Advertisement

Cardiovascular Risk in Climacteric Women: When to Begin the Hormone Treatment?

  • Néstor Siseles
  • Pamela Gutiérrez
  • Maria Alejandra Schüle
  • Nilson Roberto de Melo
Chapter
Part of the ISGE Series book series (ISGE)

Abstract

Hormonal changes determine a greater vulnerability in the cardiovascular system and thus, when considering the cardiovascular health of a menopausal woman, personalized medicine is decidedly required to ensure she is an appropriate candidate for menopausal hormone therapy (MHT). Tailoring to the individual patient is important for establishing the optimal dose, the formulation, and the administration route, as well as for ascertaining the effects of MHT initiated prior to the onset of a cardiovascular disease (CVD), for assessing whether there is a special group of women whose risk for CVD may increase or diminish with the therapy, and for clarifying the differences among the research protocols according to the MHT administration route in relation to the cardiovascular system.

Basic research studies clearly show that in early menopause estrogens promote increased vasodilation, a decrease in inflammatory factors, and a slowing down in the progression of atherosclerotic lesions. They also show that in late menopause estrogens produce the reverse effect, i.e., decreased vasodilation, an increase in inflammatory factors, and growing instability of the atherosclerotic plaque.

Randomized clinical trials (RCTs), observational cohort studies, and meta-analyses show that estrogens used as a MHT may diminish CVDs and the causes of mortality in women younger than 60 years and with less than 10 years of menopause. The data on combined estrogen–progestogen therapy in the same population are suggestive of a similar tendency; however, some RCTs did not find a significant increase or decrease in CVDS. The DOPS study was the only long-term study to include women approaching menopause or going through it and have them begin MHT. It provided evidence that prevention benefits surpass the risks and confirmed the data accumulated in the last 50 years that MHT reduces CVDs and mortality when prescribed for women at the very beginning of postmenopause.

They corroborate the findings that MHT, including tibolone and the combination of conjugated estrogens with a SERM (bazedoxifene), is the most effective treatment for the vasomotor symptoms associated with menopause. The benefits surpass the risks when therapy is initiated before age 60 in women with less than 10 years of menopause.

They highlight the distinction between estrogen therapy and combined MHT, stress the difference in the risk of venous thromboembolism and ischemic stroke between the oral and the transdermal routes, and emphasize that treatments should be individualized and their dosages and duration should conform to their objectives and to safety issues. The MHT poses no danger for the cardiovascular system; on the contrary, if given to the right woman at the right time, it may reduce the risk of a CVD. This is what is known as the “window of opportunity.”

Keywords

Cardiovascular disease Vasomotor symptoms Menopausal transition Postmenopause Menopausal hormone therapy (MHT) Estrogens Window of opportunity 

References

  1. 1.
    Collins P, et al. Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists. Eur Heart J. 2007;28:2028–40. ISGE Congress, Florence, 2016.CrossRefGoogle Scholar
  2. 2.
    Manson JE. The role of personalized medicine in identifying appropriate candidates for menopausal estrogen therapy. Metabolism. 2013;62(Suppl 1):S15–9.CrossRefGoogle Scholar
  3. 3.
    Clarkson TB, et al. Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future. Menopause. 2013;20(3):342–53.CrossRefGoogle Scholar
  4. 4.
    Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science. 2005;308:1583–7.CrossRefGoogle Scholar
  5. 5.
    WHI. 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.CrossRefGoogle Scholar
  6. 6.
    Grodstein F, et al. A prospective observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med. 2000;133:933–41.CrossRefGoogle Scholar
  7. 7.
    Harman M et al. NAMS 23rd Annual Meeting, 3–6 October 2012.Google Scholar
  8. 8.
    Hodis HN, et al. The early versus late intervention trial with estradiol: a randomized trial to test the timing. NAMS Annual Meeting, October 8, 2013.Google Scholar
  9. 9.
    Hodis HN, et al. Vascular effects of early vs late postmenopausal treatment with estradiol. N Engl J Med. 2016;374:1221–31.CrossRefGoogle Scholar
  10. 10.
    Hulley S, 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.CrossRefGoogle Scholar
  11. 11.
    Lakoski S, et al. Interleukin-10 concentration and coronary heart disease (CHD). Event risk in the estrogen replacement and atherosclerosis (ERA) study. Atherosclerosis. 2008;197:443–7.CrossRefGoogle Scholar
  12. 12.
    Schierbeck LL, et al. Effect of hormone replacement therapy on cardiovascular events in recently menopausal women: randomised trial (Danish Study). BMJ. 2012;345:e6409.CrossRefGoogle Scholar
  13. 13.
    Taylor H, Manson JAE. Update in hormone therapy use in menopause. J Clin Endocrinol Metabol. 2011;96:255–64.CrossRefGoogle Scholar
  14. 14.
    Rossouw JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2008;299:1426. 297:1465–1477.Google Scholar
  15. 15.
    Santen RJ, et al. Scientific statement: postmenopausal hormone therapy. J Clin Endocrinol Metab. 2010;95(Suppl 1):S7–S66.Google Scholar
  16. 16.
    La Croix A, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy. JAMA. 2011;305(13):1305–14.CrossRefGoogle Scholar
  17. 17.
    Hodis NH, et al. The timing hypothesis for coronary heart disease prevention with hormone therapy: past, present and future in perspective. Climacteric. 2012;15(3):217–21.CrossRefGoogle Scholar
  18. 18.
    de Villiers TJ, et al. Global Consensus Statement on menopausal hormone therapy. Maturitas. 2013;74:391–2.CrossRefGoogle Scholar
  19. 19.
    de Villiers TJ, et al. Revised Global Consensus Statement on menopausal hormone therapy. Maturitas. 2016;91:153–5.CrossRefGoogle Scholar

Copyright information

© International Society of Gynecological Endocrinology 2019

Authors and Affiliations

  • Néstor Siseles
    • 1
    • 2
    • 3
    • 4
    • 5
  • Pamela Gutiérrez
    • 6
  • Maria Alejandra Schüle
    • 6
    • 7
  • Nilson Roberto de Melo
    • 2
    • 3
    • 8
    • 9
    • 10
    • 11
  1. 1.University of Buenos Aires (UBA)Buenos AiresArgentina
  2. 2.Latin American Federation of the Societies of Climacteric and Menopause (FLASCYM)San JoseCosta Rica
  3. 3.International Society of Gynecological Endocrinology (ISGE)PisaItaly
  4. 4.National Academy of Medicine of the Republic of UruguayMontevideoUruguay
  5. 5.International Menopause Society (IMS)CornwallUK
  6. 6.Argentine Society of Menopause (AAPEC)Buenos AiresArgentina
  7. 7.Menopause SectionCordoba Society of Obst/Gynec (SOGC)CordobaArgentina
  8. 8.Brazilian Federation of Societies of Gynecology and Obstetrics (FEBRASGO)SalaBrazil
  9. 9.Latin American Federation of Societies of Obstetrics and Gynecology (FLASOG)San JoseCosta Rica
  10. 10.Brazilian Society of Human Reproduction (SBRH)SalaBrazil
  11. 11.Ibero American Society of Osteology and Mineral Metabolism (SIBOMM)LisbonPortugal

Personalised recommendations