Skip to main content
Log in

Estroprogestinic pill normalizes IGF-I levels in acromegalic women

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

In some acromegalic patients medical treatment does not succeed in normalizing GH/IGF-I values. Data showing IGF-I suppression in acromegaly by estrogen and by tamoxifen use prompted us to reevaluate the effects of estro-progestins (EP) supplementation on GH/IGF-I levels in acromegalic women resistant or only par-tially sensitive to medical treatment. Eight active acromegalic women (30–52 yr, 4 with regular menses) entered a prospective open pilot study. Three of them, resistant to medical treatment, were off therapy; the remaining five, partially sensitive, maintained it at the maximally effective dosages throughout the study. Patients were treated with a triphasic pill (ethynil-estradiol 30–40–30 μg/day and desogestrel 50–70–100 mg/day) for 13±7 months. IGF-I levels fell from 512 (median, interquartile 436–657) μg/l to 282 (244–526) μg/l (p=0.0414); the decrease was observed in 6 patients (75%), and normal values were reached in 4 (50%). GH levels did not change [basal 7.6 (6.2–8.6) μg/l, final 7.6 (6.5–8.3) μg/l]. Effectiveness of treatment was not dependent on concomitant anti-GH treatment or gonadal status. In all patients IGF-I levels re-increased after EP withdrawal. This pilot study shows a marked IGF-I lowering effect of pill in acromegalic women, and warrants a prospective randomized study in patients resistant or partially sensitive to other medical treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Melmed S., Jackson I., Kleinberg D., et al. Current treatment guidelines for acromegaly. J. Clin. Endocrinol. Metab. 1998, 83: 2646–2652.

    CAS  PubMed  Google Scholar 

  2. Clemmons D.R., Underwood L.E., Ridgway E.C., et al. Estradiol treatment of acromegaly. Reduction of immunoreactive somatomedin-C and improvement in metabolic status. Am. J. Med. 1980, 69: 571–575.

    Article  CAS  PubMed  Google Scholar 

  3. Cozzi R., Attanasio R., Oppizzi G., et al. Effects of tamox-ifen on GH and IGF-I levels in acromegaly. J. Endocrinol. Invest. 1997, 20: 445–451.

    Article  CAS  PubMed  Google Scholar 

  4. Heaney A.P., Manory F., Melmed S. Functional role of estrogen in pituitary tumor pathogenesis. J. Clin. Invest. 2002, 109: 277–283.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Anderson S.M., Shah N., Evans W.S., et al. Short-term estradiol supplementation augments growth hormone (GH) secretory responsiveness to dose-varying GH-releasing peptide infusions in healthy postmenopausal women. J. Clin. Endocrinol. Metab. 2001, 86: 551–560.

    CAS  PubMed  Google Scholar 

  6. Bellantoni M.F., Harman S.M., Cho D.E., et al. Effects of progestin-opposed transdermal estrogen administration on growth hormone and insulin-like growth factor-I in postmenopausal women of different ages. J. Clin. Endocrinol. Metab. 1991, 72: 172–178.

    Article  CAS  PubMed  Google Scholar 

  7. Weissberger A.J., Ho K.K., Lazarus L. Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulinlike growth factor I, and GH-binding protein in postmenopausal women. J. Clin. Endocrinol. Metab. 1991, 72: 374–381.

    Article  CAS  PubMed  Google Scholar 

  8. Hartmann B., Kirchengast S., Albrecht A., et al. Effects of hormone replacement therapy on growth hormone secretion patterns in correlation to somatometric parameters in healthy postmenopausal women. Maturitas 1995, 22: 239–246.

    Article  CAS  PubMed  Google Scholar 

  9. Bellantoni M.F., Vittone J., Campfield A.T., et al. Effects of oral versus transdermal estrogen on the growth hormone/insulin-like growth factor I axis in younger and older postmenopausal women: a clinical research center study. J. Clin. Endocrinol. Metab. 1996, 81: 2848–2853.

    CAS  PubMed  Google Scholar 

  10. Friend K.E., Hartman M.L., Pezzoli S.S., et al. Both oral and transdermal estrogen increase growth hormone release in postmenopausal women — A clinical research center study. J. Clin. Endocrinol. Metab. 1996, 81: 2250–2256.

    CAS  PubMed  Google Scholar 

  11. Malarkey W.B., Burleson M., Cacioppo J.T., et al. Differential effects of estrogen and medroxyprogesterone on basal and stress-induced growth hormone release, IGF-1 levels, and cellular immunity in postmenopausal women. Endocrine 1997, 7: 227–233.

    Article  CAS  PubMed  Google Scholar 

  12. Moe K.E., Prinz P.N., Larsen L.H., et al. Growth hormone in postmenopausal women after long-term oral estrogen replacement therapy. J. Gerontol. 1998, 53: B117–B124.

    Article  CAS  Google Scholar 

  13. Shah N., Evans W.S., Veldhuis J.D. Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion. Am. J. Physiol. — Regul. Integr. & Compar. Physiol. 1999, 276: R1351–R1358.

    CAS  Google Scholar 

  14. Shah N., Evans W.S., Bowers C.Y., et al. Oral estradiol administration modulates continuous intravenous growth hormone (GH)-releasing peptide-2-driven GH secretion in postmenopausal women. J. Clin. Endocrinol. Metab. 2000, 85: 2649–2659.

    CAS  PubMed  Google Scholar 

  15. Heald A., Selby P.L., White A., et al. Progestins abrogate estrogen-induced changes in the insulin-like growth factor axis. Am. J. Obstetr. Gynecol. 2000, 183: 593–600

    Article  CAS  Google Scholar 

  16. Veldhuis J.D., Evans W.S., Bowers C.Y., et al. Interactive regulation of postmenopausal growth hormone insulin-like growth factor axis by estrogen and growth hormone-releasing peptide-2. Endocrine 2001, 14: 45–62.

    Article  CAS  PubMed  Google Scholar 

  17. Chapman I.M., Hartman M.L., Straume M., et al. Enhanced sensitivity growth hormone (GH) chemilumi-nescence assay reveals lower post-glucose nadir GH concentrations in men than in women. J. Clin. Endocrinol. Metab. 1994, 78: 1312–1319.

    CAS  PubMed  Google Scholar 

  18. Kam G.Y., Leung K.C., Baxter R.C., et al. Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex. J. Clin. Endocrinol. Metab. 2000, 85: 1918–1922.

    CAS  PubMed  Google Scholar 

  19. Cano A., Castelo-Branco C., Tarin J.J. Effect of menopause and different combined estradiol-progestin regimens on basal and growth hormone-releasing hormone-stimulated serum growth hormone, insulin-like growth factor-1, insulin-like growth factor binding protein (IGFBP)-1, and IGF-BP-3 levels. Fertil. Steril. 1999, 71: 261–267.

    Article  CAS  PubMed  Google Scholar 

  20. Paassilta M., Karjalainen A., Kervinen K., et al. Insulin-like growth factor binding protein-1 (IGFBP-1) and IGF-I during oral and transdermal estrogen replacement therapy: Relation to lipoprotein(a) levels. Atherosclerosis 2000, 149: 157–162.

    Article  CAS  PubMed  Google Scholar 

  21. Cardim H.J.P., Lopes C.M.C., Giannella-Neto D., et al. The insulin-like growth factor-I system and hormone replacement therapy. Fertil. Steril. 2001, 75: 282–287.

    Article  CAS  PubMed  Google Scholar 

  22. Raudaskoski T., Knip M., Laatikainen T. Plasma insulin-like growth factor-I and its binding proteins 1 and 3 during continuous nonoral and oral combined hormone replacement therapy. Menopause 1998, 5: 217–222.

    Article  CAS  PubMed  Google Scholar 

  23. 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: 2390–2397.

    CAS  PubMed  Google Scholar 

  24. Helle S.I., Omsjo I.H., Hughes S.C., et al. Effects of oral and transdermal oestrogen replacement therapy on plasma levels of insulin-like growth factors and IGF binding proteins 1 and 3: a cross-over study. Clin. Endocrinol. (Oxf.) 1996, 45: 727–732.

    Article  CAS  Google Scholar 

  25. Lawrence A.M., Kirsteins L. Progestins in the medical management of active acromegaly. J. Clin. Endocrinol. Metab. 1970, 30: 646–652.

    Article  CAS  PubMed  Google Scholar 

  26. Parkinson C., Ryder W.D.J., Trainer P.J., et al. The relationship between serum GH and serum IGF-I in acromegaly is gender-specific. J. Clin. Endocrinol. Metab. 2001, 86: 5240–5244.

    Article  CAS  PubMed  Google Scholar 

  27. Eden Engström B., Burman P., Karlsson F.A. Men with acromegaly need higher doses of octreotide than women. Clin. Endocrinol. (Oxf.) 2002, 56: 73–77.

    Article  Google Scholar 

  28. Cook D.M., Ludlam W.H., Cook M.B. Route of estrogen administration helps to determine growth hormone (GH) replacement dose in GH-deficient adults. J. Clin. Endocrinol. Metab. 1999, 84: 3956–3960.

    CAS  PubMed  Google Scholar 

  29. Wolthers T., Hoffman D.M., Nugent A.G., et al. Oral estrogen antagonizes the metabolic actions of growth hormone in growth hormone-deficient women. Am. J. Physiol. Endocrinol. Metab. 2001, 281: E1191–1196.

    CAS  PubMed  Google Scholar 

  30. Shupnik M.A., Pitt L.K., Soh A.Y., et al. Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors. J. Clin. Endocrinol. Metab. 1998, 83: 3965–3972.

    CAS  PubMed  Google Scholar 

  31. Chaidarun S.S., Swearingen B., Alexander J.M. Differential expression of estrogen receptor-beta (ERbeta) in human pituitary tumors: Functional interactions with ERalpha and a tumor-specific splice variant J. Clin. Endocrinol. Metab. 1998, 83: 3308–3315.

    CAS  PubMed  Google Scholar 

  32. Huynh H., Pollak M. Enhancement of tamoxifen-induced suppression of insulin-like growth factor I gene expression and serum level by a somatostatin analogue. Biochem. Biophys. Res. Comm. 1994, 203: 253–259.

    Article  CAS  PubMed  Google Scholar 

  33. Fournier B., Gutzwiller S., Dittmar T., et al. Estrogen receptor (ER)-alpha, but not ER-beta, mediates regulation of the insulin-like growth factor I gene by antiestrogens. J. Biol. Chem. 2001, 276: 35444–35449.

    Article  CAS  PubMed  Google Scholar 

  34. Bates A.S., Van’t Hoff W., Jones J.M., et al. An audit of outcome of treatment in acromegaly. Q. J. Med. 1993, 86: 293–299.

    CAS  PubMed  Google Scholar 

  35. Rajasoorya C., Holdaway I.M., Wrightson P., et al. Determinants of clinical outcome and survival in acromegaly. Clin. Endocrinol. (Oxf.) 1994, 41: 95–102.

    Article  CAS  Google Scholar 

  36. Swearingen B., Barker F.G., Katznelson L., et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J. Clin. Endocrinol. Metab. 1998, 83: 3419–3426.

    CAS  PubMed  Google Scholar 

  37. Le Roith D., Bondy C., Yakar S., et al. The Somatomedin Hypothesis: 2001. Endocr. Rev. 2001, 22: 53–74.

    Article  PubMed  Google Scholar 

  38. Scheidegger K.J., Cenni B., Picard D., et al. Estradiol decreases IGF-1 and IGF-1 receptor expression in rat aortic smooth muscle cells: Mechanisms for its athero-protective effects. J. Biol. Chem. 2000, 275: 38921–38928.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Renato Cozzi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cozzi, R., Barausse, M., Lodrini, S. et al. Estroprogestinic pill normalizes IGF-I levels in acromegalic women. J Endocrinol Invest 26, 347–352 (2003). https://doi.org/10.1007/BF03345183

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345183

Key-words

Navigation