The doctor says: The risks of hormone therapy have been, and continue to be, a source of concern to some women.
Although hormone therapy (HT) was started for women aged 55 years or more in 89% of subjects, who were largely without menopausal symptoms, in the Women’s Health Initiative (WHI) trial reported in 2002, its findings were directly generalised to younger populations of women or to individual women.
Since then, the WHI findings have been re-analysed and other studies have been reported, all of which are of relevance to women considering HT, as its benefits have to be weighed against its risks.
Media attention on the risks of HT studies have almost invariably focused on the relative risks. This approach has not empowered the consumer, as it has made HT appear worse than it actually is.
Perspective has not been maintained and uninformed discussion has contributed much to the confusion and fear about HT.
Absolute and relative risks
How common disease events are is termed absolute risk.
Relative risks are an indication of the magnitude of the increase in disease events attributable to an intervention, but without reference to absolute risks.
A small increase in relative risk for a disease event, which occurs very frequently, will result in a large increase in the number of patients affected (large absolute risk).
On the other hand, a large increase in relative risk for a disease event, which occurs infrequently, will result in only a tiny increase in the number of patients affected (small absolute risk).
For example, a common condition may affect 10% of the women population, i.e. 100 out of 1,000 women will be affected (absolute risk). If the relative risk is increased by 5%, the number affected will then be 105 out of 1,000 women.
An uncommon condition may affect 1% of the women population, i.e. 10 out of 1,000 women will be affected (absolute risk). If the relative risk is increased by 100%, the number affected will then be 20 out of 1,000 women.
This example illustrates the need to consider both absolute and relative risks when interpreting studies.
As breast tissue is sensitive to hormones, there has been concern about breast cancer risk among HT users and those considering it.
The oestrogen and progestogen trial of the WHI reported a small increase in the risk of breast cancer after five years’ use of HT – about one extra case per 1,000 women per annum.
However, the oestrogen-alone trial of the WHI reported a small, but statistically significant decrease in breast cancer risk after five years of use of HT, i.e. four fewer cases per 1,000 women aged 50-59 years, five fewer cases aged 60-69 years and one fewer case aged 70-79 years.
The Million Women Study (MWS) in the United Kingdom published in 2003 raised concerns about the long-term safety of HT in respect of breast cancer with all HT regimens used.
Reanalysis of the WHI and MWS revealed a number of important flaws that limited the ability of the trials to establish a causal association between HT and breast cancer.
Unopposed oestrogen increases the development of endometrial hyperplasia and the risk of endometrial cancer.
The addition of progestogen reduces the risk of endometrial cancer.
Most studies recommend at least 10 days of progestogen per cycle in all women with a uterus, to effectively avoid any increased risk of endometrial cancer.
Long-term use of combined oestrogen-progestogen for more than five years may be associated with a small increase in the risk of breast cancer.
But continuous combined oestrogen-progestogen is associated with a significant lower risk of endometrial cancer when compared to those not on HT.
The data on the risk of ovarian cancer is conflicting.
Some studies suggest a significant increased risk with oestrogen only, and a smaller or no increase in risk with combined oestrogen-progestogen.
However, the WHI reported no increase in risk.
The WHI reported that the risk of colorectal cancer was reduced with combined oestrogen-progestogen, but there was no change with oestrogen-only taken orally.
There are no data on the effects of transdermal HT.
HT after cancer treatment
The treatment of breast cancer has improved survival, but has side effects.
The main side-effects of vasomotor symptoms and impaired sexual functioning are related to premature menopause due to chemotherapy and/or anti-hormonal therapy.
HT is not prescribed to breast cancer survivors because of a proven increased risk of recurrence.
However, there are exceptions made in selected cases of fully informed BRCA mutation carriers with ER-negative breast cancer and severe menopausal symptoms.
Vasomotor symptoms can be relieved by lifestyle adaptation, acupuncture and non-hormonal medicines, and impaired sexual functioning by sexual counselling or psycho-educational therapy.
Painful intercourse due to vaginal dryness can be treated by vaginal lubricants and moisturisers, but is most effectively treated by vaginal oestriol. Local oestriol appears safe if used for less than six weeks.
HT can be prescribed after treatment for cervical cancer because there is no association between HT and cervical cancer.
Studies on the use of HT after treatment for endometrial cancer have either reported no increase in the risk of recurrence or a reduced recurrence rate with an increased disease-free interval.
Most of these studies have been on early stage endometrial cancer.
However, the risks in advanced endometrial cancer may be different.
HT is not prescribed in endometrial sarcomas as they are sensitive to oestrogen.
There have been no difference in survival rates or an improvement in survival rates with HT use in epithelial ovarian cancer or germ cell tumours.
There is no data on HT use in granulosa cell tumours, but it is not prescribed because they are sensitive to oestrogen.
HT can be prescribed after treatment for vulval cancer as there are no reports of oral or local oestrogen on its recurrence.
> Dr Milton Lum is a member of the board of Medical Defence Malaysia. This article is not intended to replace, dictate or define evaluation by a qualified doctor. The views expressed do not represent that of the organisations that the writer is associated with. For further information, e-mail firstname.lastname@example.org. The information provided is for educational and communication purposes only and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this column. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.