Secondary Amenorrhea
Case 1:
Large Flying Birds Delivering Gifts
Case 1:
• A 25 yo female presents to your clinic with the
co having missed her period the past couple of
months.
– Is this secondary amenorrhea?
– What is secondary amenorrhea?
Case 1:
• Secondary Amenorrhea:
– “absence of menses for more than three cycles or
six months in a woman who previously had
menses”
• (stolen un-gratuitously from UpToDate and our notes from last year)
– Does she have secondary amenorrhea?
Case 1:
• She has been having her period regularly since
she was 14. Her cycle is normally 28 days. The
last time she had her period was 90 days ago.
– Is this secondary amenorrhea?
– Yes. What could be causing it?
Case 1:
• Frequency of causes:
– Chronic anovulation (ex: PCOS) – 39%
– Hypothyroid/Hyperprolactin – 20%
– Weight Loss/Anorexia – 16%
Case 1:
• Approach to amenorrhea (of any type):
• Compartment 1:
– Disorders of the outflow tract or uterus.
• Compartment 2:
– Disorders of the ovary.
• Compartment 3:
– Disorders of the pituitary.
• Compartment 4:
– Disorders of the hypothalamus.
• 1) History and Physical
– Ask about the different compartments/common
causes of secondary amenorrhea
•
•
•
•
•
Stress, change in weight, diet, exercise, illness?
Acne, hirsutism, deepening of voice?
Rx?
Pmhx?
Headaches, visual field defects? Fatigue, polyuria,
polydypsia, etc. ?
• Hot flashes, vaginal dryness, poor sleep, decreased
libido?
Thyroid,
Functional
AI disease,
Hypothalamus/pituitary?
• Galactorrhea?
Hyperprolactinemia?
Asherman?
Estrogen
PCOS Deficiency
Sheehan?
• Obstetric hx.
renal
hypothalamic
failure,
genetic
Danazol,
OCP,
etc.
amenorrhea
anti-psychotics?
Case 1:
• Physical
–
–
–
–
BMI?
Galactorrhea?
Vagina/uterus?
Etc.
• 2) PREGNANCY TEST!!!!!
• 3) TSH and PRL levels
– PRL (and TRH) inhibit FSH and LH
• 4) Progestin Challenge
– Is there withdrawal bleeding after progesterone?
– Is their body making estrogen, and can they
respond to it?
– Positive suggests the problem is a “progesterone
deficiency. “
• Ie: they are anovulatory (PCOS, Danazol, etc.)
– Negative could mean any number of things. Need
to narrow down…
• 5) FSH level
– Low/normal suggests ovaries are good.
– High suggests ovarian failure.
• 6) Give progesterone and Estrogen.
– Bleeding suggests the problem is due to the
pituitary/hypothalamus
– No bleeding suggests the problem is the
endometrium.
Case 1:
• Physical and history are unremarkable…
though…
– Her husband and herself use condoms as their
only method of contraception.
• A urine test for b-HCG is positive…
Physical Exam
Anatomic
abnormality
bleeding
Normal
Pregnancy Test
Positive
Est/prog
Negative
High
PRL and TSH
Elevated
Normal
Progestin Challenge
bleeding
Low/normal
FSH
No blood
No blood
Case 1:
• You recommend she use an additional method
other than just condoms to avoid pregnancy in
the future.
Case 2:
She’s back
Case 2:
• The same patient comes back to see you 10
months later.
• Concerned as she’s 4mo pp and still no period.
She’s been breast-feeding.
• Is this normal? What do you tell her?
Case 2:
• During pregnancy, estrogen made by the
placenta stimulates PRL secretion (but inhibits
the effects of PRL on breast tissue)
• After birth, no more placenta  decreased
estrogen.
• Suckling  decreased PRL-IF produced by the
hypothalamus.
•  Maintained elevated PRL
– And therefore, decreased FSH and LH.
Case 2:
• Reassure her this is normal.
• Luckily, she’s on Micronor (progesterone only) for
birth control.
– (why?)
• Plans to switch to a combined OCP after finished
breast-feeding. You give her a 5 yr rx for a C-OCP.
Case 3:
5 years later…
Case 3:
• The same patient comes to your office again, 5
years later, and has brought her 5 year old
daughter with her.
• Her husband and herself have been trying for
another child, but she hasn’t been able to get
pregnant since they started trying 3ma.
Case 3:
• She stopped her C-OCP which she had used
religiously since her first pregnancy, 2 months ago.
• She also hasn’t had a period since she stopped them.
• Is this normal?
Case 3:
• Post-pill amenorrhea
– Not that common
• ~1 % of women.
– Shouldn’t last more than 6 mo. (12mo for depo)
Case 3:
• You reassure her, and tell her to keep trying.
• She comes back in, 7 months after having
stopped the OCPs. Still not pregnant. Still no
periods either.
Case 3:
• You get a more complete history.
• In her first pregnancy, she suffered a large postpartum bleed, due to retained products of
conception.
• Needed to be manually removed, via D+C.
• Also suffered acute kidney failure at the time due
to blood loss, but has had no problems since.
• Never had menses since, but thought that was
because she had always been on the pill since
then.
Case 3:
• What are you worried about based on this
history?
– Asherman?
– Sheehan?
– Chronic Kidney Failure?!?!?!?!
• Investigations?
– (Cr is normal)
Physical Exam
Anatomic
abnormality
bleeding
Normal
Pregnancy Test
Positive
Est/prog
Negative
High
PRL and TSH
Elevated
Normal
Progestin Challenge
bleeding
Low/normal
FSH
No blood
No blood
Case 3:
• You diagnose her with Asherman Syndrome.
– Because you like wasting health care resources,
you also order a U/S and a hysteroscopy.
– U/S showed lack of normal uterine stripe.
– Hysteroscopy confirmed too.
• Can she have another baby?
Case 3:
• Probably
– Lysis of adhesions via hysteroscopy
– To prevent reformation of adhesions, either
• High dose estrogen for 30d followed by progesterone for 10d
• Stick a Foley in for 10d
• Outcome
– Restoration of menstruation in 73-92% of patients
– Live delivery rates in up to 76%
• Lower in px with more severe adhesions.
• In our patient, the surgery was successful, and she was
eventually able to conceive another child
Case 4:
Just to be ridiculous…
Case 4:
• You meet your patient again, 10 years down
the road, but under different circumstances.
• Her past medical history is now more
extensive:
– GERD
– Hypertension
Case 4:
• You also find out that after her second
pregnancy, she developed post-partum
psychosis, and has been on anti-psychotics
since.
• Over the years since, she has also been
diagnosed with depression for which she is
taking a TCA.
• She has also been abusing cocaine.
Case 4:
• Her medications she takes regularly are:
– Pepcid (famotidine): 20mg BID
– Verapamil: 80mg TID
– Risperidone: 6mg OD
– Clomipramine: 100mg OD
• And guess what? She has amenorrhea again.
Case 4:
• She had been having her menses consistently
until relatively recently, when she had some of
her medications adjusted.
• On exam, you note that she has galactorrhea…
• Pregnancy test is negative.
• What’s going on? What do you do next?
Physical Exam
Anatomic
abnormality
bleeding
Normal
Pregnancy Test
Positive
Est/prog
Negative
High
PRL and TSH
Elevated
Normal
Progestin Challenge
bleeding
Low/normal
FSH
No blood
No blood
Case 4
• Hyperprolactinemia
– Tends to only cause amenorrhea when elevated to
> 4x normal value (> 100microg/L )
– When associated with amenorrhea, 34% will have
a pituitary mass.
– Can also be caused by medications, kidney failure,
increased estrogen…
(endocannabinoids)
Rimonabant
Exogenous
cannabinoids
/THC
Case 4:
• You check her PRL and it is 104 microg/L
•
•
•
•
You switch her Risperidone to Seroquil
You switch her TCA to a SSRI
You switch her Verapamil to HCTZ
You switch her Famotidine to Omeprazole. (But only
because it is associated with a better prognosis for GERD)
• She still abuses cocaine though.
• And her amenorrhea disappears (along with the
galactorrhea).
– A repeat PRL is 22 microg/L