Context Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain Objective To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States Design Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 85 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998 Interventions Participants received conjugated equine estrogens, 0625 mg/d, plus medroxyprogesterone acetate, 25 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102) Main outcomes measures The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes Results On May 31, 2002, after a mean of 52 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits This report includes data on the major clinical outcomes through April 30, 2002 Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 129 (102-163) with 286 cases; breast cancer, 126 (100-159) with 290 cases; stroke, 141 (107-185) with 212 cases; PE, 213 (139-325) with 101 cases; colorectal cancer, 063 (043-092) with 112 cases; endometrial cancer, 083 (047-147) with 47 cases; hip fracture, 066 (045-098) with 106 cases; and death due to other causes, 092 (074-114) with 331 cases Corresponding HRs (nominal 95% CIs) for composite outcomes were 122 (109-136) for total cardiovascular disease (arterial and venous disease), 103 (090-117) for total cancer, 076 (069-085) for combined fractures, 098 (082-118) for total mortality, and 115 (103-128) for the global index Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures The absolute excess risk of events included in the global index was 19 per 10 000 person-years Conclusions Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 52-year follow-up among healthy postmenopausal US women All-cause mortality was not affected during the trial The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD

/pdf/risks-and-benefits-of-estrogen-plus-progestin-in-healthy-4glim99n2t.pdf

Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial

The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.

/pdf/overweight-obesity-and-cancer-epidemiological-evidence-and-3aap682afc.pdf

Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms

Among U.S. women, breast cancer is the most commonly diagnosed cancer (excluding skin cancers) and the second leading cause of cancer death, following lung cancer. In 2012, an estimated 226,870 new cases of invasive breast cancer and 39,510 breast cancer deaths are expected to occur among U.S. women. Breast cancer rates vary largely by race/ethnicity and socioeconomic status (SES), and geographic region. Death rates are higher in African American women than in whites, despite their lower incidence rates. Historically, breast cancer was recognized as a disease of western countries. However, over the past 20 years, breast cancer incidence and mortality rates have been increasing rapidly in economically less developed regions. According to 2008 GLOBOCAN estimates, half of the new worldwide breast cancer cases (1.38 million) and 60 % of the breast cancer deaths (458,000) occurred in developing countries. This chapter reviews breast cancer incidence and mortality patterns among women in the U.S. and worldwide, and the possible explanations for these patterns.

Breast Cancer Statistics

https://openresearch-repository.anu.edu.au/bitstream/1885/35064/2/01_Banks_Breast_cancer_and_2003.pdf

Breast cancer and hormone-replacement therapy in the Million Women Study.

Results Relative to the normal weight category (BMI 18.5 to 25), obesity (BMI 30) was associated with 111 909 excess deaths (95% confidence interval [CI], 53 754170 064) and underweight with 33 746 excess deaths (95% CI, 15 726-51 766). Overweight was not associated with excess mortality (�86 094 deaths; 95% CI, �161 223 to �10 966). The relative risks of mortality associated with obesity were lower in NHANES II and NHANES III than in NHANES I. Conclusions Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease.

/pdf/excess-deaths-associated-with-underweight-overweight-and-nd9o4qjx1v.pdf

Excess deaths associated with underweight, overweight, and obesity.

N A RECENT COLLABORATIVE REanalysis of more than 90% of the world’s epidemiological data on the relationship between menopausal hormone replacement therapy (HRT) and breast cancer risk, it was found that longer durations of recent, but not past, use of HRT increased breast cancer risk, particularly among leaner women and for tumors that were less clinically advanced. 1 Unresolved issues include the extent to which the findings were due to a biological effect of hormones rather than issues of screening and ascertainment. The data were also insufficient to determine whether a combined estrogen-progestin regimen increased risk beyond that associated with estrogen alone. In 1994, we published data on HRT

https://jamanetwork.com/journals/jama/articlepdf/192332/JOC91096.pdf

Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk.

Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk

In situ and invasive vulvar cancer incidence trends (1973 to 1987).

We examined the relation between menopausal estrogen use and all-cause and cause-specific mortality in a cohort of over 49,000 women followed between 1979 and 1989 in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-Up Study. We found a lower all-cause mortality rate among women who

Susan R. Sturgeon

Papers

Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk.

Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk

In situ and invasive vulvar cancer incidence trends (1973 to 1987).

Evidence of a healthy estrogen user survivor effect

Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas