Amenorrhoea & PCOS
Dr H McMillan MBCHb MSc MRCOG MFSRH Dip Med Ed
Consultant in Obstetrics & GynaecologyCUMH/ Mercy University Hospital
4th Year Medical Student Lecture March 2011
Introduction• 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
Anatomy-Secondary Sexual Characteristics
Tanner Stages
Pubic Hair development
Physiology- Pituitary
• Anterior lobe• Adenohypophysis• Secretes • Follicle
Stimulating FSH• Luteinising
Hormone LH• (also TSH, GH,
Prolactin, ACTH, MSH)
Posterior lobeNeurohypohysisStores and releasesOxytocin 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
• 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 glandSmellSeeStress
Hypothalamic- Pituitary axis
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
Primary AmenorrhoeaDiagnosis -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 AmenorrhoeaTrauma (Pituitary /Ovarian Trauma)
Infection
Neoplasia Pituitary Tumour Prolactin Microadenoma
Connective Tissue Uterine
Vagina- Imperforate Hymen
Absent uterus norm ovariesRokintansky XX
Automimmune Myasthenia Gravis, Crohns , Addison’s39% co-exist
Naughty Drs ( Iatrogenic) Chemotherapy Radiotherapy
Blood -
Endocrine Congenital Adrenal Hyperplasia
Ovarian cyst/ PCOSHypothalamic hypopituitarism
21 hydroxlylase deficiency (more 17OH progesterone)
Kallman’s Syndrome(Anosmia)
Drugs/ Diet Chemotherapy RadiotherapyAnorexia / UnderweightGalactosaemia
Chromosomal Androgen InsensitivitySwyersTurner’s Syndrome
XY absent uterus xlinked recXY uterus presentX0 uterus present
Androgen Insensitivity
Primary Amenorhhoea - Cause Investigation Treatment
Chromosomal Karyotype HRTAdoptionSurgical removal of XY gonads
Hypothalamic FSH, LH, Prolactin,TFTs, Oestradiol, FAI
Increase weightDecrease excess exercise
Hypothalmic FSH, LH ,Prolactin, Growth HormoneTFTs, Oestradiol, FAI
HRT Growth Hormone replacementAdoptionInduce menarcheInduce puberty
Primary AmenorrhoeaCause Investigation Treatment
Pituitary tumour MRI head (Sella Turcica)
Pituitary SurgeryRadiotherapy
Congenital Adrenal Hyperplasia
17OH Progesterone DHEA FAIACTH stimulation test
COCPSteroids
Primary AmenorrhoeaCause Investigation Treatment
Ovarian cysts
PCOS
Prem Ovarian Failure
Ultrasound Pelvis
FAI SHBG(FSH:LH)
+ FSH LH Oestradiol
Surgery – cystectomy
Cons/ Medical/ Surgical
HRT,Egg donationInduce puberty
Uterine anomaliesAbsent uterus
Absent vagina
MRI Pelvis Laparoscopy
Surrogacy – egg collection from normal ovaries
Dilators/ Surgery
Imperforate Hymen External examination Surgery- Incision and drainage of haematometra
Primary Amenorrhoea
1y Amen
No sexual development
Low FSH LHLow E2
Constitutional
Chronic Illness
High FSH LHLow E2
45 X0 46XY
Uterus present Swyer syndrome
gonadal dysgenesis
Gonadectomy Induce puberty
HRT
Sexual development
High FSH LHLow E2
46XX
Prem Ovarian failure
Induce puberty
HRT
46XY
Andirogen Insensitivi
ty
GonadectomyInduce puberty
Vaginal reconstructionOes only HRT
Normal FSH Lh Normal E2
Uterus present
Vaginal septum
Surgery
Uterus absent
Rokitansky Kuster hauser
Vaginal reconstruc
tion
Secondary Amenorrhoea• Absence of menses after menarche
• NOT Oligomenorrhoea ( infrequent menses)
Secondary Amenorrhoea• Absence of menses after a preceding
Menarche
• Exclude obvious causes:• Pregnancy• Menopause• Contraception• GnRha
Hypothalamic- Pituitary axis
Hypothalamic Pituitary Ovarian Axis
Secondary Amenorrhoea• Provide a brief summary of your
presentation
Cause Investigation Treatment
HypothalamicStress/ anorexia
Alleviate stressDiet
Pituitary tumour MRI head (Sella Turcica)
Pituitary SurgeryRadiotherapy
Hypothyroidism TFTs Thyroid replacement
Congenital Adrenal Hyperplasia
17Beta Oestradiol DHEA FAIACTH
COCPCortisol/ FludrocortisoneAs for PCOS
Ovarian cysts
PCOS
Prem Ovarian Failure
Ultrasound Pelvis
+ FAI SHBG
+ FSH LH Oestradiol
Surgery – cystectomy
Cons/ Medical/ Surgical
HRT,Egg donationInduce puberty
PCOS
PCOS• Incidence• Genetics • Definition• Investigation• Treatment
PCOS Incidence• 7% in UK• 52% of South Asian Immigrants in UK
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
PCOS• Definition?
PCOSClinical 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 womenadipose tissue –peripheral conversion of oestrone, which increase LH secretionInsulin 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 - PathophysiologyGynae presentation of a metabolic disease insulin- ovarian axis
Insulin resistance (obese)LH (slim)
PCOS
• USS Pelvis• Day 21 Progesterone (Anovulatory
subfertility)• Day 2-5 bloods
LH:FSH ≥ 3:1ratioFree Androgen Index >5Decreased SHBG <16If total testosterone > 5 check other
androgens
• Investigations
PCOSInvestigations to exclude other causes
17OH Progesterone (CAH)DHEAAndrostenedione
ProlactinTFTs
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
• Endometrial pathology (>45y D&C)• PID (Endocervical swabs)• Cervical disease (Speculum)• Ovarian disease (USS pelvis)• Endometriosis
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
Differential Diagnosis of Hirsuitism• Hirsuitism
• Androgen secreting tumours- rapid• CAH • Thyroid disease• Acromegaly, Cushings Syndrome• Hyperprolactinaemia
• Drugs – phenytoin
PCOS-Treatment for hirsuitism • 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
Click icon to add picture