The
International Menopause Society (IMS) recently released 2016 Global Consensus
Statement on Menopausal Hormone Therapy (MHT).[1]
The IMS brought together 7 international
societies, including European Menopause and Andropause Society and the North
American Menopause Society to formulate comprehensive, evidence based
guidelines with practice essentials to help and guide physicians across the
globe in managing women through menopause transition and beyond.
The
guidelines are aimed at helping women across the globe to prevent chronic
diseases due to aging along with treatment of troublesome menopausal
symptoms.
The term Menopausal
Hormone Therapy (MHT) includes estrogen, progesterone and combined therapies.
The
recommendations simply provide an overview of basic principles of hormone
therapy which can be modified and adapted according to the geographical region,
country specific belief and practices, basic infrastructure of healthcare and
the variation and availability of the hormones. It also simply provides
consensus and is not a replacement for the detailed guidelines issued by each
individual societies.
Professor
Rod Baber, IMS President, commented “I believe the new Global Consensus is a
major step forward in the management of menopausal women as it provides women
and their doctors with internationally endorsed guidance”.[2]
General principles that governs the
use of MHT
The option
of starting MHT should be decided according to the need of each patient
depending upon age, time elapsed since menopause, the symptoms, risk of VTE,
breast and gynecological malignancies and CVD.
It should be
a part of overall life style change and management including diet, exercise and
smoking cessation for prevention of postmenopausal osteoporosis.
MHT include
a range of hormonal products that can be administered by various routes. It
includes Tibolone or CE/BZA too when available. Each product has its own side
effects, and risk/benefit rations.
MHT should
always begin with the lowest possible dose that alleviates the symptoms with
minimum side effects. The route of administration should be tailored to
individual need, preference and side effects.
The
benefit/risk ratio should be assessed annually for each patient. The duration
of the treatment should be planned accordingly with the lowest possible dose
schedule. Some women may require longer duration of treatment for relief of
Vaso Motor symptoms (VMS).
Use of
estrogen as single systemic agent is only advocated in case of patients who
have undergone hysterectomy, concomitant use of progesterone is always
advocated with intact uterus unless CE is combined with BZA for uterine
protection.
Testosterone
only therapy or in combination with MHT is only indicated in selective
postmenopausal women with sexual interest/arousal disorder.
Use of
custom compound hormone therapy is not recommended because of batch to batch
variability, lack of regulation standards for safety, efficacy and purity.
Safety data
on use of MHT for breast cancer survivor is limited currently. It’s use in such
patients can only be undertaken after discussing it with patient’s oncologist
when complementary options have exhausted.
Benefit/risk profile for MHT
Quality of
life, sexual satisfaction, mood changes, joint pain and sleep disturbances may
improve with MHT.
MHT with
Tibolone and combination of Conjugated Equine estrogen and bazedoxifene
(CE/BZA) is effective in treatment of osteoporosis. It has consistently seen to
be effective in reducing the risk of vertebral, hip and other
osteoporosis-related fractures in post-menopausal women.
MHT is the
only therapy that is effective in preventing fractures in postmenopausal women
with mean T-score in normal or osteopenic range. It should be initiated before
the age of 60 or 10 years within menopause for at risk women for
osteoporosis.
If started
after the age of 60 years, it is considered the second line of therapy and
risk/ benefit ratio should be compared with other first line drugs.
The most effective
treatment of VMS at any age is Tibolone and combination of Conjugated Equine
estrogen and bazedoxifene (CE/BZA). Symptomatic women derive maximum benefits
if treatment is started within 10 years of menopause or before the age of 60
years.
Vulvovaginal
atrophy(VVA) is now considered a component of genitourinary syndrome of
menopause (GSM). MHT including Tibolone relieves the symptoms of VVA. Topical
estrogen preparations are first line of treatment in patients with only local
vaginal dryness, dyspareunia or recurrent UTI. Ospemifene, a selective estrogen
receptor modulator (SERM) is also licensed in some countries for treatment of
dyspareunia due to VVA.
Many
observational studies, RCTs and meta-analysis provides data that shows
consistent benefits in standard dose estrogen alone group as compared to estrogen
plus progestogen MHT in decreasing myocardial infarction and all-cause
mortality when initiated before age of 60 or within 10 years of menopause.
The risk of
VTE and ischemic stroke increases with oral MHT as compared with transdermal
therapy (0.05 mg twice weekly or lower) when started before the age of 60
years.
The risk of
breast cancer with MHT in women over the age of 50 years is a complex issue.
Estrogen only MHT in women with hysterectomy shows a lower risk as compared to
combine therapy the medroxyprogesterone acetate in the women’s health
initiative study (WHI). However, the risk of < 1.0 per 1000 women per year
is less than that associated with sedentary life style, alcohol consumption and
obesity.
Women who
experience a natural or iatrogenic menopause before the age of 45, particularly
before the age of 40 face a consistent high risk for cardiovascular disease, osteoporosis,
mood disorders and dementia. Results of observational studies have shown that
these women benefit from MHT, but they have to be confirmed by RCTs. MHT can be
prescribed till the age of natural menopause.
In women
with major depressive disorders, antidepressant therapy remains the first line
of treatment, although MHT can be used to improve mood in women with
anxiety/depressive symptoms. MHT
initiated in early menopause and after the age of 65 years also does not have
significant effect on cognition and increase the risk of dementia. Although some observational studies have
shown that early initiation may prevent Alzheimer’s disease in later life.
[1] http://www.imsociety.org/manage/images/pdf/fd28270c02bdca95a58a471e1719e9b4.pdf
[2] http://www.imsociety.org/manage/images/pdf/d9cfd8c2b902d63b0c1bb0ada805240d.pdf
