Amenorrhea Yousef R.Badran

1
AmenorrheaYousef R.Badran
2
Amenorrhea

• Amenorrhea is the absence of menstruation.
• Primary
• Absence of menses by age 16 with normal secondary
  sexual characteristics.
• Absence of menses by age 14 without secondary
  sexual development.

3

• Secondary
• Absence of menses for 3 cycles or 6 months in a
  previously menstruating females.
• Oligomenorrhea
• Interval of more than 35 days between periods

4
Events of Puberty

• Thelarche (breast development)
• Requires estrogen
• Pubarche/adrenarche (pubic hair development)
• Requires androgens

5
Events of Puberty

• Menarche
• Requires
• GnRH from the hypothalamus
• FSH and LH from the pituitary
• Estrogen and progesterone from the ovaries
• Normal outflow tract

6

7
Epidemiology
8
Estrogen Production
9
Adrenal Hormones
10
Pathophysiology

• Inadequate hormonal stimulation of the endomerium
  Anovulatory amenorrhea
• - Euestrogenic
• - Hypoestrogenic
• Inability of endometrium to respond to hormones
  Ovulatory amenorrhea
• - Uterine absence - Utero-vaginal agenesis
• - XY-Females (
  e.g T.F.S)
• - Damaged endometrium ( e.g Ashermans
  syndrome)

11
Causes of 1ry Amenorrhea

• 1- Hypergonadotropic hypogonadism (48.5 of
  cases)
• 2- Hypogonadotropic hypogonadism (27.8)
• 3- Eugonadism (pubertal delay with normal
  gonadotropins 23.7).

12
Uptodate

• Chromosomal abnormalities causing gonadal
  dysgenesis (ovarian failure due to the premature
  depletion of all oocytes and follicles) 50
• Hypothalamic hypogonadism including functional
  hypothalamic amenorrhea 20
• Absence of the uterus, cervix and/or vagina,
  müllerian agenesis 15
• Transverse vaginal septum or imperforate hymen
  5 percent
• Pituitary disease 5

13
Causes of 2ry Amenorrhea

• 1-Disorders associated with a low or normal FSH,
  which account for 66
• 2-Disorders in which the FSH is high (12)
• 3-Disorders associated with a high prolactin
  level comprise 13 of cases
• 4- Anatomic disorders (ie, Asherman syndrome)
  account for 7.
• 5- Hyperandrogenic states as a cause of secondary
  amenorrhea (2)

14
Classification of Amenorrhea

• Outflow Tract Anomalies
• Ovarian amenorrhea
• Central Disorders
• Hypothalamic amenorrhea
• Pituitary amenorrhea

15
Which is which???

• Only 3 diagnoses are unique to primary amenorrhea
  and never cause secondary amenorrhea.
• 1- vaginal agenesis
• 2- androgen insensitivity syndrome
• 3- Turner syndrome (45,Xo)

16
Etiology Outflow Tract Anomalies

• Mullerian Anomalies
• Imperforate hymen
• Transverse vaginal septum
• Cervical Stenosis (2ry)
• Asherman syndrome (2ry)
• Mullerian Agensis
• Vaginal and uterine aplasia-Mayer-Rokitansky-Küste
  r-Hauser
• Testicular feminization

17
Imperforate Hymen
18

• Intermittent abdominal pain
• Possible difficulty with micturition
• Possible lower abdominal swelling
• Bulging bluish membrane at the introitus or
  absent vagina (only dimple

19
Transverse Vaginal Septum
20
Mayer-Rokitansky-Kuster-Hauser Syndrome
(utero-vaginal agenesis)

• Mullerian Agenesis or Dysgenesis
• Complete vaginal agenesis and absence of a uterus
  or partial vaginal agenesis with rudementary
  uterus and distal vagina.
• Karyotype 46-XX
• Ovaries present

21
Androgen Insensitivity

• Karyotype 46, XY
• X linked recessive
• Loss-of-function mutation in the androgen
  receptor (AR) gene. This AR gene has been
  localized to the long arm of the X chromosome
  (ie, Xq11-13).
• Undervirilization
• Normal breasts but no sexual hair

22
Androgen Insensitivity

• Phenotypical female
• Absent uterus and upper vagina
• Male range testosterone level
• 25 chance of developing benign testicular tumors
  and a 4-9 chance of malignancy.
• Treatment gonadectomy after puberty HRT

23
Asherman Syndrome

• Photograph of the hysteroscopic view of a
  uterine cavity with severe intrauterine synechiae
  (Ashermans syndrome) that occupied the bulk of
  the cavity. The midline fundal location of the
  abnormal tissue is similar to that seen with a
  uterine septum (the eccentric rotation of the
  scar tissue is not characteristic of a uterine
  septum).

24
Ovarian Amenorrhea

• Hypergonadotrophic hypogonadism

25
Hypergonadotrophic Hypogonadism

• Variants of Ovarian Dysgenesis
• Turner's Syndrome (XO)
• Gonadal Toxins (Chemotherapy/Radiation)
• Cytotoxic drugs (e.g. Chemotherapy)
• Glucocorticoids
• Enzyme defects
• 17 alpha hydroxylase deficiency

26
Hypergonadotrophic Hypogonadism

• Miscellaneous
• Mumps
• Pelvic radiation
• autoimmune
• Gonadal failure (in adults)
• Hypogonadism in Women
• Menopause
• Premature Ovarian Failure
• Savage Syndrome failure of response to FSH and
  LH due to receptor defect

27
Turners

• Sexual infantilism and short stature.
• High FSH and LH levels.
• Bilateral streaked gonads.
• Karyotype - 80 45, X0
• - 20 mosaic forms (46XX/45X0)
• Treatment HRT

28
Turners Syndrome
Mosaic (46-XX / 45-XO)
(Classic 45-XO)
29
Typical features of Turner Syndrome
30
Gonadal Dysgenesis

• Progressive loss of primordial germ cells. This
  loss leads to hypoplastic and disfunctioning
  gonads mainly composed of fibrous tissue, streak
  gonads.
• Absence of MIF and testesterone
• Regression of Wolffian ducts due to absence of
  testosterone.
• Absence of MIF will allow Mullerian ducts to
  differentiate into oviducts and uterus
• Genotypically male yet will with female like
  internal and external reproductive
  characteristics

31
Pure Gonadal dysgenesis

• Swyer syndrome46 XY, no functional gonads.
• Mutation of SRY gene
• Absence of breasts
• Presence of uterus and pubic hair.
• High risk of malignancy(eg.Gonadoblastoma)
• Surgical removal,HRT

32
Enzyme deficiencies, tricky tricky!!
33
Central DisordersHypothalamic amenorrhea

• GnRH release
• Kallmann syndrome
• GnRH transport compression or destruction of
  pituitary stalk or arcuate nucleus
• Tumor mass effect
• trauma
• Sarcoidosis
• Tuberculosis
• Irradiation

34
Central DisordersHypothalamic amenorrhea

• GnRH Pulsatility
• Psychological stress
• Anorexia nervosa, weight loss
• Increased exercise levels
• drug-induced amenorrhea
• Hyperprolactinemia
• Hypothyroidism
• Space-occupying lesion of CNS

35
Central DisordersPituitary amenorrhea

• Tumors
• Infiltration
• Surgery/Irradiation
• Empty sella syndrome
• Sheehan syndrome
• Hemosidrosis

36
Important notes for Diagnosis

• Breast development depends onestradiol
• Uterus Presence Absence of MIF

37
Diagnosis

• History
• Physical examination
• Physical examination begins with vital signs,
  including height and weight, and with sexual
  maturity ratings
• Laboratory evaluation

38
Hormonal Assays

• Estrogen
• FSH/LH level
• Thyroid function tests
• Karyotype
• Bone age
• Prolactin
• Testosterone, DHEAS,17-OHPRog, androstenedione
• Pelvic US, imaging
• Routine blood work looking for chronicillness

39
Hormonal Assays

• Prolactin prolactinoma, Psychotropic drugs,
  hypothyroidism, stress, and meals
• FSH, ovarian insufficiency
• LH, 17,20 lyase deficiency, 17-hydroxylase
  deficiency, and premature ovarian failure.
• Estradiol,
• Thyroid hormones
• Androgens.

40
Diagnostic Evaluation

• When to investigate?
• No menarche by 15.5-16 years
• Investigate earlier if
• Galactorrhea
• Short stature
• Dysmorphic features
• Virilisation
• Abnormal pubertal development
• Out of keeping with family historyof menarche
• Symptoms or signs of hypothalamic-pituitarydisease
  
• Parent/adolescent concerned

41
Evaluating 1ry Amenorrhea
42
Amenorrhea-Galactorrhea-hyperprolactenemia
43
Progesterone Challenge rationale
44
2ry Amenorrhea/Progesterone Challenge
45
(No Transcript)
46
The 2-Question approach

• Has puberty occurred?
• No then, normal stature or short?
• yes, then
• Feminizing or virilizing

47
Has puberty occurred?

• No
• Normal or tall
• GnRH deficiency ( FSH low)
• Pure FSH deficiency (FSH low)
• Pure gonadal dysgenesis (High FSH)

48
Has puberty occurred?

• No
• Shortsomething else is going on
• Hypopituitarism
• Turners
• Hypothyroidism
• FSH slightly high, TSH high

49
Has Puberty occurred?

• Yes
• Virilizing
• 46 xx ( Virlizing female intersex, congenital
  adrenal hyperplasia)
• 46 xy (Virilizing male intersex , Partial
  androgen insensitivity syndrome, Leydig cell
  hypoplasia)

50
Has Puberty occurred?

• Yes
• Feminizing
• 46,xx Idiopathic delay, Mullerian agenesis
• 46, xy Complete androgen insensitivity syndrome

51
Has Puberty occurred?

• Uterovaginal agenesis
• Low transverse vaginal septum
• Complete androgen insensitivity
• All the entities of secondary amenorrhea

52
Treatment

• treatment varies depending upon the causes of
  the amenorrhea. Treatment options include
• Dietary changes, including an increase in fat and
  calories in order to stimulate estrogen
  production.
• Counseling for eating disorders.
• Using stress reduction techniques to help
  regulate the period.
• Hormonal supplements, like the birth control pill
  or patch, or hormone replacement therapy.
• Surgery to remove cysts, fibroids or tumors