1. Amenorrhea Dr.F Mehrabian MD

2. Amenorrhea Primary Secondary
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
There is a 5% lifetime incidence for some form of amenorrhea.
Physiologic causes of amenorrhea are:
Prepubertal status, pregnancy, lactation, and menopause

3. 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

4. Are there secondary sexual characteristics?

5. Think hypogonadism or hypogonadotropism
Primary Amenorrhea
Is there normal development of secondary sexual characteristcs? NO
Think hypogonadism or hypogonadotropism

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

7. Primary Amenorrhea Hypogonadism Enzyme deficiencies
30% have genetic abnormality
Gonadal dysgenesis, Turner’s syndrome, mosaicism
Enzyme deficiencies
Kallmann’s syndrome, CNS tumors
Irradiation
Chemotherapy
Galactosemia

8. Primary Amenorrhea with Immature Sexual Characteristics
Hypogonadism (gonadal failure)
Gonadal dysgenesis
Irradiation
Chemotherapy
Galactosemia
Note: gonadotropins (FSH/LH) will be high, similar to menopause
Irradiation risk at >250 rads
Kallmann’s = insufficient pulsatile GnRH

9. Gonadal Dysgenesis Chromosomally abnormal
- Classic turner’s syndrome (45XO)
- Turner variants (45XO/46XX),(46X-abnormal X)
- Mixed gonadal dygenesis (45XO/46XY)
Chromosomally normal
- 46XX (Pure gonadal dysgeneis)
- 46XY (Swyer’s syndrome)

10. 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
Constitutional delay: diagnosis of exclusion after negative workup including head CT/MRI. Bone age should be delayed as well.

11. Are there secondary sexual characteristics?

12. Primary Amenorrhea
Is there normal development of secondary sexual characteristics?
YES
Think
Pregnancy
Mullerian anomaly
Androgen insensitivity
With androgen insensitivity, there will typically be more breast development than pubic hair development.

13. Primary Amenorrhea with Normal Secondary Characteristics
Mullerian Anomalies
Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome)
Imperforate hymen
Transverse vaginal septum
M-K-K-H is second most common cause of primary amenorrhea (1/4000)
Mullerian aplasia -> nl breast devlpmt, body hair, blind vaginal pouch
Check for renal abnormalities (present in 34%), skeletal abnormalities (12%)

14. 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

15. Imperforate Hymen

16. 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

17. Primary Amenorrhea Evaluation Pregnancy test
Physical exam to determine presence of uterus
FSH
Karyotype

18. 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

19. Secondary Amenorrhea Pregnancy! CNS disorders Pituitary gland Thyroid
Ovary
Uterus
Systemic disorders
Renal failure, liver disorders, DM
Medications: anti-psychotics, reserpine

20. Secondary Amenorrhea CNS disorders Chronic hypothalamic anovulation
Stress
Increased exercise levels
Anorexia nervosa
Head trauma
Space-occupying lesions

21. Secondary Amenorrhea Pituitary disorders Thyroid disorders
Hyperprolactinemia
Prolactinoma
Medications
PCOS
Renal failure
Hypoprolactinemia
Pituitary resection
Sheehan’s syndrome
Thyroid disorders
Hyper- or hypothyroidism

22. Secondary Amenorrhea Ovulation disorders Uterine abnormalities
Polycystic ovarian syndrome
Premature ovarian failure
Uterine abnormalities
Asherman’s syndrome
Cervical stenosis
Drug-induced amenorrhea
Hormonal contraceptives
GnRH analogues

23. Asherman’s Syndrome

24. Secondary Amenorrhea History Physical exam Laboratory
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
Karyotype for patients with premature ovarian failure <30yo
If hirsutism is present, consider PCOS, congenital adrenal hyperplasia, Cushing’s, or ovarian tumors: check free testosterone

25. 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.
FSH>30-40
Repeat+serum estrogen level
repeat
HSG OR hysteroscopy Asherman’s
hypothalamic-pituitary failure
PreOvFailure

26. Secondary Amenorrhea Treatment goals
Discovery and treatment of underlying disorder
Hormone replacement
Menses every 1-3 months
Pregnancy
Ovulation induction
GnRH pump
FSH/LH
Purpose for inducing menses at least every 3 months is to prevent endometrial hyperplasia and cancer

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

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

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