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Cited by 16Growth Hormone and Insulin-like Growth FactorsHormonal and reproductive studiesPituitary Gland Disorders and Treatments

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

Christiansen, Jens Juel, Fisker, Sanne, Gravholt, Claus Højbjerg, Bennett, Paul, Svenstrup, Birgit, Andersen, Marianne, Feldt-Rasmussen, Ulla, Christiansen, Jens Sandahl +1 more·2005·European Journal of Endocrinology
DOI 10.1530/eje.1.01898
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Abstract

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=or<0.001; androstenedione: 0.5 (0.1-7.1) nmol/l vs 4.3 (1.6-8.8) nmol/l, P=or<0.001; dihydrotestosterone (DHT): 0.13 (0.09-0.54) nmol/l vs 0.55 (0.09-0.89) nmol/l, P=or<0.001; testosterone: 0.28 (0.09-1.56) nmol/l vs 1.1 (0.71-2.24) nmol/l, (P=or<0.001); free testosterone: 0.004 (0.001-0.030) nmol/l vs 0.016 (0.001-0.030) nmol/l, P=or<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 microg/l, P=0.005 and IGFBP-3 (3887+/-139 vs 4309+/-138 microg/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). DeltaIGF-I correlated with DeltaSHBG (r=-0.45 P=0.033) and DeltaIGFBP-3 (r=0.67 P=or<0.001). In a regression model DeltaE2, Deltatestosterone, DeltaSHBG and DeltaIGFBP-3 explained 93% of the variation in DeltaIGF-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 DeltaIGF-I correlated positively with Deltafree 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.

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Authors
Christiansen, J. J., Fisker, S., Gravholt, C. H., Bennett, P., Svenstrup, B., Andersen, M., Feldt-Rasmussen, U., Christiansen, J. S., & Jørgensen, J. O. L.
Affiliations
  • Aarhus University Hospital (DK)
  • Statens Serum Institut (DK)
  • Odense University Hospital (DK)
Corresponding author
Gravholt, Claus Højbjerg
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2005-05
Volume
152
Issue
5
Pages
719-726
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje.1.01898
OpenAlex
W2097552145
Cited by
16
References
27
Citations by year
2021: 1 · 2018: 1 · 2017: 1 · 2016: 3 · 2014: 1
FWCI
0.83
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
Funders
Novo Nordisk
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
estrogen replacement therapy, growth hormone therapy, hypopituitarism, androgen status, insulin-like growth factor I, IGF binding proteins, insulin-like growth factor II, dehydroepiandrosterone sulfate, androstenedione, dihydrotestosterone, testosterone, cortisol, sex hormones, menopause
MeSH terms
Adult, Body Composition, Estrogens, Female, Humans, Hypopituitarism, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Middle Aged, Sex Hormone-Binding Globulin, Testosterone, Estrogen Replacement Therapy, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Dehydroepiandrosterone Sulfate, Human Growth Hormone

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