects of oestrogen on hepatic endocrine function in postmenopausal women

Nugent, Ailish G.; Leung, Kin‐Chuen; Sullivan, David; Reutens, Anne T.; Ho, Ken K. Y.

doi:10.1046/j.1365-2265.2003.01907.x

Cited by 30 publications

(26 citation statements)

References 41 publications

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“…At least the potentially stimulating effect of the synthetic progesterone on collagen turnover is overruled by the ethinyl estradiol administration. In support, exogenous progestogens have been shown to enhance the IGF-I concentration (50), whereas in the present study IGF-I was reduced after OC administration, which underlines the dominating effect of estradiol compared with the effect of progestogens.…”

Section: Effect Of Oc On Sex Hormonal Concentrationscontrasting

confidence: 48%

Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

Hansen

Miller²,

Holm³

et al. 2009

Journal of Applied Physiology

106

104

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M, Langberg H. Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women. J Appl Physiol 106: 1435-1443, 2009. First published October 9, 2008 doi:10.1152/japplphysiol.90933.2008Women are at greater risk than men for certain kinds of diseases and injuries, which may at least partly be caused by sex hormonal differences. We aimed to test the influence of estradiol in vivo on collagen synthesis in tendon, bone, and muscle. Two groups of young, healthy women similar in age, body composition, and exercisetraining status were included. The two groups were either habitual users of oral contraceptives exposed to a high concentration of synthetic estradiol and progestogens (OC, n ϭ 11), or non-OC-users tested in the follicular phase of the menstrual cycle characterized by low concentrations of estradiol and progesterone (control, n ϭ 12). Subjects performed 1 h of one-legged kicking exercise. The next day collagen fractional synthesis rates (FSR) in tendon and muscle connective tissue were measured after a flooding dose of [ 13 C]proline followed by biopsies from the patellar tendon and vastus lateralis in both legs. Simultaneously, microdialysis catheters were inserted in vastus lateralis and in front of the patellar tendon for measurement of insulin-like growth factor I (IGF-I) and its binding proteins. Serum NH 2-terminal propeptide of type I collagen (PINP) and urine COOHterminal telopeptides of type-I collagen (CTX-I) were measured as markers for bone synthesis and breakdown, respectively. Tendon FSR and PINP were lower in OC compared with control. An increase in muscle collagen FSR postexercise was only observed in control (P Ͻ 0.05). Furthermore, the results indicate a lower bioavailability of IGF-I in OC. In conclusion, synthetic female sex hormones administered as OC had an inhibiting effect on collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I. estrogen; exercise; insulin-like growth factor I; ethinyl estradiol; bone COLLAGEN is the most abundant protein in the human body and comprises a very high fraction of the tissue organic mass in bone (90%), tendon (60 -85%), ligament (70%), and intramuscular connective tissue (ϳ30% and up to 90%) (31, 57). The frequency of several diseases linked to collagen-rich tissue seems to be biased by sex (30,34,36,65). Furthermore, women are at a greater risk than men for sustaining certain kinds of soft tissue sports injuries (7, 24, 26). Several epidemiological studies have shown that women have up to six times greater risk of anterior cruciate ligament (ACL) ruptures than activity-matched men (24). It has been suggested that sex hormones may influence collagen turnover, tissue composition, and biomechanical properties of the tissues, which in part may explain sex-specific differences in risk (24). In support of this, tendon collagen synthesis is lower in women compared with men at rest and after exercise (47). In addition, a lower p...

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Section: Effect Of Oc On Sex Hormonal Concentrationscontrasting

confidence: 48%

Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

Hansen

Miller²,

Holm³

et al. 2009

Journal of Applied Physiology

106

104

View full text Add to dashboard Cite

show abstract

“…Several studies (14)(15)(16) have examined the effect of exogenous progestogens on IGF-1 levels. The most recent study found that, when used in combination with oral or transdermal oestrogen, the more androgenic progestogens resulted in either no reduction of IGF-1 levels with oral oestrogen or an actual increase in IGF-1 levels with transdermal oestrogen (16). This suggests that oral progesterone, at least in its most androgenic form, may increase GH sensitivity.…”

Section: Discussionmentioning

confidence: 99%

GH responsiveness varies during the menstrual cycle

Gleeson

Shalet²

2005

eur j endocrinol

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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

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“…Small intervention studies (2,3,4,5,6,7,8,9,10) and large cross-sectional studies (11,12,13,14,15) have demonstrated that oral estrogens reduce serum concentrations of total IGF1. These findings have been observed both in menopausal women and in those with hypopituitarism.…”

Section: Introductionmentioning

confidence: 99%

Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study

Isotton

Wender

Casagrande

et al. 2012

European Journal of Endocrinology

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Objective: To evaluate the effects of oral estradiol and transdermal 17b-estradiol on serum concentrations of IGF1 and its binding proteins in women with hypopituitarism. Design: Prospective, comparative study. Methods: Eleven patients with hypopituitarism were randomly allocated to receive 2 mg oral estradiol (nZ6) or 50 mg/day of transdermal 17b-estradiol (nZ5) for 3 months. Results: The oral estrogen group showed a significant reduction in IGF1 levels (mean: 42.7%G41.4, PZ0.046); no difference was observed in the transdermal estrogen group. There was a significant increase in IGFBP1 levels (mean: 170.2%G230.9, PZ0.028) in the oral group, but not in the transdermal group. There was no significant difference within either group in terms of median IGFBP3 levels. In relation to lipid profiles, there was a significant increase in mean high-density lipoprotein cholesterol levels in the oral group after 3 months of treatment, (27.8G9.3, PZ0.003). We found no differences in the anthropometric measurements, blood pressure, heart rate, glucose, insulin, C-peptide, or the homeostasis model assessment index after treatment. Conclusions: Our preliminary data indicate that different estrogen administration routes can influence IGF1 and IGFBP1 levels. These findings in patients with hypopituitarism have an impact on their response to treatment with GH, since patients receiving oral estrogen require increased GH dosage. These results suggest that oral estrogens may reduce the beneficial effects of GH replacement on fat and protein metabolism, body composition, and quality of life.

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Modulation by progestogens of the effects of oestrogen on hepatic endocrine function in postmenopausal women

Cited by 30 publications

References 41 publications

Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

GH responsiveness varies during the menstrual cycle

Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study

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