22 July, 2013: 

Sarrel and colleagues [1] calculated the mortality toll due to avoiding estrogen in hysterectomized women aged 50–59 between 2002 and 2011. The calculation was motivated by the Women's Health Initiative (WHI) estrogen-only trial report in 2011 [2] which indicated an excess mortality in women in this age group who did not take estrogen, i.e.. received placebo. The excess mortality was 13/10,000 women/year. Twelve of the 13 deaths were due to cardiovascular disease. An increase in deaths from invasive breast cancer was also seen in the women who received placebo [3]. The Yale research team calculated the best point estimates for the total excess mortality for hysterectomized women aged 50–59 in the United States from 2002 through 2011 to be between 40,292 and 48,835.

A calculation was made for each of the years using the excess mortality rate of 13/10,000/year, annual US Census population estimates, hysterectomy rates as reported in the peer-reviewed literature, and percent decline in estrogen use each year compared to 2001, as reported in the WHI paper [2]. Adjustment was made for different pre-2002 rates of estrogen use depending on whether or not ovaries had been retained at the time of hysterectomy. The best point estimates represent the aggregate of all the years taking into account all the assumptions.

Comment

Following the WHI estrogen plus progestogen trial report in 2002 [4], a severe decline occurred in the use of all postmenopausal hormone therapies. The differences between the effects of estrogen plus progestogen compared to estrogen alone were not clearly explained. Although the report applied to women with a uterus and to those who used a specific estrogen/progestogen combination, hysterectomized women were also affected and a generalized avoidance of estrogen-alone therapy (ET) resulted. By 2005, decline in ET use by these women reached almost 60% and by 2011 the decline was greater than 70% compared to 2001 [2]. One recent publication [5] puts the decline in ET use as high as 87%.

The current population estimate for 50–59 year olds in the United States is over 22 million. The estimate for women in this age group with no uterus is about 8 million. In the past, more than 90% of these women would have been using ET when they were in their fifties. Now, with an 87% decline in use, the current ET use rate is as low as 7.5% [5]. One reason for the 87% decline is that less than 40% of women are being offered ET at the time of hysterectomy and oophorectomy, with 25% or less using ET 10 months later [6].

Failure to differentiate between ET and estrogen plus progestogen therapy is but one reason for the avoidance of ET. Additionally, there has been little attention paid to the positive and life-saving effects of ET in hysterectomized women age 50–59 years. This important information appears not to be reaching health-care providers, the media, and the women who need to know these findings [7].

There will be millions more women at risk in the decade to come due to the baby-boomer population increase and even fewer using estrogen than in 2002–2011. The situation is urgent as the projections for excess deaths due to not using estrogen in the next decade are a multiple of the 2002–2011 mortality estimate. Hopefully, this publication will encourage a more constructive interaction between scientific reporting, media coverage, health-care provider education, and greater awareness of the results of taking ET by the women who could benefit most.

Philip M. Sarrel
Professor Emeritus of Obstetrics and Gynecology and Professor Emeritus of Psychiatry, Yale University, New Haven, Connecticut, USA

References

1. Sarrel PM, Njike Y, Vinante V, Katz DL. The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women age 50 to 59. Am J Pub Health 2013 July 18. Epub ahead of press. doi: 10.2105/AJPH.2013.301295  
2. LaCroix AZ, Chlebowski RT, MansonJE, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA 2011;305:1305-14.
http://www.ncbi.nlm.nih.gov/pubmed/21467283 
3. Chlebowski RT, Anderson GL. Changing concepts: menopausal hormone therapy and breast cancer. J Natl Cancer Inst 2012;104:517-27.
http://www.ncbi.nlm.nih.gov/pubmed/22427684 
4. Writing Group for the Women's Health Initiative Investigators. 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.
http://www.ncbi.nlm.nih.gov/pubmed/12117397
5. Sprague BL, Trentham-Dietz A, Cronin KA. A sustained decline in postmenopausal hormone use: results from the National Health and Nutrition Examination Survey, 1999-2010. Obstet Gynecol 2012;120:595-603.
http://www.ncbi.nlm.nih.gov/pubmed/22914469 
6. Chubaty A, Shandro MT, Schuurmans N, Yuksel N. Practice patterns with hormone therapy after surgical menopause. Maturitas 2011;69:69-73.
http://www.ncbi.nlm.nih.gov/pubmed/21396791 
7. Brown S. Shock, terror and controversy: how the media reacted to the Women's Health Initiative. Climacteric 2012;15:275-80.
http://www.ncbi.nlm.nih.gov/pubmed/22612615