Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women

Authors

  • Iskra Bitoska University Clinic of Endocrinology, Diabetology and Metabolic Disorders, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Branka Krstevska University Clinic of Endocrinology, Diabetology and Metabolic Disorders, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Tatjana Milenkovic University Clinic of Endocrinology, Diabetology and Metabolic Disorders, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Slavica Subeska-Stratrova University Clinic of Endocrinology, Diabetology and Metabolic Disorders, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Goran Petrovski University Clinic of Endocrinology, Diabetology and Metabolic Disorders, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Sasha Jovanovska Mishevska University Clinic of Endocrinology, Diabetology and Metabolic Disorders, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Irfan Ahmeti University Clinic of Endocrinology, Diabetology and Metabolic Disorders, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Biljana Todorova University Clinic of Endocrinology, Diabetology and Metabolic Disorders, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje

DOI:

https://doi.org/10.3889/oamjms.2016.024

Keywords:

Hormone replacement therapy, Menopause, Diabetes mellitus, Insulin resistance, HOMA - IR

Abstract

BACKGROUND: Insulin resistance (IR) is closely associated with diabetes mellitus. On the other hand, increased visceral fat in menopause is also associated with IR, which makes postmenopausal diabetic women in a big risk for cardiovascular diseases. There are conflicting reports about the effects on hormone replacement therapy (HRT) on IR.

AIM: The aim of the study was to investigate the effects of HRT on IR.

METHODS: A total of 40 postmenopausal women with type 2 diabetes were enrolled and followed for 12 months. Half of them were assigned to take HRT, while the other half made the control group. Fasting plasma glucose (FPG) and insulinemia were measured in both groups at baseline and after 12 months. IR was represented by Homeostatic model assessment for IR (HOMA-IR).

RESULTS: HRT was associated with significant decrease in HOMA-IR, FPG and insulinemia in the examined group. There was no significant reduction in FPG and no significant increase in insulinemia levels and HOMA-IR values in control group after 12 months.

CONCLUSION: HRT was associated with statistically signifficant increase of insulin sensitivity. Larger clinical trials will be necessary to understand whether HRT may improve insulin resistance and glucose homeostasis in women with diabetes, especially when given shortly after entering menopause.

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References

Stevenson JC. The metabolic and cardiovascular consequences of HRT. Br J Clin Pract. 1995;49: 87–90.

PMid:7779651

Sullivan JM, Vander ZR, Hughes JP, Maddock V, Kroetz FW, Ramanathan KB, Mirvis DM. Estrogen replacement and coronary artery disease: effect on survival in postmenopausal women. Arch Intern Med. 1990;150:2557–2562. DOI: https://doi.org/10.1001/archinte.150.12.2557

http://dx.doi.org/10.1001/archinte.1990.00390230101014 DOI: https://doi.org/10.1001/archinte.1990.00390230101014

PMid:2244772

Newton KM, LaCroix AZ, McKnight B, Knopp RH, Siscovick DS, Heckbert SR, Weiss NS. Estrogen replacement therapy and prognosis after first myocardial infarction. Am J Epidemiol. 1997;145:269–277.

http://dx.doi.org/10.1093/oxfordjournals.aje.a009100 DOI: https://doi.org/10.1093/oxfordjournals.aje.a009100

PMid:9012600

O'Keefe JH Jr, Kim SC, Hall RR, Cochran VC, Lawhorn SL, McCallister BD. Estrogen replacement therapy after coronary angioplasty in women. J Am Coll Cardiol. 1997;29:1–5.

http://dx.doi.org/10.1016/S0735-1097(96)00443-3 DOI: https://doi.org/10.1016/S0735-1097(96)00443-3

Cauley JA, Seeley DG, Browner WS, Ensrud K, Kuller LH, Lipschutz RC, Hulley SB. Estrogen replacement therapy and mortality among older women: the study of osteoporotic fractures. Arch Intern Med. 1997;157:2181–2187. DOI: https://doi.org/10.1001/archinte.157.19.2181

http://dx.doi.org/10.1001/archinte.1997.00440400031004 DOI: https://doi.org/10.1001/archinte.1997.00440400031004

PMid:9342994

Henderson BE, Paganini-Hill A, Ross RK. Decreased mortality in users of estrogen replacement therapy. Arch Intern Med.1991;151:75–78. DOI: https://doi.org/10.1001/archinte.151.1.75

http://dx.doi.org/10.1001/archinte.1991.00400010095012 DOI: https://doi.org/10.1001/archinte.1991.00400010095012

PMid:1985611

Gambacciani M, Ciaponi M, Cappagli B, Piaggesi L, De Simone L, Orlandi R, Genazzani AR. Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. J Clin Endocrinol Metab. 1997;82: 414–417.

http://dx.doi.org/10.1210/jcem.82.2.3735 DOI: https://doi.org/10.1210/jcem.82.2.3735

PMid:9024228

Poehlman ET, Toth MJ, Gardner AW. Changes in energy balance and body composition at menopause: a controlled longitudinal study. Ann Intern Med. 1995;123:673–675.

http://dx.doi.org/10.7326/0003-4819-123-9-199511010-00005 DOI: https://doi.org/10.7326/0003-4819-123-9-199511010-00005

PMid:7574222

Crook D, Godsland IF, Hull J, Stevenson JC. Hormone replacement therapy with dydrogesterone and 17 beta-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up. Br J Obstet Gynaecol. 1997;104: 298–304.

http://dx.doi.org/10.1111/j.1471-0528.1997.tb11457.x DOI: https://doi.org/10.1111/j.1471-0528.1997.tb11457.x

PMid:9091005

Cefalu WT, Wang ZQ, Werbel S, Bell-Farrow A, Crouse JR III, Hinson WH, Terry JG, Anderson R. Contribution of visceral fat mass to the insulin resistance of aging. Metabolism. 1995;44:954–959.

http://dx.doi.org/10.1016/0026-0495(95)90251-1 DOI: https://doi.org/10.1016/0026-0495(95)90251-1

Hanggi W, Lippuner K, Jaeger P, Birkhauser MH, Horber FF. Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women. Clin Endocrinol (Oxf). 1998;48(6):691–699.

http://dx.doi.org/10.1046/j.1365-2265.1998.00481.x DOI: https://doi.org/10.1046/j.1365-2265.1998.00481.x

Haarbo J, Marslew U, Gotfredsen A, Christiansen C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism. 1991;40:1323–1326.

http://dx.doi.org/10.1016/0026-0495(91)90037-W DOI: https://doi.org/10.1016/0026-0495(91)90037-W

Samaras K, Kelly PJ, Spector TD, Chiano MN, Campbell LV. Tobacco smoking and oestrogen replacement are associated with lower total and central fat in monozygotic twins. Int J Obes Relat Metab Disord. 1998;22:149–156.

http://dx.doi.org/10.1038/sj.ijo.0800558 DOI: https://doi.org/10.1038/sj.ijo.0800558

PMid:9504323

Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1995;273:199–208. DOI: https://doi.org/10.1001/jama.273.3.199

http://dx.doi.org/10.1001/jama.1995.03520270033028 DOI: https://doi.org/10.1001/jama.1995.03520270033028

Cagnacci A, Soldani R, Carriero PL, Paoletti AM, Fioretti P, Melis GB. Effects of low doses of transdermal 17 beta-estradiol on carbohydrate metabolism in postmenopausal women. J Clin Endocrinol Metab. 1992;74:1396–1400. DOI: https://doi.org/10.1210/jcem.74.6.1317387

PMid:1317387

O'Sullivan AJ, Ho KK. A comparison of the effects of oral and transdermal estrogen replacement on insulin sensitivity in postmenopausal women. J Clin Endocrinol Metab. 1995;80:1783–1788. DOI: https://doi.org/10.1210/jc.80.6.1783

PMid:7775623

Chmouliovsky L, Habicht F, James RW, Lehmann T, Campana A, Golay A. Beneficial effect of hormone replacement therapy on weight loss in obese menopausal women. Maturitas. 1999;32:147–153.

http://dx.doi.org/10.1016/S0378-5122(99)00037-7 DOI: https://doi.org/10.1016/S0378-5122(99)00037-7

Brussaard HE, Gevers Leuven JA, Frolich M, Kluft C, Krans HM. Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM. Diabetologia. 1997;40:843–849.

http://dx.doi.org/10.1007/s001250050758

PMid:9243107

Turner RC, Holman RR, Matthews D, Hockaday TD, Peto J. Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabolism. 1979;28:1086–1096.

http://dx.doi.org/10.1016/0026-0495(79)90146-X DOI: https://doi.org/10.1016/0026-0495(79)90146-X

Matthews DR,Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419.

http://dx.doi.org/10.1007/BF00280883 DOI: https://doi.org/10.1007/BF00280883

PMid:3899825

Song Y, Manson JE, Tinker L, Howard BV, Kuller LH, Nathan L, Rifai N, Liu S. Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women: the Women's Health Initiative Observational Study. Diabetes Care. 2007;30:1747–1750.

http://dx.doi.org/10.2337/dc07-0358 DOI: https://doi.org/10.2337/dc07-0358

PMid:17468352 PMCid:PMC1952235

Abbasi F, Reaven GM. Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol. Metabolism. 2011;60:1673–1676.

http://dx.doi.org/10.1016/j.metabol.2011.04.006 DOI: https://doi.org/10.1016/j.metabol.2011.04.006

PMid:21632070

Gilligan DM, Quyyumi AA, Camon RO. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994;89:2545–2551.

http://dx.doi.org/10.1161/01.CIR.89.6.2545 DOI: https://doi.org/10.1161/01.CIR.89.6.2545

PMid:8205663

Fineberg SE. Glycaemic Control and Hormone Replacement Therapy. Drugs Aging. 2000;17(6):453–461.

http://dx.doi.org/10.2165/00002512-200017060-00003 DOI: https://doi.org/10.2165/00002512-200017060-00003

PMid:11200306

Lindheim SR, Natelovitz M, Feldman EB, Larsen S, Khan FY, Lobo RA. The independent effects of exercise and estrogen on lipids and lipoproteins in postmenopausal women. Obstet. Gynecol. 1994;83(2):167–172.

http://dx.doi.org/10.1016/0020-7292(94)90488-x DOI: https://doi.org/10.1016/0020-7292(94)90488-X

The Eye Disease Care—Control Study Group. Arch. Ophtholmot. 1996;114: 545.

http://dx.doi.org/10.1001/archopht.1996.01100130537006 DOI: https://doi.org/10.1001/archopht.1996.01100130537006

Sites CK, Brochu M, Tchernof A, Poehlman ET. Relationship between hormone replacement therapy use with body fat distribution and insulin sensitivity in obese postmenopausal women. Metabolism. 2001;50(7):835–840.

http://dx.doi.org/10.1053/meta.2001.24878 DOI: https://doi.org/10.1053/meta.2001.24878

PMid:11436191

Brussaard HE, Gevers Leuven JA, Frolich M, Kluft C, Krans HM. Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM. Diabetologia. 1997;40:843–849.

http://dx.doi.org/10.1007/s001250050758 DOI: https://doi.org/10.1007/s001250050758

PMid:9243107

Lindheim SR, Presser SC, Ditkoff EC, Vijod MA, Stanczyk FZ, Lobo RA. A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin. Fertil Steril. 1993;60:664–667.

PMid:8405521

Ferrara A, Barrett-Connor E, Wingard DL, Edelstein SL. Sex differences in insulin levels in older adults and the effect of body size, estrogen replacement therapy, and glucose tolerance status: the Rancho Bernardo Study 1984–1987. Diabetes Care. 1995;18: 220–225.

http://dx.doi.org/10.2337/diacare.18.2.220 DOI: https://doi.org/10.2337/diacare.18.2.220

PMid:7729301

Andersson B, Mattsson LA, Hahn L, Marin P, Lapidus L, Holm G, Bengtsson BA, Bjorntorp P. Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Meta. 1997;82:638–643.

http://dx.doi.org/10.1210/jc.82.2.638

Brown MD, Korytkowski MT, Zmuda JM, McCole SD, Moore GE, Hagberg JM. Insulin sensitivity in postmenopausal women: independent and combined associations with hormone replacement, cardiovascular fitness, and body composition. Diabetes Care. 2000; 23:1731–1736.

http://dx.doi.org/10.2337/diacare.23.12.1731 DOI: https://doi.org/10.2337/diacare.23.12.1731

PMid:11128342

Samaras K, Hayward CS, Sullivan D, Kelly RP, Campbell LV. Effects of postmenopausal hormone replacement therapy on central abdominal fat, glycemic control, lipid metabolism, and vascular factors in type 2 diabetes: a prospective study. Diabetes Care. 1999;22:1401–1407.

http://dx.doi.org/10.2337/diacare.22.9.1401 DOI: https://doi.org/10.2337/diacare.22.9.1401

PMid:10480500

Godsland IF, Gangar K, Walton C, Cust MP, Whitehead MI, Wynn V, Stevenson JC. Insulin resistance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy. Metabolism. 1993;42:846–853.

http://dx.doi.org/10.1016/0026-0495(93)90058-V DOI: https://doi.org/10.1016/0026-0495(93)90058-V

Lindheim SR, Presser SC, Ditkoff EC, Vijod MA, Stanczyk FZ, Lobo RA. A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin. Fertil Steril. 1993;60:664–667. DOI: https://doi.org/10.1016/S0015-0282(16)56218-9

PMid:8405521

Duncan AC, Lyall H, Roberts RN, Petrie JR, Perera MJ, Monaghan S, Hart DM, Connell JM, Lumsden MA. The effect of estradiol and a combined estradiol/progestagen preparation on insulin sensitivity in healthy postmenopausal women. J Clin Endocrinol Metab. 1999;84:2402–2407.

http://dx.doi.org/10.1210/jcem.84.7.5836 DOI: https://doi.org/10.1210/jcem.84.7.5836

PMid:10404811

Andersson B, Mattsson LA, Hahn L, Marin P, Lapidus L, Holm G, Bengtsson BA, Bjorntorp P. Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1997;82:638–643.

http://dx.doi.org/10.1210/jc.82.2.638 DOI: https://doi.org/10.1210/jc.82.2.638

Puah JA, Bailey CJ. Effect of ovarian hormones on glucose metabolism in mouse soleus muscle. Endocrinology. 1985;117:1336–1340.

http://dx.doi.org/10.1210/endo-117-4-1336 DOI: https://doi.org/10.1210/endo-117-4-1336

PMid:3896756

Meier DA, Garner CW. Estradiol stimulation of glucose transport in rat uterus. Endocrinology. 1987;121:1366–1374.

http://dx.doi.org/10.1210/endo-121-4-1366 DOI: https://doi.org/10.1210/endo-121-4-1366

PMid:3653031

Kumagai S, Holmang A, Bjorntorp P: The effects of oestrogen and progesterone on insulin sensitivity in female rats. Acta Physiol Scand. 1993;149:91–97.

http://dx.doi.org/10.1111/j.1748-1716.1993.tb09596.x DOI: https://doi.org/10.1111/j.1748-1716.1993.tb09596.x

PMid:8237427

Rincon J, Holmang A, Wahlstrom EO, Lonnroth P, Bjorntorp P, Zierath JR, Wallberg-Henriksson H. Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment. Diabetes. 1996;45:615–621.

http://dx.doi.org/10.2337/diab.45.5.615 DOI: https://doi.org/10.2337/diab.45.5.615

PMid:8621012

Pedersen O, Bak JF, Andersen PH, Lund S, Moller DE, Flier JS, Kahn BB. Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM. Diabetes. 1990;39:865–870. DOI: https://doi.org/10.2337/diabetes.39.7.865

http://dx.doi.org/10.2337/diab.39.7.865 DOI: https://doi.org/10.2337/diab.39.7.865

PMid:2354749

Sanada M, Higashi Y, Nakagawa K, Sasaki S, Kodama I, Sakashita T, Tsuda M, Ohama K. Oral estrogen replacement therapy increases forearm reactive hyperemia accompanied by increases in serum levels of nitric oxide in postmenopausal women. Gynecol Endocrinol. 2001;15:150–157.

http://dx.doi.org/10.1080/gye.15.2.150.157 DOI: https://doi.org/10.1080/gye.15.2.150.157

PMid:11379012

McCrohon JA, Adams MR, McCredie RJ, Robinson J, Pike A, Abbey M, Keech AC, Celermajer DS. Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women. Clin Endocrinol. 1996;45:435–441.

http://dx.doi.org/10.1046/j.1365-2265.1996.8070816.x DOI: https://doi.org/10.1046/j.1365-2265.1996.8070816.x

Published

2016-02-01

How to Cite

1.
Bitoska I, Krstevska B, Milenkovic T, Subeska-Stratrova S, Petrovski G, Jovanovska Mishevska S, Ahmeti I, Todorova B. Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women. Open Access Maced J Med Sci [Internet]. 2016 Feb. 1 [cited 2024 Apr. 25];4(1):83-8. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2016.024

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Section

B - Clinical Sciences