Trial Results on Hormone Replacement Therapy
Study Objective: To describe the impact of the results of the Women's Health Initiative (WHI) on hormone replacement therapy (HRT) discontinuation rates.
Design: Retrospective chart review.
Setting: University-based family medicine clinic.
Subjects: Ninety-eight postmenopausal women (aged 50-79 yrs) with an intact uterus who were receiving HRT.
Measurements and Main Results: Two study periods were defined: pre-WHI (July 9, 2001-January 9, 2002) and post-WHI (July 9, 2002-January 9, 2003). Patient demographics and HRT discontinuation or persistence data were collected. Seven women were eligible for only for pre-WHI, 13 only for post-WHI, and 78 were eligible for both groups based on HRT use during both time periods. Forty-two of the 78 women were randomized to the pre-WHI group and 36 to the post-WHI group to yield equal groups of 49 each. No significant demographic differences existed between the groups. Time-to-event analysis revealed an increased probability of HRT discontinuation after WHI versus before WHI (log-rank test, p<0.01). A subset of 85 women taking HRT 1 year before WHI were followed for 18 months. Discontinuation rates were 8% (7 of 85 patients) during the 12 months before WHI and 38% (30 of 78) during the 6 months after WHI, with 80% (24 of 30) of these patients discontinuing within 3 months.
Conclusion: Increased HRT discontinuation was temporally associated with release of WHI data, which implies that highly publicized, negative outcomes data can quickly influence pharmacotherapy decisions.

In 2000, 33.2 million women in the United States were over 55 years of age. This number is expected to increase by 38% (46 million) by 2020. It is estimated that 38% of postmenopausal women in the United States are taking hormone replacement therapy (HRT) consisting of an estrogen plus progestin. With this growing population, concern is increasing regarding treatment of postmenopausal symptoms and prevention of other associated medical conditions. These symptoms, such as hot flashes, irritability, mood swings, and depression, are managed effectively with HRT. Evidence regarding the effectiveness of HRT in terms of preventing postmenopausal osteoporosis, colorectal cancer, and coronary artery disease is controversial and limited. Most traditional data suggesting benefits are primarily from observational studies and retrospective trials. The type of HRT evaluated in each trial was different, however, so it is difficult to formulate a universal conclusion about HRT.

Several observational trials showed significant protection against cardiovascular disease, with a low risk of cardiovascular and coronary artery disease mortality among healthy women taking HRT. Other trials evaluating fracture rate as a measure of osteoporosis reported significant reductions in fractures of up to 50% among HRT users. Observational studies also cited significant reduction in colorectal cancer, although some showed an increased risk of breast cancer with long-term (> 5 yrs) therapy.

The Estrogen Plus Progestin Study of the Women's Health Initiative (WHI) was a prospective, randomized, placebo-controlled trial that began in the early 1990s. It was designed to determine the risks and benefits of HRT (specifically, conjugated equine estrogen plus medroxyprogesterone acetate) in healthy postmenopausal women. It was conducted to dispel confusion regarding HRT, with coronary heart disease as the primary outcome and breast cancer as the primary adverse outcome. The trial was terminated prematurely on May 31, 2002, secondary to an increased risk of breast cancer among women taking HRT. On July 9, 2002, these results were publicized extensively in both medical and lay press, resulting in media chaos and immediate, dramatic reactions on the part of health professionals and patients. The primary objective of this study was to determine the impact of the WHI trial results on HRT discontinuation rates.