VWCA Statement
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HRT – A Changing Philosophy

July 2002 was an unsettling month regarding the use of hormone replacement therapy in menopausal women.  On July 9, partial results of the National Institute of Health’s (NIH) “Women’s Health Initiative” (WHI) were announced prematurely for the Prempro® arm of the study.  This announcement, together with the announcement regarding menopausal hormone replacement therapy and the risk of ovarian cancer released by the National Cancer Institute a week later, have raised questions about the use and safety of estrogen and progesterone therapy in menopausal women.

 Traditionally, women who reach menopause have been encouraged to use hormone replacement therapy (HRT) for the primary prevention of several diseases.  HRT means any combination of the two hormones, estrogen and progestin.  It does not refer to the use of estrogen replacement alone in women who have had their uterus removed.  It is known that HRT helps to prevent hotflashes, night sweats, and vaginal dryness, common menopausal symptoms that occur in up to 80% of women after loss of ovarian function.  It has long been postulated that HRT also helps to prevent osteoporosis, colon cancer and heart disease in this same population.

 For the last few years we have accepted that there may be a slight increased risk of breast cancer in women using HRT, but that the overall risk of taking HRT in the menopause was outweighed by the potential benefit to the heart, bone and colon. And in July, the NHI released information on a study involving 16,000 women that stated the combined estrogen-progesterone HRT (PremPro®) caused an increased number of women in the study to have a heart attack. 

 The PremPro® arm of the WHI study divided women into two groups: those on PremPro® and those on a placebo.  The data and safety monitoring board of the WHI decided on May 31, 2002 to recommend discontinuing the PremPro® arm of the study because the number of breast cancer cases in the HRT group was approaching a predetermined cutoff for the number. The committee further noticed a trend that the risk of heart attack was greater in the HRT group than in the placebo group.  These two trends taken together led the committee to determine that it was no longer safe for the HRT group to continue taking hormones because the risk of PremPro® therapy outweighed the potential benefit.

 The new data suggest that HRT in some combinations is not protective from cardiovascular disease and indeed increases risk of heart attack. This discovery will lead to a fundamental shift in our philosophy about who should use HRT and for how long they should use it. This means that the future emphasis will probably be short-term use of HRT for relief of menopausal symptoms and not long-term use as a preventative medicine.

 Relative and Absolute Risk or Benefit Seen in Estrogen Plus Progesterone Arm of WNI

(N=16,608, placebo and study drug)

 *  This means a user’s risk compared to a non-users risk, e.g. a 29% increased risk of heart attacks in a user.  The risk are cumulative over time and do not occur day one.

** This means there were 7 more heart attacks in 10,000 women on PremPro® than in 10,000 women on a placebo over a period of 5 years.

Adapted from WHI HRT Update, June 2002

 The actual risk for an individual is very small. The increase risk of a heart attack in a user of HRT computes to 0.007% over a five-year period.  However, the risk to the total group (several million women in the U.S. ) is significant.  It is this finding that will lead to a fundamental change in the way HRT is used. 

 Some of the news is good, a decrease in colorectal cancer and hip fracture.  The study does not address the role played in decreasing the symptoms hot flushes, insomnia, decreased sex drive or vaginal atrophy.  As stated, these symptoms occur in 80% of women to some degree at the time of menopause.  Fortunately, the symptoms are self limited in most women and will disappear over time. There are non-hormonal treatments available to treat menopausal symptoms. These treatments are successful in some but not all women and some treatments, such as soy, are not well tested and may have harmful side effects themselves.  Some women may choose to continue HRT once the risk are explained because of the unacceptable loss of quality of life do to hot flushes, insomnia, mood swing and other estrogen deficiency symptoms.

 The WHI concluded that combination estrogen/progestin HRT should not be initiated or continued for the primary prevention of coronary heart disease, and there is a substantial risk of breast cancer. (Writing Group for the WHI Investigators, JAMA 2002; 288:321-333)

 On August 9th, 2002 , the American College of Obstetricians and Gynecologist released a response to the news from the Women’s Health Initiative Study.   The ACOG report noted: “to date, this is the largest, most statistically valid, and well-analyzed research to evaluate the use of HRT in healthy postmenopausal women.”  The ACOG review panel concluded that while this study looked only at the drug PremProÒ, other data suggested caution with the use of any estrogen progesterone combination HRT.  It recommended that women on combination HRT be advised of the increased risk noted in the WHI study. They recommend that a decision be made by that patient and her physician about continuation or discontinuation of HRT.  That decision should based on an individual assessment of the reason she is using HRT and evaluation of potential risk, benefits and alternative treatments.  For most women, the potential risk will outweigh the potential benefit.  For women choosing to discontinue hormone use, there is no recommendation about how best to do this.  The response noted, some women will develop menopausal symptoms that will necessitate restarting HRT to maintain quality of life.  They stressed the dose should be the lowest that gives symptomatic relief.

 It is important to note that the estrogen only arm of the WHI study continues because no increase in breast cancer incidence had been noted.  We do not yet know what incidence of heart disease there is in women in this arm. This study is to be completed in 2005 and will provide additional important information.

The WHI study did not look at the effect of estrogen replacement on ovarian cancer.  The American College of Obstetrics and Gynecology did not make a comment on this issue in its report of August 2002.  On July 16, 2002 , the National Cancer Institute released a statement regarding increased risk of Ovarian Cancer in women on Estrogen therapy.  This study, “Menopausal hormone replacement therapy and risk of ovarian cancer.” JAMA 2002; 288:334-341, involved over 44,000 women followed over 20 years and concluded:

Two other recent studies have found a link between hormone use and ovarian cancer. The message is that if you are taking HRT and have ovaries you are at increased risk for breast cancer, heart disease and maybe ovarian cancer.  We do not yet know about the effect of estrogen therapy alone on breast cancer and heart disease.

If you are taking HRT, do not panic!  As stated, the consensus is that short-term (amount of time is not defined) use of HRT for the relief of symptoms of the menopause is safe. As stated, the individual risk is small. Please, discuss your individual risks and potential benefits of starting or continuing HRT with your doctor. 

Charles R. Jaynes, MD

August 2002