27.Amenorrhea

1. AmenorrheaAmenorrhea
Zhanghuiying
Department Of Obstetrics & Gynecology
Tianjin Medical University General Hospital

2. DefinitionDefinition ★★
•Amenorrhea is the absence of Amenorrhea is the absence of
menstruation.menstruation.
•Primary AmenorrheaPrimary Amenorrhea
–Absence of menses by age 16 with Absence of menses by age 16 with
normal secondary sexual normal secondary sexual
characteristics.characteristics.
–Absence of menses by age 14 without Absence of menses by age 14 without
secondary sexual development.secondary sexual development.
•Secondary AmenorrheaSecondary Amenorrhea
–Absence of menses for 6 months in a Absence of menses for 6 months in a
previously menstruating female previously menstruating female or or 3 3
normal intervals in a woman with normal intervals in a woman with
oligomenorrhea. oligomenorrhea.

3. Events of PubertyEvents of Puberty
•Thelarche Thelarche (breast development)(breast development)
–Requires estrogenRequires estrogen
•Pubarche/adrenarche Pubarche/adrenarche (pubic hair (pubic hair
development)development)
–Requires androgensRequires androgens
•MenarcheMenarche（（the first menses)the first menses)
Requires:Requires:
–GnRH from the hypothalamusGnRH from the hypothalamus
–FSH and LH from the pituitaryFSH and LH from the pituitary
–Estrogen and progesterone from the Estrogen and progesterone from the
ovariesovaries
–Normal outflow tractNormal outflow tract

4. Possible results of amenorrheaPossible results of amenorrhea
•Cannot conceiveCannot conceive
•Lead to osteoporosis and genital Lead to osteoporosis and genital
atrophyatrophy
•Increased endometrial hyperplasia Increased endometrial hyperplasia
which can increase the possibility of which can increase the possibility of
endometrial carcinoma from unopposed endometrial carcinoma from unopposed
estrogen secretionestrogen secretion
•Without secondary sexual Without secondary sexual
characteristics may give rise to major characteristics may give rise to major
social and psychosexual problems.social and psychosexual problems.

5. Classification of amenorrheaClassification of amenorrhea
•hypothalamic amenorrheahypothalamic amenorrhea
•pituitary amenorrheapituitary amenorrhea
•ovarian amenorrheaovarian amenorrhea
•uterine amenorrheauterine amenorrhea

6. Etiology -Etiology -hypothalamic hypothalamic
amenorrheaamenorrhea
–Psychological stressPsychological stress
–Anorexia nervosa, weight lossAnorexia nervosa, weight loss
– Increased exercise levelsIncreased exercise levels
–Kallmann syndromeKallmann syndrome -congenital absence of GnRH-congenital absence of GnRH
– drug-induced amenorrhea:drug-induced amenorrhea: anti-psychotics, anti-psychotics,
reserpine, reserpine, ContraceptiContraceptiveve
– Space-occupying lesion of CNSSpace-occupying lesion of CNS

7. Weight-related amenorrhoeaWeight-related amenorrhoea
Anorexia NervosaAnorexia Nervosa
•A body mass index (BMI) <17 kg/mA body mass index (BMI) <17 kg/m²²
menstrual irregularity and amenorrheamenstrual irregularity and amenorrhea
•Hypothalamic suppression Hypothalamic suppression
•Mean age onset 13-14 yrs (range 10-21 Mean age onset 13-14 yrs (range 10-21
yrs)yrs)
•Low estradiol Low estradiol  risk of osteoporosis risk of osteoporosis

8. Exercise-associated amenorrhoeaExercise-associated amenorrhoea
•Common in women who participate Common in women who participate
in sports (e.g. competitive athletes, in sports (e.g. competitive athletes,
ballet dancers)ballet dancers)
•Eating disorders have a higher Eating disorders have a higher
prevalence in female athletes than prevalence in female athletes than
non-athletesnon-athletes
•Hypothalamic disorder caused by Hypothalamic disorder caused by
abnormal gonadotrophin-releasing abnormal gonadotrophin-releasing
hormone pulsatility, resulting in hormone pulsatility, resulting in
impaired gonadotrophin levels, impaired gonadotrophin levels,
particularly LH, and subsequently particularly LH, and subsequently
low estrogen levelslow estrogen levels

9. Contraception related amenorrheaContraception related amenorrhea
•Post-pill amenorrhea is not an entityPost-pill amenorrhea is not an entity
•Depot medroxyprogesterone acetateDepot medroxyprogesterone acetate
Up to 80 % of women will have amenorrhea Up to 80 % of women will have amenorrhea
after 1 year of use. It is reversible (estrogen after 1 year of use. It is reversible (estrogen
deficiency)deficiency)
•A minority of women taking the A minority of women taking the
progestogen-only pill may have reversible progestogen-only pill may have reversible
long term amenorrhoea due to complete long term amenorrhoea due to complete
suppression of ovulationsuppression of ovulation

10. Etiology -Etiology -pituitary amenorrheapituitary amenorrhea
– tumortumor
– Empty sella syndromeEmpty sella syndrome
– Sheehan syndromeSheehan syndrome

11. SheehanSheehan’s syndrome’s syndrome
•Pituitary inability to secrete gonadotropinsPituitary inability to secrete gonadotropins
•Pituitary necrosis following massive obstetric Pituitary necrosis following massive obstetric
hemorrhage is most common cause in womenhemorrhage is most common cause in women
•Diagnosis : History and Diagnosis : History and ¯¯ E2,FSH,LH E2,FSH,LH
+ other pituitary deficiencies + other pituitary deficiencies （（ TSH Thyroid
Stimulating Hormone and ACTH
adrenocorticotropic hormone）
Treatment :Treatment :
Replacement of deficient hormonesReplacement of deficient hormones

12. Etiology -Etiology -ovarian amenorrheaovarian amenorrhea
◆◆Gonadal dysgenesisGonadal dysgenesis
•Chromosomally incompetentChromosomally incompetent
- Classic turner- Classic turner’s syndrome (45XO)’s syndrome (45XO)
- Turner variants (45XO/46XX),(46X-- Turner variants (45XO/46XX),(46X-abnormal abnormal X)X)
- Mixed gonadal - Mixed gonadal dysgenesisdysgenesis (45XO/46XY) (45XO/46XY)
•Chromosomally competentChromosomally competent
- 46XX (Pure gonadal - 46XX (Pure gonadal dysgenesisdysgenesis))
- 46XY (Swyer’s syndrome)- 46XY (Swyer’s syndrome)
◆◆resistant ovary syndromeresistant ovary syndrome
◆◆Premature ovarian failurePremature ovarian failure
◆◆Polycystic ovary syndromePolycystic ovary syndrome

13. Typical features of Turner’sTypical features of Turner’s
Syndrome Syndrome
Sexual infantilism and short statureSexual infantilism and short stature
High FSH and LH levels.High FSH and LH levels.
• • Bilateral streaked gonads.Bilateral streaked gonads.
• • Karyotype - 80 % 45, X0 Karyotype - 80 % 45, X0
-- 20% mosaic forms (46XX/45X0) 20% mosaic forms (46XX/45X0)

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

15. Ovarian dysgenesis
streak gonadstreak gonad

16. Premature ovarian failurePremature ovarian failure
•Manopause occurs before 40 Manopause occurs before 40
years old.years old.
•Serum estradiol < 50 pg/ml and Serum estradiol < 50 pg/ml and
FSH > 40 IU/ml on repeated FSH > 40 IU/ml on repeated
occasions occasions

17. EtiologyEtiology
•uterine amenorrheauterine amenorrhea
– Absence of uterusAbsence of uterus
– Asherman syndromeAsherman syndrome
•anatomic abnormalities of the anatomic abnormalities of the
reproductive tract reproductive tract
–Imperforate HymenImperforate Hymen

18. Asherman’s syndromeAsherman’s syndrome
•History of pregnancy History of pregnancy
associated D&Cassociated D&C
•Rarely after CS , myomectomy Rarely after CS , myomectomy
T.B endometritis, T.B endometritis,
•Diagnosis : HSG or Diagnosis : HSG or
hysterescopyhysterescopy
•Treatment : lysis of Treatment : lysis of
adhesions; D&C or adhesions; D&C or
hysterescopy + estrogen hysterescopy + estrogen
therapytherapy
Hysterosalpingography
Uterine synechiae

19. Imperforate HymenImperforate Hymen

20. Mayer-Rokitansky-Kuster-Hauser SyndromeMayer-Rokitansky-Kuster-Hauser Syndrome
(utero-vaginal agenesis)(utero-vaginal agenesis)
•15% 15% of primary amenorrhea of primary amenorrhea
•Normal secondary development & Normal secondary development &
external female genitaliaexternal female genitalia
•Normal female range testosterone levelNormal female range testosterone level
•Absent uterus and upper vagina Absent uterus and upper vagina
& normal ovaries& normal ovaries
•Karyotype 46-XXKaryotype 46-XX
•1515~~30% renal, skeletal and middle 30% renal, skeletal and middle
ear anomaliesear anomalies

21. Androgen InsensitivityAndrogen Insensitivity
•Normal breasts but no sexual Normal breasts but no sexual
hairhair
•Normal looking female external Normal looking female external
genitaliagenitalia
•Absent uterus and upper vaginaAbsent uterus and upper vagina
•Karyotype 46, XYKaryotype 46, XY
•Male range testosterone levelMale range testosterone level
•Treatment : gonadectomy after Treatment : gonadectomy after
puberty + HRTpuberty + HRT

22. congenital adrenal hyperplasiacongenital adrenal hyperplasia
•Autosomal recessive traitAutosomal recessive trait
•Most common form is due to 21-hydroxylase Most common form is due to 21-hydroxylase
deficiencydeficiency
•Mild forms Closely resemble PCOMild forms Closely resemble PCOSS
•Severe forms show Signs of severe Severe forms show Signs of severe
androgen excessandrogen excess
•High 17-OH-progesterone blood levelHigh 17-OH-progesterone blood level
•abnabnormal looking female external genitaliaormal looking female external genitalia
•Presence of Presence of uterus and upper vaginauterus and upper vagina
•Treatment : cortisol replacement and Treatment : cortisol replacement and
Corrective surgeryCorrective surgery

23. Other causes of Secondary Other causes of Secondary
AmenorrheaAmenorrhea
•Pituitary disordersPituitary disorders
–HyperprolactinemiaHyperprolactinemia
•ProlactinomaProlactinoma
•MedicationsMedications
•Renal failureRenal failure
–HypoprolactinemiaHypoprolactinemia
•Pituitary resectionPituitary resection
•Sheehan’s syndromeSheehan’s syndrome
•Thyroid disordersThyroid disorders
–Hyper- or hypothyroidismHyper- or hypothyroidism

24. Diagnosis ofDiagnosis of
Amenorrhea

25. DiagnosisDiagnosis
•History History
•Physical examinationPhysical examination
–Physical examination begins Physical examination begins
with vital signs, including height with vital signs, including height
and weight, and with sexual and weight, and with sexual
maturity ratings maturity ratings
•Laboratory evaluationLaboratory evaluation

26. Evaluation of Primary AmenorrheaEvaluation of Primary Amenorrhea
–Physical exam to determine presence Physical exam to determine presence
of uterusof uterus
–FSHFSH
–KaryotypeKaryotype

27. Primary AmenorrheaPrimary Amenorrhea
•Is there normal Is there normal
development of secondary development of secondary
sexual characteristics?sexual characteristics?
NONO
Think hypogonadism or Think hypogonadism or
hypogonadotropismhypogonadotropism

28. Amenorrhea with Amenorrhea with ImmatureImmature Secondary Secondary
CharacteristicsCharacteristics
FSH Serum level
Low / normal High
Hypogonadotropic
hypogonadism
Gonadal
dysgenesis

29. Hypogonadism (gonadal failure)Hypogonadism (gonadal failure)
•Gonadal dysgenesisGonadal dysgenesis
Chromosomally abnormalChromosomally abnormal
- - Classic Classic TTurnerurner’s syndrome (45XO)’s syndrome (45XO)
- Turner variants (45XO/46XX),(46X-abnormal X)- Turner variants (45XO/46XX),(46X-abnormal X)
- Mixed gonadal - Mixed gonadal dysgenesisdysgenesis (45XO/46XY (45XO/46XY))
Chromosomally normalChromosomally normal
- - 46XX (Pure gonadal 46XX (Pure gonadal dysgenesisdysgenesis))
- 46XY (Swyer’s syndrome- 46XY (Swyer’s syndrome))
•IrradiationIrradiation
•ChemotherapyChemotherapy
•galactosemiagalactosemia
•Note: gonadotropins (FSH/LSH) will be high, Note: gonadotropins (FSH/LSH) will be high,
similar to menopausesimilar to menopause

30. HypogonadotropismHypogonadotropism
–Hypothalamic dysfunctionHypothalamic dysfunction
•Kallmann’s syndromeKallmann’s syndrome
•Anorexia nervosaAnorexia nervosa
•Space-occupying lesion of CNSSpace-occupying lesion of CNS
–Pituitary damage (surgery/radiation)Pituitary damage (surgery/radiation)
–Constitutional delayConstitutional delay

31. Primary AmenorrheaPrimary Amenorrhea
•Is there normal Is there normal
development of secondary development of secondary
sexual characteristics?sexual characteristics?
YESYES
•ThinkThink
–PregnancyPregnancy
–Mullerian anomalyMullerian anomaly
–Androgen insensitivityAndrogen insensitivity

32. Mullerian AnomaliesMullerian Anomalies
–Mullerian agenesis (Mayer-Mullerian agenesis (Mayer-
Rokitansky-Kuster-Hauser Rokitansky-Kuster-Hauser
syndrome)syndrome)
–Imperforate hymenImperforate hymen
–Transverse vaginal septumTransverse vaginal septum

33. Evaluation of Secondary Evaluation of Secondary
AmenorrheaAmenorrhea
HistoryHistory
–Nutrition/exercise habits, weight Nutrition/exercise habits, weight
changechange
–Sexual/contraceptive practiceSexual/contraceptive practice
–History of uterine/cervical surgeryHistory of uterine/cervical surgery
•Physical examPhysical exam
–Height/weightHeight/weight
–HirsutismHirsutism
–GalactorrheaGalactorrhea
–Estrogen status of tissuesEstrogen status of tissues
•LaboratoryLaboratory
–hCG hCG PRL & TSH PRL & TSH  progesterone progesterone
challenge challenge  FSH FSH  if high if high karyotypekaryotype

34. Negative Pregnancy.test
TSH ,PROLACTIN,
Progesterone
challenge test
withdrawal
bleeding
without withdrawal
bleeding
hypoestrogenic
compromised
outflow tract
ve.est/progest+
challenge test
ve.est/progest-
challenge test
FSH<30-40
Normal FSH
HSG OR hysteroscopy
Asherman’s
FSH low.
repeat
Repeat+serum
estrogen level
PreOv
Failure
hypothalamic-
pituitary failure
anovulation
Procedures of DiagnosisS
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35. Treatment --Treatment --SelfstudySelfstudy
•treatment varies depending treatment varies depending
upon the causes of the upon the causes of the
amenorrhea. amenorrhea.