WHO Drug Information Vol. 17, No. 4, 2003
(2003; 58 pages) View the PDF document
Table of Contents
Open this folder and view contentsRegulatory Challenges
Open this folder and view contentsSafety and Efficacy Issues
Open this folder and view contentsAspects of Quality Assurance
Open this folder and view contentsRegulatory and Safety Action
Open this folder and view contentsPersonal Perspectives
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View the documentWHO review of NICE in the United Kingdom
View the documentNew advice on hormone replacement therapy
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View the documentAction against counterfeit medicines in Asia and Africa
Open this folder and view contentsEssential Medicines
View the documentRecommended International Nonproprietary Names: List 50
View the documentSelected WHO Publications of Related Interest
 

New advice on hormone replacement therapy

The Million Women Study has been carried out within the United Kingdom and involves around one million women aged 50 years of age and over. The main focus of the study relates to the effects of hormone replacement therapy use, but the large size of the study means that a very broad range of health issues were also investigated, including how various reproductive and lifestyle factors affect women's health, as well as diet, childbirth, breastfeeding, vitamin and mineral supplement use, oral contraceptive use and family history of illness. Results of the study were published in August 2003, and have provided new insights into the risks associated with hormone replacement therapy (HRT), in particular in relation to breast cancer(1).

The United Kingdom Committee on Safety of Medicine carefully reviews all new data on the safety of HRT. Other important information on the long-term risks of HRT - including coronary heart disease, stroke and ovarian cancer - was communicated in July 2002 following termination of one arm of the Women's Health Initiative (WHI) trial (2).

Summary table of risks and benefits associated with using HRT

Condition

Age of woman
(yr)

Number of cases/1000 non-HRT users

Extra Number of cases in 1000 HRT users over the same period

Cumulative cancer risk with time

5 years use

10 years use

Breast cancer

50 - 65

32

1.5
estrogen only
6
combined HRT

5
estrogen only
19
combined HRT

Endometrial cancer

50 - 64

5

4
estrogen only
{no data}
combined HRT

10
estrogen only
<2
combined HRT

Ovarian cancer

50 - 69

9

1
estrogen only
{no data}

3
estrogen only
{no data}

Cardiovascular risks over 5 years

 

Stroke

50 - 59

3

1

{no data}

 

60 - 69

11

4

 

VTE

50 - 59

3

4

{no data}

 

60 - 69

8

9

 

Benefits over 5 years

Reduced number of cases in 1000 HRT users over the same period

Colorectal cancer

50 - 59

3

1

2

 

60 - 69

8

3

5 - 6

Fracture of neck of femur

50 - 59

1 - 2

0 - 1

1

 

60 - 69

7 - 8

2 - 3

5

Findings of the Million Women Study showed that half the women had used HRT of which there had been 9364 incidents of breast cancer and 637 breast cancer deaths. Users of HRT were considered more likely to develop breast cancer but past users were not considered at increased risk. Incidence was significantly increased for current users of preparations containing estrogen only, estrogen-progestogen and tibolone, but associated risk for estrogen-progestogen was substantially greater than for other types of HRT. Ten years use of HRT is estimated to result in 19 additional cancers per 1000 users of estrogen-progestogen combinations. In conclusion, HRT causes a duration-dependent increase in the risk of breast cancer that begins to decline when HRT is stopped and by 5 years reaches the same level as in women who have never taken HRT.

The magnitude of the risk associated with estrogen-only products has been confirmed. For combined HRT use, the risk is significantly higher than with estrogen-only therapy. More specifically, the study demonstrates that:

• The increase in risk of breast cancer associated with combined HRT (relative risk RR = 2.00 compared with no use) is significantly higher than for estrogen-only therapy (RR = 1.30) and for tibolone (RR = 1.45).

• There is no evidence for a difference in risk of breast cancer between specific preparations or their route of administration within the classes of oestrogen-only therapy and any type of combined HRT.

• The estimated number of extra cases of breast cancer occurring after 5 and 10 years of using combined HRT were almost identical in the Million Women Study and the WHI trial.


The United Kingdom Committee on Safety of Medicine has issued the following advice to physicians and prescribers.

• For short-term use of HRT for the relief of menopausal symptoms, the benefits outweigh the risks for many women.

• For longer-term use of HRT, women must be made aware of the increased incidence of breast cancer and other adverse effects.

• Each decision to start HRT should be made on an individual basis and treatment should be regularly reappraised (at least once a year).

• For combined HRT the benefits of the lower risk of endometrial disorders, including cancer, should be weighed against the new information about the increased risk of breast cancer (see table). The risk of endometrial cancer with tibolone is not known.

• The results of the Million Women Study do not necessitate any urgent changes to women's treatment.


Summary

Hormone replacement therapy is an effective short-term treatment option for controlling symptoms of menopause. For each woman considering use of HRT, it is necessary that the benefits be weighed against the several risks that have been observed, including that of coronary heart disease within one year and breast cancer after one year of therapy.

Hormone replacement therapy should not be used for the long-term prevention of disease. For women currently taking long-term hormone replacement therapy for the treatment of osteoporosis, the risks now documented must be considered when reviewing individual circumstances as well as the consideration of the benefits and risks of alternative therapies.

For younger women with premature menopause or hypogonadism, the benefits of hormone replacement therapy would be expected to be greater and the risks probably smaller than those reported recently in the WHO study and Million Women Study (4).

References

1. Million Women Study Collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet, 362: 419 - 427 (2003).

2. Women's Health Initiative Writing Group. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Journal of the American Medical Association, 288: 321 - 333 (2002).

3. Information sheet for women available from Medicines and Healthcare Products Regulatory Agency (MHRA) website http://www.mhra.gov.uk

4. Therapeutic Goods Administration. ADEC statement on use of hormone replacement therapy. http://www.health.gov.au/tga

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