Contents

Search

Women's Health Initiative (WHI)

The Women's Health Initiative has generated several studies. Some conclusions are described below, others in Related. Key points: 2006 1) Estrogen, alone or in combination with progestin a) does NOT reduce incidence of heart disease b) increases risk for strokes & blood clots 2) breast cancer a) small increase in risk for breast cancer in women taking both estrogen & progestin b) estrogen alone does NOT increase risk of breast cancer 3) estrogen reduces risk of fractures 4) estrogen use for hot flashes a) use lower possible dose b) periodically review need for continuation 5) dietary intake of fruits & vegetables may not reduce risk of breast cancer or colon cancer 6) Ca+2 & vitamin D increase bone density & may reduce risk of fractures Other key points: - history of miscarriage or stillbirth is associated with increased risk for coronary heart disease [19] Conclusions: - NSAIDS - women taking at least 2 tablets of NSAIDs/week for 5 years or longer have a 20% lower risk of breast cancer [3] low-dose aspirin 100 mg QOD does not lower risk of cancer [9] - aspirin 100 mg QOD vs placebo (40,000 women > 45, mean age 55) with average follow-up of 10 years [7] - significant decrease in combined endpoint of MI, stroke or cardiovascular death for women > 65 ONLY - decrease in stroke 1.1% vs 1.3%/10 years (P=0.4) & TIA 0.9% vs 1.2% (P=0.01) - increased risk of GI bleeding 4.6% > 3.8% - does NOT prevent cognitive decline [15] - Vit E - vitamin E 600 IU QOD of no benefit in reducing risk of cardiovascular disease or cancer [8] - vitamin E 600 IU QOD diminished risk of venous thromboembolism & pulmonary embolism, especially in high-risk women [8] - Folate - higher plasma folate & vitamin B6 levels are associated with a lower risk of breast cancer [3] - Estrogen - women taking Prempro have a high risk of heart disease, breast cancer, stroke & dementia [4] - acute coronary syndrome less common in women age 50-59 taking conjugated equine estrogens than placebo (21 vs 34 events in 10,739 women over 7 years) [13] - premarin alone does NOT increase the risk of heart disease or breast cancer, but does increase the risk of stroke [4,6] - recipients of Prempro were less likely than placebo to be diagnosed with colon cancer (43 vs 72 per 16,000 women over average of 5 years) [5] - HOWEVER; Prempro recipients were significantly more likely than placebo recipients to present with positive lymph nodes (59% vs 29%) & with regional or metastatic disease (76% vs 29%) - NO difference in number of deaths from colorectal cancer - estrogen alone of little to no benefit for postmenopausal women [10] - HRT started 14 years after menopause increases risk of cardiovascular disease & thromboembolic events [16] - Calcium plus vitamin D supplementation [11,12] - 36,000 women, 7 year trial - 1000 mg of calcium plus 400 IU of vitamin D3 - Results: no effect on fracture [11] no risk reduction for colorectal cancer [12]

Related

hormone replacement therapy (HRT); estrogen replacement therapy; postmenopausal hormone replacement therapy Women's Health Initiative: Antihypertensives and Cardiovascular Death Women's Health Initiative: Dietary Modification Trial Womens Health Initiative (WHI) memory study

General

clinical trial

References

  1. Journal Watch 22(16) 2002 JAMA 288:321, 2002
  2. Journal Watch 23(4):34, 2003
  3. Prescriber's Letter 10(5):28 2003
  4. Prescriber's Letter 11(4):23 2004
  5. Journal Watch 24(7):58-59, 2004 Chlebowski RT et al, N Engl J Med 350:991, 2004 PMID: 14999111
  6. Journal Watch 24(10):77, 2004 Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12. PMID: 15082697
  7. Journal Watch 25(7):53, 2005 Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005 Mar 31;352(13):1293-304. Epub 2005 Mar 7. PMID: 15753114 http://content.nejm.org/cgi/content/abstract/NEJMoa050613
  8. Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):56-65. PMID: 15998891
  9. Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):47-55. PMID: 15998890
  10. Brunner RL, Gass M, Aragaki A, Hays J, Granek I, Woods N, Mason E, Brzyski R, Ockene J, Assaf A, LaCroix A, Matthews K, Wallace R; Women's Health Initiative Investigators. Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial. Arch Intern Med. 2005 Sep 26;165(17):1976-86. PMID: 16186467
  11. Jackson RD et al Calcium plus vitamin D supplementation and the risk of fractures N Engl J Med 354:669, 2006 PMID: 16481635 - Finkelstein JS Calcium plus vitamin D for postmenopausal women N Engl J Med 354:750, 2006 PMID: 16481643
  12. Wactawski-Wende J et al, Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006, 354:684 PMID: 16481363
  13. Hsia J, Langer RD, Manson JE, Kuller L, Johnson KC, Hendrix SL, Pettinger M, Heckbert SR, Greep N, Crawford S, Eaton CB, Kostis JB, Caralis P, Prentice R. Conjugated Equine Estrogens and Coronary Heart Disease: The Women's Health Initiative. Arch Intern Med. 2006 Feb 13;166(3):357-65. PMID: 16476878
  14. NHLB1 Women's Health Initiative update http://www.whi.org/updates
  15. Kang JH et al, Low dose aspirin and cognitive function in the Women's Health Study cognitive cohort BMJ 2007, 334:987 PMID: 17468120
  16. Vickers MR, MacLennan AH, Lawton B, Ford D, Martin J, Meredith SK, DeStavola BL, Rose S, Dowell A, Wilkes HC, Darbyshire JH, Meade TW; WISDOM group. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. BMJ. 2007 Aug 4;335(7613):239. Epub 2007 Jul 11. PMID: 17626056
  17. Glynn RJ et al, Effects of random allocation of vitamin E supplementation on the occurrence of venous thromboembolism. Report from the Women's Health Study. Circulation 2007, 116::1497 PMID: 17846285
  18. Roth JA et al. Economic return from the Women's Health Initiative Estrogen Plus Progestin Clinical Trial: A modeling study. Ann Intern Med 2014 May 6; 160:594 PMID: 24798522 http://annals.org/article.aspx?articleid=1867051
  19. Parker DR et al Risk of Cardiovascular Disease Among Postmenopausal Women with Prior Pregnancy Loss: The Women's Health Initiative. Ann Fam Med July/August 2014 vol. 12 no. 4 302-309 PMID: 25024237 http://www.annfammed.org/content/12/4/302.full