Progestins abrogate estrogen-induced changes in the insulin-like growth factor axis.

Abstract

OBJECTIVE:

We sought to investigate the effect of oral progestins on estrogen-mediated changes in the insulin-like growth factor axis in the peripheral circulation.

STUDY DESIGN:

Oral conjugated equine estrogen alone or in combination with medroxyprogesterone acetate, desogestrel, or norethindrone was given in a randomized triple-crossover fashion to 10 healthy postmenopausal women, and the effects on the insulin-like growth factor axis were determined.

RESULTS:

Baseline circulating insulin-like growth factor I levels were significantly reduced by conjugated equine estrogen (359 +/- 54 vs 225 +/- 44 ng/mL; P =.0001). This effect was reversed by progestins (medroxyprogesterone acetate, 254 +/- 44 ng/mL; desogestrel, 266 +/- 50 ng/mL; norethindrone, 286 +/- 48 ng/mL; F = 12.2; P =.0015). Free insulin-like growth factor I was reduced by conjugated equine estrogen (1.00 +/- 0.15 ng/mL vs 2.10 +/- 0.39 ng/mL; P =.004), but addition of progestogens had no further effect. Insulin-like growth factor II and insulin levels were unaffected by conjugated equine estrogen or progestins. Plasma insulin-like growth factor binding protein 1 concentration increased significantly from baseline with conjugated equine estrogen alone (44.1 +/- 6.0 vs 154 +/- 30 microg/L; P =.003). This rise was opposed by progestins of increasing androgenicity (medroxyprogesterone acetate, 130 +/- 26 microg/L; desogestrel, 100 +/- 16 microg/L; norethindrone, 78.0 +/- 12 microg/L; F = 12.5; P =.0015). Insulin-like growth factor binding protein 3 levels fell with conjugated equine estrogen, and this was reversed by progestins (conjugated equine estrogen, 2.17 +/- 0.13 mg/L; vs norethindrone and conjugated equine estrogen, 2.41 +/- 0.12 mg/L; F = 7.6; P =.01). Insulin-like growth factor binding protein 4 levels increased with conjugated equine estrogen with or without progestins, whereas insulin-like growth factor binding protein 2 levels were unchanged.

CONCLUSIONS:

Coadministration of androgenic progestins abrogates estrogen-related changes in circulating insulin-like growth factor I, insulin-like growth factor binding protein 1, and insulin-like growth factor binding protein 3. Such hormone replacement therapy-induced changes may have significant consequences for the development of cardiovascular disease and osteoporosis and implications for the use of insulin-like growth factor I in monitoring growth hormone replacement.

• Authors: A Heald, P L Selby, A White, J M Gibson
• Journal: American journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 183 Issue 3 Pg. 593-600 (Sep 2000) ISSN: 0002-9378 [Print] United States
• PMID: 10992179 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogens
• Insulin
• Insulin-Like Growth Factor Binding Protein 1
• Insulin-Like Growth Factor Binding Protein 2
• Insulin-Like Growth Factor Binding Protein 4
• Progestins
• Somatomedins
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II
• Desogestrel
• Medroxyprogesterone Acetate
• Norethindrone

Topics

• Cross-Over Studies
• Desogestrel (administration & dosage, pharmacology)
• Drug Interactions
• Estrogens (administration & dosage, pharmacology)
• Female
• Humans
• Insulin (blood, pharmacology)
• Insulin-Like Growth Factor Binding Protein 1 (blood)
• Insulin-Like Growth Factor Binding Protein 2 (blood)
• Insulin-Like Growth Factor Binding Protein 4 (blood)
• Insulin-Like Growth Factor I (metabolism)
• Insulin-Like Growth Factor II (metabolism)
• Medroxyprogesterone Acetate (administration & dosage, pharmacology)
• Middle Aged
• Norethindrone (administration & dosage, pharmacology)
• Progestins (administration & dosage, pharmacology)
• Somatomedins (metabolism)