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

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