Skip to main content
SpringerLink
Log in

Effects of hormonal replacement therapy on plasma sex hormone-binding globulin, androgen and insulin-like growth factor-1 levels in postmenopausal women

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

Abstract

Plasma sex hormone-binding globulin (SHBG) levels are important in the regulation of plasma free and albumin-bound androgens and estrogens. In postmenopausal women associated to the decrease of estrogen production, a decrease of plasma SHBG levels occurs. Hormone replacement therapy (HRT) in postmenopausal women modulates plasma SHBG levels, in relationship with the different regimens and routes of administration. The present study aimed to compare the effect of different HRT on plasma SHBG levels in relationship with the changes of plasma androgen [dehydroepiandrosterone sulphate (DHEAS), testosterone (T), androstenedione (A)] and insulin-like growth factor-1 (IGF-1) levels. In a retrospective study 443 postmenopausal women were studied and divided into 2 groups. The group 1 (n=170) was subdivided in 4 groups of women as follows: A) treated with transdermal 17-β estradiol + medroxyprogesterone acetate, B) treated with oral conjugated estrogens, C) treated with sequential HRT (estradiol valerate (EV) + norgestrel), and D) treated with a combined HRT (micronized estradiol (E2) + noretisterone acetate). Women of group 2 (n=273) did not receive HRT and served as controls. All groups of women treated with different HRT showed plasma estradiol levels significantly higher than controls (p<0.01), showing the highest values in women treated with oral HRT. Plasma SHBG levels were not significantly different between patients treated with transdermal 17-β estradiol + medroxyprogesterone acetate and controls. On the other hand, all the groups of patients treated with oral conjugated estrogen with or without progestagens showed plasma SHBG levels significantly higher than controls (p<0.01). Plasma SHBG levels were higher in the group treated with estrogen alone than in groups of women treated with sequential or combined HRT. Plasma DHEAS, T and A levels in patients treated with different HRT regimens were in the same range of levels as control women. Plasma IGF-1 levels were not significantly affected by the various HRT regimens and remained in the same range as controls. In conclusion, plasma SHBG levels increase following oral HRT while are not affected by transdermal HRT. Plasma IGF-1 and androgen levels are not influenced from oral or transdermal HRT.

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

Access this article

Log in via an institution

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. Walsh K.A., Titan K., Takio K., Kunar S., Hayees R., Petra R.H. Amino acid sequence of the sex steroid-binding protein of human plasm. Biochemistry 25: 7584, 1986.

    Article  PubMed  CAS  Google Scholar 

  2. Danzo B.J., Ball B.W., Black J.H. Human testosterone-binding globulin is a dimer composed of two identical promoters that are differentially glycosilated. Endocrinology 124: 2809, 1989.

    Article  PubMed  CAS  Google Scholar 

  3. Hautanen A., Sarna S., Pelkonen R., Adlercreutz H. Serum sex hormone-binding globulin, cardiovascular risk factors, and adrenal Cortisol response to dexamethasone and corticotropin. Metabolism 42: 870, 1993.

    Article  PubMed  CAS  Google Scholar 

  4. Rosner W. The function of corticosteroid-binding globulin and sex hormone-binding globulin: recent advance. Endocr. Rev. 11: 80, 1990.

    Article  PubMed  CAS  Google Scholar 

  5. Plynate S.R., Leonard J.M., Paulsen C.A., Fariss B.L., Karpes A.E. Sex hormone-binding globulin changes with androgen replacement. J. Clin. Endocrinol. Metab. 57: 645, 1983.

    Article  Google Scholar 

  6. Von Scoltz B., Carlsrom K. General review: on the regulation of sex hormone-binding globulin-challenge of an old dogma and outlines of an alternative mechanism. J. Steroid. Biochem. 32: 327, 1989.

    Article  Google Scholar 

  7. Fortunati N., Frairia R., Fissore F., Berta L., Fazzari A., Gaidano G. The receptor for human sex steroids binding protein (SBP) is expressed on membranes of neoplastic endometrium. J. Steroid. Biochem. Mol. Biol. 42: 1857, 1992.

    Article  Google Scholar 

  8. Frairia R., Fortunati N., Fissore F., Fazzari A., Zeppegno P., Berta L. The membrane receptor for sex steroid binding protein is not ubiquitous. J. Endocrinol. Invest. 15: 6177, 1992.

    Article  Google Scholar 

  9. Maruyama Y., Aoki N., Suzuki Y., Sinohora H., Yamamoto T. Variation with age in the levels of sex-steroid-binding plasma protein as determined by radioimmunoassay. Acta Endocrinol. (Copenh.) 106: 4287, 1982.

    Google Scholar 

  10. Lundberg P-A., Lindstedt G., Lapidus L., Bengtson C. Serum sex hormone-binding globulin and mortality risk in postmenopausal women. Clin. Chem. 31: 6547, 1985.

    Google Scholar 

  11. Lapidus L., Lindstedt G., Lunderberg P-A., Bengtson C., Grednark T. Concentrations of sex-hormone-binding globulin in serum in relation to cardiovascolar risk factor and to 12 year incidence of cardiovascular disease and overall mortality in postmenopausal women. Clin Chem 32: 146, 1986.

    PubMed  CAS  Google Scholar 

  12. Cuzik J., Woung D.Y., Bulbrok A. The prevention of breast cancer. Lancet 1: 83, 1986

    Article  Google Scholar 

  13. Toniolo P.G., Levitz M., Zeleniuch-Jacquotte A., Banerjee S., Koenig K.L., Shore R.E., Strax P., Pasternack B.S. A prospective study of endogenous estrogen and breast cancer in postmenopausal women. J. Nat. Cancer Ins. 87: 190, 1995.

    Article  CAS  Google Scholar 

  14. Odlind V., Elamsson K., England D.E., Victor A., Johonsson E.D.B. Effects of oestradiol on sex hormone-binding globulin. Acta Endocrinol. (Copenh.) 101: 248, 1982.

    CAS  Google Scholar 

  15. Campbells S., Whitehead M.I. Potency and hepatocellular effects of estrogen after oral, percutaneous and subcutaneous administration. In: Van Keep P.A., Ution W.H., Vermeulen A. (Eds.), The controversial climateric. MTP Press, Lancaster, 1982, p. 103.

    Google Scholar 

  16. Chetkowsky R.J., Meldrum D.R., Steingold K.A., Steingold D.R., Randle K.A., Lu J.K., Eggena P., Hershman J.M., Alkjaersig N.K., Fletcher A.P., Judd H.L. Biological effects of transdermal estradiol. N. Engl. J. Med. 314: 1615, 1986.

    Article  Google Scholar 

  17. Belfour J.A., Rennie C.H. Transdermal Estradiol. A review of its pharmacodynamic and pharmacokinetic propierties and therapeutic efficacy in the treatment of menopausal complaints. Drugs 40: 561, 1990.

    Article  Google Scholar 

  18. Jasonni V.M., Buletti C., Naldi S., Ciotti P., Di Cosmo D., Lazaretto R., Flamigni C. Biological and endocrine aspects of transdermal 17 β estradiol administration in postmenopausal women. Maturitas 10: 263, 1988.

    Article  PubMed  CAS  Google Scholar 

  19. Campagnoli C., Briglia N., Altare F., Lanza M.G., Lesca L., Cantamessa C., Peris C., Fiorucci G.C., Sismondi P. Differential effects of oral conjugated estrogens and transdermal estradiol on insuline-like growth factor 1, growth hormone and sex hormone-binding globulin levels. Gynecol. Endocrinol. 7: 251, 1993.

    Article  PubMed  CAS  Google Scholar 

  20. Metka M., Hones V., Heytmenak G. Hormone replacement therapy: lipid responses to continuous combined oestrogen and progestogen versus oestrogen monotherapy. Maturitas 15: 53, 1992.

    Article  PubMed  CAS  Google Scholar 

  21. Obel E.B., Mursk-Jensen N., Svenstrup B., Bennett P., Micic S., Jensen B.M. A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment. Maturitas 16: 13, 1993.

    Article  PubMed  CAS  Google Scholar 

  22. L’Hermke M. Risks of estrogen and progestagens. Maturitas 12: 215, 1990.

    Article  Google Scholar 

  23. Rijpkenne A.H.M., Van Der Senden A.A., Ruijs A.H.C. Effects of postmenopausal oestrogen-progestagen replacement therapy on serum lipids and lipoprotein: a review. Maturitas 12: 259, 1990.

    Article  Google Scholar 

  24. Anderson D.C. Sex hormone-binding globulin. Clin. Endocrinol. (Oxf.) 3: 69, 1974.

    Article  CAS  Google Scholar 

  25. Tazuke S., Khaw K.T., Barett-Connior E. Exogenous estrogen and endogenous sex hormone. Medicine 71: 44, 1992.

    PubMed  CAS  Google Scholar 

  26. Liu C.H., Laughlin G.A, Yen S.S.C. Marked attenuation of ultradian and circadian rythms of dehydroepiandrosterone in postmenopausal women: evidence for a reduced 17,20-desmolase enzymatic activity. J.Clin. Endocrinol. Metab. 71: 900, 1990.

    Article  PubMed  CAS  Google Scholar 

  27. Cumming D.C., Rebar R.W., Hopper B.R., Yen S.S.C. Evidence for an influence of the ovary circulating dehydroepiandrosterone sulphate levels. Clin.Endocrinol. Metab. 54: 1069, 1982.

    Article  CAS  Google Scholar 

  28. Kelijman M. Age related alterations of the growth hormone /insulin-like growth factor axis. JAGS 39: 295, 1991.

    CAS  Google Scholar 

  29. Bennett A.E., Wahner H.W., Riggs B.L., Hints R.L. Insulin-like growth factors I and II: aging and bone density in women. J. Clin. Endocrinol. Metab. 59: 701, 1984.

    Article  PubMed  CAS  Google Scholar 

  30. Franchimont P., Urban-Choffray D., Lambelin P., Fontaine M.A., Frangin G., Reginster J.Y. Effect of repetitive administration of growth hormone-releasing hormone on growth hormone secretion, insulin-like growth factor-1 and bone metabolism in postmenopausal women. Acta Endocrinol. (Copenh.) 120: 121, 1989.

    CAS  Google Scholar 

  31. Lykkesfoldt G., Bannet P., Lykkesfeldt A.E., Micic S., Svenstrup B. Abnormal androgen and oestrogen metabolism in men with steroid suppletive deficiency and recessive x-linked ichtyosis. Clin. Endocrinol. (Oxf.) 23: 385, 1985.

    Article  Google Scholar 

  32. Duursma S.A., Raymakers J.A., Boereboom F.T.J., Scheven B.A.A. Estrogen and bone metabolism. Obstet. Gynecol. Surv. 47: 38, 1992.

    Article  PubMed  CAS  Google Scholar 

  33. Chetkowski R.J., Meldrum D.R., Steingold K.A., Randle D., Judd D. Biologic effect of transdermal estradiol. N. Engl. J. Med. 314: 1615, 1986.

    Article  PubMed  CAS  Google Scholar 

  34. Dawson-Hughes B., Stern D., Goldman J., Reichelin S. Regulation of growth hormone and somatomedin-S secretion in postmenopausal women: effect of physiological estrogen replacement therapy. J. Clin. Endocrinol. Metab. 72: 172, 1991.

    Article  Google Scholar 

  35. Frohlander N., von Scholtz B. Growth hormone and somatomedine-C during postmenopausal replacement therapy with oestrogen alone and in combination with antiestrogen. Maturitas 9: 297, 1988.

    Article  PubMed  CAS  Google Scholar 

  36. Bellantoni M.F., Halman S.M., Cho D.E., Blackman M.R. Effects of progestin-opposed transdermal estrogen administration on growth hormone and insulin-like growth factor-1 in postmenopausal women of different ages. J. Clin. Endocrinol. Metab. 72: 172, 1991.

    Article  PubMed  CAS  Google Scholar 

  37. Weissberg A.J., Ho K.K.Y., Lazarus L. Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24 hour growth hormone (GH) secretion, insuline-like growth factor-1 and GH-binding protein in postmenopausal women. J. Clin. Endocrinol. Metab. 72: 374, 1991.

    Article  Google Scholar 

  38. Slowinska-Srezdnicka J., Zgliczynski S., Jeske W., Stopinska-Gluszak U., Srzednichi M., Brzezinska A., Zgliczynski W., Sadowski Z. Transdermal 17β-estradiol combined with oral progestogen increases plasma levels of insuline-like growth factor-1 in postmenopausal women. J. Endocrinol. Invest. 15: 533, 1992.

    Article  Google Scholar 

  39. Steinberg K.K., Thacker S.B., Smith S.J., Stroup D.F., Barkelman R.L. A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. J. Am. Med. Assoc. 265: 1985, 1991.

    Article  CAS  Google Scholar 

  40. Dupont W.D., Page D.L. Menopausal estrogen replacement therapy and breast cancer. Arch. Intern. Med. 151: 67, 1991.

    Article  PubMed  CAS  Google Scholar 

  41. Sillero-Arenas M., Delgado-Rodriguez M., Rodriguez-Canteras R., Bueno-Cavanillas A., Galvez-Vargas R. Menopausal hormone replacement therapy and breast cancer: a meta-analysis. Obstet. Gynecol. 79: 286, 1992.

    PubMed  CAS  Google Scholar 

  42. Brinton L.. Menopause and risk of breast cancer. Ann. N.Y. Acad. Sci. 592: 357, 1990.

    Article  PubMed  CAS  Google Scholar 

  43. Cuzik J., Wang D.Y., Bulbrook R.D. The prevention of breast cancer. Lancet 1: 83, 1986.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istituto di Clinica Ostetrica e Ginecologica, University of Pisa, Pisa, Italy

    M. Stomati, A. Spinetti, S. Rubino, F. Petraglia &  A. R. Genazzani

  2. Department of Obstetrics and Gynecology, University of Wien, Wien, Austria

    A. Albrecht & J. Huber

  3. Clinica Glandulas Scwarzstein, Rosario, Argentina

    B. Hartmann & D. Mailand

Authors
  1. M. Stomati
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Spinetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Mailand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Rubino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Albrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F. Petraglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. R. Genazzani
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stomati, M., Hartmann, B., Spinetti, A. et al. Effects of hormonal replacement therapy on plasma sex hormone-binding globulin, androgen and insulin-like growth factor-1 levels in postmenopausal women. J Endocrinol Invest 19, 535–541 (1996). https://doi.org/10.1007/BF03349013

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03349013

Keywords

Search

Navigation