Step by step menopause hormone therapy by Dr Alka Mukherjee

A Step by Step Guide to
Menopausal Hormone Therapy
DR ALKA MUKHERJEE
MBBS DGO FICOG FICMCH PGDCR
PGDMLS MA(PSY)
Dr Alka Mukherjee Nagpur 1

Steps
Step 1 - Assess if MHT is right for the patient
Step 2 – Hormonal therapy options
Step 3 – Starting MHT treatment
Step 4 – Follow-up
Step 5 – Stopping treatment

INTRODUCTION
• Menarche is achieved earlier; the age at the menopause has
not changed. A woman now expected to spend nearly 40% of
her life span after menopause.
• Perimenopause and menopause is a complex endocrine
process- oestrogen deficiency.
• HRT - effective relief from VMS & improves QOL
• HRT used in early menopause offers an important preventive
role in osteoporosis and coronary heart disease.
• HRT was first available in the 1940s but became more widely
used in the 1960s, creating a revolution in the management of
the menopause.

CONCERNS OVER THE SAFETY OF HRT – A HISTORY
• 1990s - 1. clinical randomized trial in the USA (WHI)
• 2. Observational questionnaire study in the UK (MWS)
• The results of these two studies - raised concerns regarding the safety of HRT.
• 1) that the extended use of HRT may increase the risk of breast cancer and
• 2) that the use of HRT may increase the risk of heart disease.
• After the results were published, the UK regulatory authorities issued an urgent safety
restriction - doctors should prescribe the lowest effective dose for symptom relief, should
use it only as a second line treatment for the prevention of osteoporosis, and advised
against its use in asymptomatic postmenopausal women.
• There remains widespread confusion and uncertainty amongst both doctors and HRT users
- almost a generation of women - denied the opportunity of improved quality of life during
their menopausal years.
• The women studied in the WHI were North American women in their mid-sixties, often
overweight and thus totally unrepresentative of women in the UK for whom HRT might be
considered suitable.
• Subsequent publication of the full WHI results showed the
• 1. apparent increased risk for breast cancer was only found in those who had taken HRT
before entering the study.
• 2. WHI studies have shown no increase in heart disease in women starting HRT within 10
years of the menopause.

PARADIGM SHIFT IN USE OF HRT – 1994 TILL 2020
PARAMETER EARLY NOW
HORMONAL THERAPY ALL SELECTIVE
PERIOD LONG TERM SHORT TERM
CVD PROTECTION ALL AGES  RISKS ARE MORE & NOT TO BE
SOLELY FOR PRIMARY OR
SECONDARY PREVENTION OF CVD
REGIMEN STD COMBINATION, FIXED DOSE,
CONTINUOUS COMBINED REGIMENS
NATURAL E & P COMBINATIONS,
TAILORED DOSE, LOW DOSE &
MINIMUM EFFECTIVE THERAPY
ROUTE ORAL PREFERABLY TRANSDERMAL
BREAST CANCER ALL WITH E ALONE – NO RISK
USE OF NATURAL P MAY NOT
INCREASE THE RISK OF BREAST CA
1st prescription – sheep’s ovaries given in sandwich to ovarian
extracts!

PHYSIOLOGY OF MENOPAUSE
Loss of ovarian sensitivity to
gonadotropin stimulation - follicular
attrition - the oocytes in the ovaries
undergo atresia throughout a
woman’s life cycle - decline in both
the quantity and the quality of
follicles.
The variable menstrual cycle length
during the menopausal transition
(mt) is due more to a shrinking follicle
cohort size than to follicle failure.
Anovulatory cycles and absence of
cyclicity – common
Highly variable pattern of
gonadotropin and steroid hormone
production, estrogen insensitivity,
failure of the luteinizing hormone (lh)
surge, the occurrence of the final
menstrual period, and permanent
amenorrhea.

MHT indications
• Vasomotor symptoms
• Urogenital atrophy – vaginal ET
• Bone health – prevention & t/t osteoporosis
• Menopause transition phase for relief phase
• Recurrent attacks of atrophic vaginitis
• RECURRENT UTI in menopause
• POF/early menopause
• Gonadal dysgenesis
• Surgical/radiation menopause
8
Step 1
Assess if MHT is
right for the patient
Dr Alka Mukherjee Nagpur

CONTRAINDICATIONS OF HT
• Active Endometrial And
Gynecological Hormone
Dependent Cancers
• Active Breast Cancer , Estrogen
Progestogen Receptor Positive
Cancers.
• Knows Or Suspected Pregnancy
• Undiagnosed , Abnormal Vaginal
Bleeding
• Severe Active Liver Disease With
Impaired Or Abnormal Liver
Function
• Previous Personal Or Family
History Of Venous
Thromboemblism
• Systematic Lupus Erythematosus
• Migraine headaches
• Superfical thrombophlebitis
• Strong family history of
breast cancer
• Uterine fibroids
• Endometriosis
• Gallbladder disease
• The use HT has been
proposed in selected case of
ovarian cancer that are
suffering from and are at a
high risk of debilitating
menopausal symptoms.
RELATIVE
CONTRAINDICATIONS

• There are more than 50 types of HRT available:
• Cyclical HRT mimics the normal menstrual cycle. Oestrogen is taken every day
and progestogen for 12 to 14 days.
• Estrogen alone – post-hysterectomy
• In continuous combined therapy HRT (CCT) combinations of an oestrogen and
progestogen are prescribed continuously to achieve period-free HRT. Usually,
women start on cyclical HRT and change to CCT later
• Tibolone/Raloxefene – (SERM) is a synthetic form of period-free HRT which may
have similar benefits to CCT. It is taken continuously in tablet form
• Long cycle HRT uses a formulation which causes withdrawal bleeds every three
months instead of every month, and is most suited to women who suffer side
effects when taking a progestogen. Its safety in long-term use with regard to the
endometrium is questionable
• Local oestrogen, such as vaginal tablets, creams, or rings, is used for treating local
uro-genital problems, such as dry vagina, irritations, bladder problems or
infections.
Step 2 - Hormonal therapy options

ESTROGEN THERAPY
• Oestrogen - the primary active component of HRT
• ‘Gold standard’ menopausal symptoms, especially VMS
• Conjugated equine estrogens (CEEs) and oestradiol valerate
Estrogen preparation Route of administration Bone sparing or commonly used dose
Conjugated Equine Estrogen
(Premarin)
oral 0.625 mg/24h
Micronized E2
(Estrace and others)
Oral 1 - 2 mg/24h
E2 valerate
(Progynova)
Oral 2 mg/24h
Ethinyl-E2
(Estinyl and others)
(also constituant of most oral
contraceptives)
oral 0.01 mg/24h
Transdermal E2 "patches"
(Estraderm and other newer products)
transdermal
0.05 mg/24h
3.5 day or 7 day "patches"
Percutaneous E2 gel
Oestrogel and other newer gels)
transdermal
1.5 g of gel containing approximately 0.05
mg of E2
ESTROGEN – In HRT regimens – administered at doses set to protect bone in order to avoid
osteoporosis, for each estrogen preparation available, the minimal effective dose on bone has
been determined..

• Natural estrogen
• Safer than its synthetic counterpart
• Micronized form: Increased dissolution and bioavailability
• Esterified preventing extensive first pass metabolism in liver and GIT
• Convenient oral administration
• Is safe even for long-term use (adherence is good even after 7 yrs. of
therapy)*
ESTRADIOL VALERATE: MOST TRUSTED FORM OF ESTROGEN
When a tablet of crystalline estradiol is administered orally, very low
estradiol levels appear in the systemic circulation; In order to
improve its absorption, the process of Micronization was developed,
in which crystalline estradiol is broken down to minute particles -
Results in increased surface area & hence, enhanced dissolution,
thereby improves absorption, and consequently bioavailability and
clinical efficacy of estradiol valerate
Women using oral conjugated equine estrogens (CEE) had more
than twice the risk of venous thromboembolism observed in
women using oral estradiol

E2V VS CONJUGATED EQUINE ESTROGENS
Parameters Estradiol Valerate Conjugated Estrogens (CE) Comments
Source Natural Pregnant mare’s urine product
Estrogenic activity Estradiol valerate contains the
most active estrogen i.e 17-
estradiol.
CE contains 52 –61% of estrone that is
1/3 of Estradiol activity.
CE also contains unknown ingredients.
Ten hormones present in CE are chemically
different from female hormones.
Unknown ingredients may cause any possible
adverse effect.
Mammographic
density
No significant effect1 Significant increase in mammographic
density 2
Increase in mammographic density may be a
concern as it is a predictor of cancerous growth
in the breasts.
Blood Pressure
(BP)
No effect on renin-aldosterone
system.
Stimulates the liver production
angiotensinogen, therofore increases
BP
CE by stimulating renin-angiotensin system is
associated with the risk of hypertension.
Coagulation Factor No effect on factor VII  factor VII CE ( by  factor VII) may cause abnormal
increase in clotting of blood.
Parameters Estradiol valerate Conjugated estrogen (CE) Comments
Vasomotor symptoms Hot flushes, severe throbs,
and breast tenderness is
lower 3
Presence of vasomotor
symptoms are higher with CE
EV could be an option that is better
accepted by postmenopausal women. It is
the drug approved by US FDA for such
condition.
Lipid profile and
cardioprotective effect
Offers favorable lipid profile4 Lesser favorable lipid profile. EV has better bioavailability and therefore,
is a better option in dealing with concerns of
postmenopausal cardiovascular protection
Endothelial function EV improves endothelial
function and reduces plasma
levels of endothelin-15
Vasoprotective effect not
reported
EV has fast effects on endothelial function
thus acutely vasoprotective
Plasma homocysteine
level
EV has no effect on plasma
homocysteine level6
Effect on homocysteine level
not reported
Homocysteine is a risk factor for CHD. EV
reduces the risk of CHD

Indication — All women with an intact UTERUS
Not needed post-hysterectomy
DOSES - oral natural micronized progesterone (200 mg/day for 12 days/month
(natural progesterone is safer for the cardiovascular system)
MPA; 2.5 mg daily ( MPA is endometrial protective, but with excess risk of
coronary heart disease (CHD) and breast cancer when administered with
conjugated estrogen in the WHI.
• Frequency — women taking standard doses of estrogen require
progestins/mth
• Quarterly progestin administration is not considered to be adequately
protective and cannot be recommended
• Women taking lower doses of estrogen (eg, 0.014 mg transdermal estradiol -
require very little progestin (two 12-day courses every six months).
• Vaginal progesterone inserts
PROGESTINES

ROUTES
• Transdermal benefits –
• Steady level of plasma estradiol
• Avoids hepatic 1st pass
• No significant increase in
triglycerides, CRP, SHBG
• Little effect on BP
• Lower risk of DVT,Stroke,MI
Transdermal E – as 1st line
Triglyceredemia, Hyperlipidemia
Increased CRP, Migraine
DM, Controlled HT
Existing GB Disease, Obesity
Smoking, Previous VTE
Varicose vein, Personal preference,
Tobacco users
Duration – premature menopause – till
natural age of menopause. – shared
decision
Natural menopause – safety data for
CEE+MPA is 3-5yrs; for E – 7 yrs with 4 yrs
follow up – shared decision
ORAL E – More powerful effect on lipid
metabolism – cardio-protective
Urogenital – local application
The blood levels of estradiol are well
below the postmenopausal range, P
need not be added even in women with
uterus

The presence of risk factors
not necessarily preclude use
of HT and can inform
treatment selection

Step 3
Starting MHT
treatment
Uterus intact
A. Oral E plus oral P
B. Combined transdermal (E+P) patch
Post hysterectomy
First line
management
A. Oral E
B. Transdermal E patch or gel
 HT be started as soon as menopausal signs or symptoms appear which, in
most women, is between 45 and 55 years of age
 Women with primary ovarian insufficiency require earlier and continued use
of HT (at least until the normal age of menopause) to protect against
associated postmenopausal chronic diseasesDr Alka Mukherjee Nagpur 18

ASSESS THE PROFILE OF THE WOMAN TO INDIVIDUALIZE TREATMENT
1. Detailed history
2. Type & stage of menopause
SN TYPE TREATMENT
1 SURGICAL E ALONE/TIBOLONE
2 PERIMENOPAUSE CYCLICAL P/OCP/HT
CYCLICAL(continuos combined regimens should not be used
– high risk of irregular bleeding )
3 EARLY MENOPAUSE<12 MTHS EPT (MORE ESTROGENS) SEQUENTIAL
4 LATE MENOPAUSE<12MTHS EPT CONTINUOUS COMBINED/TIBOLONE
(LOWEST ESTROGENS/TRANSDERMAL)
5 PREMATURE OCP/HT SEQUENTIAL REGIME
6 UROGENITAL ATROPHY LOCAL E
3. Evaluate woman’s need & preference
SN AGE FACT ABOUT HT
1 < 50 BENEFITS FAR OUTWEIGH THE RISK & HT SHOULD BE
OFFERED
2 50-60 WITH MENOPAUSAL SYMPTOMS BENEFITS OUTWEIGH THE RISK
3 >60 BENEFITS = RISK, INDIVIDUALIZE
4 >70 RISK OUTWEIGH THE BENEFITS
4. Evaluation of woman’s individualized risk factors

 Timing – window of opportunity – start early – to maintain estrogen benefits
 HT EFFECTIVE in preventing CVD – if started within 10 yrs of menopause
 Risk with low dose E/HT – VERY LOW- if started within 10 yrs / <60yrs
 Women with CVS/THROMBOTIC RISK FACTORS/ initiating HT >60 YRS, >10YRS since
menopause/ SIGNIFICANT OBESE – LOW DOSE TRANSDERMAL E/HT
 Early/perimenopause – initiation of HT - t/t of menopausal symptoms – low risk
b) Time since menopause
• Co- morbidities – DM, BP, HEART DISEASE, METABOLIC SYNDROME, STROKE, BREAST
CANCER, ESTROGEN DEPENDENT CANCERS, OBESITY, GENETIC ETC
• Benefit stratification – quality of life , severity of symptoms, bone health, CV health,
mood & cognition
• Physical examination – P, BP, Ht, Wt, breast, pelvic
• Investigations – CBC, URINE-R, FBG, LIPIDS, TSH, PAP, TVS, MAMOGRAM
• EYE CHECKUP – refractory errors, retina, I-O pressure
• Based on results – classify:
a) Symptomatic/asymptomatic
b) Healthy with no risk factors
c) Healthy with risk factors
d) Healthy with latent disease
e) With overt disease
• Endometrial surveillance is not
necessary in low risk
asymptomatic women.
• Unscheduled bleeding should be
investigated by an ultrasound and
endometrial biopsyDr Alka Mukherjee Nagpur 20

Cyclical/ Sequential MHT
12 months
Trial of continuous
BTB
Further 12 months cyclical MHT
Continuous MHT
• Screening testes and an annual follow – up are essential when prescribing
HT. The dose and duration of use of HT Should be individualized and a risk –
benefit assessment carried out annually.
• A Full gynecological assesment is mandatory prior to starting examination is
advise monthly and clinical breast examination at least annually. A
mammogram / ultrasound where available should be carried out 1 – 3
yearly , if the initial mammogram is normal

HORMONE TREATMENT IN HYSTERECTOMIZED WOMEN
Only E replacement - necessary.
Special conditions – use of combined E+P
Residual Endometriosis, Following Radical Surgery, Subtotal
Hysterectomy ,, Stage ONE OR TWO - Adenocarcinoma Of Endometrium
(E+P) Immediate Postop , Previously Treated For Endometroid Tumours
Of The Ovary, Post Endometrial Ablation
Micronized P / Dydrogesterone Or Tibolone

OSTEOPOROSIS
• HT – 1st line therapy for the prevention & treatment for the bone loss %
fractures.
• Increase In Life Expectancy – Protection Against Hip Fracture & Coronary
Artery Disease
• HT should no be started solely for bone protection after 10 years of
menopause. Extended use of HT in women with reduced bone mass -
consider the risk benefit analysis compared to the other available
therapies for osteoporosis.
• The bone protective effect is lost after stopping HT (Level B).
• Estradiol 1 mg/CEE 0.45mg/25microgm estradiol transdermal
patch/1.25mg Tibolon
• Estrogens may have a protective effect on osteoarthritis (GRADE B).
• Estrogen benefits verbal memory over the short period when initiated soon after
surgical menopause (GRADE B).
• HT reduces the neo-vascular macular lesions (GRADE C).
• HT in the early menopausal period improves QOL by its effects on vasomotor uro-
genital symptoms improvement on sleep , and mood (GRADE B).

Vasomotor symptoms
• E - highly effective – HOT FLUSH - blood level dependent and route of
administration independent.
• In women - high incidence of HF (> 10 HFs/day – HIGH DOSES OF E
(higher than minimal bone sparing doses) are necessary to correct
menopausal symptoms or adjunct effect of P necessary.
• Sleep disorders - E
• Younger women/ premature menopause require higher E doses to
match their level of activity.
• Improvement in quality of life . Short-term (up to 5 years) and longer-
term benefits and risks.
• E and P - women with a uterus, E alone - women without a uterus.
• NO ROUTINE - selective serotonin reuptake inhibitors (SSRIS),
• Isoflavone, black cohosh
Altered sexual function - Testosterone supplementation for
menopausal women with low sexual desire if HRT alone is
not effective. Dr Alka Mukherjee Nagpur 24

PSYCHOLOGICAL SYMPTOMS
• To alleviate low mood - E - MAINLY
• CBT
• No clear evidence for SSRIs or SNRIs
• Effect is greater for peri-menopausal symptomatic
• women than the postmenopausal women (Grade A)
• The likelihood of HRT affecting their risk of dementia is unknown.
Loss of muscle mass and strength
• There is limited evidence suggesting that HRT may improve muscle mass and
strength
• Urogenital atrophy – HRT oral/transdermal/vaginal - most appropriate if No
relief– increase the dose - Adverse effects very rare
• They should report unscheduled vaginal bleeding
• Vaginal dryness - moisturizers and lubricants can be used alone or in addition
to vaginal oestrogen
Recurrent UTI - LOCAL E - Urge incontinence decreases with E
Stress incontinence may worsen
Do not offer routine monitoring of endometrial thickness during treatment for
urogenital atrophy.

INSULIN RESISTANCE
 Oestradiol is a master regulator of body and brain bioenergetics.
Specifically, oestradiol facilitates the action of insulin, whereas
menopausal loss of oestradiol increases insulin resistance
 Menopausal HT should be recommended to women with type 2
diabetes, or a family history of diabetes, as it reduces progression and
delays the appearance- orally or transdermal
 HT (conjugated equine estrogens – medroxy – progesterone) was
associated with a decrease in the risk for type 2 diabetes(GRADE B)
 Menopausal HT can improve recent-onset hypertension, with
enhanced response to antihypertensive drugs
 In women with aggressive postmenopausal hypertension, the
option to start transdermal HT should be discussed with a
cardiologist
HYPERTENSION

DYSLIPIDEMIA
 Transdermal menopausal HT is preferred in women with dyslipidemia
• Oral Estrogens - documented to increase cholesterol-HDL and lower
cholesterol-LDL levels.
• The impact of estrogens on lipids - There is direct vascular effects of
estrogens - blood level dependent and therefore independent of the
route of administration selected.
HT & CVD
• MATTER OF DEBATE
• Observational studies including Nurses’ health study had suggested that
postmenopausal hormone Therapy was associated with a reduction of 40-50
% of the risk of CHD; despite a wealth of observational evidence, there have
been few RCT s to support these findings .
• They found that treatment with 1 mg of 17B –estradiol daily for 2 years was
associated with reduced progression of subclinical atherosclerosis , as
assessed using carotid artery intima media thickness (IMT).

Recommendations for use of hormone therapy in symptomatic
menopausal women with risk factors*
Age >60 years or more
than 10 years since onset
of menopause
 For current users of HT with an established reduction/disappearance
of symptoms and improved quality of life, HT can be continued at an
appropriate dose (lowest effective dose) for an appropriate time if no
new contraindications emerge
 For never-users of menopausal HT due to inadequate communication
of risks and benefits, for whom HT is indicated, and in the absence of
major contraindications, treatment with transdermal oestradiol (either
25 mcg patch or gel, 1 puff per day) and vaginal progesterone (either
100 mg in the evening continuously or 200 mg in the evening for 14
days a month) is preferred. If other risk factors are present, vaginal
treatment with oestradiol or oestriol is preferred

 As elevated oestrone production from adipose tissue increases the risk of
proliferative endometrial lesions, protecting the endometrium with
progesterone or progestogens (e.g. levonorgestrel or dienogest intrauterine
system) is a priority.
 Add low-dose transdermal oestradiol individual basis
 HT decreases the abdominal obesity (GRADE B).
 Lifestyle improvements – wt reduction
OBESITY (BMI > 30 MG/M2)
 Women who smoke should be counseled to quit while also increasing daily
aerobic exercise in order to improve endothelial function, reduce hypertension
and, if relevant, reduce the risk of weight gain
 For women who are not quitting - vaginal HT
 In selected cases - systemic HT may be considered
 (the woman should be fully aware of the higher
independent cardiovascular risk due to smoking)
SMOKING

• If patient complains of :
 migraine appears for the first time
 of if headache gets worsened ,
 blurring of vision
 or any symptoms suggesting of vascular occlusion
 jaundice appears,
 If there is significant rise in blood pressure
• HRT to be stopped 4 – 6 weeks before elective surgery
STEP 5 - STOPPING TREATMENT

THR MOST COMMON REASON FOR DISCONTINUATION OF HRT
– ABNORMAL UTERINE BLEEDING
Unscheduled vaginal bleeding is a common side effect of HRT within the
first 3 months of treatment but it should be reported at the 3-month
review appointment, or promptly if it occurs after the first 3 months
Usually transient: carries no risk
Offer women who are stopping HRT a choice of gradually reducing or
immediately
Most common reasons for AUB in HRT :
1. Incorrect use of HRT by patient
2. Lack of synchronization with endogenous ovarian function
3. Suboptimal E + P combination (excess E/continous regimen in a
premenopausal or shortly after menopause )
4. Endometrial atrophy
5. Previously undiagnosed – endometrial polyp, hyperplasia/ ca/
fibroid or atrophic vaginitis
Only 1 in 5 patients continue HRT for 2 yrs.

• HRT increases VTE risk by two – fold (GRADE A).
Standard dose oral HRT increased stroke risk by
about one – third in generally healthy
postmenopausal women (GRADE B).
• The risk increases with woman’s age,
BMI>30kg/m2 (3 fold), & Estrogen dose; highest
during 1st year of HRT, More with oral HRT than
transdermal HRT
• Low dose ET may not increase the risk of stroke
(GRADE C).
• H/O Thrombophilia – personal/family & blood
coagulation profile
HRT AND VTE & STROKE

HRT AND BREAST CANCER
• Concern about the relationship between HRT and breast cancer is due to
the presence of receptors for sex hormones in the breast.
• Estrogen increases the risk of breast cancer after more than 5 years of use ,
particularly in recently postmenopausal women (Level B).
• Increased risk dissipates within 5 years of discontinuing The HT (Level B).
• Use of estrogen for less than 5 years may reduce the risk especially in
women who start HT many years after menopause (Level B).
• Tumors in HT used women are usually ER positive and lobular type (Level
G).
• The benefits of hrt (such as prevention of osteoporosis and reduction of
cardiovascular disease) clearly outweigh the possible cancer risks.
• E + P Particularly with synthetic progesterone's increase the risk of invasive
breast cancer within 3 – 5 years of initiation and increases progressively
beyond that time (Level B).
• Progesterone (Micronized Progesterone / Dydrogesterone) With Estrogen
Does Not Increase The Risk If Given For Less Than 5 Years (Level C).
• With regular screening with mammography and annual breast
examination, HRT can be considered safe with regard to breast cancer risk.

ENDOMETRIAL CANCER
• Endometrial epithelium contains sex steroid receptors, and risk
factors for endometrial carcinoma are closely related to the
presence of both endogenous and exogenous female sex
hormones.
• Endometrial hyperplasia can and does develop in women not
exposed to any exogenous hormones, but it can also develop in
women receiving HRT or oestrogen replacement therapy (ERT).
• Endometrial carcinoma occurs almost exclusively after the
menopause.
• Administration of unopposed ERT to postmenopausal women
increases the risk of endometrial cancer
• After receiving conjugated oestrogens for about 18 months, more
than 30% of women develop hyperplasia. In many cases, this
progresses to adenomatous or complex hyperplasia with atypia,
and some women may even go on to develop endometrial cancer.
• Using a combination of oestrogen and progestogen for 10–13 days
of each cycle appears to decrease the risk linked to the use of
oestrogen alone. Dr Alka Mukherjee Nagpur 34

OVARIAN CANCER
• The ovaries produce oestrogens and progesterone and thus contain sex
hormone receptors.
• However, it is still not clear whether there is a connection between ovarian
cancer and sex hormones.
• Pregnancy and the use of oral combined contraceptive pills decrease the
risk of ovarian cancer
• The incidence of ovarian cancer increases after the menopause until the
age of 65 The hypothesis for this is either the decreased number of
ovulations (during pregnancy) or the decline in serum gonadotropin levels
• Although it is certain that the use of oral contraceptives reduces the risk of
ovarian cancer, there is still no consensus on the effect of HRT. Thus most
doctors would be reluctant to prescribe ERT to women who have been
treated for ovarian cancer, as 60% of ovarian cancer cells contain
oestrogen and progestogen receptors and the increased risk of ovarian
cancer due to ERT cannot be excluded.
• HRT/ERT should be prescribed cautiously in women in clinical remission
from ovarian cancer.
• Prescription should only be for serious climacteric symptoms, osteoporosis
or reduction of cardiovascular disease.

• Colorectal cancer
• In the WHI, women who took combined
estrogen-progesterone therapy had a lower
risk of getting colorectal cancer.
• However, the cancers they did have were
more likely to have spread to lymph nodes
or distant sites than colorectal cancer in
women not taking hormones

• Cervical cancer
• Although the cervical epithelium contains sex hormone receptors and
undergoes changes under their influence, no relationship has ever been
demonstrated between sex hormones and cervical cancer.
• Studies showed that the concentration of oestrogen receptors did not
differ in women with normal or abnormal cervices.
• HRT may be prescribed to women with cervical cancer if indicated.
• Cancer of the vulva and vagina
• Vulval and vaginal cancers can also be influenced by exogenous
hormones.
• They generally occur at an advanced age, although younger women can
occasionally be affected.
• Sex hormone receptors are present in the vulva and vagina.
• No relevant information is available about any correlation between HRT
and these types of cancer, which are almost exclusively of the squamous
cell type.

HRT & PRE-EXISTING CONDITION

FOLLOW UP
After one month - for efficacy and side effects , check
weight and blood pressure
After 3 month - to assess effects and compliance
Annually - to include a physical examination , update of
medical and family history , relevant laboratory and
imaging investigations , a discussion on lifestyle , and
strategies to prevent or reduce chronic disease .

Side effect strategy
Fluid retention Restrict salt intake, adequate water intake, exercise,
mild diuretic
Bloating Switch to low dose transdermal E, Lower P dose that
still protects the uterus/other P/Micronized P
Breast tenderness Lower E dose/switch E/P Restrict salt intake cut
down coffee, alcohol
Headaches Switch to transdermal E, Lower the dose of E &/OR P,
Switch to continuous combined regimen
Mood changes Lower P dose/switch P/IUS/
Nausea Take oral E tab with meals/bed time/other oral
E/Transdermal E/lower E/P dose

Alternatives to Hormone Therapy
Advice to adopting a healthy lifestyle
Don’t smoke,
Eat a variety of foods low in saturated fat, trans fat, and cholesterol and
moderate in total fat. Include grains, especially whole grains and a variety
of dark green leafy vegetables, deeply coloured fruit, and dry beans and
peas in your eating plan.
Maintain a healthy weight, and
Be physically active for at least 30 minutes most days of the week
Preventing and controlling high blood pressure
Preventing and controlling high blood cholesterol
Managing diabetes
dressing and eating to avoid being too warm, sleeping in a cool room, and
reducing stress.
Avoid spicy foods and caffeine.
Try deep breathing and stress reduction techniques, including meditation
and other relaxation methods.
Phytoestrogens. Soybeans and some soy-based foods

• HRT today: key points
• The balance of benefit to harm always needs to be assessed but
appears to have shifted favourably for HRT. Users can be reassured
provided:
• HRT is taken for the correct reasons, i.e. to alleviate the symptoms
of the menopause. It has a role in the prevention of osteoporosis
but long term use is often required
• HRT is taken for only as long as necessary at the lowest effective
dose
• HRT users are assessed by their GP at least once a year.
• If women start HRT around the time of menopause the risk is very
small, but there is only limited data for continued usage beyond the
age of 60. It is not usually appropriate for women over 60 to be
starting HRT, as the WHI study shows, the risks are increased, but
this does not mean that women who started HRT earlier should
have to stop it on reaching 60.
CONCLUSION

The only Estradiol Valerate in micronized form

Standard and low – dose oral and trans-dermal
estrogens
Dosage of estrogens
Estrogen Utra Low Low Standard High
Conjugated equine
Estrogens (mg) oral
0.15 0.3,
0.45
0.625 1.25
17 B – estradiol (mg) - Oral 0.5 1 2 4
Estradiol Valerate (mg) - Oral 1 2
Transdermal 17 B – estradioal 14 25 50 100
Advantage Disadvantages
Easy to take High dose required
Cheap Variation in absorption
Good Control Alters liver protein synthesis
Short Half - Life Minor side - effects
Wide Choice Daily dosage
All tablets contain lactose
Advantage and
disadvantages or
oral estrogen
therapy

Terminology defining type of EPT regimens
Regimen Estrogen Progestogen
Cyclic Days 1 -25 Last 10 – 14 days of
the month
Cyclic - Combined Days 1 -25 Days 1 -25
Continuous – Cyclic (Sequential) Daily 10 – 14 days every
month
Continuous Long Cycle Daily 14 days every 3 – 6
Month
Continuous Combined Daily Daily
Intermittent – Combined (Pulsed –
Progestogen ; C0ntinuous – Pulsed)
Daily Repeated Cycles of 3
Days on 3 Days off

Step by step menopause hormone therapy by Dr Alka Mukherjee

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