Hormone Replacement Therapy (HRT) and Women's Health Initiative (WHI)
Report - The Position of The Ministry Of Health Malaysia

The report of the Women's Health Initiative (WHI) trial on hormone replacement therapy (HRT) in postmenopausal women published in the Journal of the American Medical Association (JAMA) on the 17th July 2002 has raised concerns regarding its use. The Ministry of Health, related professional bodies and non-government organizations met on 20th August 2002 to discuss their stand on the findings of WHI.

This paper briefly describes the salient features of the WHI's study, its key findings with risks towards specific diseases and its limitations. Based on these, the paper makes specific recommendations which are to be noted and acted upon by health care providers.

The Study
The WHI study was designed to assess the major benefits and risks of the most commonly prescribed continuous combined HRT (conjugated equine estrogen 0.625 mg/day and medroxyprogesterone acetate 2.5 mg/day) among postmenopausal/women in the United States. The women selected were between ages 50 and 79 years with a mean age of 63 years. In this study, 16,608 women with intact uterus at baseline, were recruited in 1993 - 1998 and they were assigned to receive the continuous combined HRT of placebo (sugar pills).

The trial was planned to last 8.5 years, that is, to be completed in the year 2005. However, it was halted after 5.2 years because of an observed increased risk of cardiac disease, namely heart attacks, stroke, deep vein thrombosis and pulmonary embolism; and invasive breast cancer. The study also reported benefits in the reduction of hip fractures and colon cancer.

Findings
In summary, the results of the study indicated that for every 10,000 women taking the continuous combined HRT, there would be :

• 7 more women with heart attacks
• 8 more women with strokes
• 8 more women with breast cancer
• 18 more women blood clots
• 6 fewer colorectal cancers
• 5 fewer hip fractures
• fewer fractures in other bones

* CEE - conjugated equine estrogen
   MDA - medroxyprogesterone acetate

Limitations of the Study

1. Profile of study subjects
   It should be noted that the report was among American women whose average age was older (63 years) and the majority were overweight. The mean age is far above the age that HRT should be started for prevention purposes. About 30% already had pre-existing cardiovascular risks factors. Other recent studies showed that older women with established cardiac disease should not be started on combined continuous HRT. About 40% of the study patients were ex-smokers and 10% of the patients were still smoking during the study period.
    
2. Drop from the study
   It should be pointed out that there were 40% drop-out rate of women receiving HRT mostly due to the problem of vaginal bleeding, and another 3% of this group had to undergo hysterectomy.
    
3. Hormone preparation and regimen
   The trial tested only one regimen of continuous combined HRT, which is conjugated equine estrogen 0.625 mg/day, and medroxyprogesterone acetate 2.5 mg/day. The results do not necessarily apply to other formulations of oral estrogens and progestins or other routes of administration e.g. transdermal. The effects of progestin may be important for breast cancer and atherosclerotic disease.

Recommendations of the Ministry of Health

Based on the above, the Ministry of Health together with relevant parties make the following recommendations to be noted by health care providers.

1. General
    
   1.1 Health care providers are to recognize that what have been highlighted by the media are the relative risks to the above diseases, and that the absolute risks although significant are small.
   
   1.2 Women currently taking HRT are advised not to panic and have undue fear. They should be counseled by their doctors to weigh and benefits and the risks of continuing therapy. They are also to be informed of the many preparations and regimens of HRT available in Malaysia.
    
   1.3 All women prescribed with HRT should consult their doctors and undergo regular follow-up and health screening. Prescribing HRT is an individualized and personal decision made after consultation between a woman and her doctor and taking into account a woman's individual benefits and risks from such use.
      
2. HRT for treating menopausal symptoms
   The use of HRT whether cyclical or continuous for the purpose of relieving menopausal symptoms is justified since the benefits outweigh the risks.
    
3. HRT for preventing cardiovascular diseases
    
   3.1 The combined continuous therapy of conjugated equine estrogen and medroxyprogesterone acetate should not be initiated or continued for cardiovascular disease prevention only. However, a combined therapy of other estrogen and other progestin, a low dose HRT and transdermal therapy can be considered to be used.
    
   3.2 HRT should not be used for the sole purpose of preventing a second attack or death among women with established heart disease.
    
   3.3 Women at risk of cardiovascular disease who wish to discontinue HRT should consider dietary and lifestyle changes (weight loss, regular exercise, stop smoking) as well as the use of drugs to lower cholesterol and blood pressure.
    
4. HRT for managing osteoporosis
   Women at risks of osteoporosis who wish to discontinue HRT should be evaluated and consider the use of alternative therapies such as calcium, biphosponates and the selective estrogen receptor modulators. (SERMs)

 
Conclusion
For many women, menopause brings many uncomfortable symptoms as the body produces less estrogen hormone. Hot flushes, sleeplessness and vaginal dryness prevent some women from carrying on the day-to-day functions. Thus women should not abandon HRT altogether. The benefits should be evaluated whether they outweigh the risks. We need to make decisions about HRT on an individual basis. For many, the decision will be straightforward with potentials for significant benefits for example for symptomatic relief and in many areas. For some others, the decision will be much more difficult requiring a careful balance of the known benefits and potential risks which can be achieved after a careful consultation between the woman and the attending doctor.

 
List of Participating Organizations

1. Ministry of Health Malaysia (MOH)
2. Private Medical Practitioners Association
3. National Population and Family Development Board (NPFDB)
4. Federation of Family Planning Associations Malaysia (FFPAM)
5. Obstetrical & Gynaecological Society of Malaysia
6. Malaysian Medical Association (MMA)
7. Malaysian Menopause Society (MMS)