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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:

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case 1
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 11
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 12
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 13
Case 1:
  • Frequency of causes:
    • Chronic anovulation (ex: PCOS) – 39%
    • Hypothyroid/Hyperprolactin – 20%
    • Weight Loss/Anorexia – 16%
case 14
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.
slide8

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?
      • Galactorrhea?
      • Obstetric hx.
  • Thyroid, AI disease, renal failure, genetic etc.

Functional hypothalamic amenorrhea

  • Hypothalamus/pituitary?
  • Hyperprolactinemia?
  • Asherman? Sheehan?
  • Estrogen Deficiency

PCOS

  • Danazol, OCP, anti-psychotics?
case 15
Case 1:
  • Physical
    • BMI?
    • Galactorrhea?
    • Vagina/uterus?
    • Etc.
slide11

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…
slide12

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 16
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…
slide14

Physical Exam

Anatomic abnormality

bleeding

Normal

Pregnancy Test

Est/prog

No blood

Positive

Negative

High

Low/normal

PRL and TSH

Elevated

Normal

FSH

Progestin Challenge

No blood

bleeding

case 17
Case 1:
  • You recommend she use an additional method other than just condoms to avoid pregnancy in the future.
case 2
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 21
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 22
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
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 31
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 32
Case 3:
  • Post-pill amenorrhea
    • Not that common
      • ~1 % of women.
    • Shouldn’t last more than 6 mo. (12mo for depo)
case 33
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 34
Case 3:
  • You get a more complete history.
  • In her first pregnancy, she suffered a large post-partum 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 35
Case 3:
  • What are you worried about based on this history?
    • Asherman?
    • Sheehan?
    • Chronic Kidney Failure?!?!?!?!
  • Investigations?
    • (Cr is normal)
slide27

Physical Exam

Anatomic abnormality

bleeding

Normal

Pregnancy Test

Est/prog

No blood

Positive

Negative

High

Low/normal

PRL and TSH

Elevated

Normal

FSH

Progestin Challenge

No blood

bleeding

case 36
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 37
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
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 41
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 42
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 43
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?
slide35

Physical Exam

Anatomic abnormality

bleeding

Normal

Pregnancy Test

Est/prog

No blood

Positive

Negative

High

Low/normal

PRL and TSH

Elevated

Normal

FSH

Progestin Challenge

No blood

bleeding

case 44
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…
slide37

Rimonabant

(endocannabinoids)

Exogenous cannabinoids/THC

case 45
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
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