Tuesday, July 9, 2002 is a date that most gynecologists will not soon forget.

Why? This was the date of discontinuation of the combined estrogen / progestin arm of the Women's Health Initiative (WHI) study of hormone replacement therapy (HRT). A study is usually discontinued either because the results are so beneficial that proceeding further will not detract from the results or the results show hazardous results that may not benefit  the consumer.

What did the WHI study show?

This prospective randomized clinical trial was designed to evaluate the risks and benefits of CEE 0.625 mg and MPA 2.5 mg daily (Prempro / Premelle) vs. placebo in 16,608 menopausal women who were

50-79 years of age and who had an intact uterus. Scheduled to run until March 2005, this trial was halted after an average of 5.2 years of follow-up because the use of combined E/P HRT therapy was associated with a statistically significant increased incidence of invasive breast cancer, coronary heart disease (CHD), stroke and thrombo-embolism and a significant reduction in osteoporotic fractures and colon cancer.

Translated into numbers for us non-epidemiologists, it means that for every 10,000 women receiving HRT annually, there will be --- 8 more breast cancers, 8 more strokes, 7 more heart attacks, 18 more venous thrombotic events BUT 6 fewer colon cancers and 5 fewer hip fractures.

In addition, the WHI data and the recent findings from HERS II (plus the initial HERS reports) confirm an increased risk of venous thromboembolic events and no overall protective benefit against coronary heart disease (CHD) with the use of CEE/MPA in women with preexisting CHD.

What are the clinical implications of these data? Some authors advise the following approaches:

A.         Unequivocal recognition that combination HRT is not indicated for treating or preventing

cardiovascular disease.

B.         For women where HRT is appropriate, the duration of use will optimally be less than 5

years.

C.         There may be an increased emphasis on prescribing combination estrogen / progestin

regimens that are formulated with progestins other than Medroxyprogesterone acetate

[MPA].

D.         Clinicians may prescribe combination HRT regimens using lower doses  of estrogens   

            and progestins.

E.         Combination regimens employing nontraditional approaches to   progestin endometrial

protection like cyclic progestin and the use of the levonorgestrel IUD.

             F.         There will be a shift to non-hormonal therapies such as oral bisphosphonates and

selective estrogen receptor modulators for the prevention of osteoporosis.

             G.        To prevent or treat cardiovascular disease, use of traditional lipid-lowering therapy such

as statins will likely increase.

A final advice to the reader: Although the WHI findings apply only to women with an intact uterus using combination HRT, reevaluation of the pros and cons of estrogen replacement therapy [ERT] for many women who had a hysterectomy will be appropriate once the ERT study arm of the WHI is published.

Well, colleagues, what do you think?

WALFRIDO W. SUMPAICO, MD, FPOGS

AOFOG Secretary General

Charter President, Philippine Society of Maternal and Fetal Medicine

Email Address: wwsumpaico@aofog.org