HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Christiansen, J. J. Articles by Jørgensen, J. O. L. Search for Related Content PubMed PubMed Citation Articles by Christiansen, J. J. Articles by Jørgensen, J. O. L.

Discontinuation of estrogen replacement therapy in GH-treated hypopituitary women alters androgen status and IGF-I

Medical Department M, Århus Sygehus, Århus University Hospital, Nørrebrogade 44, DK-8000 Århus C, Denmark, ¹ Statens Serum Institut, Copenhagen, Denmark, ² Department of Endocrinology, Odense University Hospital, Odense, Denmark and ³ Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark

(Correspondence should be addressed to C H Gravholt; Email: ch.gravholt{at}dadlnet.dk)

Objective and design: Compared with their male counterparts, healthy females secrete more growth hormone (GH) and those with GH-deficiency have lower insulin-like growth factor I (IGF-I) levels and are less responsive to GH substitution. To test whether this gender difference is related to sex hormones we measured androgen status and IGF-I related parameters in 38 hypopituitary women (mean (range) age 41.5 (20–58) years) during continued GH substitution as compared with a control group of 38 healthy women matched for age and menopausal status. Twenty six patients were studied twice: with estrogen replacement and after 28 days of estrogen discontinuation in a randomised design.

Results: The patients were androgen deficient compared with controls (median, range), dehydroepiandrosterone sulphate (DHEAS): 185 (99–7800) nmol/l vs 4400 (820–13 000) nmol/l, P = < 0.001; androstenedione: 0.5 (0.1–7.1) nmol/l vs 4.3 (1.6–8.8) nmol/l, P = < 0.001; dihydrotestosterone (DHT): 0.13 (0.09–0.54) nmol/l vs 0.55 (0.09–0.89) nmol/l, P = < 0.001; testosterone: 0.28 (0.09–1.56) nmol/l vs 1.1 (0.71–2.24) nmol/l, (P = < 0.001); free testosterone: 0.004 (0.001–0.030) nmol/l vs 0.016 (0.001–0.030) nmol/l, P = < 0.001. The circulating levels of IGF-I, IGF-II, IGF-binding protein 1 (IGFBP-1), and IGFBP-3 did not differ between patients and controls. The subgroup of patients receiving hydrocortisone (HC) replacement (n = 24) had significantly lower levels of androgens (suppressed by 80–100%) as well as IGF-I and IGFBP-3 as compared with the patients not receiving HC. IGF-I was correlated to free testosterone in patients (r = 0.57, P = 0.0005) as well as controls (r = 0.43, P = 0.008), and free testosterone was a significant positive predictor of IGF-I. Estrogen discontinuation induced an increase in IGF-I (167 ± 15 vs 206 ± 14 µg/l, P = 0.005 and IGFBP-3 (3887 ± 139 vs 4309 ± 138 µg/l, P = 0.0005). Estrogen discontinuation was associated with a significant increase in median (range) free testosterone (0.004 (0–0.02) vs 0.0065 (0–0.03) nmol/l, P = 0.001) and a significant decrease in median (range) sex-hormone binding globulin (SHBG; 93 (11–278) vs 55.5 (20–142) nmol/l, P = 0.001). IGF-I correlated with SHBG (r = –0.45 P = 0.033) and IGFBP-3 (r = 0.67 P = < 0.001). In a regression model E2, testosterone, SHBG and IGFBP-3 explained 93% of the variation in IGF-I.

Conclusions: Androgen levels are low in hypopituitary women and free testosterone correlates with IGF-I. Discontinuation of estrogen replacement in these patients induces elevations in IGF-I as well as free testosterone, and IGF-I correlated positively with free testosterone. These effects may contribute to the gender differences observed in the GH–IGF axis in healthy adults as well as in the responsiveness of hypopituitary patients to GH substitution.

This article has been cited by other articles:

				A. A van der Klaauw, N. R Biermasz, P. M J Zelissen, A. M Pereira, E. G W M Lentjes, J. W A Smit, S. W van Thiel, J. A Romijn, and F. Roelfsema Administration route-dependent effects of estrogens on IGF-I levels during fixed GH replacement in women with hypopituitarism Eur. J. Endocrinol., December 1, 2007; 157(6): 709 - 716. [Abstract] [Full Text] [PDF]

				G Hudelist, T Wagner, M Rosner, A Fink-Retter, D Gschwantler-Kaulich, K Czerwenka, R Kroiss, M Tea, K Pischinger, W J Kostler, et al. Intratumoral IGF-I protein expression is selectively upregulated in breast cancer patients with BRCA1/2 mutations Endocr. Relat. Cancer, December 1, 2007; 14(4): 1053 - 1062. [Abstract] [Full Text] [PDF]

				P. M. Mah, J. Webster, P. Jonsson, U. Feldt-Rasmussen, M. Koltowska-Haggstrom, and R. J. M. Ross Estrogen Replacement in Women of Fertile Years with Hypopituitarism J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 5964 - 5969. [Abstract] [Full Text] [PDF]