1. Amenorrhoea & PCOS Dr H McMillan MBCHb MSc MRCOG MFSRH Dip Med Ed
Consultant in Obstetrics & Gynaecology
CUMH/ Mercy University Hospital
4th Year Medical Student Lecture March 2011
Amenorrhoea & PCOS

2. Introduction Relevant to : Obstetrics & Gynaecology GP
General Medicine
Cardiology
Endocrinology
General Surgery

3. Overview Basic Science Amenorrhoea PCOS Puberty Menstrual Cycle
Primary
Secondary
PCOS

4. Puberty Thelarche- breast development Adrenarche- axillary +pubic hair
Menarche- start of periods

5. Anatomy- Secondary Sexual Characteristics
Pubic Hair development
Tanner Stages

6. Physiology- Pituitary
Anterior lobe
Adenohypophysis
Secretes
Follicle Stimulating FSH
Luteinising Hormone LH
(also TSH, GH, Prolactin, ACTH, MSH)
Posterior lobe
Neurohypohysis
Stores and releases
Oxytocin and vasopressin

7. Menstrual cycle

8. Menstrual cycle in action

9. Menstrual Cycle Day 1 is 1st day of bleeding Days 1-4 FSH high
Signals to develop follicle in ovary
Follicle produces OESTROGEN
Oestrogen causes -
Cervical mucus to be receptive to sperm
Endometrium “proliferative”
Down-regulates FSH

10. Menstrual Cycle Day 14 (if 28 day cycle) OESTROGEN so high
Positive feedback to pituitary leads to LH surge
LH stimulates ovulation
egg released from matured follicle

11. Menstrual Cycle
Rest of follicle = corpus luteum (cyst) secretes PROGESTERONE
Progesterone causes -
Endometrium to thicken “secretory” ready for implantation
Cervical mucus becomes hostile
FSH down-regulated
No more follicles recruited

12. Menstrual Cycle If ovum not fertilized + no implantation
Corpus luteum breaks down
Oestrogen and progesterone falls
Endometrium not being maintained so sloughs off = period

13. Amenorrhoea Primary Absence of Menarche No period by age 14
with absence of secondary sexual characteristics
No period by age 16
with normal secondary sexual characteristics

14. Primary Amenorrhoea Differential Diagnosis- Work it out
Anatomical sieve

15. Hypothalamic- Pituitary axis
Pineal gland
Smell
See
Stress

16. Hypothalamic- Pituitary axis

17. Primary Amenorrhoea (Constitutional delay) (Chronic systemic illness)
Chromosomal
Hypothalamic
Hypopituitarism
Congenital Adrenal Hyperplasia
Premature Ovarian failure/ Ovarian cysts/ PCOS
Uterine anomalies- absence of uterus/ vagina
Vaginal anomalies- Imperforate hymen

18. Primary Amenorrhoea Diagnosis -Work it out T- Trauma I- Infection
N-Neoplasia
C- Connective Tissue
A- Autoimmune
N –Naughty Drs (Iatrogenic)
B – Blood Disorders
E- Endocrine
D –Drugs/ Diet

19. Primary Amenorrhoea Trauma (Pituitary /Ovarian Trauma) Infection
Neoplasia
Pituitary Tumour
Prolactin Microadenoma
Connective Tissue
Uterine
Vagina- Imperforate Hymen
Absent uterus norm ovaries
Rokintansky XX
Automimmune
Myasthenia Gravis, Crohns , Addison’s
39% co-exist
Naughty Drs ( Iatrogenic)
Chemotherapy Radiotherapy
Blood -
Endocrine
Congenital Adrenal Hyperplasia
Ovarian cyst/ PCOS
Hypothalamic hypopituitarism
21 hydroxlylase deficiency (more 17OH progesterone)
Kallman’s Syndrome
(Anosmia)
Drugs/ Diet
Anorexia / Underweight
Galactosaemia
Chromosomal
Androgen Insensitivity
Swyers
Turner’s Syndrome
XY absent uterus xlinked rec
XY uterus present
X0 uterus present

20. Androgen Insensitivity

21. Primary Amenorhhoea - Cause Investigation Treatment Chromosomal
Karyotype
HRT
Adoption
Surgical removal of XY gonads
Hypothalamic
FSH, LH, Prolactin,
TFTs, Oestradiol, FAI
Increase weight
Decrease excess exercise
Hypothalmic
FSH, LH ,Prolactin, Growth Hormone
Growth Hormone replacement
Induce menarche
Induce puberty

22. Primary Amenorrhoea Cause Investigation Treatment Pituitary tumour
MRI head (Sella Turcica)
Pituitary Surgery
Radiotherapy
Congenital Adrenal Hyperplasia
17OH Progesterone
DHEA FAI
ACTH stimulation test
COCP
Steroids

23. Primary Amenorrhoea Cause Investigation Treatment Ovarian cysts PCOS
Prem Ovarian Failure
Ultrasound Pelvis
FAI SHBG
(FSH:LH)
+ FSH LH Oestradiol
Surgery – cystectomy
Cons/ Medical/ Surgical
HRT,
Egg donation
Induce puberty
Uterine anomalies
Absent uterus
Absent vagina
MRI Pelvis
Laparoscopy
Surrogacy – egg collection from normal ovaries
Dilators/ Surgery
Imperforate Hymen
External examination
Surgery-
Incision and drainage of haematometra

24. Primary Amenorrhoea 1y Amen No sexual development Low FSH LH Low E2
Constitutional
Chronic Illness
High FSH LH
45 X0
46XY
Uterus present Swyer syndrome gonadal dysgenesis
Gonadectomy Induce puberty
HRT
Sexual development
46XX
Prem Ovarian failure
Induce puberty
Andirogen Insensitivity
Vaginal reconstruction
Gonadectomy
Oes only HRT
Normal FSH Lh Normal E2
Uterus present
Vaginal septum
Surgery
Uterus absent
Rokitansky Kuster hauser

25. Secondary Amenorrhoea
Absence of menses after menarche
NOT Oligomenorrhoea ( infrequent menses)

26. Secondary Amenorrhoea
Absence of menses after a preceding Menarche
Exclude obvious causes:
Pregnancy
Menopause
Contraception
GnRha

27. Hypothalamic- Pituitary axis

28. Hypothalamic Pituitary Ovarian Axis

29. Secondary Amenorrhoea
Provide a brief summary of your presentation
Cause
Investigation
Treatment
Hypothalamic
Stress/ anorexia
Alleviate stress
Diet
Pituitary tumour
MRI head
(Sella Turcica)
Pituitary Surgery
Radiotherapy
Hypothyroidism
TFTs
Thyroid replacement
Congenital Adrenal Hyperplasia
17Beta Oestradiol DHEA FAI
ACTH
COCP
Cortisol/ Fludrocortisone
As for PCOS
Ovarian cysts
PCOS
Prem Ovarian Failure
Ultrasound Pelvis
+ FAI SHBG
+ FSH LH Oestradiol
Surgery – cystectomy
Cons/ Medical/ Surgical
HRT,
Egg donation
Induce puberty

30. PCOS

31. PCOS
Incidence
Genetics
Definition
Investigation
Treatment

32. PCOS Incidence
7% in UK
52% of South Asian Immigrants in UK

33. PCOS Familial Inheritance Genetic link Probably Autosomal Dominant
Male line- Premature baldness
Cholesterol side chain cleavage (CYP11a)
Polymorphisms in INSR gene- insulin receptor function
VNTR on chromosome 11p15.5 on nearby microsattelite locus

34. PCOS
Definition?

35. PCOS Clinical definition (Old fashioned) 1) Hyperandrogensim
Acne, hirsuite, alopecia – not virilisation
2) Menstrual irregularity
3) Anovulatory Infertility
Usually associated with obesity

36. Hypothalamic- Pituitary –Ovarian axis
SHBG are the buses of the blood stream that carry androgens.
If there are fewer buses there is more free androgen free to cause symptoms

37. PCOS- Obese Women Obese women
adipose tissue –peripheral conversion of oestrone, which increase LH secretion
Insulin insensitivity- leads to hyperinsulinaemia – less SHBG, more free androgen

38. PCOS & Obesity
Weight
Loss

39. PCOS – Lean women
Lean women with PCOS – LH hypersecretion

40. PCOS Diagnostic definition – ESHRE / ASRM /Rotterdam Criteria
2 out of 3 criteria
1) US features of PCOS
2) Oligo or anovulation
3) Clinical or biochemical hyperandrogenism
With exclusion of other aetologies

41. 1. Ultrasound of Polycystic Ovaries
(> 12 peripheral follicles 2-9mm, per ovary
>10cm3 volume)
Truly a “polyfollicular ovary”
Seen in 20-33% of general population

42. 1. Ultrasound of Polycystic ovaries
“Ring of pearls”

43. 2. Oligomenorrhoea or Anovulation

44. 3. Clinical Hyperandrogenism
Ferriman Gallwey Hirsuitism Score

45. 3. Biochemical Hyperandrogenism
Weight
Loss

46. PCOS - Pathophysiology
Gynae presentation of a metabolic disease insulin- ovarian axis Insulin resistance (obese) LH (slim)

47. PCOS Investigations USS Pelvis
Day 21 Progesterone (Anovulatory subfertility)
Day 2-5 bloods
LH:FSH ≥ 3:1ratio
Free Androgen Index >5
Decreased SHBG <16
If total testosterone > 5 check other androgens

48. PCOS Investigations to exclude other causes 17OH Progesterone (CAH)
DHEA
Androstenedione
Prolactin
TFTs
GTT/ Lipid profile
D&C/ Pipelle for endometrial hyperplasia

49. Differential Diagnosis Menstrual Disturbance
Weight gain> 10%
NIDDM/ IGT
Hypothalamic
stress, over-exercise, eating disorder
Pituitary causes
Perimenopausal
Hypothyroidism

50. Differential Diagnosis Menstrual Disturbance
Endometrial pathology (>45y D&C)
PID (Endocervical swabs)
Cervical disease (Speculum)
Ovarian disease (USS pelvis)
Endometriosis

51. PCOS- Menstrual Treatment
For cycle control:
Diet and Exercise (PCOS Diet)
Dianette/ cOCP (if <70kg)
Cyclical norethisterone (non-contraceptive)
Metformin
For heaviness:
Tranexamic acid +Mefenamic acid
Mirena

52. Differential Diagnosis of Hirsuitism
Androgen secreting tumours- rapid
CAH
Thyroid disease
Acromegaly, Cushings Syndrome
Hyperprolactinaemia
Drugs – phenytoin

53. PCOS-Treatment for hirsuitism
Diet and Exercise (PCOS)
COCP- Dianette
+Further cyproterone acetate for 10/7 (LFTs)
Yasmin ( Drosperinone)
Spironolactone
Metformin
Flutamide
Finasteride

54. PCOS Treatment for subfertility
Diet & Exercise
PCOS diet book by Colette Harris
Clomid* – Anti-oestrogen
days 2-6 of cycle
with follicle tracking
Metformin
start at 250mg od increase to max 500mg tds
GnRHa*
Laparoscopic ovarian drilling
* Risk of OHSS

55. PCOS Long term management
NIDDM
Yearly GTT
CVS disease
Yearly BP/ Weight
Dyslipidaemia
Yearly lipid profile
Endometrial hyperplasia
induce a regular bleed/ Mirena/ D&C
Breast cancer
due to elevated endogenous oestrogens
Breast examinations/ screening

56. Useful websites
www. rcog.org.uk
www. library.nhs.uk