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

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Presentation on theme: "Amenorrhoea & PCOS Dr H McMillan MBCHb MSc MRCOG MFSRH Dip Med Ed Consultant in Obstetrics & Gynaecology CUMH/ Mercy University Hospital 4 th Year Medical."— Presentation transcript:

1 Amenorrhoea & 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

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

3 Overview Basic Science Puberty Menstrual Cycle Amenorrhoea Primary Secondary PCOS

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

5 Anatomy- Secondary Sexual Characteristics Tanner Stages Pubic Hair development

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 NeoplasiaPituitary TumourProlactin Microadenoma Connective TissueUterine Vagina- Imperforate Hymen Absent uterus norm ovaries Rokintansky XX AutomimmuneMyasthenia Gravis, Crohns, Addisons 39% co-exist Naughty Drs ( Iatrogenic)Chemotherapy Radiotherapy Blood- EndocrineCongenital Adrenal Hyperplasia Ovarian cyst/ PCOS Hypothalamic hypopituitarism 21 hydroxlylase deficiency (more 17OH progesterone) Kallmans Syndrome (Anosmia) Drugs/ DietChemotherapy Radiotherapy Anorexia / Underweight Galactosaemia ChromosomalAndrogen Insensitivity Swyers Turners Syndrome XY absent uterus xlinked rec XY uterus present X0 uterus present

20 Androgen Insensitivity

21 Primary Amenorhhoea - CauseInvestigationTreatment ChromosomalKaryotypeHRT Adoption Surgical removal of XY gonads HypothalamicFSH, LH, Prolactin, TFTs, Oestradiol, FAI Increase weight Decrease excess exercise HypothalmicFSH, LH,Prolactin, Growth Hormone TFTs, Oestradiol, FAI HRT Growth Hormone replacement Adoption Induce menarche Induce puberty

22 Primary Amenorrhoea CauseInvestigation Treatment Pituitary tumourMRI head (Sella Turcica)Pituitary Surgery Radiotherapy Congenital Adrenal Hyperplasia 17OH Progesterone DHEA FAI ACTH stimulation test COCP Steroids

23 Primary Amenorrhoea CauseInvestigation 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 HymenExternal examinationSurgery- Incision and drainage of haematometra

24 Primary Amenorrhoea 1y AmenNo sexual development Low FSH LH Low E2 ConstitutionalChronic Illness High FSH LH Low E2 45 X046XY Uterus present Swyer syndrome gonadal dysgenesis Gonadectomy Induce puberty HRT Sexual development High FSH LH Low E2 46XXPrem Ovarian failure Induce puberty HRT 46XYAndirogen Insensitivity Gonadectomy Induce puberty Vaginal reconstruction Oes only HRT Normal FSH Lh Normal E2 Uterus presentVaginal septumSurgeryUterus absent Rokitansky Kuster hauser Vaginal reconstruction

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 CauseInvestigation Treatment Hypothalamic Stress/ anorexia Alleviate stress Diet Pituitary tumourMRI head (Sella Turcica) Pituitary Surgery Radiotherapy HypothyroidismTFTsThyroid 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 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 >10cm 3 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 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 Investigations

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 Menstrual disturbance - Weight gain> 10% NIDDM/ IGT Hypothalamic stress, over-exercise, eating disorder Pituitary causes Perimenopausal Hypothyroidism

50 Differential Diagnosis Menstrual Disturbance 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 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

57


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