Philippine Society of Climacteric Medicine

POGS Building, 56 Malakas St., Diliman, Quezon City

Telefax No.: 433-9776 P.O. Box 1252, Quezon City, P.O. 1152, Quezon City

The Officers and Board Members

President
Vice President
Secretary
Treasurer
P.R.O.
Auditor
Board Members

Immediate Past President

Corazon T. Lim, M.D.

Santiago A. del Rosario, M.D.
Evelyn Palaypayon, M.D.
Eileen M. Manalo, M.D.
Lyra Ruth Clemente-Chua, M.D.
Erlinda G. Germar, M.D.
William T. Lavadia, M.D.
Esperanza Cabral, M.D.
Evelyn Gonzaga, M.D.
Edgardo Tolentino, M.D.
Julita R. Jalbuena, M.D.
Ma. Trinidad R. Vera, M.D.

Committee Members
Chairman
Committee Members

Reviewers

Ma. Trinidad R. Vera, M.D.

Leonardo A. Almeda, M.D.
Florante P. Gonzaga, M.D.
Corazon T. Lim, M.D.
Santiago A. del Rosario, M.D.
Sylvia A. Carnero, M.D.
Lyra Ruth Clemente-Chua, M.D.
Erlinda G. Germar, M.D.
Julita R. Jalbuena, M.D.
William T. Lavadia, M.D.
Lilia P. Luna, M.D.
Eileen M. Manalo, M.D.
Delfin A. Tan, M.D.
Ma. Hilaria R. Vera, M.D.

137

HORMONE REPLACEMENT THERAPY cpm 4TH eDITION

PSCM Guidelines for Clinical Practice for

Management of Menopause
MISSION STATEMENT

Hormone Replacement Therapy

The Philippine Society of Climacteric Medicine

(PSCM) believes that menopause is a state of
hormone deficiency that should be treated. Our
mission is to ensure that women receive appropriate
guidance and medical management during their
menopausal years. The purpose of these guidelines is
to provide a reference source for the evaluation and
treatment of the menopausal state. In the Philippines,
fewer than 10% of the postmenopausal women currently
receive hormone replacement therapy (HRT).

In the management of the menopausic patient, the timing

of medical evaluation and intervention is somewhat
arbitrary and dependent on the issues that prompt a
patient to seek a consultation. If the woman is apparently
fit and healthy with no complaints, it is better to leave her
at that. The most common symptoms at the time of initial
assessment of the menopausal patient are vasomotor
instability, mood swings, insomnia, decrease libido
and cessation of menses or irregular menses, usually
associated with shortening of menstrual cycles. Other
patients, because of self-education and media exposure,
consult a physician to explore their own risk factors
and the preventive health issues that HRT can address.
Despite these differences in symptoms and issues of
interest to the patient, a standard of approach should be
used for the assessment of the menopausal woman.

This documents consists of recommendations for the

clinical management of menopause and is intended
for use by physicians to support their treatment of
womens reproductive health issues. We recognize that
these guidelines should be used in conjunction with
the best clinical judgement and the patients individual
needs. These guidelines will be revised and updated
periodically to reflect the latest developments in the
management of menopause.
INTRODUCTION
Menopause is customarily defined, for statistical and
epidemiologic purposes, as the absence of menses for
1 year. This definition, however, is merely a guidepost
in an ongoing process of declining ovarian function,
usually beginning by age 35 to 40 years, with the
resultant hormone deficiencies causing progressive
systemic damage. Menopause is adult-onset ovarian
failure, with the loss of estrogens, progesterone, and
ovarian androgens.
The loss of estrogens can lead to vasomotor symptoms,
sleep disturbances, mood alterations, depressions,
urinary tract and vaginal atrophy, and increased
health risks for several chronic disorders including
osteoporosis, cardiovascular disease, and loss of
cognitive function. Thus, both the organic and
the psychologic consequences must be addressed.
Perimenopause is a clinically pre-defined interval
that begins with sporadic abnormalities or failure of
development and function of the ovarian follicles,
corpus luteum or both. It progresses to persistent
anovulation, loss of production of progesterone, and
erratic secretion of estrogen. The earliest evidence
for ovarian failure is a gradual increase in plasma
gonadotropin levels, manifesting as early as age 35 years
as a minimal elevation of follicle-stimulating hormone
(FSH) in day 2 of the menstrual cycle.

Diagnostic Evaluation
The initial consultation is not only the time for eliciting
the history, performing a physical examination, and
ordering appropriate studies but also an opportunity to
educate the patient. To make a rational decision about
whether to use HRT, the patient must have a thorough
knowledge about the benefits and risks of taking sex
hormones. In this context, the patients knowledge,
attitude and perceptions regarding menopause and
perimenopause as well as her ideas about management
must be explained to provide diagnostic perspective,
reveal biases, and present a basis for optimizing
adherence to eventual recommendations.
HISTORY

The history should routinely include the following
informations:
A detailed chronologic reproductive history including
time of menarche, gravidity and parity, history of
breast-feeding, gynecologic surgical history, and a
detailed menstrual history
History of hormonal treatment, including
contraceptives, estrogens, progesterone, and
androgens.
Detailed sexual history, including frequency of
intercourse, ease of arousal, libido, orgasm and
dyspareunia.
Symptoms of pelvic floor relaxation and bladder
dysfunction
Bone or joint pain, arthritis, fractures, osteoporosis
Loss of height

CPM 4TH EDITION

General current and past personal medical history,

family history, and social history
History of lactose intolerance and achlorhydria
History of weight fluctuations, physical activity, and
exercise tolerance
Quality-of-life assessment, psychiatric history,
premenopausal mood disorders, pre-menstrual
dysphoria and cognitive functioning.
Family history, especially of early menopause,
cardiovascular disease, osteoporosis, cancer and
dementia
Dietary history with emphasis on intake of sodium,
vitamins (especially Vitamin D) and calcium
Medications (e.g. corticosteroids)
Understanding of fears and expectation surrounding
menopause.
Physical Examination
As part of the comprehensive physical examination,
particular attention should be paid to the following:
Posture (signs related to osteoporotic compression
changes), gait, muscle tone, coordination, height and
body proportions
Body mass index, body composition, and waist
circumference
Breast examination
Pelvic examination, which should include size and
shape of the uterus and adnexal structures, evaluation
of estrogenic status of the vaginal mucosa, elasticity
and thickness of the vaginal wall (discharge, atrophy),
integrity of the pelvic floor (cystocele, rectocele) and
levator ani function
Eyesight and hearing acuity (in terms of fracture risk,
quality of life)
Laboratory Studies
1. Hormonal Evaluation
D2 or D3 serum FSH (levels of >10-12 mIU/mL)
indicates diminished ovarian reserve. Levels >40
mIU/mL is associated with menopause.
Estradiol level <30 g/mL
Testosterone, DHEAS
Serum thyrotropin (hyperthyroidism is common in
menopausal patients)
2. Special Baseline Studies
The following studies may be necessary or useful at
the time of initial assessment;
Pap Smear
Mammography
Bone Density Measurement
Assessment of Endometrium
Pelvic Ultrasound Scanning

HORMONE REPLACEMENT THERAPY

Therapy
All women should consider HRT not only as essential
replacement of missing hormones but also as a type of
preventive medicine. The risks and benefits of HRT
should be individualized in the basis of quality-of-life
consideration and a personal risk assessment, with
consideration of cardiovascular, osteoporosis, dementia
and cancer risk factors. Therefore our mission should
be to educate women and fill this void relative to the
health benefits of HRT and to convey the proper balance
of risk versus-benefit information.
The aim of the first consultation must be to ensure
that the patient has an understanding of the risks and
benefits of both short-term and long-term therapy, and
that the doctors appreciates the womans particular
needs and goals.
How long can HRT be given safely?
Although there is considerable evidence about the health
effects of long-term use of HRT, recommendations about
long-term use of HRT are more difficult. For many
women the benefits of long-term HRT use will outweigh
the risks; for others, risks outweigh the benefits. The use
then of HRT has to be tailored to the needs and desires
of the individual.
What are the long-term goals of HRT?
They are:
Relief of subjective and objective symptoms
Prevention of osteoporosis
Prevention of cardiovascular disease
Prevention of dementia
Prevention of carbohydrates intolerance
Prevention of Osteoporosis
Osteoporosis is characterized by low bone mass
and microarchitectural deterioration of bone tissue,
leading to increase bone fragility and therefore its
susceptibility to fracture. Low bone-mineral density is
associated with increase risk of fracture, and women
in the lowest quartile of bone-mineral density have
a 12-fold increased risk of hip fracture. The lifetime
risk of fragility fractures in a 50-year-old woman is
30-40%. In healthy women, there is only slight bone
loss before the menopause. The menopause induces
accelerated bone loss within 5-6 years, followed by a
linear rate of bone loss that may accelerate after the age
of 75 years. Postmenopausal bone loss is related to an
increase of bone turnover that is estrogen dependent,
even in the elderly.
Women usually begin HRT early after the menopause

HORMONE REPLACEMENT THERAPY cpm 4TH eDITION

and often stop after a few years, whereas most

osteoporotic fractures occur after age 65. Long-term
use is necessary to decrease substantially the incidence
of fractures:
Several placebo-controlled trials over 2-3 years have
shown that HRT prevents bone loss in women in
the early and late menopause. Although the size of
the effect varies between the sites measured, HRT is
effective throughout the skeleton. HRT reduces serum
& urinary markers of bone-turnover, which return to
premenopausal values. Doses of 0.625 mg conjugated
estrogens, 1-2 mg 17 estradiol, and 50-100 micrograms
of transdermal 17 beta estradiol are effective with less
than 10% of women showing bone loss. Recently, it
has been found that smaller doses prevent bone loss,
specially in the late postmenopausal period. The type
of progestogen added to the regimen does not affect
the skeletal response to estrogen, with the exception
of some compounds with androgenic effects, such as
norethisterone acetate which has an anabolic effect on
bone tissue. Current use of HRT, specially long-term
use, is associated with a 30-50% reduction of hip, spine
and waist fractures, but past users are not protected.
After HRT is stopped, bone loss resumes within a year
and bone turnover increases to the level of untreated
women within 3-6 months which probably accounts
for the lack of fracture protection in past users. The
addition of calcium and of Vitamin D to HRT, maybe
beneficial, specially in elderly women. The combination
of HRT with either another antiresorptive drug (such as
a BIPHOSPHONATE) or a bone-forming agent is an
interesting possibility that should be explored.
Cardiovascular Disease
Cardiovascular disease remains to be the leading cause
of mortality among Filipinos (39.4%) with coronary
heart disease as the single leading cause of death and
significant cause of morbidity among women.
Although a cause and effect relations is not proved,
evidence that HRT lowers the risk of coronary heart
disease in women without a history of this disease is
sufficiently strong to consider this potential benefit when
deciding to use HRT.
HRT raises the risk of venous thromboembolism, but the
absolute risk is small in women without predisposing
conditions.
Several meta-analysis of observational studies have
demonstrated a 35-50% lower relative risk (RR) of
cardiovascular mortality in HRT users relative to
non users.
The mechanism of estrogen-related cardiovascular

protection include the following factors:

1. improved lipid profile, with increased high-density
lipoprotein (HDL) cholesterol, decreases low density
- lipoprotein (LDL) cholesterol and decrease total
cholesterol.
2. potentiation of endothelium - derived relaxing
factors (nitric oxide) leading to coronary artery
vasodilitation.
3. antioxidant effect in LDL cholesterol, reducing plaque
formation
4. reduction of serum fibrinogen
5. calcium channel blocking effect
6. increased prostacyclin biosynthesis
The one completed large randomized trial is HERS
(Heart and Estrogen/Progestin Replacement Study
published in 1998), a trial among women with coronary
heart disease. Continuous combined therapy of 0.625
mg conjugated estrogen and 2.5 mg MPA was compared
with placebo. Over a mean of 4.1 years follow up,
this trial reported no net effect of HRT on recurrence
of coronary heart disease, but there was a significant
trend for decreasing risk with longer duration. Risk was
unexpectedly substantially increased in the first 4 month
in the HRT group, followed by a decline to a relative
risk of 0.67 in the final 2 years. The same pattern of
an early increase in risk, followed by a late decrease,
was found in the setting of secondary prevention in
the Nurses Health Study Control. These findings raise
concern about prescribing hormones to women with a
prior myocardial infarction, but do suggests long term
benefit.
The effects of HRT on stroke risk are uncertain. The
weight of evidence suggests neither a decrease nor an
increase in risk.
Dementia
Dementia (loss of intellectual functioning) affects 10%
of women older than 65 years and 50% of women older
than 85 years. Alzheimers diseases is 2 to 3 times
more likely to develop in women than in men. The
risk of developing Alzheimers disease is 50% lower
in ever users, than in one users of HRT (RR=0.5) This
effect crosses genetic phenotypes and socio-economic
class; however, lower biologic intelligence increases
the risk for Alzheimers disease. A meta-analysis of the
observational studies of the effect of estrogen therapy
on the risk for developing dementia did support a 29%
decreased risk among estrogen users. If validated by
scientific studies, the risk reduction would be of major
public health importance.
The role of HRT in the treatment of Alzheimers Disease
is still highly debatable. What is known is that it is
more putative rather than curative. It can ameliorate

CPM 4TH EDITION

symptoms of dementia by increasing cerebral blood

flow and glucose utilization, at the same time lessen
anti-inflammatory effects of the degradation products
of beta-amyloid proteins. It is a mood stabilizer in
that it enhances the production of nor-adrenaline, the
deficiency of which is implicated in certain types of
depression.
Prevention of Carbohydrate Intolerance
The menopause is a diabetogenic state. After the
cessation of menses, reduced levels of estrogen are
associated with an increase in insulin resistance. Insulin
resistance in turn and the resultant hyperinsulinemia
predispose to lipid abnormalities and increase the
risk of atherosclerosis. This helps explain the close
association of diabetes mellitus with coronary heart
disease. About a decade ago, diabetes mellitus was
considered one of the relative contraindications for use
of hormone replacement therapy. Recent data suggest
that use of hormone replacement therapy is safe for the
postmenopausal diabetic women.
Various studies have shown that HRT is associated
with a decrease in the likelihood of developing
diabetes by a factor of nearly 5; improves blood
glucose control, and is associated with a decrease in
the risk of MI in women with diabetes (RR = 0.51;
95% confidence interval 0.22 to 1.15 overall and RR =
0.78; 95% CI 0.56 to 1.08 per year of HRT use). HRT
reduces insulin resistance and may be administered
continuously and safely.
How should the woman on HRT be monitored?
What do we monitor? The response of the patient
to treatment and the development of complications.
Special baseline studies not done at the initiation
of treatment must be done during the first year of
HRT.
HRT associated with uterine bleeding is a major
cause for poor compliance. How do you go about
with this problem?
Most postmenopausal HRT regimens lead to
endometrial bleeding. However, the response
to any one regimen varies greatly from every
individual. The response of women will depend on
the estrogen and progestogen dosages, the regimen
and route by which these are administered and their
respective potencies. The role of vaginal sonography,
hysteroscopy and endometrial biopsy is emphasized
to monitor changes in the endometrium or other
causes of postmenopausal bleeding. Patients should
be appropriately counselled.

HORMONE REPLACEMENT THERAPY

How then is HRT administered with regards to

its main clinical goal taking to consideration its
contraindications?
The main clinical goal of HRT (estrogen, progestogen)
is to alleviate the symptoms of menopause. It can be
administered orally, transdermally, topically, internally
or as subcutaneous implants. In a woman with a uterus,
HRT must include an estrogen and a progestational
agent because the use of estrogen alone can produce
endometrial hyperplasia or carcinoma (or both). In
the absence of a uterus, a progestational agent is
unnecessary. In patients with a subtotal hysterectomy,
it is always prudent to start the patient on sequential
type of HRT for at least 3 months, if with bleeding
you can continue giving your estrogen & progestogen
continuously, combined. If no bleeding the giving of
estrogen alone is sufficient.
Estrogens
The following are the most commonly used estrogens:

-
-
-
-
-
-

conjugated equine estrogens

Esterified estrogens
Estropipate and other estrone sulfate preparation
micronized 17 B- estradiol
transdermal estradiol patches
vaginal estrogenic preparation including a
vaginal ring
- Ethinyl Estradiol
In addition, other available preparation such as estrogen
pellets, gels, creams, intranasal sprays or injections
(Depo-Estradiol) have been used. The major differences
among these formulation are in the mode of absorption
and the pharmacokinetics. Few, if any, clinically
significant qualitative differences exists between free
and conjugates estrogens.
The oral & transdermal routes are the most frequently
used. Patient acceptance and prior experience are
the major factors in determining the preferred route
of delivery. The oral route is distinguished by firstpass enterohepatic removal of a substantial fraction
of the estrogen, followed by hepatic metabolism and
conjugation to sulfates and gluconomides, which are
then excreted through the bile back into the digestive
tract. Here, the sulfates are deconjugated to some
extent and reabsorbed. All drugs subject to the firstpass effect show greater interindividual variability,
in the blood levels attained. This findings is true of
the estrogens - a fact that is of considerable clinical
relevance. Furthermore, the high concentration of
estrogen delivered to the liver by the oral route (in
comparison with transdermal absorption directly into
the peripheral circulation) induce increased synthesis

HORMONE REPLACEMENT THERAPY cpm 4TH eDITION

of triglycerides and certain proteins such as cortisolbinding globulin (transcortin), sex hormone-binding
globulin and angiotensinogen. Therefore, transdermal
estrogen is preferred in certain clinical situations, such
as in women with hypertension, hypertriglyceridemia,
and a history of an increased risk for cholelithiasis.
Vaginal administration of estrogen has been used for
treatment of vaginal atrophy. Estrogens are readily
absorbed through the vaginal mucosa and result in
appreciable blood levels of estrogen.
The dosage of estrogen used to initiate HRT should
be individualized because it is strongly dependent
on age of the patient and various others factors. In a
reproductive - age woman who had recent bilateral
oopherectomy, a larger dosage of estrogen (e.g. orally
administered micronized estradiol 2-4 mg/day; equine
estrogen 1.25 - 2.5 mg/day; or ethinyl estradiol 0.02
- 0.05 mg/day) is required than for a woman who has
been amenorrheic and symptomatic for a long time (e.g.
orally administered micronized estradiol, 1-2 mg/day,
transdermal estradiol 0.05-0.1 mg/day; equine estrogen
0.625 to 0.9 mg/day, or ethiyl estradiol 0.01 to 0.02
mg/day. A patient who has been deprived of estrogens
for years is likely to be too sensitive to the usual dosages
and should initially receive even lower doses than those
used for maintenace therapy. The desired effects of
therapy manifest themselves slowly.
Progestins
After hysterectomy, progestins are unnecessary. In a
woman with an intact uterus, the endometrium must be
protected against hyperplasia and possible progression
to dysplasia and carcinoma by the use of progestational
agents.
The classic regimen consists of 5 to 10 mg of
medroxyprogesterone acetate (MPA) used for 10 to
14 days each month. Levonorgestrel, norethindrone,
or micronized progesterone can also be used for this
purpose. Cyclic administration of the progestins usually
produces monthly menstrual periods. Because persistent
menstrual bleeding is often cited as the major reason
for non-compliance with HRT, amenorrhea maybe
achieved by using a low dose of a progestin administered
continuously (daily) in conjunction with estrogen. Some
women, however, will continue to experience episodes
of breakthrough bleeding. Alternatively, a progestin can
be administered at 2, 3 or 6 month intervals and still
prevent endometrial hyperplasia. This non-conventional
use of progestin requires careful monitoring of the
endometrium with ultrasonography and endometrial
biopsy.
Micronized progesterone has been shown to be an

effective alternative to MPA in dosages of 100 to 200 mg

daily. Reported outcomes here included <1% incidence
of hyperplasia and improved lipid profiles.
Androgens and Anabolic Agents
Does an androgen-deficiency state exist in postmenopausal
women? The menopausal ovarian stroma continues to
produce testoserone and androstenedione in response
to increased pituitary gonadotropin stimulation.
With advancing age, however, adrenal androgen
production gradually declines. Bilateral oophorectomy
in premenopausal, perimenopausal, or postmenopausal
women leads to approximately 50% reduction of
testosterone levels. The initiation of HRT leads to a
suppression of gonadotropins, and a decrease in ovarian
androgen production. In addition, estrogen stimulates the
production of sex-hormone-binding globulin thereby leads
to decreased free testosterone. Therefore, menopausal
women receiving HRT have a loss of androgen effect
in comparison with the premenopausal state. Sexual
dysfunction, loss of libido, depression, decrease energy,
and other symptoms have been attributed to the loss of
androgen production. Observational and cross sectional
studies of postmenopausal women have generally
failed to demonstrate a correlation between circulating
androgen levels & libido.
The androgen preparations commonly used include
methyltestosterone, parenterally administered
testosterone; transdermal patches, and orally
administered micronized testosterone as well as
DHEAS. The most widely used oral androgen
formulation is Methyltestosterone.
Methyltestosterone dose used is 1.25 to 2.5 mg/day
DHEAS-25 to 100 mg/tablet
Micronized testosterone for oral use is 2.5-5.0 mg in
vegetable oil capsule.
In general, side effects of excessive androgen therapy,
including seborrhea, acne, hirsutism, alopecia, voice
changes and clitoral hypertrophy, are dependent on the
dose, duration and individual patient. Androgen may
alter the HDL/LDL ratio by lowering HDL levels.
Four general groups of women are considered candidates
for estrogen + androgen therapy:
1. women who have had their ovaries removed
2. those who have not experienced relief of vasomotor
symptoms with a maximally tolerable dose of
estrogen
3. Those at risks for osteoporosis in whom other
modalities are not satisfactory or suitable
4. Those with unsatisfactory sexual functions, especially
loss of libido.

CPM 4TH EDITION

Because no consensus exists about the use of androgen

therapy, the potential benefits and risk should be
explored for each patient.
What are the adverse effects and contraindications
to the use of HRT?
Adverse effects of HRT
1. Increased risk of thromboembolism, usually occuring
within the first year of therapy, that applies to all forms
of estrogen. Women who have had documented deep
vein thrombophlebitis or pulmonary embolism in the
past should, most probably, not be prescribed any
form of HRT.
2. Increased risk of cholelithiasis has been found in
women who use orally administered estrogens.
3. Increased risk of breast cancer for women taking HRT
>10 years, which applies to all forms of estrogen.
Contraindications to use of HRT
1. A history of breast cancer is still the main
contraindication.
2. Previous venous thrombo embolism
3. Undiagnosed genital bleeding
4. Gall Bladder disease
5. Hypertension
6. Migraine and other headache
HRT and Risk of Cancer
About 1.5 million cancers are diagnosed annually in
women and almost half are cancers of the reproductive
organs. Over 80% of the cancers occur in postmenopausal
women. Breast cancer is the most common (422,000
cases), and the risk increases with earlier menarche and
later menopause).
Based on a reanalysis of data on 51,000 women with
breast cancer and 108,000 controls (from 51 worldwide
studies) the collaborative group in hormonal factors
in Breast Cancer reported that ever-use of HRT was
associated with an overall 14% increase in the relative
risk of breast cancer, with no heterogeneity between
studies. The excess risk was largely confined to current
and recent users, in whom the relative risk increased
by 2.3% for each year of use. This increase is roughly
equivalent to the increased linked to a 1-year delay
in the menopause. Overall, use of HRT for 1-2 years
is associated with no risk. By 5 years after stopping
HRT, the effects in breast cancer risk has essentially
disappeared. About 80% of the users were on estrogen
only preparation.
The excess risk was mainly confined to localized breast
cancers. Collaborative Group and a recent report from

HORMONE REPLACEMENT THERAPY

the Iowa Womens Health Study showed that the cancers

were less aggressive and survived longer in HRT users
than in non-users, which may be a biological effect
of the hormones or because the cancers are detected
earlier in HRT users. To put the collaborative Group
data absolutely, the cumulative excess incidence
in 1000 women who used HRT for 5 and 10 years
starting at age 50 is 2 and 6 cases respectively. In the
collaborative group analysis, the increased risk of
breast cancer associated with HRT is mostly restricted
to leaner women.
In 1999 case-control study from Sweden of about 3,000
women with breast cancer showed a higher relative
risk: odds ratio of 1.65 for ever versus never users of
estrogen or estrogen/progestogen preparation. There
was a statistically significant trend for increasing risk
with increasing duration to use.
Colorectal cancer is the second most common cancer
in women in developed countries. The overall relative
risk of this cancer associated with ever-use of HRT
was, from 14 observational studies, 0.8-ie, a protective
effect. The relative risk for current users was 0.7 and
for past users, 0.8 although the date for past users are
very heterogenous.
An association of endometrial cancer and HRT
with estrogens alone has long been recognized, and
was the reason that progestogens were added to the
regimen. An overview of four studies that looked at
ever-use of a combined preparation showed a relative
risk of 1.3.
Cancer of the cervix and HRT - HRT maybe offered to
patient with cervical cancer.
Cancer of the ovaries and HRT - HRT maybe given
safely after surgical management of the ovarian
cancer.
Vulvar cancer and HRT - no information
There is two little information to comment on any link
between HRT use and other concerns.
HRT in women with a history of breast or endometrial
cancer
Should HRT be given in patients who have had breast
or endometrial cancer? There are no data to answer this
question adequately. In six retrospective series ( total
of 490 patients), the rate of recurrence of breast cancer
in women on HRT was 0-9%, with 0-6% deaths. Thus,
HRT should be prescribed only after the woman has
been advised to the uncertainty about risk.

HORMONE REPLACEMENT THERAPY cpm 4TH eDITION

Management when HRT cannot be used

Alternatives are available when HRT is contraindicated
or not tolerated. These options are:
1. Selective Estrogen Receptor Modulators (SERM)
- these have a selective estrogen like activity
on some tissues and anti-estrogen activity on
other estrogen- responsive tissues. Raloxifene has
been approved for the prevention and treatment
of osteoporosis in postmenopausal women. In
the (MORE) Multiple Outcomes of Raloxifene
Evaluation study, approximately a 50% reduction
in vertebral fractures was noted at 24 months and
a 40% reduction at 36 months in women with
osteoporosis. The study was not statistically proved
to assess hip fracture. Like estrogen raloxifene lowers
LDL levels: However unlike estrogen, raloxifene
does not increase total HDL levels or triglycerides.
Cardiovascular disease prevention trials are currently
being conducted (RUTH) Trial Raloxifene use for
the heart, to determine whether raloxifene reduces
the risks of cardiac events. Early studies suggest
that Raloxifene may significantly reduce the risk of
breast cancer. A comparison study with tamoxifene
is underway to analyze these findings further. Unlike
tamoxifene, Raloxifene does not stimulate the
endometrium and can be used for women with intact
uterus. Raloxifene does not relieve hot flushes and in
fact may increase their occurrence; therefore it will
not benefit perimenopausal women with vasomotor
symptoms. The incidence of deep venous thrombosis
associated with use of Raloxifene is similar to that
with estrogen.
2. Phytoestrogens - may act as selective estrogen
modulators and are currently being studied.
3. Alendronate, a biphosphonate has been shown
to decrease significantly the risk of osteoporotic
fractures in the hip and spine. In the Fracture
Intervention Trial (FIT) a 40-50% decrease in spine,
hip and waist fractures was noted at 3 years in women
with previous fractures given Alendronate.
4. Calcitonin - is available in nasal spray form for
treatment of osteoporosis. In the current Prevent
Recurrence of Osteoporotic Fractures (PROOF)
Study, a 37% reductions in vertebral fractures was
noted at 5 years in postmenopausal women with
osteoporosis.
5. In general, sufficient calcium, vitamin D, and exercise
are important factors in helping to maintain bone
density. Exercise is also important for maintaining
muscle tone and helping to reduce the risk of
falling.
CONCLUSION
In the use of these guidelines to assess and manage

perimenopausal and menopausal women, the primary

goal is to inform the patient as completely as possible
about the benefits and risk of HRT. Although HRT is
preventive medicine at its best, its use-like all issues in
preventive medicine - is elective. Menopausal women
will comply with HRT if they are confident in their
decisions, receive continued support and encouragement
for adherence, and accept the potential adverse effects
and risks in comparison with he benefits.
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CPM 4TH EDITION

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28. The Writing Group for the PEPI trial. Effects of estrogen or
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29. Barret-Connor, E., Wingard DL, Criqui, MH. Postmenopausal
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30. Kritz-Silverstein, D., Barret-Connor, E. Long-term Postmenopausal Hormone Use, Obesity and Fat Distribution in Older Women.
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31. Mayo, CP., Oberman, A., Heimburger, DC, et al. Association of
Hormone Replacement Therapy with estimated intraabdomonal fat
among postmenopausal women. Am J Clin Nuti 1997; 66:221.
32. Lobo, RA., Pickar, JH., Wild RA, et al. Metabolic impact of adding
medroxyprogesterone acetate to conjugated estrogen therapy in
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33. Rincon, J., Holmang, A., Wahlstrom, ED., et al. Mechanisms behind
insulin resistance in rat skeletal muscle after oophorectomy and
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34. Elkind-Hirsch, KE., Sherman, LD., Malinak, R. Hormone Replacement Therapy alters insulin sensitivity in young women with premature ovarian failure, J. Clin Endocrinol Metab. 1993; 76:472.
35. Duncan, Ac. Lyall, H. Roberts, RN, et al. The effect of estradiol and
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38. Ferrara, A. Karter, A., Glei, D., Ackerson, L., Darbinian, J., Selby,
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39. Lutola, H., Pyorala, T., Loikkanen, M. Effects of natural estrogen/
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55. Collaborative Group on the Hormonal Factors in Breast Cancer.
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reanalysis of data from 51 epidemiological studies of 52,705
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56. Newcomb PA, et al Long Term HRT and risk of Breast Cancer
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58. Schairer C, et al Estrogen Replacement Therapy and breast Cancer
Survival in a large Screening study. J. Natl. Cancer Institute 1999;
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HORMONE REPLACEMENT THERAPY cpm 4TH eDITION

Drugs Mentioned in the Treatment Guideline

This index lists drugs/drug classifications mentioned in the treatment guideline. Prescribing Information of these
drugs can be found in the Philippine Pharmaceutical Directory (PPD) 8th edition. Opposite the brand name is its
page number in the PPD 8th edition.
Biphosphonates
Alendronate
Fosamax

Q231

Calcium Preparations
Agre-Calvit
(Reformulated)*
K161
Anlene Gold Hi-Calcium
Nonfat Milk
K183
Anlene Hi-Calcium
Low Lactose
K183
Anlene Hi-Calcium
Nonfat Milk
K183
Athena Hi-Calcium
Nonfat Milk for
Women
K183
Calcebone
K161
Calci-Aid
K161
Calciumade
K183
Calcium-D-Redoxon* K161
Calcium Sandoz
K161
Calcium Sandoz +
Vit C*
K161
Calsan
K161
Caltrate Plus*
K161
Carnation Calcium Plus K184
Carnation Non-Fat
K184
Tridin*
K161
United Home
Ca Lactate
K161
Calcitonins
Salmon Calcitonin
Miacalcic
Tonocalcin
Estrogens
Estradiol
Climara
Estraderm MX
Estrofem
Progynova
Estradiol/
Cyproterone acetate
Climen
Estradiol/Dydrogesterone
Femoston
Estradiol/Norethisterone
acetate
Estracomb TTS

Q231
Q231

P225
P226
P226
P226
P226
P227
P227

Kliogest
Trisequens*
Estriol
Ovestin
Estrogen-Conjugated
Premarin
Estrogen-Conjugated/
Medroxyprogesterone
acetate (MPA)
Premelle 2.5/Premelle 5
Premelle Cycle 5
Estrogen-Conjugated/
Medrogestone
Prempak
Ethinylestradiol/
Cyproterone acetate
Diane-35
Ethinylestradiol/
Desogestrel
Gracial
Marvelon 28
Mercilon
Ethinylestradiol/
Gestodene
Gynera
Meliane
Minulet
Ethinylestradiol/
Levonorgestrel
Logynon
Microgynon 30
Nordette
E 21
Rigevidon 21 + 7
Trinordiol
Tri-Regol
Ethinylestradiol/
Norethindrone
Micropil
Ethinylestradiol/
Norgestrel
Femenal

P227
P228
P226
P226

P227
P227
P227
P226
P229
P229
P229
P229
P229
P230
P229
P229
P230
P230
P230
P230
P230
P230
P229

Progestogens (Progestins)
Allylestrenol
Turinal
P228
Dydrogesterone
Duphaston
P228
Hydroxygesterone caproate

Proluton Depot
Lynestrenol
Exluton
Medroxyprogesterone
acetate (MPA)
Depo-Provera
Provera
Norethisterone
Primolut N
Noristerat

P228
P228
P228
P228
P228
P230

Selective-estrogen receptor
modulator (SERM)
Raloxifene
Evista
P227
Tamoxifen
Cox Tamoxifen
E72
Kessar
E72
Nolvadex/Nolvadex-D
E73
Tamoplex
E73
Tamoxsta
E73
Zitazonium
E73
Vitamin D & Derivatives
Agre-Calvit
(Reformulated)*
Calcium-D-Redoxon*
Caltrate Plus*
Cod Liver Oil Forte*
Alfacalcidol
Alpha D3
Calcitriol
Rocaltrol

K161
K161
K161
K158
Q231
K158