First Global Summit on menopause-related issues
Zürich, March 2008
HRT in the early menopause: scientific evidence and
common perceptions
Aim: to bridge the gap between clinical facts
and fears that are based on misperceptions
and misinformation in regard to hormone
replacement therapy, with a focus on women less
than 60 years old.
(The full summary is available on www.imsociety.org)
Evidence vs. perception
Both physicians and the lay public do not address postmenopausal
hormone therapy as an ordinary medication. There is a tendency to
‘judge’ hormone therapy by other standards (for example, feminism
and sexism are erroneously linked to the debate).
While the benefits of hormone therapy are very subjective (vasomotor
symptoms) or preventive in nature (fractures), the potential risks involve
serious, frightening diseases (breast cancer, stroke). It seems difficult for
most people to put on the same scale and to weigh objectively these
benefits and risks. Perception-wise, in the post-WHI era, risks are overvalued and generalized to the whole postmenopausal population and to all
forms of hormone therapy.
Evidence vs. perception
Vast amounts of information exist. People tend to be
selective and pick pieces of it according to their
beliefs and personal experience; thus an overall
perspective may be missing.
Quality of life
Achieving good quality of life is a prime target in
menopause medicine, which is as important as prevention
and treatment of diseases. There is no argument that HRT
is the first choice and the best modality to improve quality
of life and sexuality in symptomatic postmenopausal
women.
Cardiovascular system (1)
Perception
HRT increases the risk of coronary heart disease (CHD)
throughout the whole postmenopausal period.
Evidence
HRT in women aged 50–59 years does not increase CHD
risk in healthy women and may even decrease the risk in
this age group. [A]
Rossouw J. JAMA 2007;297:1465
Cardiovascular system (2)
Perception
HRT causes an increase in coronary events in the first 1–2
years in all women.
Evidence
Early harm (more coronary events during the first 2 years
of HRT) was not observed in the early postmenopausal
period. The number of CHD events decreased with
duration of HRT in both WHI clinical trials. [A]
Lobo R. Arch Intern Med 2004;164:482
Cardiovascular system (3)
Perception
Stroke risk is substantially increased in women receiving
HRT.
Evidence
It is unclear at present whether there is a statistical increase in
ischemic stroke with standard HRT in healthy women aged 50–
59. The WHI data showed no statistically significant increase in
risk; nevertheless, even if statistically increased, as found in the
Nurses’ Health Study, the low prevalence of this occurrence in
this age group makes the attributable risk extremely small. [A,B]
Hendrix SL. Circulation 2006;113:2425
Grodstein F. Arch Intern Med 2008;168:861
Cardiovascular system (4)
Perception
The risk of venous thromboembolism is increased during HRT.
Evidence
The risk of venous thrombosis in the early menopause is
approximately two-fold higher with standard doses of oral
HRT, but is a rare event in that the background prevalence
is extremely low in a healthy woman under 60 years of
age. [A]
The risk of venous thrombosis is possibly less with
transdermal, compared with oral estrogen therapy. [B]
Cushman M. JAMA 2004;292:1573
Canonico M. Circulation 2007;115:840
Breast (1)
Perception
All types of HRT cause an increased risk of breast
cancer within a short duration of use.
Evidence
After 5 years’ use of combined estrogen and progestogen,
the WHI cohort showed a small increase in risk of breast
cancer of about eight extra cases per 10,000 women per
year. Risk was not increased in first-time hormone users.
[A]
Chlebowski RT. JAMA 2003;289:3243
Stefanic ML. JAMA 2006;295:1647
Breast (1) cont.
Perception
All types of HRT cause an increased risk of breast
cancer within a short duration of use.
Evidence
In the WHI estrogen-only arm, there was no increase in
breast cancer risk for up to 7 years. However, the risk of
invasive breast cancer was significantly lower in first-time
users of estrogen. [A]
In observational studies, a small increase in risk during
estrogen-alone therapy was recorded only after long-term
use. [B]
Anderson GL. JAMA 2004;291:1701; Stefanic ML. JAMA 2006;295:1647
Chen WY. Arch Intern Med 2006;166:1027
Breast (2)
Perception
The reported decline in breast cancer rates in the
US following the publication of the WHI data proves
that HRT causes cancer.
Evidence
A decline in the incidence of breast cancer in the USA
started before the WHI publication and can be partially
related to fluctuation in screening. There has been no
decline in breast cancer registration in the UK following the
Million Women Study report, nor in Norway, Canada, the
Netherlands and countries with stable screening programs.
[B]
Li CI. Cancer Epidemiol Biomarkers Prev 2007;16:2773
Kliewer EV. NEJM 2007;357:509; Zahl PH. NEJM 2007;357:510
Breast (3)
Perception
HRT causes an increase in mammographic breast density.
Increase in mammographic breast density is associated
with an increased risk of breast cancer.
Evidence
Increased baseline breast density is a risk factor for breast cancer.
Boyd NF. Lancet Oncol 2005;6:798 (review)
Combined E + P therapy may cause increased breast density in up to
50% of postmenopausal women, dependent on the regimen (dosage,
type of progestogen. The average increase in breast density with
standard dose is up to 10%). The effect of estrogen alone is smaller. [A]
Greendale GA. Ann Intern Med 1999;130:232
There are no data to support a direct association between HRT-induced
breast density changes and the risk of developing breast cancer.
Bone (1)
Perception
HRT should not be used for bone protection because of
its unfavorable safety profile. Official recommendations
by health authorities (EMEA, FDA) limit the use of HRT
to a second-line alternative. HRT could only be considered
when other medications failed, were contraindicated or not
tolerated, or in the very symptomatic woman.
Evidence
For the age group 50–59, HRT is safe and cost-effective.
Overall, HRT is effective in the prevention of all
osteoporosis-related fractures, even in patients at low risk
of fracture. [A]
Rossouw J. JAMA 2007:297:1465; Cauley JA. JAMA 2003;290:1729
Jackson RD. J Bone Min Res 2006;21:817
Bone (2)
Perception
HRT is not as effective in reducing fracture risk as other
products (bisphosphonates, etc.).
Evidence
Although no head-to-head studies have compared HRT to
bisphosphonates in terms of fracture reduction, there is no
evidence to suggest that bisphosphonates or any other
antiresorptive therapy are superior to HRT.
Cognition (1)
Perception
Menopause transition is associated with cognitive decline.
Evidence
There is no evidence of substantial cognitive decline across the
menopausal transition. [A]
However, many women experience cognitive difficulties in
association with vasomotor symptoms, sleep disturbances and
mood changes. [B]
Meyer PM. Neurology 2003;61:801; Maki PM. Menopause 2008 (in press)
Woods NF. J Womens Health 2007;16:667
Cognition (2)
Perception
HRT increases the risk of cognitive/memory impairment and
dementia at any age.
Evidence
No cognitive benefit was found among women initiating HRT
late in the postmenopausal period (after age 65). [A]
Observational studies show a decreased risk of Alzheimer’s
disease in hormone users and typically involve women who
initiated estrogen therapy early in the menopausal transition.
[B]
Cognitive benefits from estrogen therapy appear to depend
on age at initiation. [B]
Espeland MA. JAMA 2004;291:2959; Tang M-X. Lancet 1996;348:429
Bager YZ. Menopause 2005;12:12
Cognition (3)
Perception
Progestogens counteract estrogen effects in the brain.
Evidence
Limited data exist on the effect of progestogen added to
estrogen in the early postmenopause period.
Conclusions
Menopause symptoms and the incidence of illnesses
associated with menopause or HRT may vary to a large
extent in different parts of the world, as well as
priorities in medical care. In addition, cultural and social
attitudes may have a substantial impact, all affecting
perceptions and decision-making in regard to
menopause management and the use of hormones.
Each regional/national menopause society should adapt
the general framework according to its local situation
and needs.
Actions to be taken
The forum agreed that education and dissemination of the
clinical data are crucial in the process of closing the gap
between the scientific evidence on HRT and its perception.
Three main targets were identified: the health-care
providers, the consumers and the journalists.
The message to be delivered should be simple and clear,
stressing the benefits of HRT and relieving fears according to
the best-quality clinical evidence. The most frequent
misperceptions should therefore be identified and balanced by
the corresponding data that have been published in the
medical literature.
Take-home message
Many people read only headlines or short messages.
For these people, a short take-home message is the following:
• The target population for initiation of HRT is usually
women up to age 55.
• HRT initiated in the early postmenopausal period in healthy
women is safe.
• Like all medicines, HRT needs to be used appropriately,
but it is essential that women in early menopause who are
suffering menopausal symptoms should have the option of
using HRT.