Hrt menopause

Menopause and HRT
Dr REJI MOHAN
Assistant professor
Govt Medical College
Kottayam

Introduction
200 years ago, fewer than 30% of women lived long
enough to experience menopause.
100 years ago the average women’s life expectancy just
reached 50 years of age.
NOW-Average life expectancy is 80 and most of you
will far surpass that.
Ready or not, you can already expect a better
QUANTITY of life.
So the question really becomes - “How can I maintain
the best QUALITY of life?”
3/9/2017 2drrejimohan@gmail.com

Menopause
• Cessation of menstrual periods due to
declining estrogen and progesterone
production by the ovaries
• Refers to the final menstrual period – must be
free of periods for one year to be called
menopause

Stages of Menopause
Menopause Post-menopause
Pre-
menopause
Climacteric

TYPES
• Natural Menopause
diagnosis is established when
menstruation stops for 12
months in the absence of an
organic or a pathological cause.
– This usually occurs at the
age of 45-50 years. Avg 51
– If it occurs before the age of 40
years, it is referred to as
“Premature Menopause”.
• Induced Menopause
May be:
• Surgical after bilateral
oophorectomy
• Radiological after irradiation of
the ovaries
• Chemotherapeutic after exposure
to chemotherapy during
treatment of malignant diseases

PATHO-PHYSIOLOGY
Endocrine Changes:
The squeal of endocrine changes is as follows:
• Decrease in inhibin production by the ovary.
• Decrease in oestradiol blood level.
• Increase in follicle stimulating hormone (FSH) production by the pituitary
gland (> 30 lU/ml).
• Increase in lutenizing hormone (LH) production.
• The menstruation may stop abruptly but more commonly after a period of
oligo and/or hypomeorrhoea.
• During this climacteric period, bleeding from a proliferative endometrium
(because of anovulation) may be irregular and acyclic.
– In such cases, endometrial carcinoma should be excluded before attributing it
to hormonal changes.

The Menopausal Syndrome

The Golden Rule Is :
•Always try to be empathetic and
NEVER underestimate your patient
complaints
•Avoid telling her about a complaint: “It
will take its time and fade away”

Symptoms of Menopause
• Irregular menses
• Hot flashes
• Vaginal dryness
• Urinary incontinence
• Loss of Libido

Hot flashes
• Sudden rush of heat to upper body, followed by
sweating and chills.
• Preceded by a prodrome of palpitations and
pressure within the head.
• A vasomotor “FLUSH” affecting the upper thorax,
neck and face may be objectively demonstrated.

• Affect 50 to 85% women at some point:
– 85% for > 1 year
– 25-50% for up to 5
• 15% find them troubling and interfering with
their life:
– Poor quality of sleep, irritability, chronic fatigue.
– Public embarassement
• 20% have more than one attack /day
– Seasonal variations
– Tend to occur by night
• More in Slim women who smoke

Etiology
• Thermoregulatory and Vasomotor Instability
– involving α-adrenergic mechanisms and
endogenous opioid peptides.
– The Hypothalamic thermostat is reset at a lower
set-point
• Triggered by hormonal changes:
– Estrogen Withdrawal rather tan hypoestrenemia
– Pulsatile LH release
– DHEA, Androstenedione, ACTH, β-lipotropin and β-
endorphin.

Management
• Estrogen
– Effectively stops hot flashes
– Hot flashes return as soon as ERT is withdrawn
– Tapering Estrogen dose over several week is advisable.
• Progestins
– 10 mg Provera, 150 mg DMPA
– Reseting of the hypothalamic thermostat at a higher set
point.
– Side-effects
• Clonidine
– Stabilizes the thermoregulatory mechanisms
– 0.1 to 0.2 mg twice daily
– Rarely used because it relieves HF by only 30 % (a little different from
placebo)

• Veralipride
– 100mg daily for 20 days/month
– Antidopaminergic
– Side effects
• Herbs
– Phytoestrogens: Soy flour, Ginseng black Cohash
• Home remedies:
– Dress in light layers; small fan to cool the face; light
bedclothes and cotton blanket
– Avoid alcohol and caffeine.

Vaginal Dryness
• Definition: reduced vaginal secretions and thinning of
the mucous membranes lining the vagina  dryness,
itching, and painful intercourse
• Cause and pathophysiology:
– Declining estrogen levels
– Lowered vaginal acidity
– The vagina becomes shorter, narrower and inelastic
– The vaginal skin becomes brittle, thin and vulnerable to
infection.
• Diagnosis
– Clnical examination

Management
• Treatment:
– Topical estrogens:
• Premarin®
• Ovestin ®
– nonprescription lubricant

Urinary Issues
• Complaints
– Incontinence:
• Stress or urge incontinence
• Recurrent urethritis
• Cause: declining estrogen levels  thinning of urethra
and bladder tissue; anatomical changes in pelvic organs
such as cystocele, rectocele or uterine prolapse
• Treatment: varies by cause; estrogen therapy may
improve bladder control
• Other remedies: Kegel exercises; avoid caffeine,
alcohol, and high dose Vit C; bladder retraining

Skin Collagen
• After menopause:
– 2.1% of the skin collagen are lost per year
– Up to 30% are sometime lost in the first 5 years.
• Estrogen
– Improves both amount and quality of Collagen
– Improves skin hydrophilic capacities
– Reduces wrinkles
• Other alternatives
– Moisturizing preparations
– Primrose oil

HRT

Types of HRT
• Hysterectomy – Oestrogen alone
• Peri-menopausal – Cyclical HRT
• Post-menopausal – Continus Combined
• Local vaginal/urological symptoms - Topical

Possible mechanism of cardioprotection by
HRT
• Favourable lipid profile:  HDL,  LDL, 
Lipoprotein (a)
• Other effects:  insulin sensitivity, vascular
dilatation,  coagulation factors

Why Alternatives to HRT are requested?
• Contraindication to HRT
• Belief that HRT interfere with nature
• Desire to be in control
• Fear of long term effects of HRT
• Fear of adverse effects.
• Lack of information about HRT

Facts about alternatives for HRT
1.Most treat only a single problem
2.There is potential harm, because of a lack of
efficacy or possible risks
3.There is a lack of evidence to confirm benefits
or possible adverse effects.
4.There is a widespread belief that “natural”
means harmless, but herbs may contain potent
chemicals & should be used with caution.

Hormone replacement therapy
• Informed choice
• Risks and benefits of taking HRT
• Role of doctor: weighing up the pros
and cons for individual woman

Indications for HRT
• Relief of menopausal symptoms
• Long term prevention of osteoporosis

Absolute contraindications
• Existing breast cancer
• Existing endometrial cancer
• Venous thrombo-embolism
• Acute liver disease

Routes of administration of oestrogen
• Oral
• Transdermal
• Implants
• Local vaginal preparation

Oral therapy
• Natural occurring oestrogens: includes
premarin and various oestradiol preparations. These
oestrogens are metabolised in the liver to the weaker
metabolite oestrone and then converted to oestradiol in
the peripheral circulation and in the target tissue.
• Tibolone: a steroid hormone that has oestrogenic,
progestogenic and androgenic properties.
• Synthetic oestrogens: such as mestranol or ethinyl
oestrodiol are not generally prescribed for older women
for HRT.

Transdermal therapy
• Patches (oestrogen only or combined
preparation) or oestrogen gels
• Women’s preference
• Skin irritation may be a problem but new matrix
patches and the gels are usually well tolerated
• Route of choice for women with risk factors for
venous thrombo-embolism, liver disease or
gastro-intestinal problems

Oestrogen implants
• Now less widely used
• Implants should be given no more than
every 6 months

Local vaginal therapy
• Useful for local vaginal dryness and
symptoms of urgency
• Contraindication to systemic HRT but
require oestrogen for local symptoms

HRT regimens
• Women who have had a hysterectomy only
need to take oestrogen
• Women with an intact uterus must take
progestogen for endometrial protection to
prevent endometrial cancer or hyperplasia
• Regular surveillance of endometrium is
required for women (extreme intolerance of
progestogen) on unopposed oestrogen

An algorithm for the administration of HRT
No HRT
Yes
Unopposed oestrogen therapy
Previous hysterecomy
Cyclical / sequential HRT
Intact uterus + amenorrhoea < 2 yrs
Continuous combined HRT
Intact uterus + amenorrhoea > 2 yrs
Commence HRT
Baseline investigations completed
No
Absolute contra-indication?
Decision made to user HRT

HRT regimens
• Sequential preparation: progestogen added
for 12-14 days each month. Some women will not
bleed on sequential preparations and this is not a
cause for concern provided that the progestogen is
taken correctly.
• Continuous combined HRT: give oestrogen
and progestogen daily. These preparation induces
endometrial atrophy. Intermittent bleeding and
spotting are common in the first few month of use.
More suitable for women who are at least one year
since their last spontaneous period.

Progestogen
• Oral or transdermal form
• Levo-norgestrel releasing intra-uterine
system

HRT …

Side effects of HRT
• Nausea
• breast pain
• heavy or painful withdrawal period
• premenstrual syndrome type of side
effects
• weight gain

Risk of HRT
• Thrombo-embolism
• Breast cancer-long term
• Gall bladder disease
• Endometrial carcinoma-unopposed
estrogen

Length of time on
HRT
Extra breast cancers in HRT
users, above the 45
occurring in Non-users, over
20 years
5 years use 2 per 1000
For women aged 50-70 years not using HRT, about 45 in every 1000 will have
breast cancer diagnosed over the next 20 years.
Collaborative Group on Hormone Factors in Breast Cancer Lancet 1997;350:1047-59

HRT and venous thrombo-embolism
• Natural oestrogens
• Women taking HRT have a 2-4 fold increase in
risk of venous thrombo-embolism (VTE).
• Overall risk remain small: 1 in 5000 and mortality
from VTE is around 1-2%.
• Women with significant past history of VTE
should have a thrombophilia screen before
commercing HRT

• Duration of treatment will depend upon the
women’s preference and the presence of
risk factors
• In the absence of risk factors, HRT can be
stopped after 2 years

• The extra risk of developing breast cancer on HRT
does not persist beyond about 5 years after stopping
treatment.
• Women taking HRT diagnosed with breast cancer are
less likely to have tumours with metastatic spread
and therefore have an improved prognosis.
• Regular mammography is indicated for women on
HRT after 50 years old.
• There is no indication to arrange mammography
routinely for women commencing HRT under the age
of 50 years.

Monitoring of women on HRT
• Compliance of treatment, symptoms
control, side effects and bleeding pattern
• Cervical smear

Monitoring of women on HRT
Visits Tests
First History and physical examination,
Blood pressure, FSH/LH, lipid profile,
liver function test, bone biochemistry,
mammography and urinanalysis
At each visit Blood pressure
Urinanalysis
Every 2 years Physical examination, lipid profile,
liver function test, determination of
fasting glucose level, mammography
As indicated Bone mineral density

Latest reviews-2013 IMS recommendations
• HRT is an effective treatment for the prevention
of fracture in at risk women before age 60 years
or within 10 years after menopause
• Randomised clinical trials (RCT) and observational
data as well as meta-analyses have provided
strong evidence that standard dose estrogen
alone HRT decreases coronary disease and all
cause mortality in women younger than 60 years
of age and within 10 years of menopause.
• Data on estrogen plus progestogen in this
population show a similar trend but with less
precision

• HRT does not cause an increase in coronary
events in healthy women less than 60 years of
age or within 10 years of menopause
• The risk of venous thromboembolism (VTE) and
ischemic stroke increases with oral MHT but the
absolute risk is rare below age 60 years.
• Observational studies point to a lower risk with
transdermal therapy

• The risk of breast cancer in women over 50 years
associated with MHT is a complex issue
• The increased risk of breast cancer is primarily
associated with the addition of a progestogen to
estrogen therapy and related to the duration of use
• The risk of breast cancer attributable to MHT is small
and the risk decreases after treatment is stopped.
• There is a lack of safety data supporting the use of
MHT (estrogen therapy(ET) or estrogen progestogen
therapy (EPT)) in breast cancer survivors.

Alternatives…
• Lifestyle Changes
• Dietary changes & supplements
• Complementary therapies
• Drugs

Life Style Changes
• Avoidance of Triggers for Vasomotor Changes
• Avoidance of Risk Factors for osteoporosis
• Exercise

Multivitamins
• Vit E: 400-1200 IU daily
– Reduces VM symptoms
– Reduces the risk of CHD (100 IU daily for 2 years)
– Low level of Vit E is a better predictor of CHD than
elevated cholesterol or blood pressure

• Vitamin D: 400 IU daily with calcium
significantly reduced fracture risk
• Oily fish eaten at least twice a week reduced
mortality from CHD
• Garlic: reduction of cholesterol is doubtful

Minerals
• Adequate calcium intake: 1500 mg daily: reduction
of hip fracture
• Adequate intake of magnesium is crucial for
osteoporosis prevention
• The dietary ratio of calcium to magnesium is best
maintained at 2:1.
•

Selective Estrogen Receptor Modulators
(SERM)
SERMs are compounds that engage the estrogen receptors and
– exert estrogen agonist effects in desired target tissues such as bone and
the cardiovascular system
– together with estrogen antagonism (or clinically neutral effect) in the
reproductive tissues such as the uterus and breast. this is differential
activity in human tissues.
– Tamoxifen: Is a first generation SERM.
– Raloxifen: Is a benzothiophene derivative and comes closer to be the
ideal estrogen.
• It displayes activity against breast cancer comparable to tamoxifen,
selectivity inhibited uterine tissues, and simultaneously maintained bone
density and favorable serum lipid profile,
• yet failed to control postmenopausal vasomotor symptoms and even may
exagerate them..

Tibolon
• Tibolon is a steroid with tissue-specific activities which has the
capacity to exert estrogenic or progestogenic/androgenic
effects, depending on the tissue substrate.
• These tissue-specific properties of tibolon enable it to act in
specific parts of the body like an estrogen:
– Providing effective relief of climacteric symptoms.
– Preventing osteoporotic bone loss.
– Having beneficial androgenic effects on mood and libido.
• Tibolon has the following advantages:
– On the endometrium: It does not act as an estrogen. Therefore does
not stimulate endometrial proliferation. In contrast to conventional
HRT, the use of Tibolon does not require the addition of a progestogen
to induce regular withdrawal bleedings to limit endometrial
proliferation, nor to protect against endometrial hyperplasia.
– On the breast tissue: It does not act as an estrogen in breast tissue.
This leads to low incidence of breast tenderness and causes no
increased mammographic density.

Natural hormones
A. Phytoestrogens [Derived from plants ]
– Asian women experience fewer menopausal symptoms than
western women & their traditional diet contain high level of
phytoestrogens, about 200 mg daily compared with < 5 mg
daily in western diet.
• Types
– Isoflavones: soya beans (richest source), chick peas, lentils
– Lignans: apples, stone fruits, onion, garlic, seed oils, cereals,
fruit & vegetables.
– Coumestans: clover
• Available in:
– tablet (Klimadynon=cimicifugae)
– food supplements in bread,
– snack bars,
– health drinks.

Natural progestagen creams
• Extracted from: plant source, mainly yams &
soya.
• Effects: An improvement in vasomotor
symptoms but no effect on bone

Osteoporosis
• Most debilitating sequelae of menopause
• Risk assessed by BMD
• DEXA is used –spine radius and hip
• T score
• +2.5 to -1=normal
• -1 to -2.5= osteopenia
• Less than -2.5=osteoporosis

For prevention & treatment of
osteoporosis
Non pharm
• Calcium vit D
• Physical activity exercise
• Cessation of smoking
Pharm
Hrt
• Bisphosphonates
– Alendronates
– Residronates
• Raloxifene and other SERMs
• Tibolone

Prevention of Osteoporosis
• 10 years after HRT has been stopped, bone
density and fracture risk are similar in women
who had used HRT and those have not
• Long term treatment (>10-15 years) is required
to prevent osteoporosis
• Constant reassessment (general health, risk
factors and life expectancy) is required.

Summary
• Menopause provides an excellent
opportunity for the woman to see a doctor
and discuss about her own health
• Health education
• Promotion of healthy life style

Thanks for being with
me
&
God bless you all
Queries to;
drrejimohan@gmail.com,
9447044485

Hrt menopause

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