Amenorrhea

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Amenorrhea

• Jean Amoura, MD, MSc

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Amenorrhea

• Primary
• Absence of menses by age 16 with normal secondary
  sexual characteristics
• Absence of menses by age 14 without secondary
  sexual development
• Secondary
• Absence of menses for 6 months in a previously
  menstruating female

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Events of Puberty

• Thelarche (breast development)
• Requires estrogen
• Pubarche/adrenarche (pubic hair development)
• Requires androgens
• Menarche
• Requires
• GnRH from the hypothalamus
• FSH and LH from the pituitary
• Estrogen and progesterone from the ovaries
• Normal outflow tract

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Are there secondary sexual characteristics?
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Primary Amenorrhea

• Is there normal development of secondary sexual
  characteristcs?
• NO
• Think hypogonadism or hypogonadotropism

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Amenorrhea with Immature Secondary Characteristics
FSH Serum level
Low / normal
High
Hypogonadotropic hypogonadism
Gonadal dysgenesis
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Primary Amenorrhea

• Hypogonadism
• 30 have genetic abnormality
• Gonadal dysgenesis, Turners syndrome, mosaicism
• Enzyme deficiencies
• Kallmanns syndrome, CNS tumors
• Irradiation
• Chemotherapy
• Galactosemia

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Primary Amenorrhea with Immature Sexual
Characteristics

• Hypogonadism (gonadal failure)
• Gonadal dysgenesis
• Irradiation
• Chemotherapy
• Galactosemia
• Note gonadotropins (FSH/LH) will be high,
  similar to menopause

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Gonadal Dysgenesis

• Chromosomally abnormal
• - Classic turners syndrome (45XO)
• - Turner variants (45XO/46XX),(46X-abnormal X)
• - Mixed gonadal dygenesis (45XO/46XY)
• Chromosomally normal
• - 46XX (Pure gonadal dysgeneis)
• - 46XY (Swyers syndrome)

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Primary Amenorrhea with Immature Sexual
Characteristics

• Hypogonadotropism
• Hypothalamic dysfunction
• Kallmann syndrome
• Anorexia nervosa
• Space-occupying lesion of CNS
• Marijuana use
• Pituitary damage (surgery/radiation)
• Constitutional delay

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Are there secondary sexual characteristics?
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Primary Amenorrhea

• Is there normal development of secondary sexual
  characteristics?
• YES
• Think
• Pregnancy
• Mullerian anomaly
• Androgen insensitivity

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Primary Amenorrhea with Normal Secondary
Characteristics

• Mullerian Anomalies
• Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser
  syndrome)
• Imperforate hymen
• Transverse vaginal septum

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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

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Imperforate Hymen
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Androgen Insensitivity

• Normal breasts but no sexual hair
• Normal looking female external genitalia
• Absent uterus and upper vagina
• Karyotype 46, XY
• Male range testosterone level
• Treatment gonadectomy after puberty HRT

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Primary Amenorrhea

• Evaluation
• Pregnancy test
• Physical exam to determine presence of uterus
• FSH
• Karyotype

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Primary Amenorrhea

• Treatment
• Cyclic estrogen/progestin
• Remove gonadal streaks if XY or mosaic
• Increased (52) risk of gonadoblastomas,
  dysgerminomas, and yolk sac tumors
• Pulsatile GnRH for ovulation induction in select
  patients
• Surgical resection of intrauterine, cervical, and
  vaginal adhesions/septa

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Secondary Amenorrhea

• Pregnancy!
• CNS disorders
• Pituitary gland
• Thyroid
• Ovary
• Uterus
• Systemic disorders
• Renal failure, liver disorders, DM
• Medications anti-psychotics, reserpine

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Secondary Amenorrhea

• CNS disorders
• Chronic hypothalamic anovulation
• Stress
• Increased exercise levels
• Anorexia nervosa
• Head trauma
• Space-occupying lesions

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Secondary Amenorrhea

• Pituitary disorders
• Hyperprolactinemia
• Prolactinoma
• Medications
• PCOS
• Renal failure
• Hypoprolactinemia
• Pituitary resection
• Sheehans syndrome
• Thyroid disorders
• Hyper- or hypothyroidism

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Secondary Amenorrhea

• Ovulation disorders
• Polycystic ovarian syndrome
• Premature ovarian failure
• Uterine abnormalities
• Ashermans syndrome
• Cervical stenosis
• Drug-induced amenorrhea
• Hormonal contraceptives
• GnRH analogues

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Ashermans Syndrome
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Secondary Amenorrhea

• History
• Nutrition/exercise habits, weight change
• Sexual/contraceptive practice
• History of uterine/cervical surgery
• Physical exam
• Height/weight
• Hirsutism
• Galactorrhea
• Estrogen status of tissues
• Laboratory
• BhCG ?PRL TSH ? progesterone challenge ? FSH ?
  if high ?karyotype

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Negative Pregnancy.test
TSH ,PROLACTIN, Progesterone challenge test
without withdrawal bleeding
withdrawal bleeding
compromised outflow tract
hypoestrogenic
anovulation
ve.est/progest challenge test
-ve.est/progest challenge test
Normal FSH
FSH norm.
FSH30-40
Repeatserum estrogen level
repeat
HSG OR hysteroscopy Ashermans
hypothalamic-pituitary failure
PreOvFailure
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Secondary Amenorrhea

• Treatment goals
• Discovery and treatment of underlying disorder
• Hormone replacement
• Menses every 1-3 months
• Pregnancy
• Ovulation induction
• GnRH pump
• FSH/LH

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Amenorrhea

• 26 yo Gravida 0 with menarche at age 14 presents
  with one-year history of amenorrhea.

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Amenorrhea

• Sexually active, using condoms
• No recent change in weight, skin, hair
• Occasional heat intolerance
• No cyclic pain
• No gynecologic surgery
• Regular menses (every 28-30 days) prior to past
  year

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Amenorrhea

• Exam
• Overweight
• No galactorrhea
• Normal hair distribution
• Normal pelvic exam
• Pregnancy test
• Progestin challenge, TSH, serum prolactin
• Estrogen/progestin cycle, FSH