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DR. TENO
O&G DEPT, MPHA
6TH OCTOBER 2022

Outline
Definitions
Physiology of menopause
Signs and Symptoms
Treatment
References

Definitions
Term Definition
Pre-menopausal or
perimenopause
Years leading up to menopause. Change from normal oculatory cycle to
cessation of menses.
Menopause Final menstrual period and is diagnosed after 12 months of
amenorrhoea.
Climacteric Peridod of time when a woman passes from reproductive stage,
through perimenopausal transition AND menopaus to post-
menopausal years.

Peri-menopuse Menopuse
Post--
menopuse
On going process
Age Range: 42 – 44
years
Hormones are
fluctuating
End point of a process
Age Range: 45 – 55 years
Hormones are stable
Climacteric
End point of a process
1– 3 years after
menopause
Hormones are stable

Peri-
menopause or
Premenopause
■ Also known as premature ovarian failure
(POF)
■ Transition phase when a women passess
from reproductive to non-reproductive
stage
■ May start 8 years before menopause
■ Characterized by irregular cycles and
climacteric symptoms
– Vasomotor Symptoms: hot flushes,
diaphoresis, vaginal dryness
– Sleep disturbances, mood changes
and sexual problems (↓ libido,
dyspareunia)

Menopause
■ Greek origin: pausis (cessation) and men
(month)
■ Transition from reproductive to non-
reproductive age
■ Permanent cessation of menstruation
following loss of ovarian activity (> 12
months)
■ Median age: 50-52yrs

Menopause
■ Symptoms:
– Hot flushes
– Night sweats
– Joint and muscle pain
– Vaginal dryness
– Mood changes
– Lack of interest in sex

ENDOCRINOLOGY
OF PERI-
MENOPAUSE
Premature Ovarian
Failure (POF)

Physiology of
Menstrual
Cycle
• Follicle  Estrogen
• Corpus Luteum 
Progesterone
• Menstrual cycle lenght:
determined by rate & quality
of follicular growth &
development

Regular Menstrual Cycle
■ Maintained by the number of ovarian follicules
■ 20 weeks of gestation: 7 million
■ At birth: 2.5 million Reduced by atresia
■ Menarche: 400 000
■ Every month a woman releases 400 000 - 500 000 via their menses
■ Maintained by the hypothalamus pituitary gland, ovary, cortex, thyroid and
adrenal gland

Perimenopausal Transition
Decreasing
ovarian
oocytes/follicles
↓ estrogen
↑ FSH
Inhibits
ovulation/annovulation
↓ Inhibin
MENSTRUAL
IRREGULARIT
Y

■ Menstrual irregularity is percieved as:
– Skipped menstrual periods or
– longer durations (40– 60 days)

Post-
menopause:
Source of
Estrogen
■ Ovarian oocytes/follicles no longer
produce/secrete estrogen
Estrogen is derived from:
■ Peripheral conversion in the adipose
tissue
– Androstenedione  Estrone
– Testosterone  Estradiol
■ Adrenal glands:
– Androstenedione  estradiol
■ Ovary (granulosa cells):
– testosterone  estradiol

Inhibin B inhibits
the production of
FSH

Early menopausal
transition
Irregular cycles
↓ inhibin B
Fluctuating ant. Pituitary
gonadotrophins
↑ FSH
Negative feedback
removed
↑ Estradiol
(Ovary)
↓ No of follicles
↑ Aromatase
activity
Converts
Testosterone to
estradiol
↓ Progesterone

When all
follicles are
depleted
increased FSH
increased
estradiol
ovary becomes
unresponsive
What happens when all follicles are
depleted???
LH continues to stimulate the secretion of
androgens

Hormone Production
after Menopause
■ 10-20 fold ↑ in FSH
– Half life: 3-4hrs
■ 3-fold ↑ in LH
– Higher clearance rate
– Half life: 20min
– No –ve feedback peptide
■ Levels reach max in 1-3yrs then
decline due to:
– Aging of gonadotrophin
secreting cells
– Reduced ability to respond
to GnRH

Clinical
Manifestations of
Estrogen Deficiency
Signs and symptoms
Ovaries and Endometrium
Brain
Cardiovascular System
Urogenital Tract
Bone

Signs and
Symptoms
■ Hot flashes: related to episodic
elevations of LH
■ Upper body vasodilatoin
■ Intense perspiration
■ Unpleasant psychological symptoms and
functioning
■ Vulvovaginal and urinary disorders

Ovaries
■ Ovarian senescence is accelerated as the woman ages
■ Marked anatomical differences:
– Smaller volume
– Lack of follicular cysts
– Increased atretic follicles
– Persistent corpora albicans
■ Ovarian Size
– Premenopause: 3.5x2x1.5cm
– Early menopause (1-2yrs): 2x1.5x0.5cm
– Late menopause (2-5yrs): 1.5x0.75x0.5cm

Effect of estrogen on Endometrium
■ Early: fluctuant endometrial thickening in reposnse to estrogen levels (opposed by
progesterone)
■ Later: anovulation  estrogen no longer opposed by progesterone  increased
proliferation and disorganization of endometrial tissue
■ Estrogen derived from aromatization of androgen (androstenedione) to estrogen
– ↓ sex-hormone binding globulin (SHBG) increases bioavilability of estrogen
– Post-menopause: no estrogen  atrophic and cystic changes
■ Women are at risk of gynecologic complications: endometerial Ca, Endometriosis,
Adenomyosis and ovarian Masses (benign or malignant)

Psychological
Functioning
■ Depressive symptoms
■ Memory difficulties
■ Concentration difficulties
■ Sleep disorders
■ Reduced sexual interest and activity

Effect of
Estrogen on
the Brain
■ Limbic system: increase synaptic density
in the hipocampus
■ Acetylcholine: increase neurotransmitter
activity
■ Stimualte neurons growth  repairation
■ Act as an antioxidant
💡estrogen
receptors: Pituitary,
hypothalamus,
Limbic forebrain,
cerebellum, cerebral
cortex, brain stem,
spinal cord

Effect of
Estrogen
Deficiency
on the CNS
■ Hot flushes
■ Sleep disorders
■ Loss of memory
■ Faitgue
■ Irritability

Effect of
Estrogen on
the CVS
■ Estrogen is cvardioprotective
■ Lower CHD incidence in women before
menopause
■ After menopause, similar CHD incidence
in men and women
■ Ovarian functin protevcts against CHD

Effect of
Estrogen on
Lipoprotein
Metabolism
■ Decreases Low density Lipoprotein (LDL)
– ↑ catabolic rate
– ↑ hepatic receptors
■ Increases High density lipoproteins (HDL)
– ↑ HDL lipoprotein synthesis
– ↓ HDL clearance
– ↓ heaptic receptors of HDL

Effect of
Estrogen
Deficiency
on Lipid
Profile
■ ↑ total cholesterol (CHOL)
■ ↑ low density lipoproteins (LDL)
■ ↑ triglycerides (TG)
■ ↓ high density lipoproteins (HDL) 
ATHEROGENIC

Effect of
Estrogen
Deficiency on
the
Urogynaecologi
c Mucosa
■ Vaginal atrophy leading to vaginal
dryness
■ Urethral mucosa atrophy 
pollakiuria
■ Bladder mucosa atrophy  urge
incontinence

Effect of
Estrogen
deficiency
on the Bone
■ Gonadal failure  ↑ bone reapsorption
– More remodelling sites are activated
– More bone is removed than
synthesized
■ Biochemical markers that are increased in
urine:
– Desoxypiridinolone, hydroxyproline,
calcium
■ Bone loss  osteoporosis
■ ↓ intestin absorption of Calcium
■ ↑ renal loss of calcium
💡estrogen
receptors are
located in the
osteoblasts and
osteoclasts

Diagnosis
■ Diagnosis is based on age and symptoms
■ Blood tests to measure FSH
■ Done 4-6 weeks apart (due to changes of
FSH levels during menstrual cycle)

Treatment
■ Hormonal Replacement
Therapy (HRT)
■ AIM: relieve symptoms of menopause
and replace homones that are at lower
levels

■ Combined Hormonal
contraceptive
■ Estrogen Therapy:
– Daily pill
– Patch
– Vaginal ring, gel or
spray

References
■ Nendaz, G. Menopause, perimenopause, postmenopause. 2001. Hospital
University, de Geneve
■ Speroff et al. Clinical Gynaecologic Endocrinology and Infertility, 8th Edition.
2010

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