This document provides an overview of amenorrhea, including: 1. Definitions of primary and secondary amenorrhea and classifications based on cause and presentation. 2. Requirements for normal menstruation including a coordinated neuroendocrine axis and patent reproductive tract. 3. Causes of pathological amenorrhea including hypothalamic-pituitary disorders, gonadal dysgenesis, weight changes, and structural abnormalities of the reproductive tract.

1. 1
Amenorrhea
Made Easy
By:
Mohammad Emam
Prof. OB & GYN
Mansoura Faculty of Medicine
EGYPT
2015

2. Definition OfDefinition Of AmenorrheaAmenorrhea
•Is complete absence ofIs complete absence of
menstruation in themenstruation in the
childbearing period.childbearing period.

3. Definition OfDefinition Of AmenorrheaAmenorrhea
Absence of menstruation.

4. Background
• Understanding normal menstruation.
• Classification of amenorrhea.
• Amenorrhea is a Symptom not a disease, so
the final diagnosis should be pathological .

5. Pre-requisities for normality of menstruation
• Coordinated Neuro endocrine Axis.Coordinated Neuro endocrine Axis.
• Responsive ,patent Utero vaginal canalResponsive ,patent Utero vaginal canal..
• Good general health .Good general health .

6. CONSTANTVARIABLE
Coordinated pituitary- ovarian –uterine Axis

7. Classifications Of AmenorrheaClassifications Of Amenorrhea
• According to the onset:According to the onset:
– Primary amenorrhea.Primary amenorrhea.
– Secondary amenorrhea.Secondary amenorrhea.
• According to the cause:According to the cause:
– Physiological.Physiological.
– PathologicalPathological
• According to Hidden or apparantAccording to Hidden or apparant::
– False amenorrheaFalse amenorrhea ((Crypto menorrheaCrypto menorrhea).).
– True amenorrhea.True amenorrhea.
• These are complementary to each otherThese are complementary to each other

8. Primary & Secondary
PrimaryPrimary SecondarySecondary

9. pubertal changespubertal changes-- Marshall & TannerMarshall & Tanner
Regular sequence of events between ages of 10-16 yrs in girlsRegular sequence of events between ages of 10-16 yrs in girls
GROWTH SPURT 8 - 14 yrs (9 yrs)
6 - 10 cm / yr peak
2.5 yrs duration
BREAST GROWTH (Thelarche) 8 - 13 yrs (11 yrs)
PUBIC HAIR (Pubarche) 9 - 13 yrs
1st Pubertal Sign in 25%
AXILLARY HAIR (Adrenarche) 9.5 - 15 yrs
may follow menarche
MENSTRUATION (Menarche) 10 - 16 yrs (13 yrs)

10. Pathological:Pathological:
Primary:Primary:
TrueTrue
(( physiologic & pathologic)physiologic & pathologic)
FalseFalse
Secondary:Secondary:
TrueTrue
( physiologic & pathologic)( physiologic & pathologic)
FalseFalse
Physiological.Physiological.
•Before puberty.Before puberty.
•After menarcheAfter menarche..
•During pregnancyDuring pregnancy..
•During lactationDuring lactation .
•During menopauseDuring menopause
According to causeAccording to cause

11. Hidden or true :
Crypto menorrhea =
Obstruction of outflow tract below internal OS :Obstruction of outflow tract below internal OS :
• Primary:Primary:
» Cervical atresia .Cervical atresia .
» Vaginal aplasia.Vaginal aplasia.
» Transverse vaginal septumTransverse vaginal septum
» Imperforate hymenImperforate hymen
•Secondary:Secondary:
» Cervical Cauterization.Cervical Cauterization.
» Cervical conization ( LeepCervical conization ( Leep
diathermy)diathermy) ..
» Vaginal synechiaeVaginal synechiae

12. Workup FOR DIAGNOSIS
•Exclude physiologic causes
•Exclude anatomical.
•Clinical workup

13. Exclude physiologic causes

14. Exclude anatomical:
Cryptomenorrhea Ambiguous genitalia

15. Crypto menorrhea
- Intermittent abdominal pain
- Possible difficulty with micturition
- Possible lower abdominal swelling
- Bulging bluish membrane at the
introitus or absent vagina (only
dimple)

16. 16
Imperforate hymen

17. 17
False (crypto menorrhea)
hematometra
hematocolpos

18. Imperforate hymen
Hymenotomy or curiciate incision

19. Clinical workup
Four phenotypes (Breast & uterus )
1. Absent breast + presence of uterus
2. Presence breast + absence uterus
3 Absence breast + absence uterus
4. Presence breast + presence uterus

20. Breast is absent in cases with
Hypogonadism

21. Serum FSHSerum FSH
Absent breast + presence of uterus
(Hypogonadism)
LOWLOW (less than 5 IU/l.)(less than 5 IU/l.)
HIGHHIGH ((more than 20 IU/lmore than 20 IU/l))
GnRH challengeGnRH challenge ..
LOW FSHLOW FSH HIGH FSHHIGH FSH
PITUITARYPITUITARY HYPOTHALAMICHYPOTHALAMIC
History , exam & investigationHistory , exam & investigation
PRIMARY OV. FAILUREPRIMARY OV. FAILURE
Gonadal dysgenesisGonadal dysgenesis
KARYOTYPEKARYOTYPE
Gonadal biopsyGonadal biopsy
Hypothalamo - pituitary

22. Gonadal dysgenesis (Turner’s syndrome)
•• Sexual infantilism and short stature.Sexual infantilism and short stature.
•• Associated abnormalities:Associated abnormalities:
– webbed neck,webbed neck,
– cubitus valguscubitus valgus
– coarctation of the aorta,coarctation of the aorta,
– high-arched palate,high-arched palate,
– broad shield-like chest with widely spaced nipples,broad shield-like chest with widely spaced nipples,
– short metacarpal bonesshort metacarpal bones
– Renal anomalies.Renal anomalies.
•• Bilateral streaked gonads.Bilateral streaked gonads.
•• Karyotype - 80 % 45, X0Karyotype - 80 % 45, X0
-- 20% mosaic forms (46XX/45X0)20% mosaic forms (46XX/45X0)
•• TreatmentTreatment: HRT: HRT

23. Gonadal Dysgenesis (Turner’s syndrome)

24. Mosaic (46-XX / 45-XO)(Classic 45-XO)
Turner’s syndrome

25. Causes of hypothalmo - pituitary
• CongenitalCongenital
• TraumaticTraumatic
• InflammatoryInflammatory
• NeoplasticNeoplastic
• MiscellaneousMiscellaneous

26. Hypothalamus & Pituitary
(Hypogonadotropic )Hypogonadotropic )
• HypothalamusHypothalamus ::
• StressStress
• Weight changes :anorexia nervosa ,bulimiaWeight changes :anorexia nervosa ,bulimia
• ExerciseExercise
• PsuedocyesisPsuedocyesis ( ?!!!) Thanks for sonar( ?!!!) Thanks for sonar
• SyndromesSyndromes
• Pituitary :Pituitary :
• Craniopharyngioma.Craniopharyngioma.
• Adenomas.Adenomas.
• syndromessyndromes . e.g. Sheehan's syndrome. e.g. Sheehan's syndrome

27. Emotional stress
• EmotionalEmotional
shockshock
• StressStress
EndorphinsEndorphins
Gn RGn Rhh

28. 28
Weight changes
• Weight lossWeight loss ((15% of ideal wt for15% of ideal wt for
age)age) whether By:whether By:
• Diet regimenDiet regimen
• Anorexia nervosaAnorexia nervosa
• Excess weight gain :Excess weight gain :
• simple overeatingsimple overeating
• Bulimia nervosaBulimia nervosa..

29. Kallmann Syndrome
• Deficient secretion of GnRHDeficient secretion of GnRH ++ anosmia.anosmia.
• Possible co-existing featuresPossible co-existing features include:include:
• Bone anomalies.Bone anomalies.
• Renal anomalies.Renal anomalies.
• Cleft lip and palate.Cleft lip and palate.
• Color blindness.Color blindness. ..

30. Frolich syndrome
–Primary amenorrhea.Primary amenorrhea.
–Hypogonadism.Hypogonadism.
–Trunkal obesity.Trunkal obesity.

31. Laurence-Moon -Biedle syndrome
• AsAs FrolichFrolich syndrome with:syndrome with:
– Polydactyl.Polydactyl.
– Syndactly.Syndactly.
– Mental retardation.Mental retardation.
– Retinitis pigmentosaRetinitis pigmentosa..

32. Craniopharyngioma
• Arises from remnants ofArises from remnants of Rathke'sRathke's pouchpouch
• Compresses the hypothalamusCompresses the hypothalamus
• SuppressSuppress GnRHGnRH secretion .secretion .
• Interrupt portal flow ofInterrupt portal flow of GnRHGnRH in the pituitary stalk.in the pituitary stalk.
• Calcifications may be apparent on radiography ofCalcifications may be apparent on radiography of
thethe sella turcica.sella turcica.
• Frequent manifestations includeFrequent manifestations include visual field defectsvisual field defects
and blurring visionand blurring vision..

33. GalactorrhoeaGalactorrhoea ++ amenorrhea.amenorrhea.
• Chiari-Frommel syndrome
–It occursIt occurs after deliveryafter delivery: due to: due to
persistentpersistent ProlactinProlactin secretion.secretion.
• Delcastello syndrome:
•It is not preceded by delivery.It is not preceded by delivery.

34. Levi- Lorian Syndrome
(Pituitary infantilism)
–Amenorrhea.Amenorrhea.
–Hypogonadism.Hypogonadism.
–Short stature (Dwarfism).Short stature (Dwarfism).

35. Sheehan's syndrome &Simmonds
• Postpartum hge.Postpartum hge.
• Failure of gonadotrphic function +Failure of gonadotrphic function + failure offailure of
lactationlactation..
• More extensive damage lead to :More extensive damage lead to :
• Simmonds :Simmonds : (Destruction of the anterior pituitary gland(Destruction of the anterior pituitary gland
due todue to septic emboliseptic emboli due todue to puerperal sepsispuerperal sepsis.).)

36. Pituitary Adenoma
• Evaluation of theEvaluation of the sella turcicasella turcica withwith (MRI)(MRI) ++ radiographyradiography isis
necessary.necessary.
• Vary in size.Vary in size.
• Micro adenomasMicro adenomas (less than 10 mm).(less than 10 mm).
• Macro adenomasMacro adenomas (more than 10 mm).(more than 10 mm).
• May beMay be associatedassociated with:with:
– Visual changes.Visual changes.
– Galactorrhoea.Galactorrhoea.
– Hypothyroidism.Hypothyroidism.
– AmenorrheaAmenorrhea

37. Work up for : hypothalamic- pituitary
• History
• Exam
• Investigation…
• Then:
• Categorize as primary or secondary
• Categorize cause……..

38. History in primary amenorrhea
• Developmental milestones (age of growth
spurt ,age of thelarche, adrenarche)
• Chronic illness (CRI ,TB, Bl disease).
• Weight changes
• Excessive exercise
• History of anosmia

39. Examination
•General condition
•Height
•BMI
•2ndary sex characters

40. Investigations
• Bed –side:
• Visual field in suspected pituitary adenoma
• Laboratory:
• BHCG: to exclude pregnancy
• Serum prolactin
• TSH
• Imaging:
– Ultrasound : prove presence or absence of uterus, measure its size
– CT
– MRI
• Instrumental:
– Hysteroscopy: uterine synechia
– Laparoscopy

41. Sexual hair &
Karyotype
46-XX
Mullerian
Agenesis
(MRKH syndrome)
Andogen
Insenitivity
(TSF
syndrome)
46-XY
Presence of
sexual hair
Absent sexual
hair
2. Presence breast + absence uterus

42. 42
Utero-vaginal Agenisis
Mayer- Rokitansky- Kuster-Hauser syndrome
• Normal breasts.Normal breasts.
• N. sexual hair development .N. sexual hair development .
• Normal looking external female genitaliaNormal looking external female genitalia
• Normal female range testosterone levelNormal female range testosterone level
• Absent uterus and upper vaginaAbsent uterus and upper vagina
• Normal ovariesNormal ovaries
• Karyotype 46-XXKaryotype 46-XX
• 15-30% renal, skeletal and middle ear15-30% renal, skeletal and middle ear
anomalies.anomalies.
• Treatment :Treatment :
STERILE? Vaginal creation : Dilatation &STERILE? Vaginal creation : Dilatation &
VaginoplastyVaginoplasty))

43. 43
Testicular feminization syndrome
• Normal breasts but no sexual hairNormal breasts but no sexual hair
• Normal looking female externalNormal looking female external
genitaliagenitalia
• Absent uterus and upper vaginaAbsent uterus and upper vagina
• Karyotype 46, XYKaryotype 46, XY
• MaleMale range testosterone levelrange testosterone level
• TreatmentTreatment ::
– gonadectomy after puberty + HRTgonadectomy after puberty + HRT
– ? Vaginal creation? Vaginal creation (Vaginoplasty )(Vaginoplasty )

44. Vaginal Agenesis: Comparison of Two Syndromes
Mullerian AgenesisMullerian Agenesis AndrogenAndrogen
InsensitivityInsensitivity
SyndromeSyndrome
VaginaVagina absentabsent absentabsent
Pubic hairPubic hair presentpresent absentabsent
BreastsBreasts presentpresent PresentPresent
GonadsGonads ovariesovaries TestesTestes
UterusUterus absentabsent AbsentAbsent
Testestrone levelTestestrone level Female levelFemale level Male levelMale level
KaryotypeKaryotype 46 XX46 XX 46 XY46 XY

45. 3. absence breast + absence
uterus
•17, 20 desmolase deficiency
•17 a hydroxylase deficiency
•Agonadism
Very rare
all are 46
Xy

46. AGONADISM
•Degeneration of the
testes (in utero) after
the production of the
MIF

47. PREGESTERONEPREGESTERONE
BLEEDINGBLEEDING NO BLEEDINGNO BLEEDING
CHRONIC ANOVULATION
e.g PCOS
COMBINED OESTROGENCOMBINED OESTROGEN
& PROGESTERONE& PROGESTERONE
BLEEDINGBLEEDING NO BLEEDINGNO BLEEDING
OVARIAN FAILURE
( Non dysgenetic)
SERUM FSHSERUM FSH
UTERINE FACTOR
( Ashermann syndrome)
4. Presence breast + presence uterus (Like secondary
amenorrhea)

48. Summary of Sub-phenotypes Amenorrhea
BreastBreast
––
aBsentaBsent
UterUs
absent
UterUs Present
17, 20 desmolase
deficiency
1. Gonadal failure turner 45X
17 a hydroxylase
deficiency 46xy
Gonadal dysgenisis
Agonadism 17 a hydroxylase deficiency with
46XX
2. Hypothalamic failure
3. Pituitary failure

49. General Principles of management
• Try causative Treatment.
• Do not forget general factors
• Remember stress is common cause in
adolescents
• Pregnancy is the commonest cause of
secondary amenorrhea

50. General Principles of management
. HRT: (estrogen and progesterone)
In hypo-estrogenic amenorrheic women (to prevent
osteoporosis)
. Periodic progestogen:
In euestrogenic amenorrheic women (to avoid endometrial cancer)
. If Y chromosome is present: gonadectomy is indicated
. Many cases require frequent re-evaluation

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