Amenorrhea

Question 1

How is amenorrhea defined?

Answer 1

Primary: absence of menarche by age 16 or 4 years after thelarche

Secondary: absence of menses for 3 cycles, or a total of 6 months in women with previously normal menstruation

Question 2

What categories can the causes of primary amenorrhea be divided into?

Answer 2

Outflow tract obstruction
End-organ disorder
Central regulatory disorders

Question 3

What are some causes of outflow tract obstruction?

Answer 3

Imperforate hymen - failure to canalize
Transverse vaginal septum - failure of upper vagina to fuse with lower vagina, or the septum to fully canalize
Vaginal agenesis - MRKH (mullerian agenesis/dysgenesis) = complete or partial (has normal ovaries)
Testicular feminization - Androgen insensitivity syndrome = absence of testosterone receptor = phenotypic female that is 46XY. Presence of testes produces mullerian inhibiting factor = no mullerian derived structures. Still need to worry about testicular cancer

Question 4

What are some causes of end-organ disoders?

Answer 4

Ovarian failure - hypergonadotropic hypogonadism
-Savage syndrome = failure to respond to FSH and LH due to receptor defect
-Turner syndrome = rapid ovarian atresia
- 17-hydroxylase defect causing lack of estradiol
Gonadal agenesis with 46XY chromosomes
- 17-alpha hydroxylase or 17,20 desmolase defects = no testosterone production, but still MIF = no female reproductive organs
Sywer syndrome = congenital absence of testes in 46XY. Without testes, no MIF so patient has internal and external female genitalia, but no estrogen so no breasts

Question 5

How is gonadal agenesis different from testicular feminization?

Answer 5

Gonadal agenesis = problem with testosterone production (no testosterone)
Testicular feminization = problem with testosterone recpetor (yes testosterone)

Question 6

What are some causes of central disorders?

Answer 6

Hypothalamic - failure of GnRH production (hypogonadotropic hypogonadism)

• Kallmann syndrome = congenital absence of GnRH, associated with anosmia, failure of GnRH neuron migration
• Compression of pituitary stalk or arcuate nucleus

Pituitary defects
- Hemosiderin deposition

Question 7

How to differentiate between hypergonadotropic hypogonadism and hypogonadotropic hypogonadism?

Answer 7

Serum FSH is high in hypergonadotropic hypogonadism

Question 8

What is the most common cause of secondary amenorrhea?

Answer 8

Pregnancy

Question 9

What are the causes of secondary amenorrhea divided into?

Answer 9

Anatomic abnormalities
Ovarian dysfunction
Prolactinoma/hyperprolactinemia
CNS/hypothalamic disorders

Question 10

What are the common anatomic abnormalities in secondary amenorrhea?

Answer 10

Asherman syndrome = intrauterine synechiae (adhesions)
Cervical stenosis = scarring of surgical os

these are typically secondary to surgery

Question 11

How can ovarian dysfunction arise?

Answer 11

Torsion
Surgery
Infection
Radiation
Chemotherapy
Premature ovarian failure (idiopathic)

Question 12

How is PCOS diagnosed?

Answer 12

2 of the following:
Oligo/anovulation
Hyperandrogenism (hirsutism, mall pattern hair loss, acne)
Polycystic ovaries on US

Question 13

How is PCOS treated?

Answer 13

WEIGHT LOSS
Metformin
Desires pregnancy: Clomiphene citrate (Clomid) for ovulation induction
Does not desire pregnancy: OCPs

Question 14

How does hyperprolactinemia cause amenorrhea?

Answer 14

Hyperprolactinemia leads to decreased dopamine which causes abnormal FSH and LH

Question 15

How is prolactin regulated?

Answer 15

Inhibited by dopamine (which is constantly released by hypothalamus)
Stimulated by serotonin and thyrotropin releasing hormone

Question 16

What are causes of hyperprolactinemia?

Answer 16

Hypothyroidism causing elevated TRH and TSH
Dopamine antagonists (haldol, reglan, phenothiazine)
prolactinoma

Question 17

What can you do if prolactin levels are normal?

Answer 17

Progesterone challenge test - 10 mg PO for 7-10 days
If withdrawal bleeding occurs, then estrogen is present and outflow tract is patent = anovulation is cause of amenorrhea
If no bleeding, then give estrogen and progesterone and if no bleeding then there is outflow tract disorder
If bleeding, then there is intact uterus, but decreased endogenous estrogen

Question 18

How is hyperprolactinoma treated?

Answer 18

if micro, then bromocriptine (dopamine agonist) - can also induce ovulation
if macro, surgery