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1. PHYSIOLOGY
MENSTRUATION AND
MENSTRUAL DISORDERS
Amnan Haziq Bin Ahamad Tarmizi 59211118140
Muhammad Arifin bin Rosley 59211118122
Muhammad Zarif bin Mohd Rashid 59211118120

2. Learning Objectives
1.Brief description on physiology of menstruation
2.Definition of the various terms used to describe abnormal menstruation
3. Causes of heavy menstrual bleeding (HMB) (menorrhagia)
4. Symptomatology of heavy menstrual bleeding including assessment of the
severity
5. Investigations in patients with HMB
6. Drugs used for treatment of HMB
7. Basic principles of management of HMB including treatment options

3. PHYSIOLOGY OF MENSTRUAL CYCLE
• A tightly coordinated cycle of 28 days with stimulatory and inhibitory effects that result in the
release of single mature oocyte from multiple primordial follicles
• Normal menstrual cycle
o Flow of 2-6 days
o Cycle length of 21-35 days
o Amount of blood less than 80 ml
• This occurs as a result of the shedding of endometrial lining due to
• Failure of fertilization of the oocyte.
• Failure of implantation.
• The cycle depends on changes occur after puberty within ovaries and fluctuation in ovarian
hormone levels.
• Ovarian hormone levels are controlled by the pituitary and hypothalamus within the
hypothalamo-pituitary-ovarian axis(HPO)

4. • Hyphothalamus
Secretes GnRH which will stimulate the
basophil cells in anterior pituitary gland for
hormone synthesis and secretion
• Pituitary gland
Releases FSH and LH
Controlled by ovarian sex steroid
hormones(oestrogen and progesterone)
• Oestrogen
-low: Negative feedback on LH production
-High: positive feedback on LH production by
increasing receptors on pituitary gland
• Progesterone
Low: Positive feedback on FSH and LH
secretion
High: negative feedback, inhibit FSH and LH
production

5. •Physiological events of menstrual cycle can be described as
o Ovarian cycle -changes that occur in the follicles of the ovary
o Uterine cycle - changes in the endometrial lining of the uterus
•Ovarian cycle
• Follicular phase
• Ovulation
• Luteal phase
•Uterine cycle
• Proliferative phase
• Secretory phase
• Menstrual phase

6. Ovarian cycle
• Follicular phase
➢ First day of menstrual cycle :
o Oestrogen, progesterone and inhibin
levels are low.
o Increase of follicle stimulating
hormone (FSH)
○ will stimulates small antral follicles on
the ovaries to grow (Folliculogenesis)
➢ The follicles that reaches maturity is
called a graafian follicle
➢ Within the follicles there are two cell types
that are involved in processing steroids
○ Theca
○ Granulosa cells

7. ➢ LH stimulates production of androgen from cholesterol within the theca
cells
➢ These androgens are converted into oestrogens under the influence of
FSH
➢ As the follicles grow and oestrogen secretion increases.
○ This will cause negative feedback on pituitary gland.
○ Assist in selection of one follicle to continue its development towards ovulation
(dominant follicle).
➢ Dominant follicle
○ The most efficient aromatase activity.
○ The highest concentration of FSH-induced LH receptors.
➢ Smaller follicle will undergo atresia
➢ At the end of this phase, ovulation occurs

8. Ovulations
• During the follicular phase, oestrogen suppress
production of LH from pituitary gland
• As the ovum nearly mature, oestrogen level
increases above threshold and cause a positive
feedback on hypothalamus and pituitary.
• This will cause the LH level increases sharply .
• Physical ovulation of oocyte after breakdown of
follicular wall takes place under the influence of :
• LH
• FSH
• Proteolytic enzymes (plasminogen activators and
prostaglandin)

9. Luteal phase
• The remaining granulosa and theca cells form the
corpus luteum.
○ The corpus luteum undergoes extensive vascularization
to supply granulosa cells with rich blood supply for
continued steroidogenesis.
○ This is aided by vascular endothelial growth factor
(VEGF).
• Ongoing pituitary LH secretion and granulosa cell
activity ensure a supply of progesterone, which
stabilizes the endometrium in preparation for
pregnancy.
• Progesterone levels are at their highest in the cycle
during the luteal phase.
• This also has the effect of suppressing FSH and LH
secretion to a level that will not produce further
follicular growth in the ovary during that cycle.

10. • In the absence of beta- human chorionic gonadotrophin (βhCG) being produced from
an implanting embryo, the corpus luteum will regress in a process known as luteolysis.
• With the disintegration of corpus luteum, causes sharp decline of progesterone
• The withdrawal of progesterone due to absence of corpus luteum has the effect on
the uterus of causing shedding of the endometrium and thus menstruation.
• Reduction in levels of progesterone, oestrogen and inhibin feeding back to the pituitary
cause increased secretion of gonadotrophic hormones, particularly FSH.
• New preantral follicles begin to be stimulated and the cycle begins anew.

11. Menstrual phase
• Menstruation is the shedding of the dead
endometrium ceases as the endometrium
regenerate.
• A fall in circulating levels of oestrogen and
progesterone approximately 14 days after
ovulation. This leads to:
A. Loss of tissue fluid
B. Vasoconstriction of spiral arteriole and
causes endometrial ischemia
• Vaginal bleeding will cease after 5-10 days
• This results in tissue breakdown and loss of the
upper layers along with bleeding fragments of
the remaining arterioles, seen as menstrual
bleeding
• Enhanced fibrinolysis reduces clotting

12. Uterine cycle
• Proliferative phase
➢ Starts after menstruation
○ Glandular and stromal growth
start.
➢ The epithelium lining the endometrial
glands changes from a single layer of
columnar cells to a pseudostratified
epithelium.
○ From 0.5 mm at menstruation to
3.4-5 mm at the end of
proliferative phase.

13. •SECRETORY PHASE
➢ Occur after ovulation (generally
around day 14).
➢ LH surge, the oestrogen-induced
cellular proliferation is inhibited.
➢ Endometrial glands will become more
tortuous, spiral arteries will grow and
fluid is secreted into glandular cells
and into the uterine lumen.
➢ Later in the secretory phase,
progesterone induces the formation
of a temporary layer.

15. DEFINITION OF THE VARIOUS TERMS USED TO DESCRIBE ABNORMAL MENSTRUATION
Term Definition
Amenorrhea Absence of menstrual bleeding
Menorrhagia Excessive (>80 ml) or prolonged menstruation at regular
intervals.
Metrorrhagia Heavy bleeding at irregular times
Menometrorrhagia Combination of Metrorrhagia and Menorrhagia
Polymenorrhea Frequent and regular heavy bleeding with interval of 21
days or fewer
Oligomenorrhea Reduced frequency with frequency of menstruation is
greater than 45 days
Dysmenorrhea Lower abdominal pain or pelvic pain associate with
menstruation

16. Heavy menstrual bleeding(HMB)
(Menorrhagia)

17. Pathophysiology of Menorrhagia
1. Anatomical alterations of uterus
a. E.g. fibroids (30%), endometrial polyps, endometrial hyperplasia
b. Growths → blood supply is greater → impede venous return → heavy pooling →
endometrium weaken
c. Growths → inhibit muscle contracture → poor haemostasis
d. Clinical presentation depends on the location and size of lesion
2. Anovulation
a. E.g. polycystic ovary syndrome(PCOS)
b. No ovulation → no corpus luteum → no progesterone → oestrogen unopposed →
excessive endometrial thickening → blood supply outgrow → asynchronous
breakdown of the endometrial lining at different levels
3. Coagulation disorders
a. e.g. von Willebrand disease, thrombocytopenia
b. Deficiencies of platelets and fibrin → less thrombi (acts as ‘plugs’) → blood overflow

18. FIGO System classification (PALM-COEIN)
PALM (Structural causes) COEIN (Non-structural causes)
● Polyp
● Adenomyosis
● Leiomyoma
○ Submucosal myoma
○ Other myoma
● Malignancy and hyperplasia
● Coagulopathy
● Ovulatory dysfunction
● Endometrial
● Iatrogenic
● Not defined (dysfunctional uterine
bleeding)
Aetiologies of HMB - Structural & Non-Structural

19. Causes of menorrhagia
● Endometrial polyps
● Adenomyosis
● Uterine fibroids
● Endometrial/cervical carcinoma
● Coagulation disorder (i.e: Von Willebrand disease)
● Polycystic ovarian syndrome (PCOS)
● Intrauterine contraceptive device (IUCD)
● Drug therapy (i.e: warfarin)

20. Endometrial Polyps
● Also known as uterine polyps, overgrowths
of cells that usually benign.
● Uterine polyps are oestrogen-sensitive,
meaning they grow in response to circulating
oestrogen
● Clinical features : Bleeding between
menstrual periods (intermenstrual bleeding),
Excessively heavy menstrual periods
(menorrhagia), Vaginal bleeding after
menopause, Infertility
Adenomyosis
● Tissue that normally lines the uterus (endometrial
tissue) grows into the muscular wall of the uterus. The
displaced tissue continues to act normally thickening,
breaking down and bleeding during each menstrual
cycle.
● Clinical features : heavy or prolonged menstrual
bleeding (menorrhagia), severe cramping or sharp,
knifelike pelvic pain during menstruation
(dysmenorrhea), chronic pelvic pain, painful
intercourse (dyspareunia)

21. Uterine fibroids
● Benign tumour of uterus which consists of
smooth muscle and fibrous tissues which
arises from muscular wall of the uterus
● Clinical features : heavy menstrual bleeding
(duration or amount), post coital bleeding,
dysmenorrhea, palpable mass and pressure
symptoms, pelvic pain
Cervical carcinoma
● Cervical cancer is a type of cancer that occurs in the
cells of the cervix. Various strains of the human
papillomavirus (HPV), a sexually transmitted
infection, play a role in causing most cervical
cancer.
● Clinical features : vaginal bleeding after
intercourse, between periods or after menopause,
watery, bloody vaginal discharge that may be heavy
and have a foul odour, pelvic pain or pain during
intercourse

22. Polycystic Ovarian Syndrome (PCOS)
● A hormonal disorder common among women of
reproductive age. Women with PCOS may have
infrequent or prolonged menstrual periods or
excess male hormone (androgen) levels.
● The ovaries may develop numerous small
collections of fluid (follicles) and fail to regularly
release eggs.
● Clinical features : Irregular periods. Infrequent,
irregular or prolonged menstrual cycles are the
most common sign of PCOS. For example, you might
have fewer than nine periods a year, more than 35
days between periods and abnormally heavy
periods.
Coagulation disorder (Von
Willebrand disease)
● A lifelong bleeding disorder in which blood doesn't
clot well. People with the disease have low levels of
von Willebrand factor, a protein that helps blood clot,
or the protein doesn't perform as it should.
● Clinical features : Excessive bleeding from an injury
or after surgery or dental work, nosebleeds that
don't stop within 10 minutes, heavy or long
menstrual bleeding (menorrhagia), blood in urine or
stool, easy bruising or lumpy bruises

23. Drug therapy
● Certain medications, including anti-inflammatory
medications, hormonal medications such as
oestrogen and progestins, and anticoagulants such
as warfarin (Coumadin, Jantoven) or enoxaparin
(Lovenox), can contribute to heavy or prolonged
menstrual bleeding
Intrauterine contraceptive
device
● Intrauterine contraceptive device is an
intrauterine device (IUD) that can provide
long-term birth control (contraception).
It's sometimes referred to as a
non-hormonal IUD option
● Clinical features : bleeding between
periods, cramps, severe menstrual pain and
heavy bleeding

24. Symptomatology of Heavy
Menstrual Bleeding

25. Symptoms
● Soaking through one or more sanitary pads or
tampons every hour for several consecutive hours
● Needing to use double sanitary protection to
control your menstrual flow
● Needing to wake up to change sanitary protection
during the night
● Bleeding for longer than a week
● Passing blood clots larger than a quarter
● Restricting daily activities due to heavy menstrual
flow
● Symptoms of anaemia, such as tiredness, fatigue
or shortness of breath

26. Related Pathologies Towards Menorrhagia
Associated symptoms Suggestive of
Irregular bleeding
Endometrial or cervical polyp or other cervical abnormality
Intermenstrual bleeding
Postcoital bleeding
Excessive bruising/bleeding from other sites
Coagulation disorder (coagulation disorders will be present in 20% of those
presenting with ‘unexplained’ heavy menstrual bleeding)
History of post partum haemorrhage
Excessive postoperative bleeding
Excessive bleeding with dental extractions
Family history of bleeding problems
Unusual vaginal discharge Pelvic inflammatory disease
Urinary symptoms, abdominal mass or fullness Pressure from fibroids
Weight change, skin changes, fatigue Thyroid disease

27. History Taking
1. Quantity and quality of bleeding
a. For how many day does the bleeding last?
b. How many day is bleeding heavy?
c. What type and how much sanitary
protection is needed?
d. Does she experience flooding?
e. Does she pass clots of blood? If so, what
size?
f. Does it affect her daily activities or work?
g. Is there anything mixed with blood?
2. Symptoms of anaemia
3. Menses pattern from menarche
4. Pain associated
Physical Examination
1. Signs of anaemia.
2. Abdominal examination
a. Pelvic masses
3. Pelvic examination
a. Bimanual examination
i. tenderness, uterine size, adnexal
masses
b. Speculum examinations
i. Visualized for polyps/carcinoma
4. An enlarged, ‘bulky’ uterus suggests
uterine fibroids, and tenderness
suggests endometriosis, pelvic
inflammatory disease or adenomyosis.

28. Investigation in patient with
menorrhagia

29. ❖ Full blood count
➢ To determine in need of iron therapy or blood transfusion
in worse case
❖ Coagulation screen
➢ In patient with heavy menstrual bleeding since menarche
❖ Family history of coagulation defects
➢ Transvaginal ultrasound scan
➢ In patient with postcoital bleeding, intermenstrual
bleeding, pain/pressure symptoms or enlarged uterus or
vaginal mass is palpable on pelvic examination
❖ High vaginal endocervical swabs
➢ To test for presence of vaginal thrush, bacterial vaginosis
and trichomonas vaginalis
High vaginal swabs

30. ❖ Pipelle endometrial biopsy
➢ Age over 45 years old
➢ High risk for endometrial pathology
❖ Thyroid function test
➢ Only when history is suggestive of a thyroid disorder
❖ Hysteroscopy
➢ Endometrial biopsy attempt fail
➢ Endometrial biopsy sample is insufficient for
histopathology assessment
➢ There is an abnormality on transvaginal ultrasound scan
suggesting endometrial polyp or submucosal fibroid

31. Basic principle of management of HMB including
treatment options
Prior to management;
1. Patient’s Preference
2. Risk or Benefits of each option
3. Contraceptive Requirements
4. Past Medical History
5. Past Surgical History
Can be divided into :
● Medical
● Surgical
Medical Surgical
Levonorgestrel
Intrauterine System
Endometrial ablation
Tranexamic acid Umbilical artery embolization
Norethisterone Myomectomy
GnRH Agonist Transcervical Resection of
Fibroid
Hysterectomy

32. Levonorgestrel intrauterine system (LNG IUS)
● T shaped intrauterine device that releases the
hormone levonorgestrel into the uterus.
● First option for treatment of heavy periods
● The most effective medical treatment and suitable
for most women.
● It is used for heavy menstrual periods, birth controls
and to prevent excessive build of the lining of the
uterus in those on estrogen replacement therapy.
● It provides long-term use of at least 12 months

33. Tranexamic acid (TXA)
● Red blood cells and platelets bound together
with fibrin make blood clots.
● Plasmin, which breaks down the fibrin and
allows the clots to break up.
● Tranexamic acid inhibits activation of
plasminogen, thereby reducing conversion of
plasminogen to plasmin.
● Tranexamic acid interferes with the
fibrinolytic process. This reduces the
breakdown of fibrin and stops clots
dissolving, which in turn helps to reduce
bleeding.
● Risk of DVT

34. Mefenamic acid and other NSAIDS
● Endometrial prostaglandins are elevated with excessive menstruation, and NSAIDS reduce
prostaglandin levels through the inhibition of the cyclooxygenase enzyme.
● Reduce blood loss by 30 %.
● These drugs are also taken just at the time of menstruation

35. Combined oral
contraceptive pills (COCP)
● 50% reduction in menstrual blood loss.
● Shorten the menstrual period
● The main side effects can include irregular
vaginal bleeding, mood changes and breast
tenderness.
Gonadotropin-releasing
hormone (GnRH) agonist
● Only used in the short term due to the resulting
hypoestrogenic state that predisposes to
osteoporosis.
● May be used preoperatively to shrink fibroids or
cause endometrial suppression to enhance
visualization at hysteroscopy.
● In severe HMB, they allow the patient to improve
their Hb by allowing respite from bleeding

36. Injectable Progestogens
● Progestogen causes atrophy of
endometrium lining.
● Depot medroxyprogesterone acetate
(DMPA) can induce amenorrhea in up to 50%
of users after 1 year and 80 % after 1 year
● Side effects: weight gain, acne, bloating.
Progestins therapy
● Taken 15 mg daily in cyclical pattern from
day 6 to day 26 of the menstrual cycle.
● Safe and effective oral preparation, can
regulate bleeding pattern.
● Can cause breakthrough bleeding
● Eg: Norethisterone

37. Endometrial ablation
● Endometrial ablation is a surgical procedure that is used to remove (ablate) or destroy the
endometrial lining of the uterus to prevent regeneration of endometrium
● Should never be performed on women who wish to have children.
● Most often employed in women who suffer from excessive menstrual bleeding, who have
failed medical therapy and do not wish to undergo a hysterectomy.
● Useful in adenomyosis,uterine fibroids.
● The first generation techniques have now largely been replaced by newer second
generation techniques.

38. Endometrial ablation
First generation
Rollerball endometrial ablation
Second generation
1. Thermal Uterine Balloon Therapy 2. Microwave ablation
3. NovaSure Endometrial Ablation

39. Hysterectomy
● Hysterectomy is the surgical removal of the
uterus.
● Indicated for older women who have completed
their their family
● The surgery is normally recommended only
when other treatment options are not available
or have failed.
● Tx for adenomyosis , fibroid, cervical ca

40. Laparoscopic Myomectomy
● HMB secondary to large fibroid with pressure symptoms who wish
to conceive
● Contraindication:Pregnant, malignancy, Asymptomatic fibroids
(medical tx)
● Complication : Bleeding, infection, visceral damage,
thromboembolism and fever.
Uterine Artery Embolization
● Useful HMB associated with fibroids, adenomyosis
Transcervical Resection of Fibroid
● May reduce HMB and appropriate to women wishing to conceive.

42. Other disease causes menorrhagia:
1. Thyroid disease: Medication (Carbimazole/ Levothyroxine)
2. PID: Antibiotics, Treatment for your partner, Temporary abstinence
3. Drugs : Change the medication/dose.

43. Treatment in Amenorrhea
Need of the treatment depends on;
Underlying Causes
● Turner Syndrome: HRT
● Imperforate hymen :Surgery
● Thyroid disease: appropriate
medical treatment
● PCOS: appropriate treatment
Trying to conceive
● Anovulation : respond well with
ovulation induction treatment
● PCOS: ovulation may resume with
weight reduction
Want a regular period
● OCP
● HRT
Need a contraception
● Confirmed ovarian failure does not
need contraception
● Women requiring contraception -
OCP methods of choice.

44. Treatment in Dysmenorrhea
1. NSAIDs are 1st line treatment
○ Propionic acid derivatives ( Ibuprofen, Naproxen)
○ Fenamates Mefenamic acid)
2. OCP
○ If NSAIDs is not effective/ contraindicated
○ 90% effective within 3 4 months used
3. Some patients require combining both drugs

45. Treatment in Polymenorrhea
Treatment depends on the underlying causes.
● If no underlying causes, no need for tx
● If a woman is bothered by her polymenorrhea but is not trying to conceive, then contraceptive
pills to lengthen her cycle can be a good option.