The insulin-like growth factor-I system and hormone replacement therapy

Background: IGF-I suppression in acromegaly obtained by tamoxifen, a selective estrogen receptor modulator (SERM), prompted us to evaluate the effects of the administration of a newer SERM, raloxifene (RAL), devoid of estrogenic activity at uterine level, on GH/IGF-I levels in patients with this disease. Patients: Thirteen post-menopausal acromegalic women (aged 55-84 years) with active acromegaly entered a prospective open pilot study of RAL treatment at 60 mg/day. Nine of the patients, who were resistant to somatostatin analog and dopamine agonist treatment, were not undertaking therapy; the other four, who were partially sensitive to medical treatment, maintained treatment at the maximally effective dosages throughout the study. Results: IGF-I levels fell significantly from 444 (median, interquartile 393-590) mg/l to 300 (216 -608) mg/l ðP ¼ 0:0192Þ after 1 month of RAL administration and this fall remained stable up to the final evaluation at 5^1 months from the start of RAL treatment (260 (187-410) mg/l). An IGF-I decrease greater than 30% of basal values was observed in 10 patients (mainly in patients with IGF-I levels lower than 600 mg/l) and normal values were reached in seven (54%). GH levels did not change (basal 6 (4.1 -8) mg/l, final 5.5 (3.2-7.4) mg/l). The clinical picture improved in patients sensitive to RAL. RAL withdrawal was followed by the return of IGF-I levels to pretreatment values within 8 weeks in all patients. Conclusions: RAL decreases IGF-I levels in most acromegalic women with mild or intermediate disease (i.e. with values lower than 600 mg/l) and normalizes it in many. A prospective randomized study in patients resistant or partially sensitive to other medical treatments is warranted.

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“…However, no change in these proteins has been reported in most studies after the administration of oral estrogen or SERMs (22,24,26,42,43).…”

Section: Discussionmentioning

confidence: 96%

Raloxifene lowers IGF-I levels in acromegalic women

Attanasio

Barausse

Cozzi

2003

European Journal of Endocrinology

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“…Serum IGFBP1 levels are inversely related to the development of diabetes mellitus type 2, particularly in the presence of reduced IGF1 concentrations (24). Helle et al (6) demonstrated a 46% increase in serum IGFBP1 levels after use of oral estrogens, and their findings were later confirmed by other authors (4,5).…”

Section: Introductionmentioning

confidence: 92%

“…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%

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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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“…In postmenopausal women, oral estrogen supplementation caused no change (34, 37, 44, 45) or a limited decrease (35, 47) in IGFBP-3 levels. Transdermal estrogen supplementation had no effect on IGFBP-3 either (34, 45,46,48). Circulating IGFBP-3 levels also remained unchanged in adult Turner women who started estrogen therapy.…”

Section: Discussionmentioning

confidence: 92%

Ethinylestradiol and testosterone have divergent effects on circulating IGF system components in adolescents with constitutional tall stature

et al. 2005

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Objective: Pharmacological doses of estrogens or testosterone are used to limit the final height of girls or boys with constitutional tall stature but the mechanism behind this growth inhibition is still debated. We therefore studied the changes in the circulating components of the insulin-like growth factor (IGF) system during high dose sex steroid therapy. Design and methods: Twenty three girls and twenty boys with constitutional tall stature were treated with 100 mg ethinylestradiol per day or 250 mg testosterone ester every 14 days respectively. In 19 girls and 18 boys, the levels of IGF-I, free IGF-I, IGF-II, acid-labile subunit (ALS) and IGF binding proteins (IGFBP)-2 to -6 were measured before and 3-6 months after the start of therapy (group 1). In 18 girls and 11 boys, samples were collected at the end of therapy and 3 to 6 months afterwards (group 2). Fourteen girls and nine boys belonged to both groups. All parameters were measured by radioimmunoassay or ELISA. Results: Levels of IGF-I were decreased significantly by estrogen treatment but remained unchanged during testosterone treatment. Free IGF-I decreased during estrogen treatment but increased during testosterone therapy. Estrogens increased IGF-II and testosterone reduced it. The important reduction of IGFBP-2 during estrogen therapy is not reproduced by androgen therapy, neither is the stimulation by estrogens of IGFBP-4. IGFBP-3 is not modulated by either sex steroid. We found that IGFBP-6 is up-regulated by testosterone but not by estrogens; the reverse is true for ALS, which increased during estrogen treatment but remained unchanged during testosterone treatment.Conclusions: Our findings demonstrate that androgens and estrogens exert differential effects on the circulating levels of several IGF components.European Journal of Endocrinology 152 597-604

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The insulin-like growth factor-I system and hormone replacement therapy

Cited by 55 publications

References 29 publications

Raloxifene lowers IGF-I levels in acromegalic women

Raloxifene lowers IGF-I levels in acromegalic women

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

Ethinylestradiol and testosterone have divergent effects on circulating IGF system components in adolescents with constitutional tall stature

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