PRESS
STATEMENT
Issued on behalf of the Board of the International Menopause Society by
Amos Pines, President, David Sturdee, General Secretary, Martin Birkhäuser, Treasurer, Marco Gambacciani and Nick
Panay
Recommendations on postmenopausal hormone therapy
February 27, 2007
The following Statement expresses the views of the
International Menopause Society (IMS) on the principles of hormone therapy (HT)
in the peri- and postmenopause period. Throughout the statement, the term HT
will be used to cover all therapies including estrogens, progestogens, combined
therapies and tibolone.
The
previous IMS Statement in 2004 is still valid and serves as a basis for the
current updated version.
We
are aware of the geographical variations related to different priorities of
medical care, different prevalence of diseases, and country-specific attitudes
of the public, the medical community and the health authorities toward
menopause management, which may all impact on hormone therapy. The following
recommendations, therefore, give a global and simple overview that serves as a
common platform on issues related to the various aspects of hormone treatment.
This statement was reviewed and discussed by representatives of more than 60
National and Regional Menopause Societies from all continents. These
recommendations can be easily adapted and modified according to local needs.
Hormone therapy should be part of an overall
strategy including lifestyle recommendations regarding diet, exercise, smoking
and alcohol for maintaining the health of postmenopausal women. HT must be
individualized and tailored according to symptoms and the need for prevention,
as well as personal and family history, results of relevant investigations, the
woman’s preferences and expectations. The risks and benefits of HT differ for
women around the time of menopause compared to those for older women.
HT includes a wide range of hormonal products and
routes of administration, with potentially different risks and benefits. Thus,
the term ‘class effect’ is confusing and inappropriate.
Women experiencing a spontaneous or iatrogenic
menopause before the age of 45 years and particularly before 40 are at higher
risk for cardiovascular disease and osteoporosis. They will benefit from hormone
replacement, which should be given at least until the normal age of menopause.
Counselling should convey the benefits and risks of
HT in simple terms, e.g. absolute numbers rather than as percentage changes
from baseline. This allows a woman and her physician to make a well-informed
decision about HT.
HT should not be recommended without a clear
indication for its use.
Women taking HT should have at least an annual
consultation to include a physical examination, update of medical history,
relevant laboratory and imaging investigations and a discussion on lifestyle.
There are no reasons to place mandatory limitations
on the length of treatment.
Whether or not to continue therapy should be decided
at the discretion of the well-informed hormone user and her health
professional, dependent upon the specific goals and an objective estimation of
benefits and risks.
Dosage should be titrated to the lowest effective
dose. Lower doses of HT than have been used routinely can maintain quality of
life in a large proportion of users. Long-term data on lower doses regarding
fracture risk and cardiovascular implications are still lacking.
In general, progestogen should be added to systemic
estrogen for all women with a uterus to prevent endometrial hyperplasia and
cancer. However, progesterone and some progestins have specific beneficial
effects that could justify their use besides the expected actions on the
endometrium. Low-dose
vaginal estrogens administered for the relief of urogenital atrophy do not
require progestogen co-medication. Direct delivery of progestogen to the
endometrial cavity from the vagina or by an intrauterine system is logical and
may minimize systemic effects.
Androgen replacement should be reserved for women
with clinical signs and symptoms of androgen insufficiency. In women with
bilateral oophorectomy or adrenal failure, androgen replacement has significant
beneficial effects, in particular on health-related quality of life and sexual
function.
BENEFITS OF
HORMONE THERAPY
General
HT
remains the most effective therapy for vasomotor and estrogen-deficient
urogenital symptoms. Other menopause-related complaints, such as joint and
muscle pains, mood swings, sleep disturbances and sexual dysfunction (including
reduced libido) may improve during HT. Quality of life and sexuality are key
factors to be considered in the management of the aging individual. The
administration of individualized HT (including androgenic preparations when
appropriate) improves both sexuality and overall quality of life.
HT is effective in
preventing the bone loss associated with the menopause and decreases the
incidence of all osteoporosis-related fractures, including vertebral and hip,
even in patients at low risk. Although the magnitude of decline in bone
turnover correlates with estrogen dosage, even lower than standard dose
preparations maintain a positive influence on bone indices in most women. Based
on updated evidence on effectiveness, cost and safety, HT is an appropriate first-line
therapy in postmenopausal women presenting with an increased risk for fracture,
particularly under the age of 60 years and for the prevention of bone loss in
women with premature menopause. The protective effect of HT on bone mineral
density declines after cessation of therapy at an unpredictable rate, although
some degree of fracture protection may remain after cessation of HT.
The
initiation of standard-dose HT is not recommended for the sole purpose of the
prevention of fractures after the age of 60 years. Continuation of HT after the
age of 60 years for the sole purpose of the prevention of fractures should take
into account the possible long-term effects of the specific dose and method of
administration of HT, compared to other proven therapies.
Regulatory
Authorities should review their current recommendations as a priority.
Cardiovascular
disease is the principal cause of morbidity and mortality in postmenopausal
women. Major primary prevention measures (besides smoking cessation and diet
control) are weight loss, blood pressure reduction, and diabetes and lipid
control. There is evidence that HT may be cardioprotective if started around
the time of menopause and continued long-term (often referred to as the ‘window
of opportunity’ concept). HT reduces the risk of diabetes and has positive
effects on other risk factors for cardiovascular disease such as the lipid
profile and metabolic syndrome.
In
women less than 60 years old, recently menopausal and without prevalent
cardiovascular disease, the initiation of HT does not cause early harm and may
reduce cardiovascular morbidity and mortality. Continuation of HT beyond the
age of 60 should be decided as a part of the overall risk–benefit analysis.
HT
has benefits for connective tissue, skin, joints and intervertebral disks. HT
may reduce the risk of colon cancer. HT initiated around the time of menopause
or by younger postmenopausal women is associated with a reduced risk of
Alzheimer’s disease.
Studies
on the risks of postmenopausal hormone use have mainly focused on breast and
endometrial cancer, venous thromboembolism (pulmonary embolism or deep vein
thrombosis), stroke and coronary events.
The
incidence of breast cancer varies in different countries. Therefore, currently
available data cannot necessarily be generalized. The degree of association
between breast cancer and postmenopausal HT remains controversial.
Women
should be reassured that the possible risk of breast cancer associated with HT
is small (less than 0.1% per annum). For combined HT, observational data from
the Million Women Study suggested that breast cancer risk was increased as
early as the first year, raising serious reservations on possible methodologic
flaws. On the contrary, randomized controlled data from the Women’s Health
Initiative (WHI) study indicate that no increased risk is observed in women
initiating HT, for up to 7 years. It should be noted that the majority of
subjects in the WHI were overweight or obese.
Data
from the WHI and Nurses’ Health Study suggest that long-term estrogen-only
administration for 7 and 15 years, respectively, does not increase the risk of
breast cancer in American women. Recent European observational studies suggest
that risk may increase after 5 years.
There
are insufficient data to evaluate the possible differences in the incidence of
breast cancer using different types and routes of estrogen, progestin and
androgen administration.
Baseline
mammographic density correlates with breast cancer risk. This does not
necessarily apply to the increase in mammographic density induced by HT.
The
combined estrogen–progestogen therapy-related increase in mammographic density
may impede the diagnostic interpretation of mammograms.
Unopposed
estrogen administration induces a dose-related stimulation of the endometrium.
Women with a uterus should have progestogen supplementation.
Continuous
combined estrogen–progestogen regimens are associated with a lower incidence of
endometrial hyperplasia and cancer than occurs in the normal population.
Direct
intrauterine delivery systems may have advantages. Regimens containing low-/ultra-low-dose
estrogen and progestogen cause less endometrial stimulation and less bleeding.
The
HT-related risk for serious venous thromboembolic events increases with obesity
and thrombophilia. By avoiding first-pass hepatic metabolism, transdermal estrogen
may avert the risk associated with oral HT. Late starters of standard-dose HT
may have a transient slightly increased risk for coronary events. The risk of
stroke is correlated with age. HT may increase the risk of ischemic stroke.
Safety
data from studies of low-dose and ultra-low-dose regimens of estrogen and
progestogen are encouraging.
ALTERNATIVE
TREATMENTS
The efficacy and safety
of complementary alternative medicines have not been demonstrated and further
studies are required.
Selective
serotonin reuptake inhibitors, selective noradrenaline reuptake inhibitors and
gabapentin are effective in reducing vasomotor symptoms in short-term studies.
Their long-term safety needs further evaluation.
There
are no medical or scientific reasons to recommend unregistered ‘bioidentical
hormones’. The measurement of hormone levels in the saliva is not clinically
useful. These ‘customized’ hormonal preparations have not been tested in
studies and their purity and risks are unknown.
RESEARCH
There is urgent need for
further research especially into the relative merits of lower doses, regimens
and routes of administration.
The original IMS Position Statement was published in
Climacteric 2004;7:8–11.
For
further information, contact:
IMS Executive Director,
Mrs Jean Wright, PO Box 687, Wray,
Lancaster
LA2 8WY, UK
Telephone: +44 15242 21190; e-mail: jwright.ims@btopenworld.com
www.imsociety.org