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Effects of intranasal 17beta-estradiol on bone turnover and serum insulin-like growth factor I in postmenopausal women.
J Clin Endocrinol Metab. 1999 Jul; 84(7):2390-7.JC

Abstract

Estrogen therapy, using either oral or transdermal routes, decreases bone turnover and prevents postmenopausal bone loss. It has been suggested that oral and transdermal 17beta-estradiol (E2) may have different effects on serum insulin-like growth factor I (IGF-I), a potent bone-forming growth factor. In this study we investigated the effects of a new route of administration, the intranasal E2 spray (S21400), on bone turnover and circulating IGF-I and IGF-binding protein-3 (IGFBP-3). Four hundred and twenty early postmenopausal women (<5 yr since menopause; mean age, 52 yr) were enrolled in a 3-month, double blind, placebo-controlled study of four doses of intranasal E2 (100, 200, 300, and 400 microg/day), two doses of oral E2 valerate (1 or 2 mg/day), and placebo. One hundred and twelve women were further treated for 12 months with intranasal E2 (300 microg/day, i.e. the dose that has been shown to be adequate for the majority of postmenopausal women). Markers of bone resorption (urinary type I collagen C telopeptides) and formation [serum osteocalcin, serum type I collagen N-terminal extension propeptide (PINP), and serum bone alkaline phosphatase (BAP)] were measured at baseline, 1 month, 3 months, and 15 months. Serum IGF-I and IGFBP-3 were measured at baseline, 1 month, and 3 months. Urinary type I collagen C telopeptides decreased significantly in all active treatment groups as soon as 1 month (P<0.001 vs. placebo) and continued to decrease at 3 months with a dose effect for intranasal E2. Serum osteocalcin and PINP did not change at 1 month for oral E2 (1 and 2 mg), but decreased significantly at 3 months. In contrast, formation markers increased significantly at 1 month for the two highest doses of intranasal E2 (P<0.01 vs. placebo for osteocalcin and BAP) and did not decrease at 3 months. Oral E2 induced a marked decrease in circulating IGF-I as early as 1 month, which was amplified at 3 months (-29% and -32% for 1 and 2 mg, respectively), whereas no significant change from placebo was observed for intranasal E2 during the 3-month period. Changes in circulating IGF-I correlated significantly (P<0.01) with changes in osteocalcin, PINP, and BAP at 3 months. Oral and intranasal E2 did not induce any significant change from placebo in serum IGFBP-3 at both 1 and 3 months. After 1 yr of treatment with intranasal E2 (300 microg/day), both resorption and formation markers decreased, reaching the levels in premenopausal women, regardless of the type of treatment during the first 3 months. We conclude that E2 administered by this new nasal route normalizes bone turnover to premenopausal levels. The delayed decrease in bone formation observed with intranasal E2 compared to oral E2 may be related to different effects on serum IGF-I levels.

Authors+Show Affiliations

INSERM U-403, Hôpital E. Herriot, Lyon, France. patrick.garnero@synarc.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

10404809

Citation

Garnero, P, et al. "Effects of Intranasal 17beta-estradiol On Bone Turnover and Serum Insulin-like Growth Factor I in Postmenopausal Women." The Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 7, 1999, pp. 2390-7.
Garnero P, Tsouderos Y, Marton I, et al. Effects of intranasal 17beta-estradiol on bone turnover and serum insulin-like growth factor I in postmenopausal women. J Clin Endocrinol Metab. 1999;84(7):2390-7.
Garnero, P., Tsouderos, Y., Marton, I., Pelissier, C., Varin, C., & Delmas, P. D. (1999). Effects of intranasal 17beta-estradiol on bone turnover and serum insulin-like growth factor I in postmenopausal women. The Journal of Clinical Endocrinology and Metabolism, 84(7), 2390-7.
Garnero P, et al. Effects of Intranasal 17beta-estradiol On Bone Turnover and Serum Insulin-like Growth Factor I in Postmenopausal Women. J Clin Endocrinol Metab. 1999;84(7):2390-7. PubMed PMID: 10404809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of intranasal 17beta-estradiol on bone turnover and serum insulin-like growth factor I in postmenopausal women. AU - Garnero,P, AU - Tsouderos,Y, AU - Marton,I, AU - Pelissier,C, AU - Varin,C, AU - Delmas,P D, PY - 1999/7/15/pubmed PY - 1999/7/15/medline PY - 1999/7/15/entrez SP - 2390 EP - 7 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 84 IS - 7 N2 - Estrogen therapy, using either oral or transdermal routes, decreases bone turnover and prevents postmenopausal bone loss. It has been suggested that oral and transdermal 17beta-estradiol (E2) may have different effects on serum insulin-like growth factor I (IGF-I), a potent bone-forming growth factor. In this study we investigated the effects of a new route of administration, the intranasal E2 spray (S21400), on bone turnover and circulating IGF-I and IGF-binding protein-3 (IGFBP-3). Four hundred and twenty early postmenopausal women (<5 yr since menopause; mean age, 52 yr) were enrolled in a 3-month, double blind, placebo-controlled study of four doses of intranasal E2 (100, 200, 300, and 400 microg/day), two doses of oral E2 valerate (1 or 2 mg/day), and placebo. One hundred and twelve women were further treated for 12 months with intranasal E2 (300 microg/day, i.e. the dose that has been shown to be adequate for the majority of postmenopausal women). Markers of bone resorption (urinary type I collagen C telopeptides) and formation [serum osteocalcin, serum type I collagen N-terminal extension propeptide (PINP), and serum bone alkaline phosphatase (BAP)] were measured at baseline, 1 month, 3 months, and 15 months. Serum IGF-I and IGFBP-3 were measured at baseline, 1 month, and 3 months. Urinary type I collagen C telopeptides decreased significantly in all active treatment groups as soon as 1 month (P<0.001 vs. placebo) and continued to decrease at 3 months with a dose effect for intranasal E2. Serum osteocalcin and PINP did not change at 1 month for oral E2 (1 and 2 mg), but decreased significantly at 3 months. In contrast, formation markers increased significantly at 1 month for the two highest doses of intranasal E2 (P<0.01 vs. placebo for osteocalcin and BAP) and did not decrease at 3 months. Oral E2 induced a marked decrease in circulating IGF-I as early as 1 month, which was amplified at 3 months (-29% and -32% for 1 and 2 mg, respectively), whereas no significant change from placebo was observed for intranasal E2 during the 3-month period. Changes in circulating IGF-I correlated significantly (P<0.01) with changes in osteocalcin, PINP, and BAP at 3 months. Oral and intranasal E2 did not induce any significant change from placebo in serum IGFBP-3 at both 1 and 3 months. After 1 yr of treatment with intranasal E2 (300 microg/day), both resorption and formation markers decreased, reaching the levels in premenopausal women, regardless of the type of treatment during the first 3 months. We conclude that E2 administered by this new nasal route normalizes bone turnover to premenopausal levels. The delayed decrease in bone formation observed with intranasal E2 compared to oral E2 may be related to different effects on serum IGF-I levels. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/10404809/Effects_of_intranasal_17beta_estradiol_on_bone_turnover_and_serum_insulin_like_growth_factor_I_in_postmenopausal_women_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.84.7.5848 DB - PRIME DP - Unbound Medicine ER -