1) The document discusses how to approach cases of amenorrhea by evaluating the hypothalamic-pituitary-ovarian axis and ruling out common causes such as pregnancy, thyroid disorders, prolactin disorders, anovulation, outflow tract obstructions, CNS/hypothalamic dysfunction, and drugs/stress/nutrition. 2) It presents several case examples of patients with primary or secondary amenorrhea and suggests diagnoses and next steps such as evaluating for eating disorders, PCOS, Asherman's syndrome, or Sheehan's syndrome. 3) Key factors in evaluating amenorrhea include measuring beta-HCG, TSH, prolactin, doing a progestin challenge

1. How to approach a case of
amenorrhea
Dr Manal Behery
Assistant professor
ZAGAZIG University 2013
Dr Manal Behery
Assistant professor
ZAGAZIG University 2013

2. “Doctor, I’m not getting my period”
(blank, like no period……)

3. Amenorrhea:
“absence of menses”
 Normal cycle is 28 days
 This occurs in 15% of cycles Normal
 Highest rate of anovulatory cycles <20 or >40
yo age
 Average duration 4-6 days (3-8 normal)
 Average blood loss per cycle = 30 ml.
– > 80 ml. Leads to risk for anemia
Menarche age 12
9
years
16
years

4. Menstrual cycle
Source Undetermined

5. PRIMARY AMENORRHEA
 Patient has never menstruated
– No period by age 14 with no secondary
sexual characteristics
– No period by age 16 regardless of
secondary sexual characteristics

6. SECONDARY AMENORRHEA
– absence of menses in women who previously
had menses.
– Absence must be for
> 3 cycles according to certain sources
> 6 months according to most sources

7. ALWAYS RULE OUT
PREGNANCY!!!!!!!
No matter WHAT!!!
Then evaluate the four parts of the
system

8. Don’t forget PREGNANCY!
Is the Most common cause of secondary
amenorrhea
 Consider each level of the control of the
menstrual cycle:
– Hypothalamus
– Pituitary
– Ovary
– Uterus
– Cervix
– Vagina
Involved structurally in the outflow of
menstrual blood
Involved in endocrine regulation of
the menstrual cycle
Responds to endocrine cues from
the HPG axis

9. The Hypothalamic-Pituitary-Ovarian
Axis
http://www.shen-nong.com/eng/images/exam/missedperiods/img_mp1a.gif

10. REASONS FOR AMENORRHEA
 Pregnancy
 Menopause
 Thyroid/Prolactin Disorders
 Anovulation
 Outflow obstruction
 CNS/hypothalamic dysfunction
 Drugs/Stress/Nutrition
 Chromosomal/Abnormal Sexual Differentiation

11. STEP ONE –
will diagnose pregnancy, thyroid disorder,
hypoprolactinemia and anovulation
 LABS
– Beta hcg
– TSH
– Prolactin
 MEDS
– Progestin challenge
 {If galactorrhea, obtain MRI of
pituitary/sella turcica}

12. STEP TWO –
will diagnose outflow tract
obstruction
 Give estrogen “priming”, followed by progestin
– Estrogen x 21 days
– Add progesterone for the last 5 days

13. STEP 3- will determine if lack of
estrogen is due to ovarian failure
vs. altered CNS/pituitary axis
FSH
(LH)

16. I. UTERUS – VAGINA –
OUTFLOW TRACT
 Asherman’s – secondary amenorrhea
 Imperforate hymen – primary amenorrhea
 Vaginal septum – primary amenorrhea
 Agenesis – primary amenorrhea
 Testicular feminization – primary amenorrhea

17. Asharman syndrome(intrauterine
synechea)

18. Imperforate Hymen

19. Transverse Vaginal Septum

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

21. Testicular feminization syndrome
 Phenotype:female
 Genotype46xx
 Internal gentilia:no mullerin
ducts
 Male androgen level 7.8ngl
ml

22. 11 OVARY
 Chromosomes Normal-
– Menopause
– Radiation/Chemo
– Autoimmune Disorder
– Infection
 Chromosomes Abnormal-
– Primary Amenorrhea
– Premature Menopause

24. Turner syndrome” ovarian
dysgensis”

25. Streak gonads

26. III. ANTERIOR PITUITARY
 Prolactin Secreting Tumors
 Sheehan’s Syndrome

27. IV. CNS / HYPOTHALAMUS
 Weight loss, anorexia, stress, intense exercise
 Hypothyroidism – TRH/drugs which affect
dopamine
 Anovulation
 Hypothalamic Suppression

28. Case 1: 17 yo female with primary
amenorrhea
 Normal pubertal development
 Normal health
 No family history of delayed puberty
 Not involved in athletics
 Does well in school
 Not taking any meds

29. Case 1: Physical Exam
 Thin young woman (10% below IBW)
 Normal genitalia
 No galactorrhea
 Tanner stage 4
Laboratory values
 Urine and serum B-HCG negative
 Prolactin, FSH, TSH all normal

30. Case 1: Further history
Patient’s parents concerned about her eating
habits (very low fat intake and restricting
calories)

31. Diagnosis: Hypothalamic Amenorrhea
 Etiology is most likely inadequate caloric and
fat intake.
 Patient should be referred for evaluation for an
eating disorder.
 Chances of normal menstruation are very good
if patient takes in adequate calories.

32. Case 2: 24 yo woman with secondary
amenorrhea
 Menarche at age 12
 Periods have always been irregular
 Now c/o amenorrhea x 10 months
 Overweight
 Wants to get pregnant

33. Case 2: Physical Exam
 Obese female
 Acne
 Normal genitalia
 Mild hirsutism

34. Case 2: Laboratory findings
 Urine B-HCG negative
 TSH, FSH and Prolactin wnl
 Testosterone 180 ng/dL
 Pelvic U/S findings show polycystic ovaries

35. Laparoscopic &U/S findings in
PCOS

36. Case 3: 29 yo woman with 18-month h/o
amenorrhea
 Normal development
 No family history of amenorrhea
 Does not exercise excessively or restrict diet
 Denies galactorrhea
 Has h/o SAB with subsequent D & C

37. Case 3: Physical Exam
 WDWN young woman
 Normal exam
 No galactorrhea

38. Case 3: Laboratory findings
 Urine B-HCG negative
 Prolactin wnl
 TSH, FSH, LH all wnl

39. Case 3: Further work-up
 Fails Provera challenge
 Fails 1-month trial of estrogen + progesterone
 Pelvic U/S shows no uterine stripe
 Hysteroscope confirms diagnosis of…
Asherman’s Syndrome

40. Case 4
 A 24-year-old G2 P2 woman delivered vaginally
8 months previously.
 Her delivery was complicated by postpartum
hemorrhage requiring curettage of the uterus and
a blood transfusion of two units of erythro-cytes.
 She complains of amenorrhea since her delivery.

41.  She denies taking medications or having
headaches or visual abnormalities.
 Her pregnancy test is negative.
 She was not able to breast-feed her baby
 ➤ What is the most likely diagnosis?
 Sheehan syndrome (anterior pituitary
necrosis).
 ➤ What are other complications that are likely
with this condition?
 Hypothyroidism or adrenocortical
insufficiency

42.  A 19-year-old G1 p1 woman underwent a uterine
curettage after amiscarriage. She has had no
menses since then and is not pregnant.
The physician is suspecting intrauterine adhesions.
 Which of the following is a feature of
intrauterine synechiae (Asherman syndrome)?
 A. Usually occurs after uterine curettage
 B. Associated with low gonadotropin levels
 C. Associated with a monophasic basal body
temperature chart
 D. Associated with low cortisol level

43.  A 24-year-old G1 P1 woman is seen in the office
with secondary amen-orrhea after her delivery.
She is given a diagnosis of pituitary necrosis
(Sheehan syndrome).
 Which of the following is consistent with her
presumed diagnosis?
 A. Usually associated with hypertensive crisis at
or soon after a delivery
 B. Is caused by an ischemic necrosis of the
posterior pituitary gland
 C. Is associated with decreased prolactin levels
 D. Is often associated with elevated TSH levels

44.  A 32-year-old G2 P1 woman presents to the
gynecologist’s office with secondary amenorrhea of
8 months’ duration. She had normal and regular
menses before this time.
 And diagnosed as intrauterine adhesions
 Which ofthe following is the best description of the
mechanism of intrauterine synechiae
 A. Trophoblastic hyperplasia
 B. Pituitary engorgement
 C. Myometrial scarring
 D. Endometrial hypertrophy
 E. Disruption of large segments of the endometrium

45.  A 25-year-old woman presents with a 6-month
history of amenorrhea.Her pregnancy test is
negative. She is evaluated for other causes of
secondary amenorrhea, and diagnosised as (PCOS)
 . Which of the following is consistent with this
disorder?
 A. Estrogen deficiency and vaginal atrophy
 B. Osteoporosis
 C. Endometrial hyperplasia
 D. Hypoglycemia
 E. A history of regular menses each month prior to 6
months

46. Case 5
A 30-year-old parous woman notes a watery
breast discharge of 6 months’ duration.
 Her menses have been somewhat irregular.
 She denies a family history of breast cancer.
 The patient had been treated previously with
radioactive iodine for Graves disease.
 Currently, she is not taking any medications.

47. On examination
 ,She appears alert and in good health.
 Blood pressure (BP) is 120/80 mm Hg, and
heart rate (HR) is 80 (bpm).
 Breasts are symmetric and without masses.
No skin retraction is noted.
 A white discharge can be expressed from both
breasts.
 No adenopathy is appreciated.
 The pregnancy test is negative.

48.  What is the most likely diagnosis?
 Galactorrhea due to hypothyroidism.
 ➤ What is your next step?
 Check serum prolactin and TSH levels
 ➤ What is the likely mechanism for this disorder?
 Hypothyroidism is associated with an elevated
thyroid-releasing hormone (TRH) level, which
acts as a prolactin-releasing hormone.

49.  A 25-year-old woman presents with galactorrhea
and irregular menses of 10 months duration.
 Her pregnancy test is negative.
 Laboratory tests reveal normal TSH and serum-
free T4 and hyperprolactinemia.
 Which of the following is most likely to be a
cause of her condition?
 A. Posterior pituitary adenoma
 B. Abdominal wall trauma
 C. Psychotropic medication
 D. Hyperthyroidism

50.  A 38-year-old woman is seen by her physician
because of headaches,amenorrhea, and galactorrhea.
 Her pregnancy test was negative. prolactin level was
markedly elevated and TSH was normal.
 A diagnosis of pituitary adenoma and an MRI of the
brain was orderd .
 Which of the following clinical presentations is con-
sistent with a prolactin-secreting pituitary adenoma?
 A. Diabetes insipidus
 B. Occipital cerebral defect
 C. Central field visual defect
 D. Amenorrhea due to inhibition of gonadotropin-
releasing hormone pulsations

51.  A 47-year-old woman is being evaluated for a
possible pituitary tumor.
 She complains of headaches and some visual
difficulties.
 The MRI shows a mass in the posterior pituitary
gland
 Which of the following is a hormone contained in
the posterior pituitary gland?
 A. Follicle-stimulating hormone (FSH)
 B. Prolactin
 C. Thyroid-stimulating hormone (TSH)
 D. Oxytocin

52.  A 33-year-old woman with a microadenoma of the
pituitary gland becomes pregnant.
,
When she reaches 28 weeks’ gestation
she complains of headaches and visual
disturbances.
 Which of the following is the best therapy?
 A. Craniotomy and pituitary resection
 B. Tamoxifen therapy
 C. Oral bromocriptine therapy
 D. Expectant management
 E. Lumbar puncture

53. Case 6
 A 33-year-old woman complains of 7 months of
amenorrhea following a spontaneous abortion.
 She had a dilation and curettage (D and C) at
that time.
 Her past medical and surgical histories are
unremarkable.
 menarche at age 11 years and her menses
have been every 28 to 31 days until recently

54.  A 33-year-old woman complains of 7 months of
amenorrhea following a spontaneous abortion.
She had a dilation and curettage (D and C) at
that time.
 Her past medical and surgical histories are
unremarkable.
 menarche at age 11 years and her menses
have been every 28 to 31 days until recently

55.  Her general physical examina-tion is
unremarkable.
 The thyroid is normal to palpation, and breasts
are without discharge.
 The abdomen is nontender.
 The pelvic examination shows a normal uterus,
closed and normal-appearing cervix, and no
adnexal masses.
 A pregnancy test is negative

56.  What is the most likely diagnosis?
 Intrauterine adhesions (IUA):Asherman
syndrome
 ➤ What is the next test to
 confirm the diagnosis?
Hysterosalpingogram,.Hystroscopy

57.  A 34-year-old woman states that she has had no
menses since she had a uterine curettage and
cone biopsy of the cervix 1 year previously.
 Since those surgeries,she complains of severe,
crampy lower abdomi-nal pain “similar to labor
pain” for 5 days of each month.
 Her basal body temperature chart is biphasic,
rising 1°F for 2 weeks of every month.


58.  Which of the following is the most likely
etiology of second-ary amenorrhea?
 A. Hypothalamic etiology
 B. Pituitary etiology
 C. Uterine etiology
 D. Cervical condition

59.  A 29-year-old woman G2 P0 underwent an
evaluation for amenorrhea of 10 months duration.
 Her menses had been regular previously.
 A pregnancy test, TSH, prolactin level, FSH, and
LH levels were normal.
 The patient had sequential estrogen and
progestin therapy without vaginal bleeding.
 Her presumptive diagnosis was intrauterine
adhesions, which was con-firmed with imaging.

60.  Which of the following statements is most
accurate?
A. Her condition usually occurs after uterine
curettage for a pregnancy-related process.
B. She would best be diagnosed by laparoscopy.
C. The patient likely has cramping pain every
month.
D. Her treatment includes endometrial ablation

61.  A 32-year-old G1 P1 woman presents with an 8-
month history of amenorrhea. A pregnancy test
is negative. TSH and prolactin levelsare normal.
The FSH level is elevated at 40 IU/L.
 Which of the following is the most likely
complication for this patient?
 A. She is at significant risk for endometrial
cancer.
 B. She is at increased risk for ovarian cancer.
 C. She is at increased risk for osteoporosis.
 D. She is at increased risk for multiple
gestations.

62.  A 41-year-old woman is suspected of having
intrauterine adhesions because she has had
irregular menses since a spontaneous abortion
18 months previously.
 Which of the following would support this
diagnosis?
 A. Presence of hot flushes
 B. FSH level too low to be measurable
 C. Normal estradiol levels for a reproductive-
aged woman
 D. Monophasic basal body temperature chart

63. CASE 7
 . A 17-year-old nulliparous adolescent female
complains that she has not yet started menses
 She denies weight loss or excessive exercise.
 Each of her sisters achieved menarche by 13
years of age.
 The patient’s mother recalls a doctor mentioning
that her daughter had a missing right kidney on an
abdominal x-ray film.

64. On examination
 She is 5 ft 6 in tall and weighs 140 lb. Her blood
pressure is 110/60 mm Hg.
 Her thyroid gland is normal on palpation. She
has Tanner stage IV breast development and
female external genitalia.
 She has Tanner stage IV axillary and pubic hair.
There are no skin lesions.

65.  What is the most likely diagnosis?
 Müllerian (or vaginal) agenesis.
 ➤ What is the next step in diagnosis?
 Serum testosterone, or karyotype

66.  An 18-year-old nulliparous adolescent female
complains of not having started her menses.
 Her breast development is Tanner stage V. She
has a blind vaginal pouch and no cervix. Which of
the following describes
 the most likely diagnosis?
 A. Müllerian agenesis
 B. Kallman syndrome
 C. Gonadal dysgenesis
 D. Polycystic ovarian syndrome

67.  A 20-year-old G0 P0 woman is told by her
doctor that there is a strong probability that her
gonads will turn malignant.
 She has not had a menses yet. She has Tanner
stage I breast development.
 Which of the following describes the most likely
diagnosis?
 A. Müllerian agenesis
 B. Androgen insensitivity
 C. Gonadal dysgenesis
 D. Polycystic ovarian syndrome

68.  A 19-year-old girl has primary amenorrhea,
Tanner stage IV breast development, and a
pelvic kidney.
 Which of the following describes the most likely
diagnosis?
 A. Müllerian agenesis
 B. Androgen insensitivity
 C. Gonadal dysgenesis
 D. Polycystic ovarian syndrome

69.  Which of the following is the best explanation
for breast development in a patient with
androgen insensitivity?
 A. Gonadal production of estrogens
 B. Adrenal production of estrogen
 C. Breast tissue sensitivity to progesterone
 D. Peripheral conversion of androgens
 E. Autonomous production of breast-specific
estrogen

70.  A 15-year-old adolescent female is brought into
the pediatrician due to absence of breast
development and short stature.
 A karyotype is performed which reveals 46 XY.
 Which of the following is the most likely
diagnosis?
 A. Androgen insensitivity
 C. Gonadal dysgenesis
 B. Kallmann syndrome
 C. Testicular atrophy syndrome

71. Thank you