Research Article| Volume 49, ISSUE 3, P253-263, November 15, 2004

Download started.


The effects of 17β-oestradiol plus dydrogesterone compared with conjugated equine oestrogens plus medroxyprogesterone acetate on lipids, apolipoproteins and lipoprotein(a)


      Objective: To compare the effects of 17β-oestradiol plus dydrogesterone with conjugated equine oestrogens plus medroxyprogesterone acetate on serum lipids, apolipoproteins and lipoprotein(a) in postmenopausal women. Methods: A multi-centre, prospective, randomised, double-blind, comparative one-year study in 362 healthy postmenopausal women aged 39–74 years with an intact uterus. Fasting blood samples were taken at baseline and after 28 and 52 weeks of treatment. Participants received daily oral treatment with continuous combined 1 mg micronised 17β-oestradiol/5 mg dydrogesterone (E/D: n = 180) or 0.625 mg conjugated equine oestrogens/5 mg medroxyprogesterone acetate (CEE/MPA: n = 182). Results: Significant differences between the two groups after 52 weeks were observed for total cholesterol (E/D: −1.7%; CEE/MPA: −7.3%), LDL-cholesterol (E/D: −4.5%; CEE/MPA: −11.3%), HDL-cholesterol (E/D: +15.3%; CEE/MPA: +7.5%), triglycerides (E/D: +9.8%; CEE/MPA: +16.6%), VLDL-triglycerides (E/D: −3.3%; CEE/MPA: +10.0%), lipoprotein(a) (E/D: 0.0%; CEE/MPA: −25.2%) and for the ratio apolipoprotein B/LDL-cholesterol (E/D: +0.9%; CEE/MPA +5.9%). Conclusions: E/D and CEE/MPA differ in their anti-atherogenic effects on lipids and lipoproteins. This however can not easily be translated to differences in clinical cardiovascular outcomes.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Maturitas
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Stampfer M.J.
        • Colditz G.A.
        • Willett W.C.
        Menopause and heart disease: a review.
        Ann. NY Acad. Sci. 1990; 592: 193-203
        • Colditz G.A.
        • Willett W.C.
        • Stampfer M.J.
        • Rosner B.
        • Speizer F.E.
        • Hennekens C.H.
        Menopause and the risk of coronary heart disease in women.
        N. Engl. J. Med. 1987; 316: 1105-1110
        • Campos H.
        • Mc Namara J.R.
        • Wilson P.W.
        • Ordovas J.M.
        • Schaefer E.J.
        Differences in low density lipoprotein subfractions and apolipoproteins in premenopausal and postmenopausal women.
        J. Clin. Endocrinol. Metab. 1988; 67: 30-35
        • Matthews K.A.
        • Meilahn E.
        • Kuller L.H.
        • Kelsey S.F.
        • Caggiula A.W.
        • Wing R.R.
        Menopause and risk factors for coronary heart disease.
        New Engl. J. Med. 1989; 321: 641-646
        • Stevenson J.C.
        • Crook D.
        • Godsland I.F.
        Influence of age and menopause on serum lipids and lipoproteins in healthy women.
        Atherosclerosis. 1993; 98: 83-90
        • Bruschi F.
        • Meschia M.
        • Soma M.
        • Perotti D.
        • Crosignani P.G.
        Lipoprotein(a) and other lipids after oophorectomy and estrogen replacement therapy.
        Obstet. Gynecol. 1996; 88: 950-954
        • Lobo R.A.
        • Notelovitz M.
        • Bernstein L.
        • Khan F.Y.
        • Ross R.K.
        • Paul W.L.
        Lp(a) lipoprotein: relationship to cardiovascular disease risk factors, exercise, and estrogen.
        Am. J. Obstet. Gynecol. 1992; 166: 1182-1190
        • Smith E.B.
        • Keen G.A.
        • Grant A.
        Factors influencing the accumulation in fibrous plaques of lipid derived from low density lipoprotein.I. Relation between fibrin and immobilization of ApoB-containing lipoprotein.
        Atherosclerosis. 1990; 84: 165-171
        • Hajjar K.A.
        • Gavish D.
        • Breslow J.L.
        • Nachman R.L.
        Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis.
        Nature. 1989; 339: 303-304
        • Marcinova S.M.
        • Koschinsky M.L.
        Lipoprotein(a) as a risk factor for coronary artery disease.
        Am. J. Cardiol. 1998; 82: 57U-66U
        • Kim C.J.
        • Min Y.K.
        • Ryu W.S.
        • Kwak J.W.
        • Ryoo U.H.
        Effect of hormone replacement therapy on lipoprotein (a) and lipid levels in postmenopausal women.
        Intern. Med. 1996; 156: 1693-1700
        • Mijatovic V.
        • Kenemans P.
        • Netelenbos J.C.
        • et al.
        Oral 17β-oestradiol continuous combined with dydrogesterone lowers serum lipoprotein(a) in healthy postmenopausal women.
        J. Clin. Endocrinol. Metab. 1997; 82: 3543-3547
        • Seed M.
        • Sands R.H.
        • McLaren M.
        • Kirk G.
        • Darko D.
        The effect of hormone replacement therapy and route of administration on selected cardiovascular risk factors in post-menopausal women.
        Fam. Pract. 2000; 17: 479-507
        • Godsland I.F.
        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
        • Vehkavaara S.
        • Silveira A.
        • Hakala-Ala-Pietilä T.
        • et al.
        Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women.
        Thromb Haemost. 2001; 85: 619-625
        • Grady D.
        • Gebretsadik T.
        • Kerlikowske K.
        • Ernster V.
        • Petitti D.
        Hormone replacement therapy and endometrial cancer risk: a meta-analysis.
        Obstet. Gynecol. 1995; 85: 304-313
        • Grodstein F.
        • Stampfer M.J.
        • Manson J.E.
        • et al.
        Postmenopausal estrogen and progestin use and the risk of cardiovascular disease.
        N. Engl. J. Med. 1996; 335: 453-461
        • Barrett-Connor E.
        • Grady D.
        Hormone replacement therapy, heart disease, and other considerations.
        Ann. Rev. Public Health. 1998; 19: 55-72
        • Hulley S.
        • Grady D.
        • Bush T.
        • et al.
        Randomized trial of estrogen plus progestin for secondary prevention coronary heart disease in postmenopausal women.
        JAMA. 1998; 280: 605-613
      1. Writing group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002;288:321–33.

        • Clarkson T.B.
        • Appt S.E.
        MPA and postmenopausal coronary artery atherosclerosis revisited.
        Steroids. 2003; 68: 941-951
        • Van der Mooren M.J.
        • Demacker C.M.G.
        • Thomas C.M.G.
        • Borm G.F.
        • Rolland R.
        A 2-year study on the beneficial effects of 17β-oestradiol-dydrogesterone therapy on serum lipoproteins and Lp(a) in postmenopausal women: no additional unfavourable effects of dydrogesterone.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 1993; 52: 117-123
        • Voetberg G.A.
        • Netelenbos J.C.
        • Kenemans P.
        • Peters-Muller E.R.A.
        • van de Weijer P.H.M.
        Estrogen replacement therapy continuously combined with four different dosages of dydrogesterone: effect on calcium and lipid metabolism.
        J. Clin. Endocrinol. Metab. 1994; 79: 1465-1469
        • Gelfand M.M.
        • Fugere P.
        • Bissonnette B.
        Cardiovascular risk factors during sequentially combined 17β oestradiol and dydrogesterone (Femoston®); results from a one-year study in postmenopausal women.
        Maturitas. 1997; 26: 125-132
        • Crook D.
        • Godsland I.F.
        • Hull J.
        • Stevenson J.C.
        Hormone replacement therapy with dydrogesterone and 17β-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up.
        Br. J. Obstet. Gynecol. 1997; 104: 298-304
        • Mijatovic V.
        • Kenemans P.
        • van Baal W.M.
        • Peters-Muller E.R.A.
        • van der Mooren M.J.
        A randomised controlled study of the effects of 17β-estradiol-dydrogesterone on plasma homocysteine in postmenopausal women.
        Obstet. Gynecol. 1998; 91: 432-436
        • Van Baal W.M.
        • Smolders R.G.V.
        • van der Mooren M.J.
        • Teerlink T.
        • Kenemans P.
        Hormone replacement therapy and plasma homocysteine levels.
        Obstet. Gynecol. 1999; 94: 485-491
        • Mattson L.A.
        • Christiansen C.
        • Colau J.-C.
        • et al.
        Clinical equivalence of intranasal and oral 17β-estradiol for ostmenopausal symptoms.
        Am. J. Obstet. Gynecol. 2000; 182: 545-552
        • Pornel B.P.
        • Chevallier O.
        • Netelenbos J.C.
        Oral 17β-estradiol (1 mg) continuously combined with dydrogesterone improves the serum lipid profile of postmenopausal women.
        Menopause. 2002; 9: 171-178
        • Stumpf P.G.
        Pharmacokinetics of estrogen.
        Obstet. Gynecol. 1990; 75: 9S-14S
        • Kuhl H.
        Pharmacokinetics of oestrogens and progestogens.
        Maturitas. 1990; 12: 171-197
        • Foster R.H.
        • Balfour J.A.
        Estradiol and dydrogesterone. A review of their combined use as hormone replacement therapy in postmenopausal women.
        Drugs Aging. 1997; 11: 309-332
        • Van Baal W.M.
        • Emeis J.J.
        • van der Mooren M.J.
        • Kessel H.
        • Kenemans P.
        • Stehouwer C.D.A.
        Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study.
        Thromb Haemost. 2000; 83: 29-34
        • Clarkson T.B.
        The new conundrum: do estrogens have any cardiovascular benefits?.
        Int. J. Fertil. 2002; 47: 61-68