Glycaemic control and plasma lipoproteins in menopausal women with type 2 diabetes treated with oral and transdermal combined hormone replacement therapy (original) (raw)

Abstract

To compare the effect of a fixed combination of an oestrogen (17-b oestradiol) with a cyclical progestagen (norethisterone) on glycaemic control, plasma lipoproteins and haemostatic factors in women with Type 2 diabetes. Methods: Oral and transdermal hormone replacement therapy (HRT) were compared to no HRT treatment in 33 postmenopausal women with Type 2 diabetes, in a 12-week randomised prospective open parallel group study. Results: In the 11 women who received 12 weeks of oral HRT, there was a significant fall in total cholesterol (5.9 91.0 (S.D.) to 4.7 9 1.0 mmol l − 1 , P= 0.005), low density lipoprotein cholesterol (3.44 9 0.89 to 2.77 9 0.92 mmol l − 1 , P=0.005) and triglyceride values (median (range)), (2.46 (0.96-5.52) to 2.29 (1.00-3.87) mmol l − 1 , P B0.05). Oral HRT improved glycated haemoglobin (HbA 1c ) (7.49 1.4 to 6.8 91.2%, P0 0.005). Oral HRT additionally reduced the cell adhesion factor E-selectin (82 933 to 60 9 20 mg l − 1 , PB 0.01) and factor VII (143 925 to 1099 24% pooled plasma activity, PB0.01). No improvement in any of these parameters, except E-selectin (65 9 19 to 589 18 mg l − 1 , PB0.01), occurred in the nine women receiving transdermal HRT, and no improvement occurred in the 13 controls randomised to no treatment. Conclusion: In women with Type 2 diabetes, cyclical oestrogen and progestagen taken orally for 12 weeks significantly improved glycaemic control and lipoprotein concentrations. These metabolic benefits were not apparent when a similar HRT preparation was administered transdermally.

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References (44)

  1. C.E. Barrett, D.L. Wingard, Sex differential in ischemic heart disease mortality in diabetics: a prospective popula- tion-based study, Am. J. Epidemiol. 118 (1983) 489 -496.
  2. T. Gordon, W.B. Kannel, M.C. Hjortland, P.M. McNa- mara, Menopause and coronary heart disease. The Fram- ingham Study, Ann. Intern. Med. 89 (1978) 157 -161.
  3. K.A. Matthews, E. Meilahn, L.H. Kuller, S.F. Kelsey, A.W. Caggiula, R.R. Wing, Menopause and risk factors for coronary heart disease, New Engl. J. Med. 321 (1989) 641 -646.
  4. J.C. Stevenson, D. Crook, I.F. Godsland, Influence of age and menopause on serum lipids and lipoproteins in healthy women, Atherosclerosis 98 (1993) 83 -90.
  5. M.A. Espeland, P.E. Hogan, S.E. Fineberg, G. Howard, H. Schrott, M.A. Waclawiw, T.L. Bush, Effect of post- menopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators. Postmenopausal es- trogen/progestin interventions, Diabet. Care 21 (1998) 1589 -1595.
  6. A.A. Nabulsi, A.R. Folsom, A. White, W. Patsch, G. Heiss, K.K. Wu, M. Szklo, Association of hormone-re- placement therapy with various cardiovascular risk fac- tors in postmenopausal women. The Atherosclerosis Risk in Communities Study Investigators, New Engl. J. Med. 328 (1993) 1069 -1075.
  7. S. Hulley, D. Grady, T. Bush, C. Furberg, D. Herrington, B. Riggs, E. Vittinghoff, Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and estrogen/ progestin Replacement Study (HERS) Research Group, J. Am. Med. Assoc. 280 (1998) 605 -613.
  8. M.D. Feher, A.J. Isaacs, Is hormone replacement therapy prescribed for postmenopausal diabetic women?, Br. J. Clin. Pract. 50 (1996) 431 -432.
  9. B. Andersson, L.A. Mattsson, L. Hahn, P. Marin, L. Lapidus, G. Holm, B.A. Bengtsson, P. Bjorntorp, Estro- gen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent dia- betes mellitus, J. Clin. Endocrinol. Metab. 82 (1997) 638 -643.
  10. D. Owens, P.B. Collins, A. Johnson, G.H. Tomkin, Lipo- proteins and low-dose estradiol replacement therapy in post-menopausal Type 2 diabetic patients: the effect of addition of norethisterone acetate, Diabet. Med. 17 (2000) 308 -315.
  11. H.E. Brussaard, L.J. Gevers, M. Frolich, C. Kluft, H.M. Krans, Short-term oestrogen replacement therapy im- proves insulin resistance, lipids and fibrinolysis in post- menopausal women with NIDDM, Diabetologia 40 (1997) 843 -849.
  12. C.H. Floren, R.S. Kushwaha, W.R. Hazzard, J.J. Albers, Estrogen-induced increase in uptake of cholesterol-rich very low density lipoproteins in perfused rabbit liver, Metabolism 30 (1981) 367 -375.
  13. B.D. Applebaum, P. McLean, A. Steinmetz, D. Fontana, C. Matthys, G.R. Warnick, M. Cheung, J.J. Albers, W.R. Hazzard, Lipoprotein, apolipoprotein, and lipolytic en- zyme changes following estrogen administration in post- menopausal women, J. Lipid Res. 30 (1989) 1895 -1906.
  14. B.W. Walsh, I. Schiff, B. Rosner, L. Greenberg, V. Ravnikar, F.M. Sacks, Effects of postmenopausal estro- gen replacement on the concentrations and metabolism of plasma lipoproteins, New Engl. J. Med. 325 (1991) 1196 - 1204.
  15. J.C. Cohen, G.L. Vega, S.M. Grundy, Hepatic lipase: new insights from genetic and metabolic studies, Curr. Opin. Lipidol. 10 (1999) 259 -267.
  16. E.A. Brinton, Oral estrogen replacement therapy in post- menopausal women selectively raises levels and produc- tion rates of lipoprotein A-I and lowers hepatic lipase activity without lowering the fractional catabolic rate, Arterioscler. Thromb. Vasc. Biol. 16 (1996) 431 -440.
  17. D. Crook, M.P. Cust, K.F. Gangar, M. Worthington, T.C. Hillard, J.C. Stevenson, M.I. Whitehead, V. Wynn, Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipo- proteins, Am. J. Obstet. Gynecol. 166 (1992) 950 -955.
  18. E. Hirvonen, M. Malkonen, V. Manninen, Effects of different progestogens on lipoproteins during post- menopausal replacement therapy, New Engl. J. Med. 304 (1981) 560 -563.
  19. M.J. Tikkanen, E.A. Nikkila, T. Kuusi, S. Sipinen, Dif- ferent effects of two progestins on plasma high density lipoprotein (HDL2) and postheparin plasma hepatic li- pase activity, Atherosclerosis 40 (1981) 365 -369.
  20. J. Haarbo, C. Hassager, S.B. Jensen, B.J. Riis, C. Chris- tiansen, Serum lipids, lipoproteins, and apolipoproteins during postmenopausal estrogen replacement therapy combined with either 19-nortestosterone derivatives or 17-hydroxyprogesterone derivatives, Am. J. Med. 90 (1991) 584 -589.
  21. D. Crook, M. Seed, Endocrine control of plasma lipo- protein metabolism: effects of gonadal steroids, Baillieres Clin. Endocrinol. Metab. 4 (1990) 851 -875.
  22. W.N. Spellacy, W.C. Buhi, S.A. Birk, The effects of norgestrel on carbohydrate and lipid metabolism over one year, Am. J. Obstet. Gynecol. 125 (1976) 984 -986.
  23. H. Gershberg, E. Zorrilla, A. Hernandez, M. Hulse, Effects of medroxyprogesterone acetate on serum insulin and growth hormone levels in diabetics and potential diabetics, Obstet. Gynecol. 33 (1969) 383 -389.
  24. R.C. Turner, H. Millns, H.A. Neil, I.M. Stratton, S.E. Manley, D.R. Matthews, R.R. Holman, Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23), Br. Med. J. 316 (1998) 823 -828.
  25. J.F. Dunn, B.C. Nisula, D. Rodbard, Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid- binding globulin in human plasma, J. Clin. Endocrinol. Metab 53 (1981) 58 -68.
  26. K.A. Steingold, D.W. Matt, D. DeZiegler, J.E. Sealey, M. Fratkin, S. Reznikov, Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure, J. Clin. Endocrinol. Metab. 73 (1991) 275 -280.
  27. J.R. Gates, B. Parpia, T.C. Campbell, C. Junshi, Associa- tion of dietary factors and selected plasma variables with sex hormone-binding globulin in rural Chinese women, Am. J. Clin. Nutr. 63 (1996) 22 -31.
  28. A.C. Duncan, H. Lyall, R.N. Roberts, J.R. Petrie, M.J. Perera, S. Monaghan, D.M. Hart, J.M. Connell, M.A. Lumsden, The effect of estradiol and a combined estra- diol/progestagen preparation on insulin sensitivity in healthy postmenopausal women, J. Clin. Endocrinol. Metab. 84 (1999) 2402 -2407.
  29. T. Kuusi, E.A. Nikkila, M.J. Tikkanen, S. Sipinen, Ef- fects of two progestins with different androgenic proper- ties on hepatic endothelial lipase and high density lipoprotein2, Atherosclerosis 54 (1985) 251 -262.
  30. M.J. van-der-Mooren, P.N. Demacker, C.M. Thomas, R. Rolland, Beneficial effects on serum lipoproteins by 17 beta-oestradiol-dydrogesterone therapy in post- menopausal women; a prospective study, Eur. J. Obstet. Gynecol. Reprod. Biol. 47 (1992) 153 -160.
  31. M.J. van-der-Mooren, J. de-Graaf, P.N. Demacker, A.F. de-Haan, R. Rolland, Changes in the low-density lipo- protein profile during 17 beta-estradiol-dydrogesterone therapy in postmenopausal women, Metabolism 43 (1994) 799 -802.
  32. C. Maziere, M. Auclair, M.F. Ronveaux, S. Salmon, R. Santus, J.C. Maziere, Estrogens inhibit copper and cell- mediated modification of low density lipoprotein, Atherosclerosis 89 (1991) 175 -182.
  33. E. Arteaga, A. Rojas, P. Villaseca, M. Bianchi, The effect of 17beta-estradiol and alpha-tocopherol on the oxidation of LDL cholesterol from postmenopausal women and the minor effect of gamma-tocopherol and melatonin, Menopause 7 (2000) 112 -116.
  34. G.Y. Lip, A.D. Blann, A. Jones, D.G. Beevers, Effects of hormone-replacement therapy on hemostatic factors, lipid factors, and endothelial function in women undergoing surgical menopause: implications for prevention of atherosclerosis, Am. Heart J. 134 (1997) 764 -771.
  35. G. Kennedy, M. Mclaren, J.J. Belch, M. Seed, Elevated levels of E-selectin in post-menopausal females are de- creased by hormone replacement therapy to levels ob- served in pre-menopausal females, Thromb. Haemost. 82 (1999) 1433 -1436.
  36. W. van Baal, M. Mooren, U. Vischer, C.D. Stehouwer, Long-term effects of combined hormone replacement therapy on markers of endothelial function and inflamma- tory activity in healthy postmenopausal women, Fertil. Steril. 71 (1999) 663 -670.
  37. A.R. Folsom, P.J. Mink, T.A. Sellers, C.P. Hong, W. Zheng, J.D. Potter, Hormonal replacement therapy and morbidity and mortality in a prospective study of post- menopausal women, Am. J. Public Health 85 (1995) 1128 -1132.
  38. F. Grodstein, M.J. Stampfer, J.E. Manson, G.A. Colditz, W.C. Willett, B. Rosner, F.E. Speizer, C.H. Hennekens, Postmenopausal estrogen and progestin use and the risk of cardiovascular disease, New Engl. J. Med. 335 (1996) 453 -461 see comments (published erratum appears in New Engl. J. Med. 335(18) (1996) 1406.
  39. P. Collins, J. Shay, C. Jiang, J. Moss, Nitric oxide ac- counts for dose-dependent estrogen-mediated coronary relaxation after acute estrogen withdrawal, Circulation 90 (1994) 1964 -1968.
  40. P. Collins, G.M. Rosano, C. Jiang, D. Lindsay, P.M. Sarrel, W.P. Poole, Cardiovascular protection by oestro- gen -a calcium antagonist effect?, Lancet 341 (1993) 1264 -1265.
  41. M.A. Valverde, P. Rohas, J. Amigo, D. Cosmelli, P. Orio, M.I. Bahamonde, G.E. Mann, C. Vergara, R. Latorre, Acute activation of maxi-K channels (hSlo) by estradiol binding to the beta subunit, Science 285 (1999) 1929 - 1931.
  42. J. Goodfellow, M.W. Ramsey, M.J. Lewis, F. Dunstan, Endothelium and inelastic arteries: an early marker of vascular dysfunction in non-insulin dependent diabetes, Br. Med. J. 312 (1996) 744 -745.
  43. J. Chen, M. Gall, M. Deckert, Increased serum concen- tration of von Willebrand factor in non-insulin dependent diabetic patients with and without diabetic nephropathy, Br. Med. J. 311 (1995) 1405 -1406.
  44. G. McVeigh, G. Brennan, G. Johnston, B. McDermott, L.T.H.W. McGrath, J. Andrews, J.R. Hayes, Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mel- litus, Diabetologia 35 (1992) 771 -776.