TUTORIAL 10 : MENOPAUSAL

SYMPTOMS IN A 52 YEAR OLD

WOMAN
 Menopause
Final menstrual period
Menopausal age: 45 55 years old, average
age: 51
When the supply of oocytes becomes
exhausted & oestrogen level drops
 Menopause continued..
Proportion of anovulatory
cycles increases
Progesterone production
declines
FSH & LH rises due to
diminished feedback from
oestrogen
Recognised only after 12
months of amenorrhoea
 Premature Menopause
When final menstrual period happens
before the age of 40 (45)
Possible causes:
Primary
Chromosomal anomalies eg Turner
A/I diseases eh MG, hypothyroidism
Enzyme deficiency eg galactosaemia
Secondary
Surgical
Chemo/radioTx
Infections eg TB, mumps, malaria, varicella
 Climacteric
The phase in the aging process of women marking
the transition from the reproductive stage of life to
the non-reproductive stage
Denotes hormonal changes and clinical symptoms
over a period leading up to and immediately
following menopause
Symptoms may begin months or years before the last
menstrual period; may continue for years afterwards
 Case

A 52 YEAR OLD WOMAN ATTENDS YOUR

CLINIC COMPLAINING OF HOT FLUSHES AND
NIGHT SWEATS. SHE HAS HAD NO PERIODS
FOR THE LAST 14 MONTHS.
 Hot flushes/ flashes
Uncomfortable feeling of warmth in the upper
body, usually lasting approx. 3 minutes
Sometimes accompanied by nausea,
palpitations and sweating
Can occur day or night, at night night
sweats
Physiological changes: sweating & cutaneous
vasodilation
 Etiology & mechanism
still not understood
Long-standing
assumption:
Transient dysregulation
of the thermoregulatory
system, triggering
homeostatic heat loss
mechanisms to return
the system to normal
 Question 1
1. Please take a further history on other
symptoms related to the climacteric in this
patient
Short Term Problems (0-5 years)

Vasomotor (constriction or dilatation of blood

vessels) symptoms
Hot flushes
Night sweats
Palpitations
Headaches
Insomnia
Psychological symptoms (due to disruption in the
mood-regulating hormones e.g. serotonin, or sleep
deprivation)
Emotional lability
Anxiety
Depressed mood
Loss of self-esteem
Poor memory & concentration
Irritability
Decreased libido
Generalised aches
Lethargy
 Questions

How have the symptoms affect your daily life?

Are you coping well with your job?
Have your symptoms cause any friction with
your family, friends, or colleagues?
 Greene Climacteric Scale
A measure of climacteric symptomatology
Domains: psychological symptoms, somatic
symptoms, vasomotor symptoms, sexual
Also to assess response to treatment or to
compare different treatment regimes
 Question 2
2. Patient: Dr, Can you please explain the
main consequences of lack of oestrogen
in the medium and long term?
Medium Urogenital urethral syndrome
term uterine prolapse
(3-10 years) stress/ urge incontinence
dyspareunia
genital tract atrophy
breast atrophy (replaced by adipose
tissue)
Cutaneous/ vaginal dryness
connective dry skin
tissue dry hair
brittle nails (dehydration; oestrogen
important in body water regulation &
water retention)
Long term Arterial cardiovascular disease
(>10 years)
Skeletal osteoporosis
Urethral Syndrome/ Symptomatic Abacteruria
Inflamed/ irritated urethra (no clear cause)
Symptoms
Lower abdominal pain
A feeling of pressure in the abdomen
Urgency
Frequency
Trouble urinating
Pain during urination or sex
Hematuria
Discomfort in the vulva
Possible causes: hormonal imbalance/ dysfunction of
the pelvic floor musculature
 Prolapse
Fascial framework (e.g. vesical fascia) & intra-pelvic ligaments
(transverse cervical, pubovesical, uterosacral) supporting
bladder & genitalia are weakened
 Genital tract atrophy
1. Vulva
Flattening of labia
majora
Labia minora
becomes more
evident
Sexual hair grey and
sparse, clitoris
shrinks
2. Atrophic vaginitis
Symptoms
Thinning of the vaginal walls
Shortening and tightening of the vaginal canal
Vaginal dryness
Vaginal burning (inflammation)
Spotting of blood after intercourse
Dyspareunia
Pain or burning with urination
More frequent UTIs
3. Uterus
Small, relatively large cervix

4. Tube and ovaries

Tubes become thin
Ovaries reduced to small white wrinkled bodies 2-
3cm in length
 Cardiovascular Disease

Effects of oestrogen
Increases HDL cholesterol & lowers LDL
cholesterol
Increases arterial flow
 Osteoporosis
Oestrogens have been shown to stimulate
osteoblasts directly
Excess bone resorption over bone formation
a/w loss of oestrogen
Increased risk of fractures, particularly of the
distal radius, vertebral body and hip
 Question 3
3. Patient : What treatment is available Dr. to
control my symptoms? (What would you
suggest would be most appropriate? What
are the potential benefits of combined
oestrogen/progestogen (E/P) hormone
replacement therapy (HRT) if it was given?)
 What treatment is available Dr. to
control my symptoms?
1. Hormone replacement therapy (HRT)
Oestrogen: Only preparation (oral/
transcutaneous/ subcutaneous implants/ vaginal
preparations)
Combined oestrogen: Progesterone preparation
(oral/ transcutaneous)
Progesterone 12-14 days for every 28
days of estrogen (cyclical) or together
(continuous)
 Tibolone
Synthetic steroid with weak oestrogenic,
progesteronic & androgenic effects
May be started 2 yrs after period stops

Raloxifene
Selective oestrogen receptor modulator (SERM)
Oestrogenic effects on bone & lipid metabolism;
minimal effect on uterine & breast tissue
Ineffective for controlling symptoms, but useful in
protecting against osteoporosis
2. Non-hormonal Tx
e.g. black cohosh/ isoflavones
(phytoestrogensplant-derived compounds
with estrogenic activity)
May relieve vasomotor symptoms
 Black Cohosh/ Isoflavones
Multiple preparations are available and their
safety is uncertain
Different preparations may vary
Interactions with other medicines have been
reported
 What would you suggest would be
most appropriate?
HRT
Combined oestrogen-progesterone
preparation
Assuming she still has intact uterus
To minimise risk of endometrial cancer a/w
unopposed oestrogen therapy by preventing
the overgrowth of endometrium
 Cyclical/Continuous?
Combined continuous EP therapy suitable for post-
menopausal women (at least a year since last
period)
* Cyclical - recommended for women who have
menopausal symptoms but still have their periods *
e.g. T. Premarin 0.625mg with Provera 5mg OD
Oral or transcutaneous
Transcutaneous: avoid GI side effects, appears to be
as effective as oral prep in treating symptoms &
preventing osteoporosis
 Others (in addition to HRT)
Lifestyle modifications eg exercise, proper diet, stop
smoking and alcohol
CBT to alleviate low mood or anxiety
Consider testosterone supplementation for
menopausal women with low sexual desire if HRT
alone is not effective
Vaginal oestrogen for urogenital atrophy - continue
treatment for as long as needed to relieve symptoms
Moisturisers and lubricants for vaginal dryness - can
be used alone or + vaginal oestrogen
What are the potential benefits of combined
oestrogen/progestogen (E/P) hormone replacement
therapy (HRT) if it was given?

HRT benefits:
Relieve menopausal symptoms
Prevent osteoporosis
Reduce risk of CVD (if started early, not if after
60)
 Question 4
4. What are the adverse effects taking this
treatment Dr? (Explain potential adverse
effects of E/P HRT if it was given)
HRT Risks and Benefits
Risks Benefits

Endometrial Cancer Metabolic Effects

Bone Mineral
Breast Cancer
Density

Relief of Menopause
CV Risk
Symptoms
 Common effects of E/P HRT
Headache

Breast
Carcinoma
Breast
Nausea
tenderness
Minor
Side
Effects
Endometrial Increased Thromboembolic
Carcinoma Risk of Disease X2-4

Fluid Weight
Retention Gain

Cardiovascular
Disease
 Oestrogen S/E (dose Progestogen S/E (if
related, settle in a persistent, change type)
few weeks) Fluid retention
Fluid retention Headache
Nausea
Breast tenderness
Acne
Headache
Mood swings
Breast enlargement Depression
Leg cramps Irritability
Dyspepsia Bloating
Constipation
Increased appetite
 Risks of
Stroke: 1.0 and 1.2 additional cases per 1000
women per five years of E+P and E use,
respectively (WHI)
Venous thromboembolism (VTE): 5 and 2
additional cases per 1000 women per five
years of E+P and E use, respectively (WHI)
Breast cancer: 6.8 additional cases per 1000
women per five years of E+P (Nurses Health
Study). Increased after 5 years of use.
Returned to normal after stopping for 5 years.
 Breast Cancer
If HRT used for <5 years in the early post menopause
it does not appear to increase breast cancer risk.
Small increase in risk of 1.35
(4 extra cases of breast cancer ca per 1000 in
women who use HRT from age 50 for 5 years)
Magnitude of risk similar to late natural
menopause (2.3% and 2.8% per year, respectively)
Otherwise healthy premenopausal women in their
late 40s and 50s should be assured that breast
cancer risk in the first few years due to HRT is small
 Endometrial Cancer
Unopposed oestrogen replacement therapy
increase risk
Give progestogen:
Perimenopausal: cyclical (withdrawal bleed)
Menopausal: switch to continuous
 Venous Thromboembolism
HRT increases the risk of VTE by two fold esp. in the first year
of use.
However background risk in VTE in women over 50 is small
(1.7/1000). Therefore overall impact of this increase is low.
Background risk significantly increase with:
Smoking
Obesity
Underlying thrombophilia e.g. factor V leiden
Previous Hx of VTE
*Transdermal HRT may be more suitable for this group less
impact on haemostatic mechanism
 Coronary heart disease
Oestrogen may be protective of CHD or can give
adverse effect.
In postmenopausal women aged 50-59 years:
Hormone therapy (oestrogen alone or combined)
does not increase CHD incidence.
Starts HRT shortly after menopause: May be
protective especially in premature menopause.
Starts HRT years past menopause: May have a
detrimental effect
 Stroke
Small increase with oestrogen only/combined
oestrogen progestogen.
Also significant age effect: Relatively high risk in older
women, No reported increase in 50-59 age group.
Should not be initiated in: Women >60, Strong risks for
stroke or CVS.
In postmenopausal women aged 50 -59 years:
Hormone therapy (CEE alone or combined with MPA)
does not increase stroke incidence.
Low dose estrogen is not associated with an increase in
stroke, where as higher doses show an increase in
stroke incidence
 Question 5
If the patient has experienced the same symptoms at
the age of 38 years, and her serum FSH and LH levels
were shown markedly elevated, would the treatment
advice be any different?
Are the adverse effect will be different if E/P is given
for 10 years from the age of 38 years as compared to
the same length of time from the age of 52 years
old?
 NO
Age 38 = Premature menopause
Need to rule out other causes of premature
ovarian failure
Confirm diagnosis, start HRT treatment as
soon as possible primarily to prevent
osteoporosis
Usually continue until the average
menopausal age
Advice about healthy lifestyle
 Causes of Premature Ovarian Failure
Primary
Chromosome Anomalies
e.g. Turners, Fragile X
Syndrome
Autoimmune Disease
e.g. hypothyroidism,
myasthenia gravis, Addisons
Enzyme Deficiencies
e.g. Galactosaemia
Secondary
Surgical Menopause after
bilateral oophorectomy
Chemotherapy or Radiotherapy
Infections
e.g. mumps, tuberculosis,
malaria
 Similarity & Differences
Similarity: The minor side effects are similar:
headache, nausea, breast tenderness, fluid retention,
weight gain.

Difference: The increased risk of 1.35 for breast

cancer in women taking 5 years HRT is not seen in
women who start early for premature menopause
suggesting that it may be the lifetime sex hormone
exposure that is relevant.
 Question 6
Are the benefit and adverse effect are
different if the women is only given oestrogen
HRT?
 Benefits
Relief menopausal symptoms such as hot flushes
Reduce risk of progestogenic effect :
Breast tenderness
Acne
Mood swings
Bloating
Constipation
Increase appetite
Improve urogenital function and sexual function
Lower risk of breast cancer
 Adverse Effects
Increase risk of endometrial hyperplasia
further progress to carcinoma in non-
hysterectomized women
No progesterone for secretory transformation
of endometrium, no shedding causing
hyperplasia.