MENSTRUAL CYCLE

PHYSIOLOGY AND
PATHOPHYSIOLOGY

Dr. Supriyatiningsih, M.Kes, SpOG

Department of Obstetrics & Gynecology

Faculty of Medicine Muhammadiyah University
Yogyakarta Indonesia

THE NORMAL MENSTRUAL CYCLES IS

DETERMINED BY A COMPLEX INTERACTION
BETWEEN REPRODUCTIVE ENDOCRINE ORGAN

HYPOTHALAMUS
ANTERIOR PITUITARY GLAND
OVARY
ENDOMETRIUM
But the main regulation is
intraovarian

The Menstruation Cycle

3 activity during Menstrual Cycle :
Hypothalamus and Pituitary activity
Ovarian activity

Uterine activity

Environment
CNS
Compartemen
IV
Hypothalamus
GnRH
Anterior
pituitary

Compartemen
III

LH

FSH
Compartemen
II

Ovary
Estrogen

Comparteme
nI

Progesterone

Uterus
Menses

To survive, the follicle must be exposed to a wave

of gonadotropic hormone release

Ovulasi

Number of oocytes at different ages

Age
3-6 weeks of
gestation
8 weeks
8-20
20-40 weeks
Birth to puberty
Reproductive
years

# of cells
Endoderm of the
yolk sac

10,000

Proliferation by
mitosis

600,000

Mitosis, meiosis,
atresia

6-7,000,000

80% loss

1-2,000,000

Loss to atresia

300,000

Ovulation

400-500

Membran sel
LISOSOM
Asam fosfatase
Enzim litik

Upregulated
MMP

Penurunan
aliran darah
Vasokonstriksi
a. spiralis

Prostaglandin

Iskemia

Sekresi dan
aktivasi sitokin

Makrofag
PMN
LImfosit granulasi

Menstruasi
Triptase &
kimase
Regenerasi endometrium

Degranulasi

Sel Mast
VEGF & FGF

Normal menstrual bleeding

Occurs approximately once a month
(every 26 to 35 days).
Lasts a limited period of time (3 to 7 days).
May be heavy for part of the period, but
usually does not involve passage of clots.
Often is preceded by menstrual cramps,
bloating and breast tenderness, although
not all women experience these
premenstrual symptoms.

Definitions
Normal:
Mean interval is 28 days
+/- 7 days.
Mean duration is 4 days.
More than 7 days is
abnormal.

Abnormal Bleeding
Abnormal bleeding (DUB or dysfunctional
uterine bleeding) includes:
Too frequent periods (more often than every 26
days).
Heavy periods (with passage of large, egg-sized
clots).
Any bleeding at the wrong time, including
spotting or pink-tinged vaginal discharge
Any bleeding lasting longer than 7 days.
Extremely light periods or no periods at all

Dysfunctional Uterine Bleeding

(DUB)
Most common menstrual disorder.
Can affect any women from menarche to
menopause.
Often the first clinical diagnosis for any
excessive menstrual bleedings.
Diagnosis has to be confirmed by a
process of exclusion of pathological
causes.

Abnormal Uterine Bleeding: Terminology & Definitions

Term

Definition

Pattern

Amenorrhea

No uterine bleeding for at least 6 months

Menorrhagia

Excessive amount (>80 mL/cycle) or Occurs

prolonged duration >7days, also called irregular
hypermenorrhea
intervals

Metrorrhagia

Uterine bleeding occuring at irregular but irregular

frequent interval, amount varies

at

Menometrorrha Irregular, heavy, and prolonged menstrual irregular

gi
bleeding
Oligomenorrhe
a

Decreased,
scanty
flow,
the
term Interval > 36-40
hypomenorrhea is used for regular timing days
with scanty amount.

Polymenorrhea Regular, frequent menstruation

Intermenstrual

Bleeding
periode

or

spotting

between

Interval
days.

<21

normal Between
periods (usually
light flow)

Average blood loss with

menstruation is 35-50cc.
95% of women lose <60cc.

Definitions
Menorrhagia:

Prolonged > 7 days or > 80 cc

occurring at regular intervals.
Synonymous with
hypermenorrhea

Menorrhagia occurs in 914% of healthy women.

Definitions
Metrorrhagia:
Uterine bleeding occurring
at irregular but frequent
intervals.

Etiologies AUB
Organic
Systemic
Reproductive
tract disease
Iatrogenic
Dysfunctional
Ovulatory
Anovulatory

Reproductive Tract
Causes of Benign Origin

Atrophy
Leiomyoma
Polyps
Cervical lesions
Infection

60% of women with PMB

will be found to have
atrophy. 10% will have
polyps and 10% will have
hyperplasia.
Karlsson, et al., 1995

Incidence of Endometrial Cancer

in Premenopausal Women

2.3/100,000 in 30-34 yr old

6.1/100,000 in 35-39 yr old
36/100,000 in 40-49 yr old
ACOG Practice Bulletin #14, 2000

DUB
Abnormal uterine bleeding
for which an organic
etiology has been excluded.
It is either ovulatory or
anovulatory in origin.

LH

FS
H

PUD

E2

Kelainan
Organik

Sistemik
Metabolik
Keganasan
Ggn kehamilan dini

Perdarahan dari uterus yang didasari oleh gangguan hormonal poros

Hipotamus-hipofisis-ovarium semata, tanpa dijumpai kelainan organik,
sistemik, metabolik, keganasan maupun gangguan kehamilan dini

Premenstrual Syndrome
Premenstrual Syndrome (PMS) is defined as the cyclic
recurrence in the luteal phase of the menstrual cycle of a
combination of distressing physical, psychological,
and/or behavioral changes of sufficient severity to result
in deterioration of interpersonal relationships and/or
interference with normal activities. Nearly 200
symptoms have been associated with this definition and
it is the clustering of these signs and symptoms that is
the hallmark of PMS.

Catamenial

The term catamenial is derived from the Greek

and signifies around menses. In general an
instance where a single recognized medical
condition presented in the premenstruum was
referred to as a catamenial disorder while a
cluster of symptoms was referred to as PMS.

Premenstrual Magnification

Many patients with psychiatric disorders also complain of

worsening of their symptoms around the premenstrual
phase, called premenstrual magnification (PMM).

PMS

Milder symptoms are believed to occur in about 30% to

80% of reproductive-age women, while severe
symptoms are estimated to occur in 3% to 5% of
menstruating women.

Concordance Rate
The concordance rate (if both twins have PMS)
was found to be significantly higher in
monozygous twins (93%) than dizygous twins
(44%) and in non-twin control women (31%).

Common Symptoms of PMS

Women with PMS
Symptom
Behavioral
Fatigue
Irritability
Labile mood with alternating
sadness and anger
Depression
Oversensitivity
Crying spells
Social withdrawal
Forgetfulness
Difficulty concentrating

Showing Symptoms (%)

92
91
81
80
69
65
65
56
47

Common Symptoms of PMS

(Continued)
Physical
Abdominal bloating
Breast tenderness
Acne
Appetite changes and
food cravings
Swelling of the extremities
Headache
Gastrointestinal upset

90
85
71
70
67
60
48

Differences Between PMS and PMDD

Diagnostic criteria Tenth Revision of

the International
Classification of
Disease (ICD-10)

Diagnostic and
Statistical Manual
of Mental
th
Disorders, 4 ed.
(DSM-IV)

Providers using
these criteria

Obstetrician/gynec Psychiatrists, other

ologists, primary
mental health care
care physicians
providers

Number of
symptoms
required

One

5 of 11 symptoms

Differences Between PMS and PMDD

(Continued)
Functional
impairment

Not required

Interference with
social or role
functioning
required

Prospective
charting of
symptoms

Not required

Prospective
daily charting of
symptoms
required for two
cycles

Patterns of PMS
Premenstrual symptoms can begin at ovulation with
gradual worsening of symptoms during the luteal phase
(pattern 1).
PMS can begin during the second week of the luteal
phase (pattern 2).

Patterns of PMS
(Continued)
Some women experience a brief, time-limited episode of
symptoms at ovulation, followed by symptom-free days
and a recurrence of premenstrual symptoms late in the
luteal phase (pattern 3).
The most severely affected women have symptoms that
at ovulation worsen across the luteal phase and remit
only after menses cease (pattern 4). These women
describe having only one week a month that is symptomfree.

Differential Diagnosis
Psychiatric disorders
Major depression
Dysthymia
Generalized anxiety
Panic disorder
Bipolar illness (mood
irritability)
Other

Medical disorders
Anemia
Autoimmune disorders
Hypothyroidism
Diabetes
Seizure disorders
Endometriosis
Chronic fatigue syndrome
Collagen vascular
disease

Differential Diagnosis
(Continued)
Premenstrual
exacerbation
Of psychiatric disorders
Of seizure disorders
Of endocrine disorders
Of cancer
Of systemic lupus
erythematosus
Of anemia
Of endometriosis

Psychosocial spectrum
Past history of sexual
abuse
Past, present, or current
domestic violence

Diagnosis of PMS
PMS
A. Does not meet DSM-IV criteria
but does meet ICD-10 criteria
for PMS
B. Symptoms occur only in the
luteal phase, peak shortly
before menses, and cease
with menstrual flow or soon
after

C. Presence of one or more of

the following symptoms
Mild psychological discomfort
Bloating and weight gain
Breast tenderness
Swelling of hands and feet
Aches and pains
Poor concentration
Sleep disturbance
Change in appetite

PMDD (DMS-IV Criteria)

A. At least five of the symptoms below, with at least
one being a core symptom, are present a week
before menses and remit a few days after onset of
menses:
Depressed mood or dysphoria (core symptom)
Anxiety or tension (core symptom)
Affective lability (core symptom)
Irritability (core symptom)
Decreased interest in usual activities

PMDD (DMS-IV Criteria)

(Continued)
Concentration difficulties
Marked lack of energy
Marked change in appetite, overeating, or food
cravings
Hypersomnia or insomnia
Feeling overwhelmed
Other physical symptoms (e.g., breast
tenderness, bloating, headache, joint or muscle
pain)

Treatment of PMS

Oral contraceptives
Vitamin B6
Bromocriptine
Monoamine oxidase inhibitors
Synthetic progestational agents
Spironolactone
Massage therapy
Chiropractic therapy
Calcium

MENOPAUSE

Irreguler menstruation

Gejolak panas

Osteoporosis

Tulang keropos
Ngilu-ngilu
Patah tulang
Bungkuk
Tambah pendek

NORMAL

Kerusakan bag tulang

The good news

Menopause and
postmenopauseosteoporosis

Kulit keriput

Sukar tidur

Jantung berdebar

Pusing
Mudah pingsan

Gangguan fungsi seks

Vagina kering
Hub. Seks sakit
Lendir sedikit
Nafsu sek turun

Libido menurun

Gangguan berkemih
Inkontinensia
Ngompol

Some benefits of estrogen replacement

therapy (ERT) for treating menopausal
related health problem
Estrogen replacement therapy (ERT) results in the relief
of menopausal symptoms such as hot flushes and
atrophy of genital tract
ERT halts postmenopausal bone loss, increases bone
mineral density (BMD) and reduces the incidence of
fractures
ERT reduces levels of total cholesterol and low-density
lipoprotein (LDL) cholesterol
Nelson H. JAMA 2004;291:1610-20

Benefits of estrogen plus progestin in

postmenopausal women

Estrogen + progestin
Plasebo

WHI study. JAMA 2002;288:321-33

Weight gain during traditional

HRT has been one of the main
reasons for discontinuation
Although it may not be the only
reason, it contributes to poor
compliance

Van Seumeren I. Maturitas 2000;34(Suppl 1):38

LIVER

te
Renin substra
ogen)
in
s
n
te
io
g
n
a
(=
Angiotens
in II
Renin
KIDNEY

Aldosterone

Increased body weight

HRT

ADRENAL GLAND

Na+/ water retention

(= weight gain)
K+ elimination

Increased edema

ESTROGE
N

Changes in body weight with

Angeliq and estradiol alone
Mean weight
change (kg)

1.5
1.0
0.5
0
0

Estradiol (n = 225)
0

10

11

12

13

-0.5
-1.0
-1.5

Angeliq (n = 224)

The end