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The independent associations of anti-Müllerian hormone and estradiol levels over the menopause transition with lipids/lipoproteins: The study of women's health across the nation

Published:November 21, 2022DOI:https://doi.org/10.1016/j.jacl.2022.11.008

      Highlights

      • AMH and E2 changes relate differently to lipid/lipoprotein profile in midlife women.
      • Lower midlife E2 may be related to atherogenic lipid/lipoprotein profile in women.
      • Lower midlife AMH may be related to HDL dysfunctionality in women.

      Background

      The menopause transition (MT) is linked to adverse changes in lipids/lipoproteins. However, the related contributions of Anti-Müllerian hormone (AMH) and estradiol (E2) are not clear.

      Objective

      To evaluate the independent associations of premenopausal AMH and E2 levels and their changes with lipids/lipoproteins levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1)] over the MT.

      Methods

      SWAN participants who transitioned to menopause without exogenous hormone use, hysterectomy, or bilateral oophorectomy with data available on both exposure and outcomes when they were premenopausal until the 1st visit postmenopausal were studied.

      Results

      The study included 1,440 women (baseline-age:mean ±SD=47.4 ±2.6) with data available from up to 9 visits (1997-2013). Lower premenopausal levels and greater declines in AMH were independently associated with greater TC and HDL-C, whereas lower premenopausal levels and greater declines in E2 were independently associated with greater TG and apo B and lower HDL-C. Greater declines in AMH were independently associated with greater apoA-1, and greater declines in E2 were independently associated with greater TC and LDL-C.

      Conclusions

      AMH and E2 and their changes over the MT relate differently to lipids/lipoproteins profile in women during midlife. Lower premenopausal and/or greater declines in E2 over the MT were associated with an atherogenic lipid/lipoprotein profile. On the other hand, lower premenopausal AMH and/or greater declines in AMH over the MT were linked to higher apo A-1 and HDL-C; the later found previously to be related to a greater atherosclerotic risk after menopause.

      Keywords

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      References

        • El Khoudary S.R.
        • Aggarwal B.
        • Beckie T.M.
        • et al.
        Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the American heart association.
        Circulation. 2020; 142 (Dec 22): e506-e532https://doi.org/10.1161/cir.0000000000000912
        • Matthews K.A.
        • Crawford S.L.
        • Chae C.U.
        • et al.
        Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition?.
        J Am Coll Cardiol. 2009; 54 (Dec 15): 2366-2373https://doi.org/10.1016/j.jacc.2009.10.009
        • Derby C.A.
        • Crawford S.L.
        • Pasternak R.C.
        • Sowers M.
        • Sternfeld B.
        • Matthews K.A.
        Lipid changes during the menopause transition in relation to age and weight: the study of women's health across the nation.
        Am J Epidemiol. 2009; 169 (Jun 1): 1352-1361https://doi.org/10.1093/aje/kwp043
        • Shufelt C.L.
        • Manson J.E.
        Menopausal hormone therapy and cardiovascular disease: the role of formulation, dose, and route of delivery.
        J Clin Endocrinol Metab. 2021; 106 (Apr 23): 1245-1254https://doi.org/10.1210/clinem/dgab042
        • Trichopoulos D.
        • Polychronopoulou A.
        • Brown J.
        • MacMahon B.
        Obesity, serum cholesterol, and estrogens in premenopausal women.
        Oncology. 1983; 40: 227-231https://doi.org/10.1159/000225731
        • Shelley J.M.
        • Green A.
        • Smith A.M.
        • et al.
        Relationship of endogenous sex hormones to lipids and blood pressure in mid-aged women.
        Ann Epidemiol. 1998; 8 (Jan): 39-45https://doi.org/10.1016/s1047-2797(97)00123-3
        • Güdücü N.
        • Görmüş U.
        • Kutay S.S.
        • Kavak Z.N.
        • Telatar B.
        Endogenous sex hormones and their associations with cardiovascular risk factors in post-menopausal women.
        J Endocrinol Invest. 2013; 36 (Sep): 588-592https://doi.org/10.3275/8881
        • Worsley R.
        • Robinson P.J.
        • Bell R.J.
        • Moufarege A.
        • Davis S.R.
        Endogenous estrogen and androgen levels are not independent predictors of lipid levels in postmenopausal women.
        Menopause. 2013; 20 (Jun): 640-645https://doi.org/10.1097/GME.0b013e318279bd4a
        • Lambrinoudaki I.
        • Christodoulakos G.
        • Rizos D.
        • et al.
        Endogenous sex hormones and risk factors for atherosclerosis in healthy Greek postmenopausal women.
        Eur J Endocrinol. 2006; 154 (Jun): 907-916https://doi.org/10.1530/eje.1.02167
        • Kuller L.H.
        • Gutai J.P.
        • Meilahn E.
        • Matthews K.A.
        • Plantinga P.
        Relationship of endogenous sex steroid hormones to lipids and apoproteins in postmenopausal women.
        Arteriosclerosis. 1990; 10 (Nov-Dec): 1058-1066https://doi.org/10.1161/01.atv.10.6.1058
        • Kim C.
        • Kong S.
        • Krauss R.M.
        • et al.
        Endogenous sex steroid hormones, lipid subfractions, and ectopic adiposity in asian indians.
        Metab Syndr Relat Disord. 2015; 13 (Dec): 445-452https://doi.org/10.1089/met.2015.0063
        • Finkelstein J.S.
        • Lee H.
        • Karlamangla A.
        • et al.
        Antimullerian hormone and impending menopause in late reproductive age: the study of women's health across the nation.
        J Clin Endocrinol Metab. 2020; 105 (Apr 1): e1862-e1871https://doi.org/10.1210/clinem/dgz283
        • Hehenkamp W.J.
        • Looman C.W.
        • Themmen A.P.
        • de Jong F.H.
        • Te Velde E.R.
        • Broekmans F.J.
        Anti-Müllerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation.
        J Clin Endocrinol Metab. 2006; 91 (Oct): 4057-4063https://doi.org/10.1210/jc.2006-0331
        • Tehrani F.R.
        • Erfani H.
        • Cheraghi L.
        • Tohidi M.
        • Azizi F.
        Lipid profiles and ovarian reserve status: a longitudinal study.
        Hum Reprod. 2014; 29 (Nov): 2522-2529https://doi.org/10.1093/humrep/deu249
        • Al Rashid K.
        • Taylor A.
        • Lumsden M.A.
        • Goulding N.
        • Lawlor D.A.
        • Nelson S.M.
        Association of the functional ovarian reserve with serum metabolomic profiling by nuclear magnetic resonance spectroscopy: a cross-sectional study of ∼ 400 women.
        BMC Med. 2020; 18 (Aug 31): 247https://doi.org/10.1186/s12916-020-01700-z
        • Lim S.
        • Kim S.
        • Kim O.
        • et al.
        Correlations among anti-Müllerian hormone levels, body mass index and lipid profile in reproductive-aged women: the Korea Nurses' Health Study.
        Nurs Open. 2021; (Aug 2)https://doi.org/10.1002/nop2.1011
        • Lambrinoudaki I.
        • Stergiotis S.
        • Chatzivasileiou P.
        • et al.
        Anti-Müllerian hormone concentrations are inversely associated with subclinical atherosclerosis in premenopausal women.
        Angiology. 2020; 71 (Jul): 552-558https://doi.org/10.1177/0003319720914493
        • Skałba P.
        • Cygal A.
        • Madej P.
        • et al.
        Is the plasma anti-Müllerian hormone (AMH) level associated with body weight and metabolic, and hormonal disturbances in women with and without polycystic ovary syndrome?.
        Eur J Obstet Gynecol Reprod Biol. 2011; 158 (Oct): 254-259https://doi.org/10.1016/j.ejogrb.2011.06.006
        • Yarde F.
        • Spiering W.
        • Franx A.
        • et al.
        Association between vascular health and ovarian ageing in type 1 diabetes mellitus.
        Hum Reprod. 2016; 31 (Jun): 1354-1362https://doi.org/10.1093/humrep/dew063
        • Kim C.
        • Pan Y.
        • Braffett B.H.
        • et al.
        Anti-Müllerian hormone and its relationships with subclinical cardiovascular disease and renal disease in a longitudinal cohort study of women with type 1 diabetes.
        Womens Midlife Health. 2017; 3: 5https://doi.org/10.1186/s40695-017-0023-9
        • Rios J.S.
        • Greenwood E.A.
        • Pavone M.E.G.
        • et al.
        Associations between anti-mullerian hormone and cardiometabolic health in reproductive age women are explained by body mass index.
        J Clin Endocrinol Metab. 2020; 105 (Jan 1): e555-e563https://doi.org/10.1210/clinem/dgz012
        • Izawa S.
        • Okada M.
        • Matsui H.
        • Horita Y.
        A new direct method for measuring HDL-cholesterol which does not produce any biased values.
        J Med Pharm Sci. 1997; 371385213881
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin Chem. 1972; 18 (Jun): 499-502
        • England B.G.
        • Parsons G.H.
        • Possley R.M.
        • McConnell D.S.
        • Midgley A.R.
        Ultrasensitive semiautomated chemiluminescent immunoassay for estradiol.
        Clin Chem. 2002; 48: 1584-1586https://doi.org/10.1093/clinchem/48.9.1584
        • Sternfeld B.
        • Ainsworth B.E.
        • Quesenberry C.P.
        Physical activity patterns in a diverse population of women.
        Prev Med. 1999; 28 (Mar): 313-323https://doi.org/10.1006/pmed.1998.0470
        • El Khoudary S.R.
        HDL and the menopause.
        Curr Opin Lipidol. 2017; 28 (Aug): 328-336https://doi.org/10.1097/mol.0000000000000432
        • El Khoudary S.R.
        • Chen X.
        • Nasr A.N.
        • et al.
        HDL (high-density lipoprotein) subclasses, lipid content, and function trajectories across the menopause transition: SWAN-HDL study.
        Arterioscler Thromb Vasc Biol. 2021; 41 (Feb): 951-961https://doi.org/10.1161/atvbaha.120.315355
        • El Khoudary S.R.
        • Wang L.
        • Brooks M.M.
        • Thurston R.C.
        • Derby C.A.
        • Matthews K.A.
        Increase HDL-C level over the menopausal transition is associated with greater atherosclerotic progression.
        J Clin Lipidol. 2016; 10 (Jul-Aug): 962-969https://doi.org/10.1016/j.jacl.2016.04.008
        • El Khoudary S.R.
        • Ceponiene I.
        • Samargandy S.
        • et al.
        HDL (high-density lipoprotein) metrics and atherosclerotic risk in women.
        Arterioscler Thromb Vasc Biol. 2018; 38 (Sep): 2236-2244https://doi.org/10.1161/atvbaha.118.311017
        • Grossman D.C.
        • Curry S.J.
        • Owens D.K.
        • et al.
        Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: US preventive services task force recommendation statement.
        JAMA. 2017; 318 (Dec 12): 2224-2233https://doi.org/10.1001/jama.2017.18261
        • Hulley S.
        • Grady D.
        • Bush T.
        • 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 (Aug 19): 605-613https://doi.org/10.1001/jama.280.7.605
        • Herrington D.M.
        • Reboussin D.M.
        • Brosnihan K.B.
        • et al.
        Effects of estrogen replacement on the progression of coronary-artery atherosclerosis.
        N Engl J Med. 2000; 343: 522-529https://doi.org/10.1056/nejm200008243430801
        • Rossouw J.E.
        • Anderson G.L.
        • Prentice R.L.
        • 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 (Jul 17): 321-333https://doi.org/10.1001/jama.288.3.321
        • Anderson G.L.
        • Limacher M.
        • Assaf A.R.
        • et al.
        Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.
        JAMA. 2004; 291 (Apr 14): 1701-1712https://doi.org/10.1001/jama.291.14.1701
        • Manson J.E.
        • Chlebowski R.T.
        • Stefanick M.L.
        • et al.
        Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the women's health initiative randomized trials.
        JAMA. 2013; 310: 1353-1368https://doi.org/10.1001/jama.2013.278040
        • 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 (Jan 18): 199-208
        • Sai A.J.
        • Gallagher J.C.
        • Fang X.
        Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-α genotypes.
        Menopause. 2011; 18 (Oct): 1101-1112https://doi.org/10.1097/gme.0b013e318217d41d
        • Angerer P.
        • Kothny W.
        • Störk S.
        • von Schacky C.
        Hormone replacement therapy and distensibility of carotid arteries in postmenopausal women: a randomized, controlled trial.
        J Am Coll Cardiol. 2000; 36 (Nov 15): 1789-1796https://doi.org/10.1016/s0735-1097(00)00969-4
        • Davidson M.H.
        • Maki K.C.
        • Marx P.
        • et al.
        Effects of continuous estrogen and estrogen-progestin replacement regimens on cardiovascular risk markers in postmenopausal women.
        Arch Intern Med. 2000; 160 (Nov 27): 3315-3325https://doi.org/10.1001/archinte.160.21.3315
        • Gregersen I.
        • Høibraaten E.
        • Holven K.B.
        • et al.
        Effect of hormone replacement therapy on atherogenic lipid profile in postmenopausal women.
        Thromb Res. 2019; 184 (Dec): 1-7https://doi.org/10.1016/j.thromres.2019.10.005
        • Sriprasert I.
        • Hodis H.N.
        • Bernick B.
        • Mirkin S.
        • Mack W.J.
        Effects of estradiol dose and serum estradiol levels on metabolic measures in early and late postmenopausal women in the REPLENISH trial.
        J Womens Health (Larchmt). 2020; 29 (Aug): 1052-1058https://doi.org/10.1089/jwh.2019.8238
        • Vaisar T.
        • Gordon J.L.
        • Wimberger J.
        • et al.
        Perimenopausal transdermal estradiol replacement reduces serum HDL cholesterol efflux capacity but improves cardiovascular risk factors.
        J Clin Lipidol. 2021; 15 (Jan-Febe0): 151-161https://doi.org/10.1016/j.jacl.2020.11.009
        • Brynhildsen J.
        • Hammar M.
        Lipids and clotting factors during low dose transdermal estradiol/norethisterone use.
        Maturitas. 2005; 50 (Apr 11): 344-352https://doi.org/10.1016/j.maturitas.2004.10.001