Amenorrhea

Question 1

What is the definition of primary amenorrhea?

Answer 1

Absence of menstruation without previous cycles
- absence till the age of 14 without secondary sexual characters
- absence till the age of 16 with secondary sexual characters

Question 2

What is the definition of secondary amenorrhea?

Answer 2

• absence of menses for 3 months after regular menses
  OR
• absence of menses for 6 months after irregular menses

Question 3

What is the classification of amenorrhea according to the cause?

Answer 3

PATHOLOGICAL
FALSE -> outflow obstruction
TRUE -> HPO axis dysfunction, endocrine pathology

PHYSIOLOGICAL
- pre puberty
- menopause
- pregnancy
- lactation

Question 4

What is the WHO classification of anovulation?

Answer 4

Class I -> hypo-gonadotropic hypogonadism (hypothalamic/pituitary defect)

Class II -> normo-gonadotropic hypogonadism (ovarian dysfunction: PCOS)

Class III -> hyper-gonadotropic hypogonadism (ovarian failure: Turner)

Question 5

What are the causes of amenorrhea?

Answer 5

1- obstruction of outflow tract
- labial fusion
- imperforate hymen
- T vaginal septum
- OHVIRA syndrome
- vaginal agenesis
- cervical agenesis/stenosis

2- disorders of the uterus
- Mullerian agenesis (MRKH)
- Testicular feminization syndrome (Androgen insensitivity)
- 5-a reductive deficiency
- aromatase deficiency
- Asherman’s syndrome
- uterine hypoplasia: rudimentary or infantile
- hysterectomy
- TB endometritis

3- disorders of the ovary
- Turner syndrome
- PCOS
- resistant ovary syndrome
- premature ovarian failure

4- disorders of anterior pituitary
- pituitary adenoma
- empty sella syndrome
- Sheehan’s syndrome

5- disorders of CNS
- Functional hypothalamic
-> vigorous exercise: increases endorphins
-> severe stress -> increases cortisol
-> weight loss -> 17% body fat is required
-> pseudocyesis -> elevated PRL & LH
-> drug induced -> TCA, methyldopa, opiates, & barbiturates
-> post-pill -> resumes within 2 - 6 months

• Non Functional hypothalamic
  -> Kallman’s syndrome (GnRH deficiency)
  -> Frolich’s syndrome
  -> Laurence-Moon-Biedl syndrome

6- endocrinal causes
- hypo/hyperthyroidism
- Cushing’s syndrome
- Diabetes

Question 6

What is the cause and presentation of labial adhesion?

Answer 6

Due to low in-utero estrogen levels

• recurrent valvular & vaginal infections
• dysuria, urine retention & cryptomenorrhea

Treat with topical estrogen for 10 days -> surgical incision if cream didn’t work

Question 7

What is OHVIRA syndrome?

Answer 7

Obstructed hemivagina & ipsilateral renal anomaly

• uterus didelphys
• unilateral obstructed hemivagina due to longitudinal sagittal vaginal septum

Question 8

How is vaginal & cervical agenesis managed?

Answer 8

If distance is < 3cm -> Foley catheter or anastomoses
If distance if >9cm -> use colon to due anastomoses

Question 9

What are the causes of cervical stenosis?

Answer 9

Congenital or acquired due to -> menopause, cervical surgery, endometrial ablation, cervical or uterine cancer, radiation

• Cervical stenosis is suspected based on inability to pass a probe into the uterine cavity

Question 10

How is cervical stenosis managed?

Answer 10

1- exclude cancer
2- dilate cervix & place Foley catheter as stent

Question 11

What are the treatment options for MRKH syndrome?

Answer 11

For pregnancy
- surrogacy
- uterine transplant

For vaginal correction
- Mc Indoe’s operation -> skin graft from thigh or fish
- William’s operation -> use the labia majora to form a tunnel

Question 12

What are the features & treatment of testicular feminization syndrome?

Answer 12

• Karyotype 46-XY -> normal testosterone level but androgen receptor is defective
• phenotype -> beautiful woman with well developed breasts & a blind vagina with NO hair

Treatment
- gonadectomy + estrogen + Mc Indoe’s vaginoplasty

Question 13

What is the presentation of 5-a reductive deficiency?

Answer 13

• karyotype 46-XY
• internal male genital organs but no external genitalia -> female looking
• absent or blind vagina + HAIR + abdominal or in inguinal testes

Treat according to sex assignment

Question 14

What is the presentation of aromatase deficiency?

Answer 14

• 46-XX
• androgen is not converted to estrogen
• phenotype: uterine hypoplasia, amenorrhea, clitoromegaly, no breasts, osteoporosis, hirsutism & acne

Question 15

What is the cause of Asherman’s syndrome & how is it diagnosed?

Answer 15

Intra-uterine adhesions secondary to over-curettage or endometrial infections

Diagnosed by
- absence of withdrawal bleeding after E+P withdrawal test
- confirm by US, HSG, & hysteroscopy

Question 16

What are the types of uterine hypoplasia?

Answer 16

Rudimentary Solid uterus
- small muscular structure with no cavity

Infantile Uterus
- length of the body of uterus is half that of the cervix 1:2 ratio

Question 17

What are the characteristics of Turner syndrome?

Answer 17

45 XO females
- fibrous streak gonads -> delayed puberty & infertility
- short stature < 60 inches
- webbing of neck
- short 4th metacarpal
- cubitus valgus

Question 18

What are the characteristics of resistant ovary syndrome?

Answer 18

• defect in LH/FSH receptor complex in the ovary
• elevated levels of GnRH with viable follicles within the ovary
• no secondary sexual characters

Question 19

How does a prolactinoma present?

Answer 19

1- inhibition of GnRH
2- low FSH/LH
3- amenorrhea + galactorrhea

• if Serum PRL level >100 ng/ml -> ask for MRI

Question 20

What are the causes of increased prolactin levels?

Answer 20

Physiological
- stress, sleep, sex, stimulation of nipple
- lactation
- pregnancy

Pathological
- PCOS
- hypothyroidism -> high TSH increases PRL levels
- drugs: methyldopa & TCA

Question 21

What are the types of empty sella syndrome?

Answer 21

Primary
- defect is diaphragma sella -> CSF pressure compresses on pituitary -> panhypopituitarism

Secondary to
- infarction
- radiation
- surgical removal of pituitary

Question 22

How does Sheehan’s syndrome present?

Answer 22

Post-partum pituitary gland necrosis due to severe hemorrhage
- decreased prolactin -> no lactation
- decreased FSH + LH -> amenorrhea
- decreased TSH -> hypothyroidism
- decreased ACTH -> Addison’s disease

Question 23

What is the presentation of Kallmann’s syndrome?

Answer 23

Primary amenorrhea due to inadequate GnRH with anosmia
- infantile sexual development

Question 24

What is Frolich’s syndrome?

Answer 24

Primary amenorrhea + genital hypoplasia + trunkal obesity

Question 25

What is Laurence-Moon-Biedl syndrome?

Answer 25

primary amenorrhea + genital hypoplasia + trunkal obesity + polysyndactly + retinitis pigmentosa

Question 26

How is primary amenorrhea diagnosed?

Answer 26

Do physical exam to check for secondary sexual characters
1- if sexual characters are present -> HPO is normal -> US to check uterus
-> if present then Asherman or outflow obstruction
-> if absent: request karyotype -> XX = MRKH & XY = TF (AIS) or 5a reductase

2- is sexual characters are not present -> HPO is defective
-> hormonal assay for FSH & LH
-> if FSH & LH are high -> ovarian failure -> Turner syndrome
-> if FSH & LH are low -> hypothalamic or pituitary cause
-> IF FSH & LH are normal -> PRL, TSH, & serum androgen

Question 27

How is secondary amenorrhea diagnosed?

Answer 27

1- exclude pregnancy
2- US to asses uterus, ovarian masses, & suprarenal gland
3- Thyroid function test
4- Prolactin
5- androgens
- testosterone only -> ovarian origin (PCOS)
- 17 hydroxyprogesterone -> CAH
- DHEA -> adrenal
6- HSG
7- laparoscopy
8- hysteroscopy

Question 28

How do we differentiate between a non functioning ovary & a uterine obstruction?

Answer 28

1- Progesterone withdrawal test (10 days of progesterone)
- If positive -> defect in ovulation -> anovulation causes (chech FSH & LH)
- if negative -> do combined E+P

2- Combined E + P
- if positive -> anovulation -> HPO axis (Check FSH & LH)
- if negative -> Asherman’s syndrome or outflow obstruction