Menstrual disorders

Dr. Shofwal Widad

Widad, SpOG(K)

Divisi
ivisi Endokrinologi Reproduksi
Bagian Obstetri & Ginekologi
Fakultas Kedokteran UGM
RSUP Dr Sardjito
Yogyakarta
 Physiology of menstruation

• Normal endometrial shedding ensues as a consequence of

progestagen withdrawal in an endometrium primed by both
estrogen & progesterone.
• Estrogen & progesterone are secreted by the ovary under
the influence of pituitary gonadotrophins (FSH & LH), which
in turn are stimulated by hypothalamic GnRH

Widad – Obgyn UGM

• Pulsatile release of GnRH leads
to release of LH and FSH from
the anterior pituitary.
• Effects of LH and FSH result in
follicle maturation, ovulation, and
production of the sex steroid
hormones (estrogen,
progesterone, and testosterone).
• Rising serum levels of these
hormones exert negative
feedback inhibition on GnRH and
gonadotropin release.
• Sex-steroid hormones vary in
their effects on the endometrium
and myometrium.
• Inhibin, produced in the ovary,
has a negative effect on
gonadotropin release.

Widad – Obgyn UGM

 Physiology of the hypothalamic-pituitary-ovarian
hypothalamic axis
• GnRH stimulates pituitary
secretion of LH and FSH.
• FSH and LH stimulate the
ovary to secrete the sex
steroids, estrogen (E) and
progesterone (P), which
feed back on the
hypothalamus and pituitary
to modulate GnRH and LH
secretion.
• Inhibins and activins feed
back on the pituitary to
modulate FSH production
and secretion.
• E and P stimulate
endometrial prostaglandin
synthesis.
• Inhibin blocks pituitary
secretion of FSH.

Silberstein SD & Merriam GR. Physiology of the Widad

menstrual cycle.UGM
– Obgyn Cephalalgia 2000;20:148-154.
2000;20:148
 CNS-Hypothalamus
Hypothalamus-Pituitary
Ovary-Uterus
terus Interaction
Neural control Chemical control

Dopamine Norepiniphrine Endorphines

(-) (+) (-)

Hypothalamus
Gn-RH
± Ant. pituitary ? –
FSH, LH
Estrogen Ovaries Progesterone

Uterus

Menses Widad – Obgyn UGM

Widad – Obgyn UGM
Widad – Obgyn UGM
 The human menstrual cycle
• After menstruation and desquamation
of the endometrium, developing
ovarian follicles generate a rise in
serum estrogen, which leads to
increased cell proliferation in the
endometrium.
• Surges of LH and FSH induce
ovulation, thereby releasing an egg
capable of fertilization and
embryogenesis.
• The blastocyst implants in a receptive
endometrium, attained by
transformation from a proliferative/
metabolic state to a less proliferative
and highly secretory state.
• Implantation does not occur after this
window of receptivity is passed
because the endometrium is already
destined for apoptosis and tissue
remodeling.
• Yellow, Endometrial glandular and
luminal epithelium; brown, endometrial
stroma; blue, leukocytes; red, spiral
arterioles.
Widad
Endocrinology, March – Obgyn
2006, UGM
147(3):1094
147(3):1094–1096
 Menstruation
• Spontaneous, revealed menstruation
therefore requires:
– Hypothalamic GnRH secretion
– Pituitary FSH & LH secretion
– Ovarian estrogen & progesterone
erone
secretion
– Endometrium
– Patent cervix & lower genital tract

Disorders at any the above levels will have

the potential to disrupt menstruation

Widad – Obgyn UGM

Regulation of the menstrual cycle
• The menstrual cycle is the cyclical
shedding of the endometrium in
response to hormonal fluctuations
occurring every 28±7days, in an
amount no greater than 50±30 ml with
or without some discomfort.
• Endometrial matrix
metalloproteinases (MMPs) and their
tissue inhibitors (TIMPs) are believed
to regulate bleeding during the normal
menstrual cycle and are known to be
altered in some cases of menstrual
dysfunction affecting the bleeding
pattern.
Widad – Obgyn UGM
 Endometrial phase

The effects of varying concentrations of estrogen and progesterone during the different phases of a
normal menstrual cycle have characteristic Widad
effects– on
Obgyn
the UGM
endometrium.
Haemostatic mechanisms at the
endometrial level
• The haemostatic factors
involved at the endometrial
level are similar to those at
other sites.
• Primary haemostasis is initiated
by platelet adherence to the
endothelial lining. This
adhesion is mediated by von
Willibrand factor.
• The activated platelets release
the contents of their granules to
activate other platelets and
white blood cells.
• Secondary haemostasis
requires the coagulation factors
to form fibrin strands, which
strengthen the platelet plug.
Widad – Obgyn UGM
 Menstrual disorders/disturbances
Quality of life

• Primary dysmenorrhoea is suffered by 50% of menstruating women.

• As many as 80% of reproductive-aged women experience physical changes
associated with menstruation, and 20–40% 40% experience menstrual cycle-related
symptoms.
• Irregular, heavy and painful periods not only cause cyclical symptoms but also
have secondary effects such as tiredness, lack of sleep, pelvic pain, sexual
dysfunction and depression.
• Painful menstruation is the leading cause of lost time from school and work
among women of childbearing age.
• Menstrual disorders are the second most common gynaecological condition
resulting in hospital referral and amount to 12% of all gynaecological referrals.
• One in 20 women in the UK aged 30–49 49 years will consult their GP each year
regarding heavy periods and a high percentage of these will subsequently be
referred to secondary care.
• In the UK, 22% of otherwise healthy pre-menopausal
pre women over the age of 35
will suffer from heavy menstrual bleeding.
bleeding

Widad – Obgyn UGM

 Types of menstrual disorders
• Menstrual disturbances are predominantly a result of
dysfunction at any point in the hypothalamic–pituitary
hypothalamic
(hypophyseal)–ovarian– endometrial axis.
• Often these abnormalities are categorised by pathoaetiology
• The clinical presentation of menstrual disturbances can be
any one or a combination of abnormalities associated with
the cycle regularity, duration, flow and pain related to the
menstrual cycle; therefore, different disorders may have
overlapping presentations.

Widad – Obgyn UGM

 Abnormal uterine bleeding
• Normal menstruation typically occurs every 28 days ± 7 days in an
amount no greater than 50±30 ml .
• Menstrual disturbances can be categorised into four major groups.
– Cycle abnormalities
• Polymenorrhea is the term used to describe cycles with intervals of up to 21 days.
• Oligomenorrhea is cycles
ycles with intervals longer than 35 days.
days
• Primary amenorrhoea and secondary amenorrhea
– Abnormalities of duration
• Hypermenorrhea (polymenorrhagia) is prolonged regular bleeding.
• Hypomenorrhea is diminished flow or shortening of menses.
• Metrorrhagia (intermenstrual bleeding),
bleeding) bleeding that is irregular both in amount
and periodicity.
– Abnormalities of flow
• Menorrhagia (heavy menstrual bleeding) is defined as heavy cyclic menstruation
(exceeding 80 mL of blood loss).
– Abnormalities with severe menstrual pain
• Dysmenorrhoea is defined as excessive menstrual pain that is severe enough to
limit normal activities or requires medication.

Widad – Obgyn UGM

Widad – Obgyn UGM
 Types of menstrual disorders
Cycle Duration Flow Pain Related

Regular Normal Normal Normal PMS

Irregular Prolonged Heavy Severe Anemia

Shortened Moderate None Tiredness

Low libido

Depression

Widad – Obgyn UGM

Widad – Obgyn UGM
 The main currently
recognized causes of
abnormal uterine
bleeding

Widad – Obgyn UGM

Widad – Obgyn UGM
 Examples of
current usage
and definitions of
the term
‘‘dysfunctional
uterine bleeding’’

Widad – Obgyn UGM

 DUB: Ovulatory or anovulatory?
Anovulatory cycle Ovulatory cycle
• Unpredictable cycle length • Reguler cycle length
• Unpredictable bleeding pattern • Premenstrual symptoms
• Frequent spotting • Dysmenorrhea
• Infrequent heavy bleeding • Breast tenderness
• Change in cervical mucus
• Monophasic temperature curve
• Mittleschmertz
• Biphasic temperature curve
• Urinary LH test indicates LH
surge
• High level of midluteal
progesteron

Widad – Obgyn UGM

 Differentiation of disturbances in menstrual
bleeding and abnormal uterine bleeding (AUB)

• Many authors include bleeding due to menstrual

disturbances under the umbrella of abnormal uterine
bleeding.
• For the purposes of clarity, we make a point of differentiating
the two.
– Abnormal uterine bleeding (AUB) refers to any bleeding from or due
to primary pathology of the female genital tract (e.g. ovary), which is
pre-malignant or malignant.. It is important always to be vigilant and to
consider gynaecological malignancies when reviewing any
presentations relating to menstrual disturbances. High-risk
High groups
can be identified if the risk factors for any particular cancer are borne
in mind. For example, risk factors for uterine cancer include high
Body Mass Index (BMI) and unopposed estrogens.

Widad – Obgyn UGM

 Investigation of menstrual
disorders
• A detailed history:
– excluding risk factors for underlying malignancies, should be taken. This is the key to making an
accurate assessment of the disorder and estimation of the impact on quality of life.
• General examination:
– body mass index (BMI) and assessment for signs of anaemia, thyroid disease, evidence of bleeding
disorders (bruising) or any other medical condition resulting in menstrual disorder, such as jaundice
leading to bleeding diatheses, or alopecia and skin rash, suggesting an autoimmune problem like
systemic lupus erythematosus.
• Abdominal examination
– should identify any organomegaly, and presence of ascites, or abdominal or pelvic mass, e.g. if the
uterus is palpable above the symphysis pubis.
• Speculum examination
– should be carried out to assess the vagina and the cervix, taking a cervical smear, endometrial biopsy
or vaginal swab as indicated.
• Bimanual pelvic examination
– reinforces the findings so far and establishes size, position, mobility and consistency of the uterus and
assesses for adenexal pathology.
• Confirmatory investigations
– should then lead to a diagnosis and management plan.

Widad – Obgyn UGM

 Estimating heavy menstrual bleeding?
• Passing clots more than 1.1
inches in diameter and changing
pads more frequently than every
3 hours (Warner et al. 2004).
• Pictorial blood assessment
chart. Scores are assigned as
follows:
– Tampon. 1 point for each lightly
stained tampon, 5 if moderately
saturated, and 10 if completely
soaked.
– Pads. Pads are similarly given
ascending scores of 1, 5, and
20, respectively.
– Clots. Small clots score 1 point,
whereas large clots score 5.
– Totals more than 100 points per
menstrual cycle have been
shown to indicate >80 mL
objective blood loss

Pictorial blood assessment

Widad – Obgyn UGM
Widad – Obgyn UGM
Saline Infusion Sonohisterography (SIS)

Widad – Obgyn UGM

Hysteroscopy demonstrating
an endometrial polyp

Widad – Obgyn UGM

Mioma uteri

Widad – Obgyn UGM

 Polip endometrium
Merupakan tumor jinak yang
terdiri atas permukaan
endometrium & stroma fibrosa

Polip besar yang mengalami

protrusi melalui ostium uteri

Widad – Obgyn UGM

Kanker serviks (carsinoma
rsinoma sel skuamosa)
stadium IIa

Widad – Obgyn UGM

 Lesi prakanker serviks
Epitel abnormal (CIN) mengandung lebih banyak protein
dan lebih sedikit glikogen
asam asetat
protein terkoagulasi

aceto--white

“Aceto-white” “mosaic pattern”

Widad – Obgyn UGM
 Kanker endometrium

Karsinoma endometrii
Widad – Obgyn UGM
Endometriosis
• Proliferasi jaringan endometrium (sel
kelenjar, stroma, hemosiderin laden
laden-
macrophages) di luar cavum uteri
(endometrial
endometrial tissue in an ectopic
location
location)
• Gejala/tanda:
– Dismenorea
– Nyeri pelvis kronis
– Dispareunia
– Infertilitas
– Kista coklat

Widad – Obgyn UGM

Medical problem related to menstruation

• Several
everal medical problems that are linked to
menstruation:
– Premenstrual syndrome (PMS)
– Premenstrual dysphoric disorder (PMDD)
– Dysmenorrhea
– Menstrual headache
– Catamenial seizures
– Premenstrual asthma
– Catamenial pneumothorax
neumothorax

Widad – Obgyn UGM

This lecture will have to be modified
because of new developments next
year (or possibly even next week!)
sh_widad@yahoo.com

Widad – Obgyn UGM

 Amenorrhea
• Amenorrhea is a sign of a disorder not a
diagnosis
• Because any abnormality of menstruation
may be associated with pregnancy,
pregnancy always must be ruled out as a
cause for the absence of menses

Widad – Obgyn UGM

 Definitions
Primary amenorrhea
Failure of menarche to occur when expected in relation to
the onset of pubertal development
• No menarche by age 16 years with signs of pubertal
development.
• No onset of pubertal development by age 14 years.

Secondary amenorrhea
Absence of menstruation for 3 or more months in a
previously menstruating women of reproductive age.

Widad – Obgyn UGM

 Classification of amenorrhea (not including
disorders of congenital sexual ambiguity)
ASRM Practice Committee.
Amenorrhea. Fertil Steril 2006

Widad – Obgyn UGM

 Causes of amenorrhea
• Physiological
– Prepuberty, pregnancy, lactation, postmenopause
• Pathological
prevalence: 3-4%
4%
– Local genital causes
• Congenital--eg,
eg, testicular feminisation
• Acquired--eg,
eg, Asherman's syndrome
– Hypothalamic
• Congenital--eg,
eg, Kallmann's syndrome
• Acquired--eg,
eg, weight loss, craniopharyngioma
– Pituitary
• Tumour--eg, prolactinoma
• Infarction--eg,
eg, Sheehan's syndrome
– Ovarian
• Congenital--eg, gonadotrophin-receptor
receptor defect, resistant ovary syndrome
• Acquired--eg, radiation
Widad – Obgyn UGM
Causes of amenorrhoea

William L. Ledger*, Jonathan Skull

Current Obstetrics & Gynaecology (2004)
14, 254–260

Widad – Obgyn UGM

 Common causes of primary amenorrhea
ASRM Practice Committee.
Amenorrhea. Fertil Steril 2006

Widad – Obgyn UGM

 Common causes of secondary amenorrhea
ASRM Practice Committee.
Amenorrhea. Fertil Steril 2006

Widad – Obgyn UGM