1. Secondary Amenorrhea

2. Case 1: Large Flying Birds Delivering Gifts

3. 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?

4. 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?

5. 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?

6. Case 1: Frequency of causes: – Chronic anovulation (ex: PCOS) – 39% – Hypothyroid/Hyperprolactin – 20% – Weight Loss/Anorexia – 16%

7. 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.

8. 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. Functional hypothalamic amenorrhea PCOS Danazol, OCP, anti-psychotics? Thyroid, AI disease, renal failure, genetic etc. Hypothalamus/pituitary? Estrogen Deficiency Hyperprolactinemia? Asherman? Sheehan?

9. Physical – BMI? – Galactorrhea? – Vagina/uterus? – Etc. Case 1:

10. 2) PREGNANCY TEST!!!!!

11. 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…

12. 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.

13. 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…

14. Physical Exam High Normal Pregnancy Test PositiveNegative PRL and TSH ElevatedNormal Progestin Challenge bleeding No blood FSH Anatomic abnormality Low/normal Est/prog bleeding No blood

15. Case 1: You recommend she use an additional method other than just condoms to avoid pregnancy in the future.

16. Case 2: She’s back

17. 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?

18. 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.

19. 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.

20. Case 3: 5 years later…

21. 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.

22. 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?

23. Case 3: Post-pill amenorrhea – Not that common ~1 % of women. – Shouldn’t last more than 6 mo. (12mo for depo)

24. 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.

25. 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.

26. Case 3: What are you worried about based on this history? – Asherman? – Sheehan? – Chronic Kidney Failure?!?!?!?! Investigations? – (Cr is normal)

27. Physical Exam High Normal Pregnancy Test PositiveNegative PRL and TSH ElevatedNormal Progestin Challenge bleeding No blood FSH Anatomic abnormality Low/normal Est/prog bleeding No blood

28. 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?

29. 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

30. Case 4: Just to be ridiculous…

31. 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

32. 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.

33. 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.

34. 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?

35. Physical Exam High Normal Pregnancy Test PositiveNegative PRL and TSH ElevatedNormal Progestin Challenge bleeding No blood FSH Anatomic abnormality Low/normal Est/prog bleeding No blood

36. 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…

37. (endocannabinoids) Rimonabant Exogenous cannabinoids /THC

38. 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