Check Programme
The Hong Kong Practitioner VOLUME 26 / October 2004

Case one:

You have been Julie Robinson's general practitioner for several years and know her well. She usually sees you when her children are unwell and for regular Pap testing. She walks every day and attends gym 3 times per week. Her breast examinations, Pap smears and blood pressure have been normal.

She is now 49 years of age and consults you to discuss the hot flushes she is experiencing. The hot flushes occur 3-4 times per day and at least once every night. She has not had a period for 3 months.

Her first question is "What do you think of hormone replacement therapy (HRT)?"
 

Note:

The Women's Health Initiative (WHI) study was stopped mid trial due to an increase in adverse outcomes and has led to change in the recommendations concerning HRT.
 
HK Pract 2004;26:451-452
 
 

Question

1: What were the major findings of the WHI study?
 
 
 
Question 2: What were the characteristics of the patients studied in the WHI?
 
 
 
 

Question

3: In this study, there was much made of relative risk. What is the difference between relative and absolute risk and what is the significance in relation to the WHI?
 
 
 

Question

4: How does the WHI study apply to Julie?
 
 
 

Question

5: How would you answer Julie's question?
 
 
 

Question

6: Julie asks about alternative hormone treatment. How would you respond?
 
 
 
Question 7: Julie asks about the availability of nonhormonal treatment. How would you respond?
     
     
 
Question 8: At the end of the consultation, Julie decides to start HRT. Assuming she is fit, well, not pregnant and there are no other contrain-dications, what regimen would you advise?
     
     
 
 

Answer 1
The WHI study demonstrated that in women treated with oestrogen and progestogen, there were significant increases in the rate of breast cancer, stroke and thromboembolism with a trend to increased risk of cardiovascular disease. There was a reduced risk of bowel and uterine cancers.
 
Answer 2
In order to maximise the chances of finding cardiovascular disease, most of the women enrolled in the study were overweight, 80% were between 60-79 years of age, and a significant proportion had cardiovascular risk factors (hypertension, prior history of smoking and hypercholesterolaemia).
 
Answer 3

In the reporting of the WHI study, the relative risks were highlighted in the press. As a way of demonstrating the difference, consider a condition with a prevalence of 1 in 10 million. If a drug increases the risk to 2 in 10 million the relative risk is 2. The absolute increase in risk is 1 in 10 million, i.e. you would need to give 10 million people the drug to develop 1 extra adverse outcome.

In relation to breast cancer, the WHI showed a relative risk of 1.26 (25% increase in risk) which results in an increase of 8 breast cancers per 10 000 women years, i.e. the number of breast cancers increases from 32 per 10 000 women years to 40 per 10 000 women years.
 
Answer 4
In reality, it probably does not apply to Julie. She is much younger with no risk factors and is symptomatic.
 
Answer 5
You would answer Julie's question by presenting the WHI information in a way she can understand, which will help her make a decision about HRT.
 
Answer 6
There is no clear evidence relating to alternative hormone treatment. None has been subject to the rigorous investigations of HRT. Anecdotally some appear to work, but whether they produce the adverse outcomes of HRT, is unknown. Even though some are natural products, it does not mean they are safe.
 
Answer 7
Nonhormonal treatments are available but are not as effective as HRT. Options include clonidine and tibolone.
 
Feedback
Clonidine is useful for controlling hot flushes, but can cause a dry mouth. Tibolone is a synthetic hormone but is thought not to have as much risk of breast cancer as HRT.
 
Answer 8
As Julie is perimenopausal, with an intact uterus, she should start on combined therapy in a cyclical manner. Commencement of oral medication is recommended.


Case Feedback

The WHI study produced unexpected findings that have altered the recommendations concerning HRT. The WHI study of oestrogens only in women who have had a hysterectomy continues, as this group did not have increased adverse outcomes. Unfortunately the Wisdom study which planned to study younger, low risk women like Julie, did not go ahead. It is unlikely that any such study would get ethical approval.

Expressing the results of studies in terms of change in absolute risk will help patients understand the figures and enable them to make the most appropriate decision.

For patients like Julie, discussion of the results of the studies is appropriate and providing her with resources will enable her to make the decision which best suits her.

In this case, osteoporosis has not been discussed and should be factored into the decision making process.

Royal Australian College of General Practitioners