The menstrual cycle and menstrual cycle abnormalities

Last updated: February 10, 2021

Summary
The menstrual cycle is a highly regulated physiological process that makes

conception

and

pregnancy

possible. From the start of menstruation (

menarche

) to its cessation (

menopause

), menstrual bleeding (menses) is regulated by

hypothalamic

and

pituitary

hormones

. Even the smallest changes in

hormone

levels can result in menstrual cycle abnormalities. Hormonal changes are not necessarily pathological;
they can be caused by a variety of conditions and factors (e.g., medication, stress). Abnormal menstrual
patterns are identified based on changes in the frequency, intensity, and onset of bleeding. Common
manifestations of menstrual cycle abnormalities include

amenorrhea

(menstrual cessation),

dysmenorrhea

(painful menstruation), and

abnormal uterine bleeding

AUB
; e.g., increased frequency and/or volume of menstruation). Discomfort prior to the onset of
menstruation that is accompanied by psychiatric, gastrointestinal, and/or neurological symptoms is
referred to as

premenstrual syndrome

PMS

).

Physiology of the menstrual cycle

Hormonal feedback loops
[1]

The menstrual cycle is a tightly regulated process in which the coordinated release of

hormones

from the

hypothalamus

pituitary gland

, and gonads produces a single mature

oocyte

. These

hormones

are controlled by positive and negative feedback loops.

 Follicular phase
o The

o hypothalamus

o releases

o gonadotropin-releasing hormone

o (
o GnRH

o ) in pulses, stimulating the

o anterior pituitary gland

o to release

o follicle-stimulating hormone

o (

o FSH

o ) and

o luteinizing hormone

o (

o LH

o ).

 FSH

 and

 LH

 stimulate the

 ovaries

 .

 In the

 ovarian follicle

 , the theca cells and

 granulosa cells

 are in charge of

 hormone

 production.

o LH

o stimulates theca cells and induces the production of

o progesterone
 o and

o androstenedione

o .

o FSH

o stimulates

o granulosa cells

o and recruits a group of maturing follicles in the

o ovary

o → production of estradiol and

o inhibin B

o in the growing follicles → negative feedback to the

o pituitary gland

o → inhibited

o FSH

o release

o The day before the

o LH

o levels rise, one follicle becomes dominant (the remaining follicles regress as

o FSH

o levels decrease) and estradiol levels peak → positive feedback to the

o pituitary gland

o →

o LH

o levels increase rapidly

 Ovulation

 :

 LH surge

 induces
  ovulation

 → the mature

 oocyte

 is released from the

 dominant follicle

 and the

 corpus luteum

 produces

 progesterone

 →

 LH

 inhibition

 Luteal phase

 : falling

 LH

 levels cause degeneration of the

 corpus luteum

 → decreased

 progesterone

 and estradiol levels → the

 endometrium

 cannot be maintained → menstruation occurs

The hormonal feedback loop is also influenced by other

hormones

(e.g.,

prolactin

) and neurotransmitters (e.g.,

opioids
,

acetylcholine

noradrenaline

). The feedback mechanisms are controlled by upregulating or downregulating

hormone

production as needed.

Menstrual cycle
[1]

[2]

 A normal menstrual cycle lasts 24–38 days (28 days on average), with the first day of menstrual
bleeding counted as day 1 of the cycle.

 [3]

 Menses lasts an average of 3–7 days, with an average blood loss of 35–50 mL.
 The menstrual cycle involves simultaneous changes in the

 ovaries

 (

 ovarian cycle

 ) and the uterus (

 uterine cycle

 ).

 The cycles relate to one another

o Ovarian changes are regulated by

o hormones

o released from the

o anterior pituitary gland

o .
o Uterine cycle

o changes are regulated by

o hormones

o released from the

o ovary

o during the

o ovarian cycle

o .

 Low estradiol levels keep

 FSH

 and

 LH

 levels low, leading to menstruation.

 High estradiol levels lead to increased

 FSH

 and

 LH

 levels, causing thickening of the

 endometrium

 .

 Estradiol and

 progesterone

 secreted by the

 corpus luteum

 allow for further development of the

 endometrium

 .

 Estradiol and
  progesterone

 also inhibit secretion of

 FSH

 and

 LH

 , preventing other follicles from developing.

 The menstrual cycle changes with age.

o First few years following

o menarche

o : irregular menstrual cycles (due to immaturity of the

o hypothalamic-pituitary-gonadal axis

o )

o Menstrual cycles are longest at 25–30 years of age, with younger and older individuals
having shorter cycles.
[4]
o

Menstrual cycle changes

Histological
Cycle Duration Phases Description Mechanism changes
[2]

Ovarian cycle  1–14  Follicu  From  FSH  During

days lar the  stimul the
phase first ates secon
day of the dary
mense develo follicle
s to pment stage,
the of cuboid
day severa al
before l  granul
the follicle osa
 LH s in cells
surge the  contin
 Accou  ovarie ue to
nts for s prolife
most  → rate.
of the granul  Multip
variabi osa le
lity in cells of layers
the follicle of
 length s thick
of the produ  granul
menst ce osa
rual  estrog cells
cycle en  surrou
 Follicle  → nd an
growt  estrog eccent
h en rically
speeds  suppre locate
up sses d
during the  oocyte
the 2nd releas  .
week e of  Most
of this  FSH secon
phase.  via dary
negati follicle
ve s
feedba becom
ck e
loop  atretic
 Selecti  , but
on of a usually
 domin only
ant one
follicle becom
 ( es a
 Graafi  domin
an ant
follicle follicle
 )  .
 Positiv
e
feedba
ck
loop:
high
 estrog
en
 levels
→
 FSH
 releas
e→
 LH
surge
 →
 ovulati
 on
 14–15  Luteal  From  In  During
days phase the ovulati the
day of on,  tertiar
the the y
 LH  Graafi follicle
surge an  stage,
 to the follicle the
beginn  ruptur  oocyte
ing of es,  is
the releasi surrou
next ng the nded
mense  oocyte by the
s  .  corona
 Follow radiat
ing a
 ovulati  and
on floats
 , the in
 granul follicul
osa ar
cells fluid.
 produ  The
ce  Graafi
 LH an
 recept follicle
ors →  moves
 LH to the
 - surfac
induce e of
d the
transf  ovary
ormati  ,
on of where
the it
 Graafi ruptur
an es and
follicle the
 into secon
the dary
 corpus oocyte
luteu is
m releas
 → ed.
 proges The
terone empty
 produ  tertiar
 ction
→
inhibiti
on of
 LH
 releas
e(
 proges
terone
 increa y
se follicle
indicat  collaps
es that es.
 ovulati  The
on  corpus
 has luteu
occurr m
ed)  atroph
 If no ies.
 pregn
ancy
 occurs
, the
 corpus
luteu
m
 regres
ses.
Uterine cycle  3–7  Mense  Menst  Absen  Contra
days s rual ce of ction
bleedi  pregn of
ng ancy  spiral
occurs  → arterie
in this resolu s
phase tion of  in the
(usuall  corpus stratu
y 14 luteu m
days m functi
after  →↓ onalis
 ovulati  proges layer
on terone →
 ).  conce  ische
ntratio mia
n→  →
vasosp degen
asms eratio
in the n of
 uterin
e
spiral
arterie
s→
the
bleedi
functi
ng
onalis
 To
layer
activel
→
y
slough
delay
ing off
mense
of the
s,
 functi
admini
onal
ster
layer
 proges
of the
terone
endo
 in the
metriu
secon
m
d half
of the
menst
rual
cycle.
 ∼10  Prolife  Charac  Growi  Prolife
days rative terized ng ration
phase by the follicle of
growt s  endo
h of produ metria
the ce l
 endo  estrog  epithel
metriu en ial
m  (  cells
 under  granul (cells
the osa show
influen cells high
ce of  expres  mitoti
 estrog s c
ens  aroma  activit
tase y)
 ,  Endo
which metria
conver l
ts  glands
 andro becom
gens e
 to straigh
 t,
tubula
r, and
lined
by
simple
 colum
nar
epithel
ium
 .
 Strom
al cells
start
to
divide,
enlarg
e, and
 estrog
accum
ens
ulate
 )→
 glycog
prolife
en
ration
 .
of the
 Uterin
 endo
e
metriu
 spiral
m
arterie
s
 start
to
regene
rate
and
extend
two-
thirds
of the
way
into
the
 endo
metriu
m
 .
 10–14  Secret  The  Proges  Intrac
days ory  functi terone ellular
phase onal  promo subnu
 layer tes clear
of the  endo vacuol
endo metria es
metriu l  Increa
m  differe sed
 is ntiatio  endo
prepar n→ metria
ed for prepar l
implan ation  gland
tation of the  tortuo
under  functi sity
the onal  Glycog
influen layer en
ce of of the  -rich
 proges endo secreti
terone metriu ons
 . m  Edema
 for tous
 oocyte  strom
 implan al cells
tation  Uterin
 ↑ e
Cervic  spiral
al arterie
mucus s
secreti  extend
on the
(preve full
nts length
sperm of the
atozoi  endo
ds metriu
from m
enteri  .
ng
uterus
)
 ↑
Basal
body
tempe
rature
 In the
absen
ce of
 pregn
ancy
  :↓
 proges
terone
 levels
→
 apopt
osis
 of the
functi
onal
layer
of the
 endo
metriu
m
 →
menst
ruatio
n

Menstrual pain and cycle abnormalities

Menstrual cycle abnormalities include changes in the frequency and intensity of menstruation as well as
symptoms such as pronounced abdominal discomfort, gastrointestinal complaints, and/or psychiatric
symptoms.

Dysmenorrhea (menstrual pain)

Primary dysmenorrhea
 Definition: recurrent lower abdominal pain shortly before or during menstruation (in the
absence of pathologic findings that could account for those symptoms)
 Epidemiology
o Prevalence

o up to 90% (most common gynecologic condition)

[5]
o

o Manifests during

o adolescence

o (typically within three years of

 o menarche

o )

 Etiology
o The etiology of

o primary dysmenorrhea

o is not completely understood.

o Associated with some

o risk factors

o (e.g., early

o menarche

o ,

o nulliparity

o , smoking,

o obesity

o , positive family history)

 Pathophysiology: increased

 endometrial

 prostaglandin

 (PGF2 alpha) production leads to

 vasoconstriction

 /

 ischemia

 and stronger, sustained uterine contractions (to prevent blood loss).

 Clinical features

 [6]

o Usually occurs during the first 1–3 days of menstruation

o Spasmodic, crampy pain in the lower abdominal and/or pelvic midline (often radiating to
the back or thighs)
o Headaches,
 o diarrhea

o , fatigue, nausea, and

o flushing

o are common accompanying symptoms.

o Normal pelvic examination

 Diagnostics
o Primary dysmenorrhea

o is a diagnosis of exclusion.

o Rule out conditions that cause

o secondary dysmenorrhea

o (e.g.,

o endometriosis

o ).

 Treatment
o Symptomatic treatment: pain relief (e.g.,

o NSAIDs

o ), topical application of heat

o Hormonal contraceptives

o (e.g.,

o combined oral contraceptive pill

o ,

o IUD

o with progestogen)

Secondary dysmenorrhea
[5]

[7]

 Definition: recurrent lower abdominal pain shortly before or during menstruation that is due to
an underlying condition
 Epidemiology
o May begin later in life than

o primary dysmenorrhea
 o Commonly affects female individuals ≥ 25 years of age.
 Etiology
o Uterine causes
 Pelvic inflammatory disease

 (

 PID

 )

 Intrauterine device

 (

 IUD

 )

 Adenomyosis
 Fibroids

 (intracavitary or intramural)

 Cervical polyps
o Extrauterine causes
 Endometriosis
 Adhesions
 Functional ovarian cysts
 Inflammatory bowel disease
 Clinical features
o Depend on the underlying cause
o Secondary dysmenorrhea

o should be suspected in the following cases:

 Abnormal pelvic examination (e.g., uterine size,

 cervical motion tenderness

 , adnexal tenderness, masses, vaginal/cervical discharge)

 The pain tends to get worse over time.

 No previous history of pain with menstruation
 Infertility

 (e.g., adhesions,

 endometriosis

 ,
  PID

 )

 Irregular cycles
 Heavy menstrual flow (e.g.,

 adenomyosis

 ,

 fibroids

 , polyps)

 Dyspareunia

 or postcoital bleeding

 Partial or no response to therapy with

 NSAIDs

 and/or

 hormonal contraceptives

 Diagnostics
o Depend on the underlying cause
o Initial laboratory testing
 CBC with differential (rules out infection)
 Urinalysis

 (rules out

 UTIs

 )

o Other
 β-hCG

 (rules out

 ectopic pregnancy

 ),

 Gonococcal/chlamydial swabs (rule out

 STDs

 and

 PID
  )

o Pelvic

o ultrasound

 Treatment: depends on the underlying cause

Amenorrhea (menstrual cessation)

Primary amenorrhea
[8]

[9]

 Definition: : the absence of

 menarche

 at 15 years of age despite normal development of

 secondary sexual characteristics

 , or absence of menses at 13 years of age in female individuals with no

 secondary sexual characteristics

 Etiology

Causes of
primary amenorrhea
FSH Estrogen
Cause Details GnRH and and
LH progesterone
 Normal
pubertal
developm
ent, but
 adrenarch  ↓ (at the
Constitutional
e  ↓  ↓ prepubert
growth delay
 and al level)
 gonadarc
he
 occur at a
later age
Hypogonadotropi  Caused by  ↓  Normal or  ↓
c deficient ↓
release of
hypogonadism  GnRH
 Examples
o K
all
 m
a
n
n
sy
n
dr
o
m
e
o Pr
a
d
er
-
W
illi
sy
n
dr
o
m
e
o C
o
m
p
e
ti
ti
ve
sp
or
ts,
st
re
ss
,
ea
ti
n
g
di
so
rd
er
s
 o C
N
S
o tu
m
or
s
(e
.g.
,
o cr
a
ni
o
p
h
ar
yn
gi
o
m
a
o )
Hypergonadotrop  GnRH  ↑  ↑  ↓
ic  is
released
hypogonadism but the
 ovaries
 fail to
produce
 estrogen
 and
 progester
one
 .
 Examples:
 gonadal
dysgenesi
s
o 4
6,
X
Y
g
o
n
a
 d
al
dy
sg
e
n
es
is
o T
ur
n
er
sy
n
dr
o
m
e
Anatomic  Outflow  Normal  Normal  Normal
anomalies tract
obstructio
n with
otherwise
normal
 puberty
 Examples
o M
ül
le
ri
a
n
ag
e
n
es
is
o I
m
p
er
fo
ra
te
hy
m
e
 n
o V
ag
in
al
at
re
si
a
o Tr
a
ns
ve
rs
e
va
gi
n
al
se
pt
u
m
Receptor and  Examples  Normal  Normal or  Normal or
enzyme o C ↑ ↓
abnormalities o
m
pl
et
e
o a
n
dr
o
ge
n
in
se
ns
iti
vi
ty
sy
n
dr
o
m
 e
o 5-
al
p
h
a-
re
d
uc
ta
se
d
e
fic
ie
nc
y
o C
o
n
ge
ni
ta
l
a
dr
e
n
al
hy
p
er
pl
as
ia
o (
o C
A
H
o ):
o 1
7-
al
p
h
a-
hy
 dr
ox
yl
as
e
d
e
fic
ie
nc
y
 Clinical features: depend on the underlying cause
 Diagnostics
o Pregnancy test
o Check for

o secondary sexual characteristics

o and anatomical anomalies (physical examination, pelvic

o ultrasound

o ).

 Uterus absent: Perform karyotyping and serum

 testosterone

 to investigate for male/female

 genotype

 and

 androgen

 sensitivity.

 Uterus present: Test

 FSH

 and

 LH

 levels.

 Exclude

 imperforate hymen

 ,
  vaginal atresia

 , and

 transverse vaginal septum

 .

 ↑

 FSH

 :

 primary ovarian insufficiency

 (e.g.,

 Turner syndrome

 ,

 Swyer syndrome

 ,

 premature ovarian failure

 )

 Normal or ↓

 FSH

 :

 constitutional growth delay

 ,

 hypogonadotropic hypogonadism

o If

o galactorrhea

o is present: Check

o prolactin

o and

o TSH

o levels.
 o If symptoms of

o hyperandrogenism

o are present:

 Check serum

 testosterone

 and

 dehydroepiandrosterone sulfate

 (

 DHEA-S

 ).

 If high: Suspect an

 androgen

 -secreting tumor.

o If blood pressure is high: Suspect

o congenital adrenal hyperplasia

o .

 Treatment
o Management of the underlying cause
 Anatomical abnormalities: surgery
 Hypogonadism

 :

 hormone replacement therapy

 with

 estrogens

 and

 progesterone

o The goal of treatment is the progression of normal pubertal development.

Secondary amenorrhea
 Definition: the absence of menses for more than 3 months in individuals with previously regular
cycles, or 6 months in individuals with previously irregular cycles
 Etiology
o Pregnancy

o : most common cause of

o secondary amenorrhea

o Ovarian disorders (e.g.,

o premature ovarian failure

o ,

o polycystic ovary syndrome

o )

o Medications (

o antipsychotics

o ,

o chemotherapy

o ,

o oral contraceptives

o )

o Hypothyroidism

o (↓ T3/T4 → ↑

o TRH

o →↑

o prolactin

o →↓

o GnRH

o →↓

o estrogens

o )

o Hyperthyroidism
o Hyperprolactinemia
o Sheehan syndrome
o Asherman syndrome
o Cushing syndrome
o Adrenal insufficiency
o Obesity
o Hypergonadotropic hypogonadism
o Hypogonadotropic hypogonadism
o Functional hypothalamic amenorrhea: a dysfunction in the pulsatile secretion of

o GnRH

 Etiology
 Excessive exercise: e.g., in competitive athletes (also called exercise-
induced

 amenorrhea

 )

 Reduced calorie intake (e.g., in eating disorders like

 anorexia nervosa

 )

 Stress
 Female athlete triad syndrome: menstrual dysfunction, calorie deficit,
and decreased bone density in athletic female young adults or

 adolescents

 Pathophysiology: decreased

 leptin

 (low body fat) and/or increased

 cortisol

 (exercise/stress) → decreased pulsatile release of

 GnRH

 from the

 hypothalamus

 → decreased secretion of

 FSH

 and

 LH

 → decreased
  estrogen

 levels →

 anovulation

 and

 secondary amenorrhea

 →

 infertility

 Clinical features: depend on the underlying cause

 Diagnostics
o Pregnancy test
o If negative, obtain

o FSH

o ,

o TSH

o , and

o prolactin

o levels.

 ↑

 FSH

 :

 ovarian insufficiency

 ↑

 TSH

 :

 hypothyroidism

 ↑

 Prolactin

 Re-check history for medication intake (

 antipsychotics
  are the most frequent cause of medication-induced

 hyperprolactinemia

 ).

 Perform brain

 MRI

 to evaluate for

 pituitary adenoma

 .

o Perform progestin challenge (10 days of

o progestin

o intake)

 Withdrawal bleeding induced:

 anovulation

 (e.g.,

 PCOS

 ,

 idiopathic

 anovulation

 ,

 premature ovarian failure

 )

 No withdrawal bleeding (may indicate uterine anomalies or estrogen

deficiency): test

 FSH

 levels.

 ↑

 FSH

 :

 hypergonadotropic hypogonadism
  or

 ovarian failure

 ↓

 FSH

 : combined

 estrogen

 and

 progesterone challenge

o Withdrawal bleeding induced:

o hypogonadotropic hypogonadism

o No withdrawal bleeding:

o endometrial

o or anatomical problem

 If

 virilization

 is present: Check

 testosterone

 ,

 DHEA-S

 , and

 17-hydroxyprogesterone

 .

 Mild elevation:

 PCOS

 ,

 congenital adrenal hyperplasia

 ,

 Cushing syndrome
  Moderate-to-high elevation:

 androgen

 -producing tumor

 Treatment
o Management of the underlying cause
 Tumors
 Surgical resection if possible
 Prolactinoma

 :

 dopamine agonists

 (

 bromocriptine

 ,

 cabergoline

 )

 Functional hypothalamic amenorrhea

 Lifestyle changes: reduce stress, improve nutrition, increase body
weight (aim for

 BMI

 > 19 kg/m2)

 Offer pulsatile

 GnRH

 therapy or

 gonadotropin

 therapy to induce

 ovulation

 .

 [8]

 [9]

 Premature ovarian failure

  :

 combined oral contraceptives

 (

 OCPs

 ) or

 hormone replacement therapy

 If trying to conceive:
 Stimulation of

 ovulation

 with

 gonadotropin

 If failed: assisted reproductive technology

 Treatment goals: prevent complications (e.g.,

 osteoporosis

 , heart disease) and maintain

 fertility

Physiological

amenorrhea

occurs before

menarche

, after

menopause

, during

pregnancy

, and during lactation.

The

female athlete triad

of

functional hypothalamic amenorrhea

: low calorie intake/strenuous physical activity, low bone mineral density, and

amenorrhea

Abnormal uterine bleeding

 Definition
o Abnormal uterine bleeding

o (

o AUB

o ; formerly known as dysfunctional

o uterine bleeding

o ) is defined as menstrual bleeding that is abnormal and/or irregular in frequency,

duration, and/or intensity.

o It may or may not be accompanied by

o dysmenorrhea

o .

 Etiology

 [10]

o The

o International Federation of Gynecology and Obstetrics

o (

o FIGO

o ) has developed a classification (the

o PALM-COEIN system

o ) to distinguish between structural and nonstructural causes of

o abnormal uterine bleeding

o .
 o Structural causes: polyps,

o adenomyosis

o , leiomyomas, and

o malignancy

o and

o hyperplasia

o (PALM)

o Nonstructural causes:

o coagulopathy

o , ovulatory dysfunction,

o endometrial

o ,

o iatrogenic

o , not otherwise classified (COEIN)

 Types

 [1]

 [11]

o Acute

o AUB

o : episodic

o uterine bleeding

o , in a nonpregnant female individual of reproductive age, that is of sufficient volume to

require intervention to prevent further blood loss

o Chronic

o AUB

o :

o uterine bleeding

o of abnormal frequency, regularity, and/or volume that has persisted for > 6 months
o According to etiology
 AUB

 -C:

 coagulopathies

 AUB

 -O:

 ovulation

 disorders (e.g., disorders of the hypothalamic-pituitary axis)

 AUB

 -E:

 endometrial

 disorders

 AUB

 -I:

 iatrogenic

 causes (e.g.,

 estrogens

 ,

 androgens

 ,

 IUD

 )

 AUB

 -N: not otherwise classified (e.g., uterine

 arteriovenous malformations

 )

Characteristics and causes of

AUB
according to
FIGO
[12]
Characteristic Normal parameters Abnormal parameters Common causes
 Absent (no  See “
bleeding):  Amenorrhea
 amenorrhea  ” above.
 Pregnancy


 (including
 Infrequent:  ectopic
cycles intervals pregnancy
Frequency  ≥ 24–38 days > 38 days  )
 PCOS
 Insufficient
caloric intake
(e.g., due to
 anorexia
nervosa
 )
 Menarche
 Frequent:  ,
cycles intervals  menopause
< 24 days  Psychological
stress
Regularity  Variation  Irregular  PCOS
between o Variati  Menopause
shortest and on
longest cycle betwee
7–9 days or n
normal cycle shortes
length ± 4 days t and
longest
cycle ≥
8–10
days
(the
amoun
t of
variatio
n
consid
ered
normal
depend
s on
the
 individ
ual)
 Endometriosis


 Endometrial
 Prolonged: > 8
Duration  ≤ 8 days hyperplasia
days


 Endometrial
cancer
 Endometrial
 atrophy
 Eating
disorders (e.g.,
 anorexia
 Light
nervosa
menstruation
 )
 Chronic
 endometritis
 OCP
 Determined by
Volume  use
the patient
 Heavy
menstrual
bleeding
 Endometrial
 : excessive
cancer
blood loss that
 /
interferes with
 hyperplasia
physical, social,
 Endometriosis
and/or
emotional
quality of life
Intermenstrual  None  Random  Endometrial
bleeding cancer
 /
 hyperplasia
 ,
 cervical cancer
 Cervicitis
 Polyps
 OCP
 use
  Ovulation
 Breakthrough
bleeding:
midcycle
bleeding due to
 hormone
 imbalance
(usually after
starting new
 OCP
 therapy)
 [11]

o Estroge
n
o breakt
hrough
o Progest
 Cyclic erone
(predictable o breakt
bleeding): hrough
minimal o Estroge
bleeding seen n
during early, o withdr
mid, or late awal
cycle  Endometriosis
 , myomas,
polyps,
 carcinomas
 Contact
bleeding (e.g.,
during
gynecological
examination in
patients with
 cervical
carcinoma
 )
 During
 pregnancy
 : may indicate
 spontaneous
abortion
 Diagnostics
o Gynecological history
 Age of

 menarche
  , last menstrual period, cycle length and regularity,

 pregnancies

 , family history, recent complaints

 Evaluation of possible causes guided by the

 PALM-COEIN system

 Characteristics of abnormal bleeding (frequency, regularity, duration, volume)

o Physical examination
 If bleeding is acute: Ensure the hemodynamic stability of the patient.
 Pelvic examination: Assess the severity and source of the bleeding (exclude
structural abnormalities,

 neoplasms

 , and trauma).

 Swabs for microbiologic testing: rule out

 cervicitis

 due to

 gonorrhea

 /chlamydial infection

o Pap smear

o : rules out

o cervical carcinoma

o Initial laboratory testing

 CBC

 : rules out

 anemia

 Platelet count

 ,

 PT

 ,

 PTT

 : rule out
  bleeding disorders

 β-hCG

 : rules out

 pregnancy

 Additional testing if required (e.g.,

 thyroid function tests

 ,

 prolactin

 , serum iron)

o Pelvic

o ultrasound
[13]
o

 Can be considered to rule out structural anomalies (e.g.,

 leiomyoma

 , adnexal mass)

 Allows for evaluation of

 endometrial

 thickness

o Endometrial biopsy

o : Indications vary by age group and the presence of

o risk factors

o .

 Postmenopausal patients with any

 uterine bleeding

 and/or

 endometrial

 thickness ≥ 4 mm

 [13]

 All patients > 45 years of age with frequent, heavy, and/or prolonged bleeding
  Patients < 45 years of age with frequent, heavy, and/or prolonged bleeding who
are at high risk for

 endometrial cancer

 (

 risk factors

 include

 obesity

 ,

 polycystic ovary syndrome

 ,

 type 2 diabetes

 ,

 tamoxifen

 therapy,

 Lynch syndrome

 ) and/or have failed medical management

 Nonsurgical management
o General measures: immediate supportive measures in hemodynamically unstable
patients such as

o fluid resuscitation

o ,

o blood transfusion

o , and intrauterine tamponade (e.g., intrauterine balloon, gauze packing)

o Pharmacological
[14]
o

 Acute

 AUB

 in a hemodynamically stable patient

 High-dose IV conjugated equine

 estrogen
  Alternatives: multi-dose regimens of

 OCPs

 or oral

 progestins

 , as well as

 tranexamic acid

 (second-line)

 Ovulatory bleeding
 OCPs

 ,

 progestin

 (PO, IV, or as an

 IUD

 )

 NSAIDs

 (decrease blood loss)

 Tranexamic acid
 Anovulatory bleeding
 Progestin

 PO for 10 days or as an

 IUD

 OCPs
 Surgical treatment

 [14]

o Indications
 Severe bleeding/hemodynamic instability
 Patient unresponsive to hormonal treatment
 Hormonal treatment contraindicated (e.g.,

 breast cancer

 ,

 endometrial cancer
  )

 Underlying medical condition requiring surgical repair

o Procedures
 Uterine

 dilation and curettage

 (D&C) with concomitant

 hysteroscopy

 Diagnostic and therapeutic

 Used to identify intrauterine pathologies, take tissue samples, and
remove the excess uterine lining
 Can decrease bleeding in less than an hour
 Preserves

 fertility

 Endometrial

 ablation

 Only indicated if other treatments have been ineffective or are

contraindicated
 Provides long-term improvement of

 uterine bleeding

 symptoms by destroying a thin layer of the

 endometrium

 (e.g., with extreme cold, heat, radiofrequency energy)

 Hysteroscopy

 prior to ablation may be useful for identifying and treating intrauterine

structural abnormalities (e.g., polyps,

 fibroids

 ).

 Does not preserve

 fertility

 Transcatheter

 uterine artery embolization

 Recommended in the case of

  fibroids

 First-line therapy in patients with

 AUB

 due to uterine

 arteriovenous malformation

 (

 AVM

 )

 Hysteroscopy

 : in case of

 endometrial polyps

 Hysterectomy

 : reserved for patients who do not respond to any other treatment, no longer
desire

 fertility

 , or have symptomatic

 anemia

In patients with acute

abnormal uterine bleeding

and onset of

menarche

within the last year, anovulatory bleeding due to immaturity of the

hypothalamic-pituitary-gonadal axis

should be considered.

Premenstrual syndrome (PMS)

Mittelschmerz

Differential diagnosis and treatment of dysmenorrhea and abnormal uterine bleeding

Differential diagnosis and treatment of
 dysmenorrhea
and
AUB
Condition Clinical features Diagnostics Treatments
 Symptomatic:
 NSAIDs
 , topical heat
 Hormonal
 Spasmodic,
contraceptives
crampy pain in
 (e.g.,
the lower  Diagnosis of
Primary dysmenorrhea  combined oral
abdominal exclusion
contraceptive
and/or pelvic
pill
midline
 ,
 IUD
 with
progestogen)
Endometriosis  Chronic pelvic  Physical  Pharmacologic
pain that examination o Combi
worsens before o Rectov ned
the onset of aginal o OCPs
menses tender o (first-
 Dysmenorrhea ness line)
 Dyspareunia o Adnexa o GnRH
 Infertility l o analogs
 Dyschezia masses ,
 Rectovaginal  Transvaginal o danazo
tenderness and ultrasound l
palpable (best initial o ,
adnexal masses test) o NSAIDs
o Uterus o ,
usually o proges
not tins
enlarge  Surgical
d o Conser
o Ovaria vative:
n cysts excisio
o ( n,
o chocol cauteri
ate zation,
cysts and
o ) ablatio
 Laparoscopy n of
 or lesions
 laparotomy o Definiti
 ( ve:
 confirmatory total
 abdomi
nal
o hystere
ctomy
o /
bilater
al
test
o salping
 )
o-
oophor
ectomy
o Remov
al of
adhesi
ons
 Pharmacologic
o NSAIDs
o (first-
 MRI line)
 and o OCPs
transvaginal o ,
ultrasound can o proges
support the tins
diagnosis  Surgical
 Dysmenorrhea
and/or assist in o Conser
 AUB
ruling out vative:
 Chronic pelvic
other o hystero
Adenomyosis pain
diagnoses scopy
 Uniformly
(particularly o followe
enlarged
 leiomyoma d by
uterus
 ) o endom
 Histopathology etrial
(only method o ablatio
that provides n/resec
definitive tion
diagnosis) o Definiti
ve:
o hystere
ctomy
Endometritis  Lower  Physical  Mild to
abdominal/pel examination moderate
vic pain  Testing for cases
 AUB typical (outpatient
 Fever (if pathogens treatment)
 peritonitis (e.g., o One
 or pelvic  chlamydia single
 abscesses  ) dose of
 IM
o ceftriax
one
o and
oral
therap
y with
o doxycy
cline
o Additio
n of
o metron
idazole
o should
 Endometrial
biopsy be
 (to evaluate consid
chronic ered in
 develop) some
 endometritis
 Infertility cases
 that is
(e.g.,
unrelated to
patient
 pregnancy
s who
 )
recentl
y
under
went
gyneco
logical
proced
ures).
 Severe cases
(inpatient
treatment):
 clindamycin
 PLUS
 gentamicin
Endometrial carcinoma  AUB  Pelvic exam is  Pharmacologic
/ often normal. o Proges
hyperplasia  Transvaginal tins
ultrasonograph o : in
y (best initial early-
test) stage
 Abdominal o endom
 ultrasonograph etrial
y carcino
 , ma
 CXR o Radiot
 herapy
o and/or
o chemot
 , CT, herapy
 MRI  Surgical
 (to exclude o Abdom
 metastases inal
 ) o hystere
 Laboratory ctomy
testing (to o with
evaluate bilater
possible al
 anemia o salping
 and other o-
causes of oophor
 abnormal ectomy
uterine o Additio
bleeding nal
 , e.g., advanc
 coagulation ed
disorders radical
 ) hystere
 Endometrial ctomy
biopsy and
 with histology remova
(definitive test l of the
to rule out upper
 endometrial o vagina
cancer o (accord
 ) ing to
Werthe
im-
Meigs)
Uterine leiomyoma  Often  Ultrasound  Treat only if
asymptomatic  (best initial symptomatic.
 AUB test)  Pharmacologic
 Back/pelvic  MRI o GnRH
pain  to evaluate agonist
 Dysmenorrhea surgical options s
 Infertility and differential o ,
 Urinary tract or diagnoses o proges
bowel tins
symptoms o ,
 Dyspareunia o levonor
gestrel
o -
releasi
 ng
o IUD
o Androg
enic
o agonist
s
o (e.g.,
o danazo
l
o )
o NSAIDs
o Antifibr
inolytic
s
 Interventional:
 uterine artery
embolization
 Surgical
o Indicati
ons:
rapidly
growin
g
o fibroid
o ,
recurre
nt
refract
ory
bleedin
g,
severe
sympto
ms
o Proced
ures:
o myome
ctomy
o or
o hystere
ctomy
o (depen
ds on
the
patient
's
prefere
 nces
and
their
ability/
desire
to
conceiv
e in the
future)
 Transvaginal
ultrasound
 Often
 Hysteroscopy
asymptomatic  Asymptomatic:
 Endometrial
 AUB observation
biopsy
 Infertility and follow-up
Endometrial polyps  : rules out e.g.,
 /difficulty  Symptomatic:
 endometrial
conceiving surgical
hyperplasia
 Incidental removal
 ,
finding
 endometrial
carcinoma