http://www.ncbi.nlm.nih.gov/entrez/...b=pubmed&list_uids=15689918&dopt=ExternalLink
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Pubertal upregulation of erythropoiesis in boys is determined primarily by androgen.
Hero M, Wickman S, Hanhijarvi R, Siimes MA, Dunkel L.
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
OBJECTIVES: To study the relative roles of androgens and the growth hormone-insulin-like growth factor I (GH-IGF-I) system in the regulation of erythropoiesis in boys during puberty. STUDY DESIGN: We treated 23 boys with constitutional delay of puberty with low-dose testosterone (T), in combination with either a potent aromatase inhibitor, letrozole (Lz; 2.5 mg/d), or placebo (P). The study design was randomized, double-blinded, and placebo-controlled between the treated groups. Treatment with T + Lz was associated with high T and low IGF-I concentrations, whereas treatment with T + P resulted in moderately increased T and high IGF-I concentrations. RESULTS: The blood hemoglobin concentration increased by 1.6 g/dL in T + Lz-treated boys, despite their low IGF-I concentrations. The estimated red blood cell volume increased more in T + Lz-treated than in T + P-treated boys (349 vs 174 mL, respectively, P = .01). Serum T concentrations during the treatment period correlated with the 12-month increments in hemoglobin and red blood cell volume. The changes in blood hemoglobin concentration and RBC in T + Lz-treated boys were similar to those we observed in a population of normal adolescent boys in the late stages of puberty. CONCLUSIONS: The pubertal increase in hemoglobin concentration in boys is related to direct androgen effects.
http://www.ncbi.nlm.nih.gov/entrez/...d&dopt=Abstract&list_uids=14623531&query_hl=1
Novel treatment of short stature with aromatase inhibitors.
Dunkel L, Wickman S.
Hospital for Children and Adolescents, University of Helsinki, PO Box 281, Helsinki 00029 HUS, Finland.
leo.dunkel@hus.fi
Estrogens have an essential role in the regulation of bone maturation and importantly in the closure of growth plates in both coïtuses. This prospective, randomized, placebo-controlled study was undertaken to evaluate whether suppression of estrogen synthesis in pubertal boys delays bone maturation and ultimately results in increased adult height. A total of 23 boys with constitutional delay of puberty (CDP) received a conventional, low-dose testosterone treatment for inducing progression of puberty. Eleven of these 23 boys were randomized to receive a specific and potent P450-aromatase inhibitor, letrozole, for suppression of estrogen action, and 12 boys were randomized to receive placebo. Estradiol concentrations in the letrozole-treated boys remained at the pretreatment level during the administration of letrozole, whereas the concentrations increased during the treatment with testosterone alone and during spontaneous progression of puberty. Testosterone concentrations increased in all groups, but during the letrozole treatment, the increase was more than fivefold higher than in the group treated with testosterone alone. The inhibition of estrogen synthesis delayed bone maturation. The slower bone maturation in the boys treated with testosterone and letrozole, despite higher androgen concentrations, than in the boys treated with testosterone indicate that estrogens are more important than androgens in regulation of bone maturation in pubertal boys. During the 18 months follow-up, an increase of 5.1 cm in predicted adult height was observed in the boys who received testosterone and letrozole, but no change was seen in the boys who received testosterone alone or in the untreated boys. This finding indicates that an increase in adult height can be attained in growing adolescent boys by inhibiting of estrogen action.
http://www.ncbi.nlm.nih.gov/entrez/...d&dopt=Abstract&list_uids=11983488&query_hl=1
Short-term effects of anastrozole treatment on insulin-like growth factor system in postmenopausal advanced breast cancer patients.
Ferrari L, Martinetti A, Zilembo N, Pozzi P, Buzzoni R, La Torre I, Gattinoni L, Catena L, Vitali M, Celio L, Seregni E, Bombardieri E, Bajetta E.
Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan, Via G. Venezian, 1, 20133 Milan, Italy.
Insulin-like growth factors (IGFs) play a fundamental role in cancer development by acting in both an endocrinal and paracrinal manner, and hormone breast cancer treatments affect the IGF system by modifying circulating growth factor levels. We evaluated total IGF-1, IGF-2, IGF binding protein (IGFBP)-1 and IGFBP-3 in the blood of 34 postmenopausal advanced breast cancer patients (median age 63 years, range 41-85) treated with anastrozole, a non-steroidal structure aromatase inhibitor (NSS-AI). The plasma samples were obtained at baseline, and after 2, 4, 8 and 12 weeks of treatment. The IGFs were quantitated by means of sensitive radioimmunoassays (RIAs). IGF-1 significantly increased during anastrozole treatment (baseline versus 12 weeks, P=0.031), IGF-2 showed a trend towards an increase, and IGFBP-1 constantly but not significantly decreased; IGFBP-3 did not seem to be affected at all. The anastrozole-induced changes in IGFs and IGFBP-1 appeared to be different in the patients receiving a clinical benefit from those observed in non-responders. We have previously shown that letrozole (a different type of NSS-AI) modifies blood IGF-1 levels, and the results of this study of the biological effects of anastrozole on the components of the IGF system confirm our previous observations.
PMID: 11983488 [PubMed - indexed for MEDLINE]
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