MENOPAUSE

BY MUZAMIL OSMAN

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OVERVIEW
Because the loss of ovarian function has a profound impact on the
hormonal milieu in women and on the subsequent risk for the development
of disease via the loss of estrogen production, improving our understanding
of reproductive aging is critical to care for all women.
Before menopause, estrogen & progesterone are produced in the ovaries.
Estrogen works to regulate a woman’s menstrual cycle & 2° sexual Cx, & also
prepare the body for fertilization & reproduction. Progesterone prepare the
uterus for possible implantation, prepare the breast for lactation.
As a woman reaches menopause the body produces less & less estrogen &
progesterone.

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INCIDENCE
• Approximately 90% of women experience menopause during the
early 50s. The other 10% of women experience menopause prior to
46 years of age (often termed early menopause), with 1% of women
experiencing menopause at an age younger than 40 years (premature
menopause or premature ovarian failure

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DEFINITIONS
Menopause: Refers to complete / permanent cessation of menstruation
at the end of reproductive life due to diminished ovarian reserves & is
indicated by the final menstrual period. Follow cessation of menstruation
[amenorrhea] for twelve consecutive months without any pathology.

Climacteric: Refers to the phase of the aging process of women during

which transition is made from the reproductive stage of life to non-
reproductive stage.
This period usually becomes clinically apparent over 2 to 5 yrs around the
menopause.

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Perimenopause – 3-5yrs preceding menopause preceding menses
become annovulatory, decreased in frequency and finally stops.

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• Post menopause (after menopause) — is defined as the first five
years after the final menstrual period. It is characterized by further
and complete dampening of ovarian function and accelerated bone
loss; many women in this stage continue to have hot flashes. Stage +2
(late) begins five years after the final menstrual period and ends with
death

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AGE OF MENOPAUSE

Age at which menopause occurs is genetically predetermined.

The age of menopause is not related to age of menarche or age at last
pregnancy. It is not related to number of pregnancy , lactation or use of
oral pills.
The age of menopause ranges between 45 -55 years, average being 50
years.

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ABNORMAL MENOPAUSE
1.PREMATURE MENOPAUSE.
• Refers to menopause that occur at or below the age of 40. Often, there is
a familial diathesis.
2. DELAYED MENOPAUSE.
Refers to menopause that fails to occur even beyond 55 years . The
common cause are uterine fibroids , diabetes mellitus and oestrogenic
tumour of the ovary.
3. ARTIFICIAL MENOPAUSE
Refers to permanent cessation of ovarian function done by artificial means
i.e surgical removal of ovaries or by radiation.
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 FACTORS AFFECTING THE AGE OF MENOPAUSE:
Early menopause:
· Family history
· Cigarette smoking ( number & duration)
.severe malnutrition
· Abnormal chromosome karyotype (turners syndrome, gonadal
dysgenesis)
· Precocious puberty
· Surgery (TAH )

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Delayed or late onset of menopause:
- Obesity,
- High socioeconomic class

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Pathophysiology
10 years before menopause; decrease in number of primordial follicle,
Increase FSH, LH cause anovulation → inadequate Leuteal phase →
decrease progesterone → DUB and endometrial Hyperplasia
• at menopause dramatic decrease of estrogen→menstruation ceases
and symptoms of menopause starts.
• But still ovarian stroma produces small androstenedione and
testosterone which is converted to estrone in peripheral fat.

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 ENDOCRINE CHANGES DURING MENOPAUSE:

Menopause is a hormone deficient state. The 1° alteration is in the

ovary, which decreases responsitivity to stimulation by pituitary
gonadotropins leading to further drop in estrogen levels.

(a) Pituitary hormones:

• There’s a gradual increase of circulating FSH towards the upper limit
of the normal menstrual cycle during the peri-menopausal period.
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• There’s a decrease in serum estradiol. No significant changes in
LH level, & only a slight decrease in progesterone levels.

• Anovulatory cycles may be more interspersed with ovulatory

cycles, & consequent anovulatory bleeding may occur.

Clinically:
• There’s variation & unpredictability in amount of flow & in
duration & timing of the bleeding.
• There can be periods of amenorrhea, with elevated serum FSH
& LH levels followed by few months of ovulatory cycles.
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b) Ovarian changes.
- There’s progressive loss of primordial follicles from the ovaries during
intrauterine life, throughout reproductive life & menopause.

- At the end of the 4th decade of life the ovaries become increasingly less
responsive to stimulation by pituitary gonadotropins.

Also recruitment & stimulation of follicles to full maturity becomes

increasingly difficult.

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• Ovulation become irregular, infrequent and finally stops

• Menstrual function stops because of insufficient estrogen to stimulate

endometrial proliferation & growth.

• Ovaries become smaller & fibrotic, with atrophy of the cortex which
contains the primordial follicles.

• The ovarian medulla become abundant with active stroma cells which are
source of ovarian androgen.
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MENOPAUSAL SYMPTOMS
1.Vasomotor symptoms
2.Psychological symptoms
3.Urogenital symptoms
4.Skin effects
5.Bone effecs [ osteoporosis and fracture]
6.Cardiovascular and cerebrovascular effects

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1. VASOMOTOR SYMPTOMS
The characteristics symptoms of menopause is ‘HOT FLUSH’ .Hot flush
is characterized by sudden feeling of heat followed by profuse
sweating.
Low oestrogen levels prerequisite for hot flush. It coincides with GnRH
pulse secrection with increase in serum LH level. The thermoregulatory
centre in association with GnRH centre in the hypothalamus is involved
in the aetiology of hot flush.
Other symptoms include fatigue, weakness and palpitation.

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2. PSYCHOLOGICAL SYMPTOMS
• There’s increased frequency of anxiety, headache, insomnia,
irritability and depression .
• They have mood swings and inability to concentrate.
• Dementia and mainly Alzheimer disease are more common in
postmenopausal women

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3.Urogenital effects
- Reduced vaginal thickness, loss of rugae
- change of vaginal pH ( 3.5-4.5 to 6-8 )
- vagina becomes small & atrophic, dyspareunia may
occur.
-there’s 30% drop in urethral closure pressure
- there’s diminished support to the pelvic organs ie bladder & urethra.
- atrophic urethritis may occur, characterized by urgency, frequency,
dysuria, suprapubic pain
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4.Skin effects

Decrease estrogenic levels after menopause reduces skin thickness 2°

decreased epidermal collagen content.

• skin is lax, more transparent, has readily visible blood vessels, & is
more easily bruised.

• ERT increases skin collagen content, alter vascularisation of the skin &
increase intracellular fluid content.

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5. Bone effects
- Osteoporosis is one of the most significant long term sequelae of menopause
- the skeleton is sufficiently compromised by reduction in the mass per unit
volume leading to fracture even in the absence of trauma.

- most fractures seen are of vertebrae, ulna, distal radius & neck of femur.
Mechanism:
-Estrogen deficiency results in declining levels of Calcitonin, which opposes
effect of Parathyroid hormone.

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• Estrogen inhibits production of prostaglandins ( PGE2) & interleukin
both of which increase bone resorption.

• Estrogen increases formation of 1,25 (OH)2 D3

• estrogen promotes renal tubular Ca++ reabsorption.

• Thus ERT can block the decline in bone mineral density & reduce
fracture rates in postmenopausal women
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6.CARDIOVASCULAR
&CEREBROVASCULAR EFFECTS.
• Risk of ischaemic heart disease, coronary artery disese and stroke are in post
menopausal women due to deficiency of oestrogen.
• Oxidation of LDL and foam cell formation cause vascular endothelial injury ,
cell death and smooth muscle proliferation. All these lead to vascular
atherosclerotic changes, vasoconstriction and thrombus formation.

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Short term . Hot flushes and night sweats
[ 0-5years] Labile mood, anxiety, tearfulness
Loss of concentration , poor memory
Dry and itchy skin
Hair changes
Decreased sexual desire

Vaginal dryness, soreness

Intermediate. dypareunia
[ 3-5years] Sensory urgency,
Skin atrophy
Recurrent urinary tract infections

Osteoporosis .
Long term. Cardiovascular disease.
[ > 10years] dementia

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EVALUATION AND WORKUP

The Triad of: 1. Hot flushes 2. Amenorrhea 3. increase FSH > 15 i.u./L.
1. Complete history
- duration,severity,type of symptoms
- h/o liver dx, gallbladder dx, TAH & BSO
2. Physical examination
- BP, breast, thyroid
3. Investigation
- lipid profile - cholesterol, HDL, LDL, TGA
4. Endometrial evaluation
- for irregular vaginal bleeding Endometrial Bx is advisable

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5. Pituitary gonadotropins & estrogen levels. Serum levels of FSH & LH need
to be evaluated if:
- the diagnosis of menopause is not clear
- there’s irregular vaginal bleeding /oligomenorrhoea/
-there’s vasomotor symptoms without amenorrhea
6. Bone mass measurement using:
- Quantitative Computed Tomography of the lumber vertebrae
- Dual-energy x-ray absorptiometry (DEX), a new method for measuring bone density
7. Screening for ovarian cancer.
- palpation of the ovaries
- measurement of serum levels of CA-125
- Ultrasonography i.e vaginal uss

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TREATMENT
1. Counseling and reassurance
2. Hormone replacement therapy
• Estrogen – a minimum of 2mg of oestradiol is needed to mentain
bone mass and relief symptoms of menopause.
• Women with uterus – add progestin at last 10 days to prevent
endometrial Hyperplasia
• Sequential Regimens - used in patient close to menopause.
Oestrogen – in the first ½ of 28 day per pack
& Oestrogen & Progetin in 2nd 1/12 of 28 day pack.

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HORMONAL REPLACEMENT THERAPY:

• CONTRAINDICATIONS
• Undiagnosed vaginal bleeding
• Acute liver disease.
-chronic impaired liver functions
• Acute vascular thrombosis
• Breast Cancer

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THERAPEUTIC REGIMENS

HRT may include;

Only estrogen
Estrogen & progesterone
Estrogen & androgens
Selective estrogen receptor modulators (SERM)
Growth H & Dehydroepiandrosterone.

Types of estrogens;
Natural estrogens; estradiol, estrone, estriol
Semisynthetic estrogens; ethinyl estradiol
Synthetic estrogens; those with steroids; mestranol or without steroids but
derivatives of diphenylene;stillbestrol

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Osteoporosis Cont……
• Prevention – improve lifestyle
- regular exercise
- eliminate smoking & alcohol
• Medication
a. ERT (Estrogen Replacement Therapy)
b. Bisphosphonate; inhibit osteoclastic activity
c. Raloxifene; is selective oestrogen receptors moderator [SERMs]
d. Calcitonin inhibit osteoclastic activity
e. Calcium Supplement & Vit D.

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THANK YOU

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