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
Introduction
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Relevant to :
Obstetrics & Gynaecology
GP
General Medicine
Cardiology
Endocrinology
General Surgery
Overview
• Basic Science
• Puberty
• Menstrual Cycle
• Amenorrhoea
• Primary
• Secondary
• PCOS
Puberty
• Thelarche- breast development
• Adrenarche- axillary +pubic hair
• Menarche- start of periods
AnatomySecondary Sexual Characteristics
Pubic Hair development
Tanner Stages
Physiology- Pituitary
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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
Menstrual cycle
Menstrual cycle in action
Menstrual Cycle
• Day 1 is 1st day of bleeding
• Days 1-4 FSH high
• Signals to develop follicle in ovary
• Follicle produces OESTROGEN
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Oestrogen causes Cervical mucus to be receptive to sperm
Endometrium “proliferative”
Down-regulates FSH
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
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
Menstrual Cycle
• If ovum not fertilized + no implantation
• Corpus luteum breaks down
• Oestrogen and progesterone falls
• Endometrium not being maintained so sloughs off =
period
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
Primary Amenorrhoea
• Differential Diagnosis- Work it out
• Anatomical sieve
Hypothalamic- Pituitary axis
Pineal gland
Smell
See
Stress
Hypothalamic- Pituitary axis
Primary Amenorrhoea
• (Constitutional delay)
• (Chronic systemic illness)
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Chromosomal
Hypothalamic
Hypopituitarism
Congenital Adrenal Hyperplasia
Premature Ovarian failure/ Ovarian cysts/ PCOS
Uterine anomalies- absence of uterus/ vagina
Vaginal anomalies- Imperforate hymen
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
Primary Amenorrhoea
Trauma
(Pituitary /Ovarian Trauma)
Infection
Neoplasia
Pituitary Tumour
Prolactin Microadenoma
Connective Tissue
Uterine
Absent uterus norm ovaries
Rokintansky XX
Vagina- Imperforate Hymen
Automimmune
Myasthenia Gravis, Crohns , Addison’s
39% co-exist
Naughty Drs ( Iatrogenic)
Chemotherapy Radiotherapy
Blood
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Endocrine
Congenital Adrenal Hyperplasia
Ovarian cyst/ PCOS
Hypothalamic hypopituitarism
Drugs/ Diet
Chemotherapy Radiotherapy
Anorexia / Underweight
Galactosaemia
Chromosomal
Androgen Insensitivity
Swyers
Turner’s Syndrome
21 hydroxlylase deficiency
(more 17OH progesterone)
Kallman’s Syndrome
(Anosmia)
XY absent uterus xlinked rec
XY uterus present
X0 uterus present
Androgen Insensitivity
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
TFTs, Oestradiol, FAI
HRT
Growth Hormone
replacement
Adoption
Induce menarche
Induce puberty
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
Primary Amenorrhoea
Cause
Investigation
Treatment
Ovarian cysts
Ultrasound Pelvis
Surgery – cystectomy
PCOS
FAI SHBG
(FSH:LH)
Cons/ Medical/ Surgical
Prem Ovarian Failure
+ FSH LH Oestradiol
HRT,
Egg donation
Induce puberty
Uterine anomalies
Absent uterus
MRI Pelvis
Laparoscopy
Surrogacy – egg collection
from normal ovaries
Dilators/ Surgery
Absent vagina
Imperforate Hymen
External examination
SurgeryIncision and drainage of
haematometra
Primary Amenorrhoea
1y Amen
Sexual development
No sexual development
Low FSH LH
Low E2
Constitutional
High FSH LH
Low E2
Chronic Illness
45 X0
High FSH LH
Low E2
Normal FSH Lh Normal
E2
46XY
46XX
46XY
Uterus present
Uterus absent
Uterus present Swyer
syndrome gonadal
dysgenesis
Prem Ovarian failure
Andirogen Insensitivity
Vaginal septum
Rokitansky Kuster
hauser
Gonadectomy Induce
puberty
HRT
Induce puberty
HRT
Gonadectomy
Induce puberty
Vaginal reconstruction
Oes only HRT
Surgery
Vaginal reconstruction
Secondary Amenorrhoea
• Absence of menses after menarche
• NOT Oligomenorrhoea ( infrequent menses)
Secondary Amenorrhoea
• Absence of menses after a preceding Menarche
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Exclude obvious causes:
Pregnancy
Menopause
Contraception
GnRha
Hypothalamic- Pituitary axis
Hypothalamic Pituitary Ovarian Axis
Secondary Amenorrhoea
Cause
Investigation
Treatment
• Provide
a brief summary
of your presentation
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
Ultrasound Pelvis
Surgery – cystectomy
PCOS
+ FAI SHBG
Cons/ Medical/ Surgical
Prem Ovarian Failure
+ FSH LH Oestradiol
HRT,
Egg donation
Induce puberty
PCOS
PCOS
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Incidence
Genetics
Definition
Investigation
Treatment
PCOS Incidence
• 7% in UK
• 52% of South Asian Immigrants in UK
PCOS
• Familial Inheritance
• Genetic link
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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
PCOS
• Definition?
PCOS
Clinical definition (Old fashioned)
• 1) Hyperandrogensim
• Acne, hirsuite, alopecia – not virilisation
• 2) Menstrual irregularity
• 3) Anovulatory Infertility
• Usually associated with obesity
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
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
PCOS & Obesity
Weight
Loss
PCOS – Lean women
Lean women with PCOS – LH hypersecretion
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
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
1. Ultrasound of Polycystic ovaries
• “Ring of pearls”
2. Oligomenorrhoea or
Anovulation
3. Clinical Hyperandrogenism
Ferriman Gallwey Hirsuitism Score
3. Biochemical Hyperandrogenism
Weight
Loss
PCOS - Pathophysiology
Gynae presentation
of a metabolic disease
insulin- ovarian axis
Insulin resistance
(obese)
LH (slim)
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
PCOS
Investigations to exclude other causes
17OH Progesterone (CAH)
DHEA
Androstenedione
Prolactin
TFTs
GTT/ Lipid profile
D&C/ Pipelle for endometrial hyperplasia
Differential Diagnosis
Menstrual Disturbance
• Menstrual disturbance • Weight gain> 10%
• NIDDM/ IGT
• Hypothalamic
• stress, over-exercise, eating disorder
• Pituitary causes
• Perimenopausal
• Hypothyroidism
Differential Diagnosis
Menstrual Disturbance
• Menstrual Disturbance
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Endometrial pathology
PID
Cervical disease
Ovarian disease
Endometriosis
(>45y D&C)
(Endocervical swabs)
(Speculum)
(USS pelvis)
PCOS- Menstrual Treatment
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For cycle control:
Diet and Exercise (PCOS Diet)
Dianette/ cOCP (if <70kg)
Cyclical norethisterone (non-contraceptive)
Metformin
• For heaviness:
• Tranexamic acid +Mefenamic acid
• Mirena
Differential Diagnosis of Hirsuitism
• Hirsuitism
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Androgen secreting tumours- rapid
CAH
Thyroid disease
Acromegaly, Cushings Syndrome
Hyperprolactinaemia
• Drugs – phenytoin
PCOS-Treatment for hirsuitism
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Diet and Exercise (PCOS)
COCP- Dianette
+Further cyproterone acetate for 10/7 (LFTs)
Yasmin ( Drosperinone)
Spironolactone
Metformin
Flutamide
Finasteride
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
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
Useful websites
• www. rcog.org.uk
• www. library.nhs.uk