After the Women's Health Initiative:
Postmenopausal Women's Experiences with Discontinuing Estrogen Replacement Therapy


June 15, 2004 -- Sally G. Haskell, M.D., Yale University School of Medicine, Department of Internal Medicine, New Haven, Connecticut, and VA Connecticut Healthcare System, West Haven, Connecticut

J Womens Health 13(4):438-442, 2004. © 2004 Mary Ann Liebert, Inc.

Introduction

In July 2002, the results of the Women's Health Initiative (WHI)[1] were published and widely disseminated by the lay press and media, stating that the risks of hormone replacement therapy (HRT) exceeded the benefits for prevention of chronic health conditions. The WHI was a large clinical trial that randomized 16,608 postmenopausal women to estrogen plus progestin or placebo. The primary outcomes were coronary heart disease (CHD) (nonfatal myocardial infarction [MI] and CHD death) and invasive breast cancer. After 5.2 years of followup, the data and safety monitoring board stopped the trial after it became evident that hazard ratios were increased for CHD, breast cancer, stroke, and pulmonary embolus, with absolute excess risks per 10,000 person-years of 7 CHD events, 8 strokes, 8 pulmonary emboli, and 8 invasive breast cancers. The WHI was the first report of a randomized trial that evaluated primary prevention of CHD with HRT, and its results radically reversed previous beliefs supported by observational studies that estrogen replacement therapy (ERT) users had a lower risk of CHD than nonusers.[2,3]

At the time of the release of the WHI results, it was estimated that 13 million women in the United States were using postmenopausal HRT.[4] The sudden reversal in recommendation for HRT, the widespread dissemination of that information, and the number of patients involved created an unprecedented situation. Several organizations, including the American College of Obstetricians and Gynecologists (ACOG),[5] the North American Menopause Society (NAMS),[6] and the U.S. Preventative Services Task Force,[7] issued recommendations against using HRT for primary prevention of chronic conditions. Many menopausal and postmenopausal women were suddenly likely to stop HRT, but there were no guidelines for the best method of discontinuing treatment to minimize recurrent postmenopausal symptoms.

Importantly, data are lacking with regard to what proportion of women will become symptomatic after stopping longterm HRT or what characteristics might distinguish women who will have difficulty stopping estrogen. Smoking, body mass index (BMI), surgical menopause, tubal ligation, and race/ethnicity have been identified as factors that may predispose women to hot flashes,[8] but whether these factors play a role in recurrent symptoms after stopping HRT is unknown.

There is no published evidence to guide the management of women stopping HRT, although several techniques have been suggested, including a dose taper, a dosing interval taper, or a day taper.[9] The dose taper involves progressively decreasing the dose, for example, from 0.625 mg to 0.3 mg of Premarin (Wyeth-Ayerst, Philadelphia, PA), and then stopping. The dosing interval taper involves taking the estrogen every other day, then every third day, and so on, and the day taper involves gradually decreasing the number of days per week, for example, taking estrogen 6 days a week, then 5 days a week, then 4 days a week, and so on. None of these approaches has been studied or compared individually.

From the Veterans Affairs (VA) Women's Health Center (VA Connecticut Healthcare System), a questionnaire was mailed to patients identified through pharmacy records as receiving combined estrogen and progesterone therapy to gather information about what proportion of women stopped HRT, how many had recurrent menopausal symptoms, and whether the technique of discontinuation affected the recurrence of menopausal symptoms.

Because a variety of alternative therapies for hot flashes exist, but none has proved as efficacious as estrogen,[10] we were also interested in gathering information about alternative treatments used by our patients and whether they had found such therapies helpful. Our project was designed as a small descriptive study of the behavior of a population of women veterans in response to the WHI.

Current Study Objective: To gather information about women's responses to the publication of the Women's Health Initiative (WHI) and to determine what proportion of women stopped hormone replacement therapy (HRT) and whether the technique of discontinuation affected the recurrence of menopausal symptoms. Methods: 73 subjects were identified through VA pharmacy records and were mailed a letter detailing the results of the WHI. A followup questionnaire was mailed several months later to the same population.

Results: 48 subjects responded and were eligible for inclusion in the study. Mean age was 62 years; 37(77%) stopped taking HRT, and 11(23%) continued. Twenty patients stopped abruptly, and 17 tapered off HRT. Eight (40%) of the group who stopped abruptly experienced recurrent menopausal symptoms, compared with 12(71%) of the group who tapered HRT.

Conclusions: In a population of women veterans, 77% stopped HRT after publication of the WHI. Tapering HRT, rather than stopping abruptly, did not reduce the recurrence of menopausal symptoms in our patient population.

In this small descriptive study of 48 postmenopausal women veterans, we found that approximately 3 of 4 (77%) stopped HRT after being sent a letter regarding publication of the WHI. The women who continued estrogen were slightly younger, and a higher proportion of them were taking estrogen for menopausal symptoms.

Among the group who discontinued HRT, 20 subjects stopped abruptly (cold turkey), whereas 17 subjects were tapered. In our sample, there was no benefit associated with tapering estrogen, and contrary to our initial hypothesis, women in the group who tapered HRT experienced a higher rate of recurrent menopausal symptoms. Our study was not randomized, and the participants sorted themselves into taper and cold turkey groups. We cannot draw any firm conclusions from these results except to report that in our particular sample, tapering HRT was not helpful. The participants may have chosen to stop abruptly vs. tapering based on unmeasured clinical characteristics, such as a previous tendency toward hot flashes or difficulty with previous attempts to discontinue HRT, thus influencing their likelihood to have recurrent menopausal symptoms. In addition, most participants who chose to taper HRT used a dosing interval taper. We cannot conclude whether other tapering regimens, such as the day or dose taper, may have been more useful. This descriptive study is not large enough to draw statistically significant conclusions, although it raises important questions about the response of women to the data from the WHI and methods of discontinuation of ERT. Larger observational studies or a randomized trial will be necessary to evaluate which methods of discontinuing HRT are the most efficacious in terms of prevention of recurrent menopausal symptoms.

References:

1.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.

2.Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992;117:1016.

3.Grodstein F, Manson JE, Colditz GA, Willet WC, Speizer FE, Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann In tern Med 2000;133:933.

4.Cyr MG. Postmenopausal hormone therapy in the aftermath of the WHI. What patients need to know. Postgrad Med 2003;113:15.

5.American College of Obstetricians and Gynecologists. Guidelines for women's health care, 2nd ed. Washington, DC: American College of Obstetricians and Gynecologists, 2002:130, 171, 314.

6.Report from the NAMS Advisory Panel on Postmenopausal Hormone Therapy. The North American Menopause Society. Accessed at www.menopause.org

7.U.S. Preventative Services Task Force. Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: Recommendations and rationale. Ann Intern Med 2002;137:834.

8.Whiteman MK, Staropoli CA, Benedict JC, Borgeest BA, Flaws JA. Risk factors for hot flashes in midlife women. J Wom Health 2003;12:459.

9.Grady D. A 60yearold woman trying to discontinue hormone replacement therapy. JAMA 2002;287: 2130.

10.Kronenberg F, FughBerman A. Complementary and alternative medicine for menopausal symptoms: A review of randomized controlled trials. Ann Intern Med 2002;137:805.

Reprint Address

Sally G. Haskell, M.D., VA Connecticut West Haven, Women's Health Center, 950 Campbell Avenue, West Haven, CT 06516. E-mail: Sally.Haskell@med.VA.Gov.

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