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Administration route-dependent effects of estrogens on IGF-I levels during fixed GH replacement in women with hypopituitarism

Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands¹ Department of Endocrinology and ² Laboratory of Endocrinology, University Medical Centre Utrecht, Utrecht, The Netherlands

(Correspondence should be addressed to A A van der Klaauw; Email: a.a.van_der_klaauw{at}lumc.nl)

Objective: GH-deficient women using oral estradiol treatment require higher doses of recombinant human GH (rhGH) to achieve similar IGF-I levels when compared with men and women on transdermal estradiol replacement. The aim of this study was to evaluate the effects of oral versus transdermal estrogen administration at similar plasma estradiol levels on IGF-I, IGF-binding protein-3, and sex hormone-binding globulin (SHBG) concentrations.

Design: Parallel crossover study in which two groups of hypogonadal and GH-deficient women with fixed and stable rhGH replacement passed through four different estradiol treatment schemes (2 and 4 mg oral, and 50 and 100 µg transdermal estradiol) with a duration of four cycles each to ensure a new steady state. Group I (18 patients using oral estradiol prior to the study) was treated with oral followed by transdermal estradiol and group II (five patients with transdermal estradiol prior to inclusion) with transdermal followed by oral estradiol.

Results: Estradiol concentrations were lowest during 50 µg transdermal and highest during 4 mg oral estradiol treatment. Estradiol concentrations did not differ during 100 µg transdermal and 2 mg oral treatment. Nevertheless, IGF-I levels were significantly higher during 100 µg transdermal when compared with 2 mg oral treatment (P=0.005 in group I and 0.02 in group II), while SHBG levels were significantly lower (P=0.002 in group I and P=0.004 in group II). SHBG and IGF-I concentrations were negatively correlated (R=–0.41, P=0.0001).

Conclusion: During fixed GH replacement, the route of estrogen administration is a determinant of IGF-I levels in hypogonadal GH-deficient women.