THE MENOPAUSE

Learning Objectives
• Define terms related to menopause
• Understand the pathophysiology of the menopause
• Know the effects of menopause
• Understand the risks and benefits of HRT and be able to explain these
to the patient
• Manage a case of menopause
LO1: Define The Terms Related
to Menopause
 Menopause
• Menopause is a deviation of Greek word: Menos (month) pause
(stop)
• Ten Teacher’s: woman’s final menstrual period and the accepted
confirmation of this is made retrospectively after 1 year of
amenorrhoea.
• CPG: states of ovarian failure and ovarian destruction/ removal with
accompanying estrogen deficiency.
• The transition to menopause and the time approaching menopause
are referred to as perimenopause.
• Perimenopause describes the time in a woman's life when menstrual
periods become irregular as she approaches menopause.
Timing of menopause
• Average age is 51 and 52 with 95% of the women had
menopause between 45-55
• Premature menopause : before 40 years old
• Late menopause : after 60 years old
 LO 2: Understand The
Pathophysiology of The
Menopause
PHYSIOLOGY
• Timing of the menopause:
• Median age between 51 and 52 years
• 95% between 45 and 55 years
• Endocrine changes
• Menopause occurs at the time of depletion of oocytes from the ovary and is
irreversible.
 PATHOPHYSIOLOGY
The ovaries produce principal steroid hormones:
oestradiol
progesterone
testosterone
androstenedione
• The majority of circulating plasma oestradiol in premenopausal
women is produced from developing follicle.
• Oestradiol synthesis principally from conversion of
androstenedione and testosterone occurs in granulosa
cell.
• The conversion is catalysed by aromatase enzyme
cascade and stimulated by FSH.
• As the ovary ages the remaining follicles, probably least
sensitive to gonadotrophins are increasingly less likely
to mature and ovulation declines thus ovarian function
gradually fails.
• The endocrine change is a fall in inhibin production by
ovary, the level of estrogen is no longer sufficient to
stimulate endometrial proliferation and menopause
ensues.
Endocrine changes
• Inhibin B is produced by follicles within the ovary,
so as the number of follicles decline the
production of inhibin decreases.
• In the perimenopausal years small declines in
inhibin drive an overall increase in the pulsatility of
GnRH secretion and overall serum FSH and LH
levels, which results in an increased drive to the
remaining follicles in an attempt to maintain
follicle production and oestrogen levels.
• Androgenic hormone production comes from ovaries,
peripheral adipose tissue and the adrenal glands, with
the ovaries producing approximately 30–50% of total
circulating levels.
• A decline in ovarian testosterone and other androgens
accompanies the process of ageing in women, although
these changes are less dependent on the
neuroendocrine axis and the processes involved in
ovulation.
• This is shown by the fact that overall androgen
concentrations in a woman in her 20s are approximately
double those at 40 years old and then slowly decline
over the rest of her life, with very low levels maintained
from about 70 years.
 Non-physiological menopause

Premature ovarian insufficiency(POI)

• Menopause which occurs before the age of 40 years.
• Sometimes called premature ovarian failure (POF), or premature
menopause.
• Occur in approximately 1% of women under 40 years and 0.1% under
30 years
• Features: unpredictable spontaneous ovarian activity, resulting in
irregular vaginal bleeding
Causes of POI
 IATROGENIC MENOPAUSE
1. Medical treatments and menopause after cancer treatment
• Menopause can be iatrogenically induced by radiotherapy,
chemotherapy for malignancy or temporarily during treatment
with GnRH analogoues.
• If GnRH is given in a constant high dose, it desensitizes the GnRH
receptor and reduces LH and FSH release.
• Drugs that are GnRH agonists (e.g. buserelin and goserelin) can
be used as treatments for endometriosis and other
gynaecological problems. Although they mimic the GnRH
hormone, when administered continuously they will down-
regulate the pituitary and consequently decrease LH and FSH
secretion.
• This will induce a temporary menopause with a relatively rapid
onset, which can be managed with the introduction of hormone
therapies and other drugs to relieve some of the unwanted
menopausalsymptoms – known as add-back therapy.
2. Surgical menopause
• Surgical menopause occurs when functioning
ovaries are removed, such as at hysterectomy for
malignancy and severe endometriosis.
• If the ovaries are conserved during hysterectomy,
menopause may occur a few years earlier.
• With surgical menopause, onset of menopausal
symptoms are abrupt and dramatic.
LO3: Know The Effect Of
Menopause
Effect of menopause by time of onset
Onset Effect
Immediate (0-5 years) - Vasomotor symptoms (eg. Hot flushes, night sweat)
- Psychological symptoms (e.G labile mood, anxiety, tearfulness)
- Loss of concentration, poor memory
- Joint aches and pains
- Dry and itchy skin
- Hair changes
- Decreased sexual desire
Intermediate (3-10 years) - Vaginal dryness, soreness
- Dyspareunia
- Urgency of urine
- Recurrent uti
- Urogenital prolapse
Long term (>10 years) - Osteoporosis
- Cardiovascular diseases
- Dementia
 CENTRAL NERVOUS
SYSTEM

VASOMOTOR PSYCHOLOGICAL COGNITIVE

SYMPTOMS SYMPTOMS FUNCTION
 Vasomotor symptoms
- Hot flush (when occur at night “night sweat”)

Aetiology:
- Unknown but is thought: loss of modulating effect of
oestrogen on seritonergic receptors within the
thermoregulatory centre in the brain, resulting in
exaggerated peripheral vasodilatory responses to
minor atmospheric changes in temperature

- Can cause sleep disturbance lead to:

• Tiredness, exhaustion, impaired quality of life
 psychological symptoms
- Can cause depression. Associated with:
• Low mood, irritability, lack of energy,
tiredness and impaired quality of life

 cognitive function
- Dementia (no clear evidence)
- Change in memory and global cognitive
function
Etiology: could be the impact of
vasomotor symptoms
 The genital tract

Urogenital tract
Endometrial
and vulvovaginal
effect
atrophy
 endometrial effects
- initially, Reduction in oestrogenic endometrial stimulation with failing
ovarian function => irregular or scanty vaginal bleeding
- Endometrium no longer stimulated => stop period
- Episodic and infrequent ovulation with fluctuation in oestrogen level
=> irregular heavy bleeding
 urogenital tract and vulvovaginal atrophy
- Vaginal dryness, irritation, burning, soreness and dyspareunia
Etiology: loss of the oestrogenic support to the vaginal epithelium leads
to reduces cellular turn- over and reduced glandular activity => vaginal
epithelium less elastic and easily traumatized

- Incontinence and prolapse

- High risk of urinary tract infection

Etiology: increase in pH of the normally mildly acidic environment of
the vagina
- Examination in postmenopausal urogenital atrophy:
 dryness mostly on the surface of vagina
 pallor
 extreme case: petechial haemorrhage
Bone Health
- Skeletal maintained by constant process of remodelling, in which
resorption and deposition occurs
- Loss of oestrogenic support of skeletal metabolism causing imbalanced of
remodelling cycle (amount of new bone formation by osteoblast cannot
keep pace with amount removed by osteoclast)

i. Resorption by osteoclast
(OC)
ii. Reversal with
disappearance of OC
iii. Deposition of osteoid by
osteoblast (OB)
iv. Mineralization of
osteoid.
- An important consideration is the attainment of peak bone mass. There
is rapid loss of bone mass due to oestrogen deficiency after menopause.

Bone density reach peak between 20-30 years of age

After peak, there is a steady decline until the menopause

Accelerate phase of bone loss until 60 years

Further steady decline until death

- After age of 60, likelihood of osteoporotic fractures of hip and spine
increases.
- Osteoporosis is defined as a “skeletal disorder characterized by compromised
bone strength predisposing to an increased risk of fracture”
- Reduced bone density  micro-architechtural deterioration of bone tissue
 increased risk of fracture
- F : M is 4:1
Risk factors for osteoporosis
• Family history of osteoporosis or hip fracture
• Smoking
• Alcoholism
• Long term steroid use
• POI and hypogonadism
• Medical treatment of gynaecological conditions with induced
menopause
• Disorders of thyroid and parathyroid metabolism
• Immobility
• Disorders of gut absorption, malnutrition, liver disease
Cardiovascular
System
- In menopausal transition, there are several changes in female
physiology that can influence individual risk of CVD
- The changes includes:
i. Lifestyle issues such as nutrition and exercise
ii. Change in the distribution in fat from gynaecoid (fat on breast and
hips) to android (abdominal fat)
iii. Changes in serum lipid levels (increase in triglycerides, total
cholesterol and LDL cholesterol with reduction of HDL cholesterol)
iv. Reduction of supportive effect of oestrogen on vessel wall
(vasodilation and prevents atherogenesis)
LO4 : Understand the risks and
benefits of HRT and be able to
explain these to the patient
 Benefits of HRT
• Symptoms improved
- vasomotor symptoms
- sleep patterns
- performance during the day

• Prevention of osteoporosis
- increased bone mineral density
- reduced incidence of fragility fractures

• Lower genital tract

- dryness
- soreness
- dyspareunia
Risks of HRT
• Breast cancer
• Cardiovascular disease and stroke
• Venous thromboembolism
LO5: Manage a case of
menopause
1. Diet and lifestyle
- Extensive evidence exists to support improved longevity with regular
exercise, stopping smoking and reducing alcohol consumption.
Lifestyle changes Beneficial effect

Stopping smoking Prevention of lung cancer

Reduction of CVD
Beneficial effects on bone loss
Reducing alcohol consumption Reduction of calorie intake
Fewer, less severe vasomotor symptoms
Beneficial effects on bone loss
Prevention of alcohol-related liver damage
Reduction in incidence of breast cancer
Reduction of CVD
Normal BMI Reduction of calorie intake
Fewer, less severe vasomotor symptoms
Beneficial effects on bone loss
Reduction in incidence of breast cancer
Reduction in incidence of endometrial cancer
Reduction of CVD
2. Non-hormonal approaches
• Alternative and complementary treatments
- Widely available but very poorly researched in the scientific manner.
- Efficacy is usually limited and of a short duration, with the potential for
interactions with other pharmaceutical agents.
• Non-hormonal prescription treatments
- This group of therapies is increasingly important to consider in management
of women to reduce symptoms of hot flushes when hormones are not
wanted or contraindicated (previous diagnosis of hormone-sensitive cancers
such as breast cancer).
- These includes vaginal moisturizers and lubricants for vaginal dryness and
some of therapies to treat osteoporosis including bisphosphonate, raloxifene,
denosumab and teriparatide.
Alternative and complementary
treatments
Complementary drug-free therapies Acupuncture
(delivered by a practitioner) Reflexology
Magnetism
Reiki
Hypnotism
Herbal/natural preparations (designed Black cohost (Actaea racemosa)
to be ingested) Dong quai (Angelica sinensis)
Evening primrose oil (Oenothera biennis)
Gingko (Panax ginseng)
Kava kava (Piper methysticum)
St. John’s wort (Hypericum perforatum)
‘Natural’ hormones (designed to be Phytoestrogens such as isoflavones and
ingested or applied to the skin) red clover
Natural progesterone gel
Dehydroepiandrosterone (DHEA)
Non-hormonal treatments for
vasomotor symptoms
Alpha-adrenergic agonists Clonidine
Beta-blockers Propanolol
Modulators of central Venlafaxine
neurotransmission Fluoxetine
Paroxetine
Citalopram
Gabapentin
3. Hormonal replacement therapy
• Types of hormones contained in HRT:
- Oestrogens
- If oestrogen is given without progestogenic opposition,
there is risk of endometrial hyperplasia and cancer.
- Systemic oestrogen-only HRT suitable for women who no
longer have a uterus following a hysterectomy.
- Oestrogen with progestogen
- Administration of progestogen necessary to protect the
endometrium in women who have not had a hysterectomy.
- Normally given cyclically in preparations over a 28 day cycle, of
which 16 to 18 days will provide oestrogen alone and 10 to 12
days will provide oestrogen and progesterone combined (cyclical
HRT).
- This results in regular monthly menstruation and is suitable for
women during the perimenopause or early postmenopausal years.
- Oestrogen and progesterone may be given continuously
(continuous combined HRT) to women who are known to be
postmenopausal or over the age of 54 years.
- These are usually preparations with the same dose of daily
oestrogen combined with smaller dose of progestogen taken
everyday. These regimes normally results in about 90% of women
not experiencing vaginal bleeding.
- Testosterone
- Traditionally given to women with disorder of sexual desire and
energy levels who have failed to respond to normal HRT.
- However, over the past years manufacturers have stopped making
testosterone drugs for women to the point that the only available
preparations available now are those licensed for use in men.
- Testosterone needs to be instigated under the care of a doctor
with specialist menopause knowledge.
Hormones used in HRT

Oestrogens:
• Oestradiol
• Oestrogen sulphate
• Oestriol
• Conjugated equine oestrogen
Progestogens:
• Norethisterone
• Levonogestrel
• Dydrogesterone
• Medroxyprogesterone acetate
• Drospirenone
• Micronized progesterone
Routes of hormone therapy administration
Two main routes of HRT delivery are oral and transdermal.
• Oral tablet is normally a daily tablet that contains the appropriate mix of
oestrogen and progestogen, depending on preparation.
- The oral route is convenient and cheap but does influence lipid metabolism and the
coagulation system through its effects on the liver during first-pass metabolism.
• The transdermal route, either given as patches applied to the skin on the
trunk or as measured amounts of gel.
- The oestradiol delivered directly into the circulation, avoiding the potentially adverse
effects on the liver and the coagulation system.
• Oestradiol is also available as small vaginal tablets and a vaginal ring, and
oestriol as measured dose vaginal cream in management of lower genital
tract symptoms.
• Progestogen in the form of levonorgestrel may be administered as an
intrauterine releasing system (IUS), Mirena. This device provides
endometrial protection for up to 5 years.
Prescribing and side effects of hormone
therapy
• Prior to prescribing HRT, important to weigh up the indications, proposed
benefits and potential risks for each patient individually.
• It is important to ensure that the woman has no contraindications to HRT
and to ensure that she has had no serious effects in the past when on the
contraceptive pill.
• Most side effects can be managed by a change in dose of oestrogen or a
change in type of progestogen. Some patients can also benefit from change
of route.
• The duration for which a woman should take HRT is frequently debated.
However, it is recommended that there should be no exact maximum age
at which a woman should stop HRT, rather employing regular assessment
of the woman and her needs along with review of the type and dose of
HRT she is taking.
Absolute contraindication Relative contraindication
Suspected pregnancy Uninvestigated abnormal bleeding
Breast cancer Large uterine fibroids
Endometrial cancer Past history of benign breast
Active liver disease disease
Uncontrolled hypertension Unconfirmed personal history or a
Known current venous strong family history of VTE
thromboembolism Chronic stable liver disease
Known thrombophilia Migraine with aura
Otosclerosis
Side-effects associated with Side-effects associated with
oestrogen progestogen
Breast tenderness or swelling Fluid retention
Nausea Breast tenderness
Leg cramps Headaches
headaches Mood swings
Depression
Acne
THANK
YOU