Transcript amennorhea and pcos
Dr H McMillan MBCHb MSc MRCOG MFSRH Dip Med Ed Consultant in Obstetrics & Gynaecology CUMH/ Mercy University Hospital 4 th Year Medical Student Lecture March 2011
Amenorrhoea & PCOS
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 Pubic Hair development Tanner Stages
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
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 gland Smell See Stress
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 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 Infection Neoplasia (Pituitary /Ovarian Trauma) Pituitary Tumour Connective Tissue Automimmune Naughty Drs ( Iatrogenic) Uterine Vagina- Imperforate Hymen Myasthenia Gravis, Crohns , Addison’s 39% co-exist Chemotherapy Radiotherapy Blood Endocrine Drugs/ Diet Chromosomal Congenital Adrenal Hyperplasia Ovarian cyst/ PCOS Hypothalamic hypopituitarism Chemotherapy Radiotherapy Anorexia / Underweight Galactosaemia Androgen Insensitivity Swyers Turner’s Syndrome Prolactin Microadenoma Absent uterus norm ovaries Rokintansky XX 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
Chromosomal Hypothalamic Hypothalmic
Investigation
Karyotype FSH, LH, Prolactin, TFTs, Oestradiol, FAI FSH, LH ,Prolactin, Growth Hormone TFTs, Oestradiol, FAI
Treatment
HRT Adoption Surgical removal of XY gonads Increase weight Decrease excess exercise HRT Growth Hormone replacement Adoption Induce menarche Induce puberty
Primary Amenorrhoea
Cause
Pituitary tumour
Investigation Treatment
MRI head (Sella Turcica) Pituitary Surgery Radiotherapy Congenital Adrenal Hyperplasia 17OH Progesterone DHEA FAI ACTH stimulation test COCP Steroids
Primary Amenorrhoea
Cause Investigation
Ovarian cysts Ultrasound Pelvis PCOS Prem Ovarian Failure FAI SHBG (FSH:LH) + FSH LH Oestradiol Uterine anomalies Absent uterus Absent vagina Imperforate Hymen MRI Pelvis Laparoscopy External examination
Treatment
Surgery – cystectomy Cons/ Medical/ Surgical HRT, Egg donation Induce puberty Surrogacy – egg collection from normal ovaries Dilators/ Surgery Surgery Incision and drainage of haematometra
Primary Amenorrhoea 1y Amen No sexual development Low FSH LH Low E2 Constitutional Chronic Illness Sexual development High FSH LH Low E2 High FSH LH Low E2 Normal FSH Lh Normal E2 45 X0 46XY 46XX 46XY Uterus present Uterus absent Uterus present Swyer syndrome gonadal dysgenesis Prem Ovarian failure Andirogen Insensitivity Gonadectomy Induce puberty HRT Induce puberty HRT Gonadectomy Induce puberty Vaginal reconstruction Oes only HRT Vaginal septum Surgery Rokitansky Kuster hauser Vaginal reconstruction
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 Hypothalamic Stress/ anorexia Alleviate stress Diet Pituitary tumour Hypothyroidism MRI head (Sella Turcica) TFTs Pituitary Surgery Radiotherapy Thyroid replacement Congenital Adrenal Hyperplasia Ovarian cysts PCOS Prem Ovarian Failure 17Beta Oestradiol DHEA FAI ACTH Ultrasound Pelvis COCP Cortisol/ Fludrocortisone As for PCOS Surgery – cystectomy + FAI SHBG + FSH LH Oestradiol Cons/ Medical/ Surgical HRT, Egg donation Induce 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?
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 >10cm 3 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
Weight Loss 3. Biochemical Hyperandrogenism
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 • Endometrial pathology • PID • Cervical disease • Ovarian disease • Endometriosis (>45y D&C) (Endocervical swabs) (Speculum) (USS pelvis)
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