HORMONE REPLACEMENT THERAPY

Hormone Therapy (HT)

- This refers to the use of estrogens (ET), estrogens plus progestins
(EPT) and androgens (AT).

Estrogen Therapy (ET)

This refers to therapy with estrogens alone.
This term is synonymous with the term estrogen replacement
therapy (ERT).

Estrogen-Progestin Therapy (EPT) / Combined HRT

This refers to therapy with estrogen in combination with a progestin.
2 subtypes:
Sequential combined HRT: estrogen daily + progesterone on days 14-
28 (patient will still have cyclical withdrawal bleeding)
Continuous combined HRT: estrogen + progesterone daily (patient
will not have any withdrawal bleeding)
 HRT- Indications
Presence of symptoms
a. vasomotor symptoms
b. joint and muscle aches and pains Commonest presentation in
Asian women
c. sleep disturbances
d. depressed mood
e. uro-genital symptoms, vaginal dryness
f. sexual dysfunction, decreased libido
g. To maintaining and improvement of quality of life
The need for prevention of osteoporosis
a. First line for prevention of bone loss in post-menopausal women
b. For prevention of fractures in post-menopausal women who
increase risk of fracture, not recommended in women > 60 y.o
 Counselling and Decision-making
Counselled on risks, benefits, and side effects
One should also take into account the
womans own preferences and expectations.
Only after this, can the woman make an
informed, individual decision on whether or
not she would want to take HT.
 Pre-treatment evaluations
History
- medical history, relevant family history
Physical examination
weight, height, BMI, blood pressure
breast examination.
bimanual vaginal examination and cervical
cytology if possible
 Relevant investigations (depend on patient)
Mammography / sonography
Cardiovascular risk profiles including lipid profile
Diabetes screening
Assessment of bone mineral density (BMD)
Other ix : FBC, LFT, TFT & Ultrasonography of the
pelvis (based on case)
 Contraindication
Absolute Relative

Suspected pregnancy Uninvestigated abnormal

Breast cancer bleeding
Endometrial cancer Large uterine fibroids
Active liver disease Past history of benign breast
Uncontrolled disease
hypertension/diabetic Unconfirmed personal history
Known VTE or strong family history of VTE
Known thrombophilia Chronic stable liver disease
Otosclerosis Migraine with aura
 Timing of initiation
Best to start between the age of 50-59 years,
or within 10 years of the menopause
For pt age >60 y.o. HT should not be initiated
unless there is a compelling indication
For pt with premature menopause (<40y.o.),
HT should be initiated as soon as possible
 Dosage

As a principle, the lowest effective dose of estrogen consistent

with treatment goals should be used, with corresponding low
dose of pregestogen.
Lower dose of progestogen will have less negative effect on
breast cancer risk
For women with premature menopause, higher dose of
estrogen may be required for relief
 In women with intact uterus
- progestogen is added to provide endometrial
protection from unopposed estrogen and prevent
the occurrence of endometrial hyperplasia and
carcinoma
- It should be given for 12-14 days for every 28 days of
estrogen (cyclical) or with estrogen on daily basis
(continuous)
When using low dose vaginal estrogen for relief of uro-
genital atrophy, not necessary to add progestogen
Progestogen supplementation is a not generally required in
woman who has a hysterectomy, and who is on ET
 Dosage regime

The dose and regime of HT need to be individualized

Older postmenopausal women generally require lower doses then younger
women
 Routes of administration
Estrogen
Oral
Available in estrogen or estrogen and progestogen
combinations
Absorbed from stomach and duodenum
Estradiol is largely converted in the liver parenchyma
into estrone, which is then released via the hepatic
veins
Higher doses needed compared to other routes due to
first pass metabolism
Widely accepted but have a first pass effect which may
contribute to pigmentation and thrombosis
 Transdermal (patch, implant, gel)
Avoid first pass metabolism
Route of choice for women with risk factors for VTE, liver
disease or gastro-intestinal problems
Also useful in older patient with osteoporosis in whom a
very gradual build-up of oestrogen is required in order to
avoid start-up effects (breast tenderness, nipple sensitivity,
increase appetite, weight gain, calf cramps)

Subdermal implant

Transdermal patch Transdermal

estrogen gel
 Patch

Small adhesive patches, requires changing once or twice a

week
Skin irritation may be a problem but new matrix patches
and the gels are usually well tolerated
Premature detachment is common in tropical climate
 Subdermal implant (estrogen only)

Less widely used

Restricted to patient who have undergone hysterectomy
with or without oophorectomy
Positioning a pellet of E2(oestradiol) in the subcutaneous
tissue, usually at the lower abdomen or buttock
Usually reviewed at the intervals of 6 months
Tachyphylaxis (progressive decrease in response to a given
dose) is biggest disadvantage
Replace when menopausal symptoms recur
 Local vaginal preparation
Useful for symptoms originated from lower genital
tract and in the bladder and urethra such as local
vaginal dryness and symptoms of urgency
Suitable for those who are contraindicated to
systemic HRT but require estrogen for local
symptoms
Cream, pessary or vaginal tablet
 Progestogens
Is required for endometrial protection from being
overstimulated by estrogen
The progestogens used in HRT formulations
C-17 hydroxyprogesterone derivatives
Medroprogesterone acetate
dydrogesterone
C-19 nortestosterone derivatives
Norethisterone(transdermal)
Levonogestrel(transdermal,intrauterine)
Routes of administration
Oral
Transdermal
Levo-norgestrel releasing intra-uterine system
 HRT Side effects
Estrogen related Progestogen related
Fluid retention Fluid retension
Nausea Breast tenderness
Headaches Headaches
Breast enlargement Acne
Leg cramps Mood swings
Dyspepsia Depression
Irritability
Bloating
Constipation
Increased appetite

Estrogen related side effects are usually dose related and settle within few
weeks
Progestogenic side effects are more troublesome and often resemble
premenstrual symptoms, if persist, change in progestogen type may be helpful
 Duration of use
No mandatory limitation to the duration of HRT use,
especially when HRT started during menopause
transition and the women is symptoms free
Should be given as long as the women wants, if
lowest effective dose is used, the women aware of
benefits and risks and there is clinical supervision
HRT can be considered even in the absence of
symptoms where there is a need for prevention of
osteoporotic fracture and preservation of bone mass
in women with osteopenia when alternative
therapies are not appropriate
Follow up assessment & frequency
Regular follow-ups, needed for longer use
First is at 3 months (effectiveness & side effectiveness)
Then once stabilize review every 6 months later and
annually thereafter
Start at lowest appropriate dose & can be increase if there
is no symptomatic improvement after a few month
Should participate in national screening programmes of
breast, cervical & colorectal ca.
(As for mammography, if the initial mammogram is normal, 2-3 yearly mammography is
recommended)

To stop HRT should de done gradually, reducing the dose

to avoid rebound symptoms & the same time, positive
lifestyle factors should be emphasized
 Premature menopause
Women with premature menopause should
be considered as a group with special needs
compared to those with natural menopause.
Special counselling in various areas needs to
be addressed.
Premature menopause is associated with a
lower risk of breast cancer, but with a higher
risk and earlier onset of osteoporosis and
cardiovascular disease.
 HT should be started as soon as possible.
HT is to be continued until the typical natural
normal age of menopause.
Higher doses of HT may be required in these
women for symptom relief.
The risks of HT attributable to these young
women are likely to be smaller and the benefits
potentially greater than those in older women.
Nevertheless, the merits of long-term use of HT
need to be assessed for each individual at regular
intervals.
Cpg July 2010
Cpg July 2010