Menopause
and HRT
Dr. Huda Muhaddien Muhammad
MBCHB ,FICOG, CABOG
Menopause refers to final menstrual
period (from the Greek meno –month- ,–
pausos- ending ) .
Represents a watershed
reproductive life of a women .
in
the
The average age of the menopause in
the western women is approximately 52
years.
Climacteric (from the Greek klimakter –rung
of ladder-) :
Signifies a major movement on life’s
ladder.
Is often used synonymously with
(perimenopause or the changes).
Is transition from the reproductive to non
reproductive state.
Occurs as a result of loss of ovarian
follicular activity leading to a fall in E2level
below the level needed for endometrial
stimulation.
It can only be said to have 12 consecutive
months of amenorrhea .
Can occurs suddenly .
For most of the women there is gradual
changes in the menstrual pattern in the
years preceding the menopause as the
ovarian activity fluctuates , which may be
accompanied by troublesome symptoms;
this is often called the perimenopause
Surgical
menopause:
occurs
when
functioning ovaries are removed as in TAH
&BSO for malignancy
or
severe
endometriosis.
Iatrogenic menopause induced by treatment
as
radio-chemotherapy or using
GnRh
analogues for a variety of conditions .
Premature menopause :
occurs if the menopause happens before
the age of 45 .
1% of women under 40 years , 0.1 % under
30 years .
It is one of the more common causes of
the primary and secondary amenorrhea .
the cause is usually unknown .
Well established causes of POF should be
excluded:-
Primary causes:
1) Chromosomal disorders as Turner’s fragile
X.
2) Auto -immune disease as hypothyroidism,
Addison’s, myasthenia gravis.
3) Enzyme deficiencies as galactosaemia ,17
α- hydroxylase definiecy.
Secondary causes:
1) Surgical menopause
oophorectomy .
after
bilateral
2) Chemotherapy or radiotherapy.
3) Infections
varicella.
like TB , mumps, malaria,
Pathophysiology:
As the ovary ages the remaining follicles (
least sensitive
to gonadotrophins)
are
increasingly less likely to mature.
Ovulation declines and ovarian function
gradually declines.
The 1st endocrine change is a fall in Inhibin
production by the ovary ( a glycoprotein that
inhibits production of FSH ).
Eventually the level of estradiol production is
no longer sufficient to stimulate endometrial
proliferation and menopause ensues.
Further decline in estradiol levels over
subsequent years has effects on all estrogen –
responsive tissues.
Menopause may only be a single event .but
is represents a significant change in
hormonal milieu and affects her future
health and quality of life.
Investigations :
In most cases the diagnosis is pretty
straightforward and doesn’t require any
further investigation
It is mandatory to investigate women suspected of
undergoing premature menopause.
What investigations:
FSH ( a level > 30 IU/L is considered diagnostic of
menopause).
There is no value of measurement of E2,
progesterone ,testostosterone in the diagnosis of the
menopause.
T4 & TSH should be checked if there clinical
suspention
Further assessment for screening for
significant diseases in late years and
introduce appropriate preventive measures:
1) Breast screening and mammography.
2) Endometrial assessment for abnormal
bleeding.
3) CV disease risk assessment.
4) Skeletal assessment including bone
density estimation and fracture risk
assessment
Effects of the menopause :
women’s experiences will vary enormously ,
some women have no symptoms at all; while
others can have a dreadful time with
debilitating symptoms that stop them
functioning properly.
The effects vary chronologically and are
categorized as following
a/ Short term (0-5 years):
•Vasomotor symptoms e.g. hot flushes ,night
sweats.
•Psychological symptoms e.g. labile mood
,anxiety and tearfulness .
•Loss of concentration ,poor memory.
•Joint aches and pains.
•Dry & itchy skin.
•Hair changes.
•Decreased sexual desire.
b/ intermediate (3-10 years):
•Vaginal dryness, soreness.
•Dyspareunia.
•Sensory urgency.
•Recurrent UTIs.
•Urogenital prolapse.
c/ long term ( >10 years ):
•Osteaporosis.
•Cardiovascular disease .
•Dementia.
Genitourinary problems :
Urogeniotal atrophy is common observational
in postmenopausal women which increases
with age.
Vaginal atrophy results in loss of the normal
architecture within the vaginal epithelium,
reducing its secretions and elasticity and
making it more prone to trauma, dryness,
spontaneous bleeding and infection.
Clinically this manifests as vaginal dryness,
Itching,
dyspareunia , vaginal pains,
bleedings, discharges , and infections .
Distal urethra and trigone of the bladdor are
also prone to atrophy as a result of estrogens
deficiency .
This can lead to urethral syndromes (
urinary frequency and dysuria in the
absence of infection) , this is respond well to
local vaginal estrogen.
Thinning of the trigon
and urethral
mucosa lead to a more sensitive and
trauma prone bladder which in turn leads
to sensory urgency and recurrent UTI . Also
this will respond to local estrogen.
Loss of estrogen plays a role in more
widespread pelvic floor dysfunction leading
to weakening of the supporting tissues and
ligaments ( already had been damaged by
childbirth) thus increase the incidence of
prolapse and stress urinary incontinence .
Long term effects:
These conditions often develop without
obvious clinical manifestation in the early post
menopause , but pose a significant economic
burden for future particularly with an
increasingly ageing population.
Those women underwent premature
menopause will spent a prolonged period
without estregens so they are at high risk .
Osteoporpsis :
Is defined as a skeletal disorders characterized
by compromised bone strength predisposing
to an increased risk of fracture .
20 % of our bone is composed from trabecular
bone ( shock absorbing capacity)
Oestrogen acts an antiresorptive agent
on the trabecular bone so E2 deficiency
after menopause is characterized by
unprecedented fall in bone density which
ultimately may lead to increase risk of
osteoporotic fractures
Bone strength is a reflection of bone
quality and density .
Current strategies of treatment target
preventive treatment at individual identified
as high risk of subsequent fracture .
Recent NICE guidance favours a very
limited role for preventive treatment for
women under 75 years unless if there was
history of previous fracture .
Cardiovascular disease :
Is relatively uncommon before menopause .
Oestrogen has
against CHD.
a productive
influence
Early menopause without estrogens is
associated with 2-4 increased fold of CHD.
Menopause is associated with adverse
metabolic changes (raise in LDL and
cholestrol and fall in HDL).
Loss of oestrgen lead to vasoconstriction
and atherogenesis.
Dementia is much more common among
women , but the evidence for a role of
estrogen and menopause
in the
pathophysiology of cognitive decline and
dementia is conflecting.
Management
the menopause is natural event and for
many women there is no need to manage it
at all.
Awareness of the long term implications,
such as osteoporosis and CV disease should
be part of good preventative medicine.
The menopause consultation :
History :
Concentrate on ascertaining the frequency
and severity of menopausal symptoms and
their impact on day to day activities.
Enquiry
into any sexual problems , in
particular vaginal dryness soreness, and
bladder symptoms should be recorded
Family and personal history should focus on
risk factors for CV disease , osteoporosis
,breast cancer ,thrombosis and ovarian
cancer.
Any previous treatment and S/E should be
noted .
Explanation
teatments
the
potential
s/E
of
all
Physical examination :
Abdominal examination .
Breast examination .
Cervical smear.
Bimanual assessment of the uterine size.
Assessment of the vagina for any atrophy,
prolapse or incontinence.
Lifestyle :
The menopause could be an ideal time to
look at changes in diet and exercise and
build for a healthy future to maximize health
potential .
Smoking cessation , eating sensibly and
avoid extra weight .
Regular physical activity
Alternative and complementary therapies:
There is little evidence for the safety and
efficacy of most of them.
as in the following;
1-Non prescriptive treatment
Lifestyle changes (diet and exercise).
Complementary therapies : acupuncture,
reflexology and magnetism.
Herbal remedies : black cohosh (actaea
racemosa), dong quai ( angelica sinensis ),
evening primose oil , gingkp , ginseng, st
jonn’s wort ( hypericum perforatum).
Bio- identical hormones :
natural
progesterone gel , DHEA , phytoestrogens (
isoflavones, red clover ).
Prescription:
α-adrenergic agonist as clonodine.
Beta blockers as propranolol
Selective serotonin reuptake inhibitors:
venlafaxine, fluoxetine, paroxitin ,citalopram
.gabapentin
HRT : estrogen alone, oestrogen and
progestogen combintion , progestogen alon
SSRI used for hot flushes in short trials ,only
used for those who cannot take HRT.
For osteoporosis , the bisphosphonates are
the principle of drug used .
Alternative include strontium and raloxofene (
type of SERM).
Those drugs have significant S/E and should
be used for women over 60 year.
Para thyroid hormone is reserved for women
with very high risk.
Hormone replacement therapy:
Is the principle treatment available for
troublesome menopausal symptoms.
Acts by replacing the hormones that are
normally produced by the human ovary at
physiological levels.
Oestrogen is the main hormone and is
either given alone or in combination with
progestogen , which should be given for all
non hysteroctemised women.
Testosterone
can also be given in
conjuction with oestrogen.
Most HRT treatment come in combination.
Oestrogen :
There are different types of oestrogen
available.
1- oestradiol ( transdermal, gel ,implant).
2- oestradiol valerate.
3- conjucated equine oestrogens.
4- oesterone sulphate.
5-oesteriol ( vaginal only).
Can be given by different doses and by
different routes.
The lowest dose should be used.
Non –oral route ( especially transdermal )
avoid the 1st pass effect, and are considered
more physiological as they release oestradiol
to the circulation, rather than oesteron.
Avoiding thr 1st pass effect reduces the
impact on various metabolic parameters, such
as haemostatic and coagulation system , so
seems a better option in women with
personal or family history of VTE or known
liver abnormalities.
Non oral routes are expensive , there can be
logiical problema administerating progestogen
component simultanously .
Subcutaneous implants is reserved for those
women who hysteroctemised with removal of
both ovaries , ( repeated every six months).
Implants also
testosterone.
allow
the
addition
of
Progesterone:
In HRT , progetogens ( synthetic
progeterone ) are added for at least 10 days
/calender month to mimic menstrual cycle .
This will reduce the risk of endometrial
hyperplasia and cancer associated with
prolonged use and unopposed oestrogen.
 It can be given either cyclically mimickining
a natural 28 day cycle -28 days result in
withdrawal
bleeding
(
used
for
perimenopausal women; Or it can be given
continuously
to prevent any bleeding –so
called no bleed _ treatment ( used for post
menopausal women)
Types of progetogens used in HRT :
C -19 nor testosterone derivatives
norethisterine
(
transdermal
levonogesterel (transdermal, intrauterine).
:
)
C-21
progesterone
derivatives
:
dydrogesterone,
medroxyprogesterone
acetate , cyproterone acetate .
C -17 derivatives : drospirenone .
Progesterone:
micronized
progesterone ( vaginal gel , pessary,
suppository.
S/E are common esp in 1st few months and
can be alleviated by changing the type or the
route
Levonogesterole IUD can be used in women
who canot tolerate systemic progestogenes .
Progestogen is not used for hystorectomized
women.
Testosterone :
50% from the ovaries and 50% from the fat
and adrenal glands .
Menopause doesn’t affect testosterone
level but decrease SHBG level this may
lead to increase the level of free
testosterone .
Surgical or chemoradiation induced
menopause can lead to relatively deficient
testosterone.
May be presented as loss of libido,
fatigue.
Risks and benefits of HRT:
Still uncertainty and controversies present
about HRT use and what exactly the risks are
and how relevant they are to the majority of
healthy post menopausal women.
HRT
Is an extremely effective treatment for
menopausal symptoms and urogenital
atrophy.
 is an effective treatment for osteoporosis,
and appears to have beneficial effects on the
cardiovascular system if it started around the
menopause .
Oestrogen is effective in relieving the hot
flush symptoms within 4-6 weeks.
Vaginal or topical oestrogens preperations
have no significant systemic activity so can
be used for those in whom HRT is
contraindicated.
Progestogen use with vaginal oestrogens is
not necessary.
For vaginal atrophy , vaginal oestrogen is
applied daily for 2 week then with the
improvement in the vaginal epithelium it
can be reduced to once or twice weekly. This
should be continued for at least 12 months at
a low maintenance dose .
Because of the uncertainty of its long
term safety
,the regular authorities
currently advice that HRT should not be
used as a 1st line treatment for osteoporosis
prevention as the potential risk outweigh
the benefits.
Protection against CVD and colon cancer is
not an indication to consider HRT
Risk ,benefits, uncertainty of HRT
Benefits
Vasomotor
symptoms
Urogenital
symptoms
Sexual
function
Stoke
Osteoporosis
Colon cancer
Risks
Breast cancer
VTE
Endometrial
cancer
Uncertainties
CVD and
stroke
Alzheimer’s
Ovarian cancer
Risks of HRT:
Breast cancer :
small increase in risk within few years of
starting HRT in healthy postmenopausal
women .
Risk is not increase with oestrogen only
type
The increase in the risk is associated with
progetogen componant.
Family history is important.
Endometrial cancer :
Unopposed oestrogen replacement therapy
increases the risk of endometrial cancer.
Any
abnormal bleeding during HRT
treatment should be investigated,although
there is a small risk of malignancy.
Ovarian cancer :
Small increase in risk with long term (>10 y)
treatment
Venous thromboembolism :
HRT increases the risk of VTE 2 fold with
highest risk occurring in the 1st year.
The background risk is increased with
obesity , smoking and history of underlying
thrombophilia such as factor V Lieden or who
have previously suffered VTE.
Transdermal HRT have less impact on
heamostatic mechanism and lower risk of
VTE.
Coronary heart disease :
Timing of oestrogen
important.
introduction is
Women staring HRT shortly after
menopause may have protective effect.
Stroke ;
Small increases in the risk with both
oestrogen only and combined oestrogen and
progestogen HRT, also its affected by age .
Practical consideration :
1-For the majority of healthy symptomatic
menopause women the potential benefits
will outweigh any small risk.
Contraindications to taking HRT:
Absolute : suspected pregnancy, breast and
endometrial
cancer,
uncontrolloed
hypertension , known VTE, known
thrombophilia and ostsclerosis.
Relative :uninvestigated abnormal bleeding,
large uterine fibroids, past history of benign
breast disease , unconfirmed personal history
or strong family history of VTE, chronic stable
liver disease and migraine with aura.
Selection which HRT regimen is a matter for
the individual prescriber .
Follow up should be arranged after about 3
months to check the treatment’s effectiveness
and any persistent S/E.
Treatment should be started at the lowest
appropriate dose and can be increased if there
is no symptomatic improvement after few
months.
Oestrogen related S/E: dose dependant
and last for few months
( fluid retention, nausea ,headaches , breast
enlargement, leg cramps and dyspepsia).
Progestogen related S/E mostly like PMS
(fluid retention , breast tenderness ,
headaches ,acne, mood swings , depression
, irritability,bloating , constipation and
increased appetite). If persist change the
type .
The average duration of treatment is 2-3
years depends on the indication and
individual circumstances.
it is recommended to take a minimum
effective dose of HRT for the shortest
duration.
Premature menopause women better to
take HRT until the age of 50.
Once the condition is stabilized , women
should be reviewed every 6 months (
individual risk of VTE, stroke and breast
cancer should be balanced against the
benefits that are gaining from the treatment
).
Women on HRt should continue to
participate in the national programmes for
breast, cervical ,colorectal cancer.
Stopping HRT should be gradually.
Contraception should be continued until 2
years after the last period in women under 50
years; and 1 year for those above 50.
Contraception could be condome ,or mirena
as contraception and as part of HRT.
Thank you