Medpage: LaCroix A, et al "Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial" JAMA 2011; 305: 1305-1314.

Blogger's Note: also see website for video

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New WHI Estrogen Analysis Shows Lower Breast Ca Risk

By John Gever, Senior Editor, MedPage Today

Published: April 05, 2011

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Action Points

• Explain that post-intervention follow-up of the WHI Estrogen-Alone Trial showed that both risks and benefits of unopposed estrogen largely disappeared after therapy stopped.
• Note that while the risk of breast cancer remained decreased for the intervention and post-intervention period combined, the decreased risk during the post-intervention period itself was not statistically significant.

In contrast to other studies of unopposed postmenopausal estrogen therapy, long-term follow-up of Women's Health Initiative (WHI) Estrogen-Alone Trial participants showed a persistent reduction in breast cancer risk, researchers said.

But other benefits and risks associated with use of conjugated equine estrogens (CEE) quickly dissipated after the therapy was stopped, according to Andrea Z. LaCroix, PhD, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

"Considering the entire follow-up period, rates of total mortality and the global index of chronic diseases were essentially the same in the conjugated equine estrogen and placebo groups," LaCroix and co-authors wrote in the April 6 issue of the Journal of the American Medical Association.
"Statistically significant age interactions for conjugated equine estrogen use, suggesting greater safety and possible benefit among women in their 50s and potential harm among older women, were observed for coronary heart disease, total MI, colorectal cancer, total mortality, and the global index of chronic diseases," they added.

An editorial in the same issue suggested more caution in interpreting the breast cancer results.

2012 Hormone Therapy Position Statement of the North American Menopause Society (PDF/repost)

POSITION STATEMENT The 2012 Hormone Therapy Position Statement of The North American Menopause Society

Stopping menopausal hormone therapy: If breast cancer really decreased, why did colorectal cancer not increase? Maturitas "Alternative explanations must be found."

Abstract

Objective

The Women's Health Initiative (WHI) study of postmenopausal hormone therapy (HT) found that estrogen plus progestogen therapy (EPT) decreased colorectal cancer risk. 

Thus, the decline in EPT use from 2002 to 2003 should have precipitated an increase in the incidence of colorectal cancer. We tested this prediction using the SEER 9 epidemiologic database.

Methods

We analyzed WHI data concerning the effects of EPT and estrogen therapy (ET) on colorectal cancer risks. We also examined HT prescription sales data, as well as SEER 9 colorectal cancer incidences from 2001 to 2004.

Results

In the WHI study, the incidence of colorectal cancer was comparable in EPT placebo-users, ET users, and ET placebo-users, but significantly lower in EPT users. Assuming that 30% of eligible women used HT in 2001, the decline in EPT sales from 2002 to 2003 of 63% should have increased the incidence of colorectal cancer by 2.8% in the overall population at risk. However, the SEER 9 colorectal cancer incidence fell by 5.9% in this population, which is comparable to the 6.7% decrease observed for invasive breast cancer from 2002 to 2003.

Conclusions

Declining EPT use from 2002 to 2003 should have precipitated an increase in the incidence of colorectal cancer, but the opposite trend was seen in the SEER 9 database during this time. The incidences of invasive breast cancer and colorectal cancer both declined by a similar amount from 2002 to 2003, despite the results of the WHI study predicting opposing trends for the two different types of cancer. Thus, the SEER 9 findings are fundamentally incompatible with expectations from the WHI findings. This implies that reductions in HT use from 2002 to 2003 cannot account for the contemporaneous changes in invasive breast cancer and colorectal cancer incidences. 

Alternative explanations must be found.

Hormone therapy for menopausal symptoms | BMJ

 Editorial

Hormone therapy for menopausal symptoms

BMJ 2012; 344 doi: 10.1136/bmj.e815 (Published 8 February 2012)

Cite this as: BMJ 2012;344:e815

Access to the full text of this article requires a subscription or payment. 

"Recent evaluations of the methods of key studies should not change how we advise wome.

A recently published and much publicised paper by Shapiro and colleagues, the last in a series of four, evaluated the effects of hormone therapy on the risk of breast cancer.1 

The authors of the four review articles applied epidemiological principles to the findings of two randomised placebo controlled studies from the Women’s Health Initiative (WHI; 27 347 women) and two observational studies—the Collaborative Reanalysis (53 865 women) and the Million Women Study (MWS). Shapiro and colleagues concluded in their fourth paper that the MWS had design defects, that it contained multiple biases, and that its findings were thus not robust enough to show that hormone therapy increased the risk of breast cancer.

All observational studies are inherently biased because subjects are not randomly assigned to treatment or control. Adjustment for confounders and careful design of observational studies help to reduce bias. However, because there is no independent variable, such studies can tell us only about association not causation.

The MWS was published in the Lancet in August 2003,2 and a flurry of letters was published in a print issue later that year, many …"

Medscape: Questions About Data Linking Breast Cancer and HRT

published Oct 2011 - full free access: The Role of Hormonal Therapy in Gynecological Cancers-Curren... : International Journal of Gynecological Cancer

Abstract (and full free access to full paper)

Many gynecological cancers, including epithelial and stromal ovarian cancers; endometrial carcinomas; and some gynecological sarcomas, in particular endometrial stromal sarcomas, express estrogen and/ or progesterone receptors. Hormonal therapy, typically progestogens or tamoxifen, is commonly prescribed to patients with potentially hormone-sensitive recurrent or metastatic gynecological cancers with very variable response rates and clinical benefit reported. Aromatase inhibitors are now widely used to treat postmenopausal women with hormone receptor-positive breast cancers as they have greater activity than tamoxifen and are generally better tolerated. The role of aromatase inhibitors in gynecological cancers is uncertain and has not been well studied, although they do appear to be active. The current evidence to support the use of hormonal therapies including aromatase inhibitors in gynecological cancers is reviewed, and the gaps in our knowledge highlighted.

(timeline) Landmarks From Two Decades of Study - NYTimes.com

By THE NEW YORK TIMES

Published: April 9, 2011

1991 National Institutes of Health embarks on a study of menopause hormones after observational data suggest that women who use hormones have lower rates of heart disease.

Related

• The Women’s Health Initiative and the Body Politic (April 10, 2011)

2002 Part of the Women's Health Initiative is stopped after women in the study taking estrogen plus progestin (E+P) show higher rates of heart attack, stroke and breast cancer. Millions of women abandon hormones overnight.
2003 Women taking E+P are not protected from mild memory loss; they are found to be at increased risk for developing dementia.
2004 The second W.H.I. hormone study is stopped one year early because women taking estrogen only show a small increased risk of stroke.
2006 An updated analysis of the estrogen-only trial shows hormone therapy does not increase the risk of breast cancer in postmenopausal women.
2007 Combined data from both hormone trials suggest that timing of therapy may affect risk; hormones may reduce heart disease in women who start therapy closer to menopause.
2009 Women using E+P for more than about five years double their annual risk of breast cancer. That risk is higher than previously thought.
2011 Follow-up of women in the estrogen-only study shows those who took just estrogen had 23 percent fewer breast cancers; younger estrogen users had 46 percent fewer heart attacks.
Sources: Women’s Health Initiative; New York Times reports

Second Look at Estrogen in Breast Cancer Protection - NYTimes.com (re: WHI)

Blogger's Note: a similar issue was reported and largely ignored regarding colorectal cancer

“The data were absolutely missed. They weren’t emphasized, and they weren’t brought to the attention of oncologists,”...

Postmenopausal Hormone Therapy: An Endocrine Society Scientific Statement abstract only/multinational statement - Journal of Clinical Endocrinology & Metabolism

Conclusions: The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Women’s Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.