Effect of Half-dose and Standard-dose Conjugated Equine Estrogens Combined with Natural Progesterone or Dydrogesterone on Components of Metabolic Syndrome in Healthy Postmenopausal Women: A Randomized Controlled Trial

Wei Xue, Yan Deng, Yan-Fang Wang, Ai-Jun Sun, Wei Xue, Yan Deng, Yan-Fang Wang, Ai-Jun Sun

Abstract

Background: Menopausal hormone therapy (MHT) has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen (CEE) and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women.

Methods: A prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups: Group A received CEE 0.3 mg/micronized progesterone (MP) 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student's t-test and analysis of variance.

Results: A total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline (all P < 0.05). Among the three groups, only Group C showed significantly increased triglycerides compared with baseline (1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P = 0.026). Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups.

Conclusions: Among Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.

Trial registration: ClinicalTrials.gov, NCT01698164; https://ichgcp.net/clinical-trials-registry/NCT01698164?term=NCT01698164&rank=1.

Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram of this study. Group A: Received CEE 0.3 mg + MP 100 mg daily; Group B: Received CEE 0.625 mg + MP 100 mg daily; Group C: Received CEE 0.625 mg + dydrogesterone 10 mg daily. MHT: Menopausal hormone therapy; CEE: Conjugated equine estrogen; MP: Micronized progesterone.

References

    1. Spencer CP, Godsland IF, Stevenson JC. Is there a menopausal metabolic syndrome? Gynecol Endocrinol. 1997;11:341–55. doi: 10.3109/09513599709152559.
    1. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–607. doi: 10.2337/diab.37.12.1595.
    1. Lovre D, Lindsey SH, Mauvais-Jarvis F. Effect of menopausal hormone therapy on components of the metabolic syndrome. Ther Adv Cardiovasc Dis. 2016 pii: 1753944716649358. [Epub ahead of print] doi: 10.1177/1753944716649358.
    1. Manson JE. Current recommendations: What is the clinician to do? Fertil Steril. 2014;101:916–21. doi: 10.1016/j.fertnstert.2014.02.043.
    1. Godsland IF. Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: Analysis of studies published from 1974-2000. Fertil Steril. 2001;75:898–915. doi: 10.1016/S0015-0282(01)01699-5.
    1. Lobo RA, Pinkerton JV, Gass ML, Dorin MH, Ronkin S, Pickar JH, et al. Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril. 2009;92:1025–38. doi: 10.1016/j.fertnstert.2009.03.113.
    1. Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: Results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004;47:1175–87. doi: 10.1007/s00125-004-1448-x.
    1. Kanaya AM, Herrington D, Vittinghoff E, Lin F, Grady D, Bittner V, et al. Glycemic effects of postmenopausal hormone therapy: The Heart and Estrogen/Progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138:1–9. doi: 10.7326/0003-4819-138-1-200301070-00005.
    1. Jensen LB, Vestergaard P, Hermann AP, Gram J, Eiken P, Abrahamsen B, et al. Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: A randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study. J Bone Miner Res. 2003;18:333–42. doi: 10.1359/jbmr.2003.18.2.333.
    1. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA. 1995;273:199–208. doi: 10.1001/jama.1995.03520270033028.
    1. Geloneze B, Repetto EM, Geloneze SR, Tambascia MA, Ermetice MN. The threshold value for insulin resistance (HOMA-IR) in an admixtured population IR in the Brazilian metabolic syndrome study. Diabetes Res Clin Pract. 2006;72:219–20. doi: 10.1016/j.diabres.2005.10.017.
    1. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. 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. JAMA. 1998;280:605–13. doi: 10.1001/jama.280.7.605.
    1. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the women's health initiative randomized controlled trial. JAMA. 2002;288:321–33. doi: 10.1001/jama.288.3.321.
    1. Lobo RA, Pickar JH, Wild RA, Walsh B, Hirvonen E. Metabolic impact of adding medroxyprogesterone acetate to conjugated estrogen therapy in postmenopausal women. The Menopause Study Group. Obstet Gynecol. 1994;84:987–95.
    1. Espeland MA, Hogan PE, Fineberg SE, Howard G, Schrott H, Waclawiw MA, et al. Effect of postmenopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Diabetes Care. 1998;21:1589–95. doi: 10.2337/diacare.21.10.1589.
    1. Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevanian A, Mahrer PR, et al. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001;135:939–53. doi: 10.7326/0003-4819-135-11-200112040-00005.
    1. Sargeant LA, Wareham NJ, Khaw KT. Hormone replacement therapy and glucose tolerance in EPIC-Norfolk: A population-based study. Diabetes Metab Res Rev. 2000;16:20–5. doi: 10.1002/(SICI)1520-7560(200001/02)16: 1<20::AID-DMRR76>;2-A.
    1. Zhang Y, Howard BV, Cowan LD, Yeh J, Schaefer CF, Wild RA, et al. The effect of estrogen use on levels of glucose and insulin and the risk of type 2 diabetes in american Indian postmenopausal women: The strong heart study. Diabetes Care. 2002;25:500–4. doi: 10.2337/diacare.25.3.500.
    1. Nabulsi AA, Folsom AR, White A, Patsch W, Heiss G, Wu KK, et al. Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. The Atherosclerosis Risk in Communities Study Investigators. N Engl J Med. 1993;328:1069–75. doi: 10.1056/NEJM199304153281501.
    1. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women's Health Initiative randomized controlled trial. JAMA. 2004;291:1701–12. doi: 10.1001/jama.291.14.1701.
    1. Kong D, Zhan Y, Liu Z, Ding T, Li M, Yu H, et al. SIRT1-mediated ERβ suppression in the endothelium contributes to vascular aging. Aging Cell. 2016 [Epub ahead of print] doi: 10.1111/acel.12515.
    1. Liu Z, Gou Y, Zhang H, Zuo H, Zhang H, Liu Z, et al. Estradiol improves cardiovascular function through up-regulation of SOD2 on vascular wall. Redox Biol. 2014;3:88–99. doi: 10.1016/j.redox.2014.11.001.
    1. Matrai M, Hetthéssy JR, Nadasy GL, Szekacs B, Mericli M, Acs N, et al. Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension. Menopause. 2016;23:778–83. doi: 10.1097/GME.0000000000000654.
    1. Tarhouni K, Guihot AL, Vessieres E, Procaccio V, Grimaud L, Abraham P, et al. Estrogens are needed for the improvement in endothelium-mediated dilation induced by a chronic increase in blood flow in rat mesenteric arteries. Vascul Pharmacol. 2016;80:35–42. doi: 10.1016/j.vph.2015.10.004.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren