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Health and financial analysis reinforces NIH's decision to fund Women's Health Initiative

An in-depth analysis of final data from one of the Women’s Health Initiative

(WHI) Postmenopausal Hormone Therapy Trials has found that the

investment in WHI resulted in a return of $140 in net economic value

for each dollar invested in the trial.

The WHI, sponsored by the National Institutes of Health’s National Heart,

Lung, and Blood Institute (NHLBI), has followed women in the study since

1993. Results of the trial of estrogen plus progestin were published in 2002.

A paper examining the national post-study long-term financial and health

outcomes of the WHI was published today in the Annals of Internal Medicine.

Women’s Health Initiative reaffirms use of short-term hormone replacement therapy for younger women

Latest results provide new details on risks and benefits of therapy across age groups and time

Investigators from the Women’s Health Initiative (WHI) Hormone Trials are reaffirming conclusions that hormone therapy is not recommended for the prevention of chronic disease, but may remain a reasonable option for the short-term management of menopausal symptoms for younger women. Investigators reached this conclusion after reviewing data from the trial and the extended post-trial follow up period.

“While the risk versus benefits profile for estrogen alone is positive for younger women, it’s important to note that these data only pertain to the short-term use of hormone therapy,” said Jacques Rossouw, M.D., chief of the Women’s Health Initiative Branch within the NHLBI’s Division of Cardiovascular Sciences. “There are no reliable data on the risks or benefits of long-term hormone therapy use for the prevention of chronic diseases.”

The update and overview, published today in the Journal of the American Medical Association (JAMA) presents the extended follow-up data for the first time and highlights findings related to conditions that affect quality of life. The paper also provides the most comprehensive look at the trials’ findings to date, with more detail on individual disease-specific outcomes, side-by-side comparisons of the two therapies (estrogen-alone and estrogen plus progestin), and a full breakdown of results by age and over time.

The WHI, which is sponsored by the National Institutes of Health’s National Heart, Lung, and Blood Institute (NHLBI), followed women during a 13-year period.

“The combination of the six to seven years of intervention combined with the extended post-intervention follow-up make these hormone therapy medications among the best studied medications in medical history,” said Dr. JoAnn Manson, a principal investigator for the Women’s Health Initiative; chief of the division of preventive medicine at Brigham and Women’s Hospital; and professor of medicine at Harvard Medical School, Boston. “There are very few other treatments with this much information about the balance of benefits and risks over such a long period of time that include such a long post-intervention phase. The ultimate goal of this paper and the analysis is to help women and their health care providers make informed decisions.”

The Women’s Health Initiative studied 27,347 U.S. women ages 50-79 who enrolled in the Women’s Health Initiative Hormone Trials between 1993 and 1998. There were 16,608 women with an intact uterus in the trial of estrogen plus progestin and 10,739 without a uterus in the trial of estrogen-alone. Women with an intact uterus were enrolled in the estrogen plus progestin trial because of the need to add progestin to the therapy to protect against endometrial cancer.

Of those who participated in the original trial, 81 percent agreed to continue follow-up after the planned end of the trials. The WHI compared the rates of developing coronary heart disease including a heart attack (myocardial infarction), stroke, breast cancer, blood clots in the lungs, colorectal cancer, endometrial cancer, hip fracture, and death among women who were assigned to hormones versus women who were assigned to placebo study pills.

Those chronic diseases and deaths were combined in a global index to provide an overall measure of the balance of harm and benefit. The WHI researchers also studied several other important outcomes including dementia, other cancers, other fractures, diabetes, gallbladder disease, urinary incontinence, and quality-of-life outcomes including hot flashes, night sweats, sleep disturbances, mood and depression, breast tenderness, and joint pain.

Rates of overall illnesses (any one of the major illnesses studied) and death were 12 percent higher in women taking estrogen plus progestin than in women taking placebo pills during the trial. In absolute numbers, there were 20 more major illnesses or deaths per year for every 10,000 women taking estrogen plus progestin compared to the same number of women taking placebo. After women stopped taking the estrogen plus progestin therapy, there were no effects on overall illness and death. These results were the same in each age group but absolute numbers of additional illnesses and deaths were low in women aged 50-59 years (12 more for every 10,000 women per year). The results are based on a trial period of 5.6 years with an average of three years of actual hormone use and then no hormone use for eight or more years.

In women taking estrogen-alone, rates of overall illness and death were similar to those for placebo during and after the trial; however, these results differed importantly by age. For women taking estrogen alone in their 50s, there was a 16 percent reduced risk of overall illness and death. In absolute numbers, there were 19 fewer major illnesses or deaths per year for every 10,000 women in this age group compared to the same number taking placebo. Women in their 70s taking estrogen-alone had a 17 percent increased risk of overall illness and death with 51 more major illnesses or deaths per 10,000 women per year compared to placebo. This pattern of results was seen during the main trial of seven years with an average of four years of actual hormone use; with additional follow-up of seven or more years, the findings became more statistically significant.

The paper adds information about common conditions and diseases in postmenopausal women which affect their health and quality of life. In both regimens, diabetes risk is decreased by 14-19 percent, while risks of gallbladder disease and urinary incontinence are increased by 50-60 percent. Benefit for diabetes and risks of urinary incontinence and gallbladder disease lessened after the drugs were stopped.

“Decisions about hormone therapy are not easy, but these findings provide an evidence base for finding a way forward,” said Rossouw. “Hormone therapy affects many organ systems in the body and changes the risks of many diseases—some in good ways, others in bad ways. Depending on hysterectomy status, age, and other individual factors, the consequences can vary dramatically. The WHI emphasizes the need for women to talk about their risk factors with their doctors before making any decisions regarding hormone therapy.”

“The Women’s Health Initiative has been a transformative study that has had a dramatic effect on medical practice,” said Michael Lauer, M.D., director of NHLBI’s Division of Cardiovascular Sciences. “The in-depth analysis of intervention trial data and 13 years of cumulative data provided in this paper will help clinicians and women make informed decisions as to hormone therapy use.”

To schedule an interview with Dr. Rossouw, please contact the NHLBI Office of Communications at 301-496-4236 or nhlbinews@nhlbi.nih.gov. To schedule an interview with Dr. Manson, please contact the Brigham and Women’s Hospital Office of Communication & Public Affairs at 617-534-1600.

Supplemental Information

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at http://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH...Turning Discovery Into Health

Health and financial analysis reinforces NIH's decision to fund Women's Health Initiative

An in-depth analysis of final data from one of the Women’s Health Initiative (WHI) Postmenopausal Hormone Therapy Trials has found that the investment in WHI resulted in a return of $140 in net economic value for each dollar invested in the trial.

The WHI, sponsored by the National Institutes of Health’s National Heart, Lung, and Blood Institute (NHLBI), has followed women in the study since 1993. Results of the trial of estrogen plus progestin were published in 2002. A paper examining the national post-study long-term financial and health outcomes of the WHI was published today in the Annals of Internal Medicine.

“I’m delighted to see these results from the WHI Postmenopausal Hormone Therapy Trial,” said NIH Director Francis S. Collins, M.D., Ph.D. “Americans should be pleased to see that their investment in NIH continues to provide such a strong return to their health and the economy.”

In assessing return on investment, the researchers looked at disease incidence, direct medical expenditure, quality-adjusted life years (a measure of disease burden, including quality and length of life), and net economic return between 2003 and 2012. The researchers’ analysis was based on a disease simulation model that used an estimate of approximately 39.1 million combined hormone therapy-eligible women between 2003 and 2012. The analysis found that the guidance provided by the WHI clinical trial results led to:

76,000 fewer cases of cardiovascular disease (coronary heart disease, coronary artery bypass graft/percutaneous transluminal coronary angioplasty, and stroke)
4.3 million fewer combined hormone therapy users
126,000 fewer breast cancer cases
145,000 more quality-adjusted life years
direct medical expenditure savings of 35.2 billion

While most of the results were positive, the analysis did find that the guidance provided by the WHI clinical trial results led to 263,000 more fractures (hip, vertebral, and other osteoporotic).

The researchers calculated the total net economic return of the trial, which cost $260 million in inflation-adjusted dollars, at $37.1 billion.

“The Women’s Health Initiative is a landmark study that has had a huge impact on medical practice and public health,” said NHLBI Director Gary H. Gibbons, M.D. “Even though the hormone therapy trial results were published more than 10 years ago, we are still learning from the women in the cohort. We anticipate that the quality of life return on investment will increase further as researchers continue to mine the data collected to uncover even more knowledge about hormone therapy and cardiovascular disease.”

Researchers compared actual observed combined hormone therapy use with a contrasting scenario based on the idea that the WHI trial had not been conducted. The net economic return of the trial was calculated as the difference in net economic value between the scenarios, less the trial cost.

The Women’s Health Initiative Hormone Trials studied 27,347 U.S. women ages 50-79 who enrolled in 1993 and 1998. There were 16,608 women with an intact uterus in the trial of estrogen plus progestin and 10,739 without a uterus in the trial of estrogen-alone. Women with an intact uterus were enrolled in the estrogen plus progestin trial because of the need to add progestin to the therapy to protect against endometrial cancer.

To schedule an interview with an NHLBI spokesperson, contact the NHLBI Communications Office at 301-496-4236 or NHLBI_News@nhlbi.nih.gov.