Amenorrhea Amenorrhea and Hirsutismand Hirsutism

05.04.200905.04.2009

Dr. Pradeep GargDr. Pradeep GargAssistant ProfessorAssistant Professor

Department of Obstetrics and GynaecologyDepartment of Obstetrics and Gynaecology

AIIMS, New DelhiAIIMS, New Delhi

Amenorrhea: DefinitionAmenorrhea: Definition

PrimaryPrimary

No menses by 16 years with normal secondary sexual No menses by 16 years with normal secondary sexual characteristics, or.characteristics, or.

No menses by 14 years with absent secondary sexual No menses by 14 years with absent secondary sexual characteristicscharacteristics

SecondarySecondary

Cessation of menses for 3 cycles / 6 months in absence of Cessation of menses for 3 cycles / 6 months in absence of pregnancy/lactation.pregnancy/lactation.

Amenorrhea: EtiologyAmenorrhea: Etiology

IVIV

IIIIII

IIII

II

MenstruationMenstruation

Hypothalamus

Pituitary

Ovaries

Outflow tract

FSH LH

E P

Amenorrhea : EtiologyAmenorrhea : EtiologyCompartment I (Uterine/Outflow tract)Compartment I (Uterine/Outflow tract) Mullerian abnormalities :Mullerian abnormalities :

-- Utero-vaginal agenesis (MRKH Syndrome)Utero-vaginal agenesis (MRKH Syndrome)

-- Imperforated hymenImperforated hymen

-- Transverse vaginal septumTransverse vaginal septum

Testicular feminization (AIS)Testicular feminization (AIS)

Asherman’s syndrome:Asherman’s syndrome:

-- Secondary to uterine/cervical surgerySecondary to uterine/cervical surgery

-- Secondary to infections (TB, PID)Secondary to infections (TB, PID)

Mayer-Rokitansky-Kuster-Hauser Syndrome Mayer-Rokitansky-Kuster-Hauser Syndrome (utero-vaginal agenesis)(utero-vaginal agenesis)

15% of primary amenorrhea 15% of primary amenorrhea Normal secondary development Normal secondary development

& external female genitalia& external female genitalia Normal female range Normal female range

testosterone leveltestosterone level Absent uterus and upper vagina Absent uterus and upper vagina

& normal ovaries& normal ovaries Karyotype 46-XXKaryotype 46-XX 15-30% renal, skeletal and 15-30% renal, skeletal and

middle ear anomaliesmiddle ear anomalies

Imperforate HymenImperforate Hymen

Androgen InsensitivityAndrogen Insensitivity Normal breasts but no sexual Normal breasts but no sexual

hairhair Normal looking female external Normal looking female external

genitaliagenitalia Absent uterus and upper Absent uterus and upper

vaginavagina Karyotype 46, XYKaryotype 46, XY Male range testosterone levelMale range testosterone level Treatment : gonadectomy after Treatment : gonadectomy after

puberty + HRTpuberty + HRT

Amenorrhea : EtiologyAmenorrhea : Etiology

Compartment II (Gonadal failure)Compartment II (Gonadal failure)

Turner syndrome 45xO/mosaic/partial deletions Turner syndrome 45xO/mosaic/partial deletions

Pure gonadal dysgenesis.Pure gonadal dysgenesis.

Mixed gonadal dysgenesisMixed gonadal dysgenesis

Premature ovarian failurePremature ovarian failure

Autoimmune/RT/CT/ galactosemia Autoimmune/RT/CT/ galactosemia

Resistant ovary syndromeResistant ovary syndrome

Turner syndromeTurner syndrome

Karyotype 45 XKaryotype 45 X Generally grow slowly so shorter Generally grow slowly so shorter Associated stigmata Associated stigmata

Lymphadema at birthLymphadema at birth Webbed neckWebbed neck Disorder of heart and kidney (most commonly horse shoe) and great vessels (most Disorder of heart and kidney (most commonly horse shoe) and great vessels (most

commonly coaraction of aorta)commonly coaraction of aorta) Diabetes mellitesDiabetes mellites Thyroid disorderThyroid disorder HypertensionHypertension Do not develop breast at pubertyDo not develop breast at puberty

Premature ovarian failurePremature ovarian failure

Ovarian failure is normal occurrence during menopauseOvarian failure is normal occurrence during menopause EtiologyEtiology

1.Genetic disorder – Mosaicism or XO or XY or deletion of portion of 1.Genetic disorder – Mosaicism or XO or XY or deletion of portion of chromosomechromosome

2.Iatrogenic causes2.Iatrogenic causes RadiationRadiation ChemotherapyChemotherapy Surgical interference with blood supplySurgical interference with blood supply InfectionInfection

3.Autoimmune disorder – as a part of polyglandular syndrome3.Autoimmune disorder – as a part of polyglandular syndrome

Amenorrhea:EtiologyAmenorrhea:Etiology

Compartment III (Pituitary)Compartment III (Pituitary)

Hormone secreting. Adenomas Hormone secreting. Adenomas

Non functional adenoms.Non functional adenoms.

TB/ sarcoid granulomas. Dermoid cystTB/ sarcoid granulomas. Dermoid cyst

Necrosis (Sheehan’s syndrome) Necrosis (Sheehan’s syndrome)

Amenorrhea:EtiologyAmenorrhea:EtiologyCompartment IV (Hypothalamic)Compartment IV (Hypothalamic) Constitutional delay (Physiological)Constitutional delay (Physiological) Malnutrition, anorexia nervosa, vigorous exercise, Malnutrition, anorexia nervosa, vigorous exercise,

stress, anxiety. stress, anxiety. Drugs: Phenothiazines, antihypertensive,Drugs: Phenothiazines, antihypertensive,

antidepressants, hormonal contraception. antidepressants, hormonal contraception. Genetic (Kallman’s)- Triad of anosmia, hypogonadism Genetic (Kallman’s)- Triad of anosmia, hypogonadism

and color blindnessand color blindness Organic disease/ Injury to mid/brain Organic disease/ Injury to mid/brain

Tumors (craniopharyngiomas, gliomas)Tumors (craniopharyngiomas, gliomas)

Infitrative lesions, trauma, irradiation. Infitrative lesions, trauma, irradiation.

Amenorrhea: EtiologyAmenorrhea: Etiology Other Endocrine dysfunctionOther Endocrine dysfunction - - --

Hyper/hypothyroidismHyper/hypothyroidism

-- CAH/Cushing’s syndromeCAH/Cushing’s syndrome

-- Virilising adrenal/ ovarian tumors.Virilising adrenal/ ovarian tumors.

-- Granulosa-theca tumor ovary, C L cystGranulosa-theca tumor ovary, C L cyst

-- Obesity, Polycystic ovarian diseaseObesity, Polycystic ovarian disease

General General --

-- Chronic renal, liver, lung diseaseChronic renal, liver, lung disease

-- Chronic infections , diabetes mellitus.Chronic infections , diabetes mellitus.

Amenorrhea: ClassificationAmenorrhea: ClassificationPhysiologicalPhysiological PathologicalPathological

- PrepubertyPrepuberty Primary Primary SecondarySecondary- PregnancyPregnancy- Lactation Lactation With (n) secWith (n) sec Without (n)Without (n)- Menopause Menopause sexual charac.sexual charac. sexual charac.sexual charac.

- Think ?- Think ? HypogonadismHypogonadismPregnancyPregnancy (gonadal failure)(gonadal failure)Mullerian anomalyMullerian anomaly - Gonadal dysgen- Gonadal dysgenAISAIS - Irradiation- Irradiation- Chemotherapy- Chemotherapy- Galectosemia- GalectosemiaOtherOther- Anorexia nervosa- Anorexia nervosa- Kallman syndrome- Kallman syndrome- Pituitary damage- Pituitary damage - Surgery, irradiation- Surgery, irradiation- Constitutional delay- Constitutional delay

Secondary AmenorrheaSecondary Amenorrhea

Pregnancy!Pregnancy! CNS disordersCNS disorders Pituitary glandPituitary gland ThyroidThyroid OvaryOvary UterusUterus Systemic disordersSystemic disorders

Renal failure, liver disorders, DMRenal failure, liver disorders, DM Medications: anti-psychotics, reserpineMedications: anti-psychotics, reserpine

Secondary AmenorrheaSecondary Amenorrhea

CNS disordersCNS disordersChronic hypothalamic anovulationChronic hypothalamic anovulation

StressStressIncreased exercise levelsIncreased exercise levelsAnorexia nervosaAnorexia nervosa

Head traumaHead traumaSpace-occupying lesionsSpace-occupying lesions

Secondary AmenorrheaSecondary Amenorrhea

Pituitary disordersPituitary disorders HyperprolactinemiaHyperprolactinemia

ProlactinomaProlactinoma MedicationsMedications PCOSPCOS Renal failureRenal failure

HypoprolactinemiaHypoprolactinemia Pituitary resectionPituitary resection Sheehan’s syndromeSheehan’s syndrome

Thyroid disordersThyroid disorders Hyper- or hypothyroidismHyper- or hypothyroidism

Secondary AmenorrheaSecondary Amenorrhea

Ovulation disordersOvulation disorders Polycystic ovarian syndromePolycystic ovarian syndrome Premature ovarian failurePremature ovarian failure

Uterine abnormalitiesUterine abnormalities Asherman’s syndromeAsherman’s syndrome Cervical stenosisCervical stenosis

Drug-induced amenorrheaDrug-induced amenorrhea Hormonal contraceptivesHormonal contraceptives GnRH analoguesGnRH analogues

Amenorrhea: Diagnostic Amenorrhea: Diagnostic Evaluation Evaluation

Rule out pregnancy Rule out pregnancy Pelvic USG: uterus, ovariesPelvic USG: uterus, ovaries KaryotypeKaryotype Screening urinary/skeletal abnScreening urinary/skeletal abnss

MRI/Laparoscopic visualization MRI/Laparoscopic visualization Stepwise evaluation & hormonal assessment Stepwise evaluation & hormonal assessment

TSH, Prolactin, FSH, LH, Estradiol, TSH, Prolactin, FSH, LH, Estradiol, TestosteroneTestosterone

If indicated

Amenorrhea : Diagnostic Amenorrhea : Diagnostic Evaluation Evaluation

Step 1Step 1

--TSH, Prolactin TSH, Prolactin

-- Progesterone Challenge testProgesterone Challenge test

Positive withdrawal bleed:Positive withdrawal bleed:

uterus: endogenous estrogen primed, reactive uterus: endogenous estrogen primed, reactive vaginal outflow vaginal outflow tract patenttract patent

minimal ovarian, pituatary, CNS Function present.minimal ovarian, pituatary, CNS Function present.

No further diagnostic evaluation neededNo further diagnostic evaluation needed

Negative: withdrawal: Go to Step2Negative: withdrawal: Go to Step2

Amenorrhea : Diagnostic Amenorrhea : Diagnostic Evaluation Evaluation

Step 2Step 2

Estrogen + Progesterone Challenge : if negative Estrogen + Progesterone Challenge : if negative withdrawalwithdrawal

Mullerian agensis/ defects Mullerian agensis/ defects

Asherman’s syndrome/TB endometritis, Asherman’s syndrome/TB endometritis, hypoestrogenism- if positive withdrawal then hypoestrogenism- if positive withdrawal then hypoestrogenismhypoestrogenism

Amenorrhea: Diagnostic Amenorrhea: Diagnostic EvaluationEvaluation

Step 3Step 3

Determination of FSH and LH levelsDetermination of FSH and LH levels

Normal 5-20 Normal 5-20 5-40 IU/ml5-40 IU/ml

Ovarian failure Ovarian failure Pituitary/CNS failurePituitary/CNS failure

FSH > 20FSH > 20 < 5 or N< 5 or N

LH >40LH >40 < 5 or N< 5 or N

(Hyper-gonadotropic) (Hypo-gonadotropic)(Hyper-gonadotropic) (Hypo-gonadotropic)

Amenorrhea: Diagnostic Amenorrhea: Diagnostic EvaluationEvaluation

Step 4Step 4

High FSHHigh FSH

-- Karytype if age< 30 yearsKarytype if age< 30 years

-- Work up for autoimmune diseaseWork up for autoimmune disease

-- CBC, ESR, free TCBC, ESR, free T44, TSH, antibodies, Ca, P, TSH, antibodies, Ca, P

-- Total protein, A:G, ANA, glucose,Total protein, A:G, ANA, glucose,

Serum progestrone, 17 OHPSerum progestrone, 17 OHP

(to rule out 17 (to rule out 17 hydroxylase deficiency) hydroxylase deficiency)

Amenorrhea: Treatment PrinciplesAmenorrhea: Treatment Principles Objectives of Treatment Objectives of Treatment

-- Initiate menstruation & reproductive Initiate menstruation & reproductive potential, potential, in whom it is possible in whom it is possible

-- Appropriate medical & surgical management Appropriate medical & surgical management for for adequate physical development and coital adequate physical development and coital relationsrelations

-- Detection and management of any of the Detection and management of any of the threatening condition.threatening condition.

-- Prevention of osteoporosisPrevention of osteoporosis

Thorough physical exam and r/o any systemic ds Thorough physical exam and r/o any systemic ds e.g. hypo or hyperthyroidism.e.g. hypo or hyperthyroidism.

Absence of sec sex character + failure of Absence of sec sex character + failure of development of pubic / axillary hair s/o turner’s development of pubic / axillary hair s/o turner’s syndrome or pituitary infantilismsyndrome or pituitary infantilism

Hirsutism + amenorrhoea --> viritizing tumour of Hirsutism + amenorrhoea --> viritizing tumour of ovary, PCODovary, PCOD

Adiposity and striae on body may suggest cushing’s Adiposity and striae on body may suggest cushing’s syndromesyndrome

Amenorrhea: Treatment Amenorrhea: Treatment PrinciplesPrinciples

Primary AmenorrheaPrimary Amenorrhea

TreatmentTreatmentCyclic estrogen/progestinCyclic estrogen/progestin

Remove gonadal streaks if XY or mosaicRemove gonadal streaks if XY or mosaicIncreased (52%) risk of gonadoblastomas, Increased (52%) risk of gonadoblastomas,

dysgerminomas, and yolk sac tumorsdysgerminomas, and yolk sac tumors

Pulsatile GnRH for ovulation induction in select Pulsatile GnRH for ovulation induction in select patientspatients

Surgical resection of intrauterine, cervical, and Surgical resection of intrauterine, cervical, and vaginal adhesions/septavaginal adhesions/septa

Amenorrhea: Treatment Amenorrhea: Treatment PrinciplesPrinciples

Treatment of underlying causeTreatment of underlying cause General General : : diet, exercisediet, exerciseHypothyroidismHypothyroidism : : ThyroxineThyroxineTB endometritisTB endometritis : : ATTATTHyperprolactemiaHyperprolactemia : : BromocryptineBromocryptinePCO with hirsutismPCO with hirsutism :: Cyclic progestins, Cyclic progestins,CAHCAH :: Corticosteroids Corticosteroids

Amenorrehea: Treatment Amenorrehea: Treatment PrinciplesPrinciples

Surgical managementSurgical management-- Correction of Obstruction collectionCorrection of Obstruction collection

-- Vaginoplasty in vaginal atresia, 5 Vaginoplasty in vaginal atresia, 5 reductase reductase deficiency & androgen end organ defectsdeficiency & androgen end organ defects

-- Removal of testicular tissue if Y cell line + Removal of testicular tissue if Y cell line + -- Neurosurgery for craniopharyngioma,Neurosurgery for craniopharyngioma,

pituitary tumor causing cushing’s disease;pituitary tumor causing cushing’s disease;prolactinomas,prolactinomas,

Amenorrhea:Treatment Amenorrhea:Treatment PrinciplesPrinciples

Asherman’s syndromeAsherman’s syndrome HSG/Hysteroscopy to confirm diagnosisHSG/Hysteroscopy to confirm diagnosisHysteroscopic lysis of adhesionsHysteroscopic lysis of adhesions

-- Foley’s 3 ml Foley’s 3 ml 3 months 3 months

-- Broad spectrum antibiotics Broad spectrum antibiotics 10 d10 d

-- High dose estrogens High dose estrogens 2 months 2 months

add MPA add MPA 3-months 3-months

HIRSUTISMHIRSUTISM

HIRSUTISMHIRSUTISM : APPEARANCE OF EXCESSIVE : APPEARANCE OF EXCESSIVE COARSE (TERMINAL)HAIR IN A PATTERN COARSE (TERMINAL)HAIR IN A PATTERN NOT NORMAL IN THE FEMALENOT NORMAL IN THE FEMALE

Definition highlights the abnormal distribution of Definition highlights the abnormal distribution of excess hair growth ,such as facial ,chest,or excess hair growth ,such as facial ,chest,or upper abdominal hairupper abdominal hair

BASIC FACTS ABOUT HAIRBASIC FACTS ABOUT HAIR

PITUITARY

ADRENAL OVARY

PITUITARY

ADRENALOVARY

DHEAS

DHEA

AND,STEN,ONE

PERIPHERALCONVERSION

TESTOSTERONE

HAIR FOLLICLE

DIHYDROTESTERONE

DHEAS

ACTH

DEFINITIONDEFINITION

HYPERTRICHOSISHYPERTRICHOSIS : GROWTH OF HAIR IN : GROWTH OF HAIR IN EXCESS OF THE NORMAL WHILE LIMITED EXCESS OF THE NORMAL WHILE LIMITED TO A NORMAL PATTERN OF DISTRIBUTIONTO A NORMAL PATTERN OF DISTRIBUTION

It is frequently associated with the use of It is frequently associated with the use of medication such as antiepileptics medication such as antiepileptics

DEFINITIONDEFINITION

VIRILIZATIONVIRILIZATION : REFERS TO CONCURRENT : REFERS TO CONCURRENT PRESENTATION OF PRESENTATION OF HIRSUTISMHIRSUTISM WITH A WITH A BROAD RANGE OF SIGNS SUGGESTIVE OF BROAD RANGE OF SIGNS SUGGESTIVE OF ANDROGEN EXCESSANDROGEN EXCESS,SUCH AS ,SUCH AS

ACNE,ACNE,DEPPENING OF THE VOICE ,DEPPENING OF THE VOICE ,A DECREASE IN BREAT SIZEA DECREASE IN BREAT SIZECLITORAL HYPERTROPHYCLITORAL HYPERTROPHY

DEFINITIONDEFINITION

INCREASED MUSCLE MASS INCREASED MUSCLE MASS

AMENORREA / OLIGOMENORRHEAAMENORREA / OLIGOMENORRHEA

Virilization is seen less frequently than hirsutism Virilization is seen less frequently than hirsutism and may reflect a severe underlying pathologic and may reflect a severe underlying pathologic condition ,such as malignancycondition ,such as malignancy

Hirsutism and virilization are closely linked and Hirsutism and virilization are closely linked and hirsutism may actually be the first manifestation of a hirsutism may actually be the first manifestation of a condition that ultimately will lead to virilization if left condition that ultimately will lead to virilization if left untreateduntreated

Etiology Etiology

Sensitivity of androgens Sensitivity of androgens Circulating androgensCirculating androgens

Total circulating testosterone Total circulating testosterone

SHBGSHBG AlbuminAlbumin FreeFree

Men Men 78%78% 19%19% 3%3%

Normal womenNormal women 80%80% 19%19% 1%1%

Hirsute womenHirsute women 79%79% 19%19% 2%2%

CAUSES OF HIRSUTISMCAUSES OF HIRSUTISM

Excess androgen production Excess androgen production Relative circulating androgen excess and low Relative circulating androgen excess and low

binding globulinsbinding globulinsExcess end organ responseExcess end organ responsePatient perceptionPatient perception

Causes Causes Idiopathic Idiopathic Drug inducedDrug induced Ovarian:Ovarian:

-- PCOS PCOS

-- HyperthecosisHyperthecosis

-- Vinilizing tumourVinilizing tumour Adrenal:Adrenal:

-- CAHCAH

-- Adrenal tumours Adrenal tumours

-- Cushing’s syndromeCushing’s syndrome Virilisation in pregnancy: LuteomaVirilisation in pregnancy: Luteoma OthersOthers:: hypothyroidism, hyperprolactinemia, anorexia nervosa, Insulin resistance hypothyroidism, hyperprolactinemia, anorexia nervosa, Insulin resistance

sydrome.sydrome.

PRESENTATION OF HIRSUTISMPRESENTATION OF HIRSUTISM

Hirsutism alone is the greatest Hirsutism alone is the greatest challenge,patients usually go to dermatologistchallenge,patients usually go to dermatologist

Hirsutism wIth acne is frequently in teenage girlsHirsutism wIth acne is frequently in teenage girlsHirsutism with ovulatory disorders comes mostly Hirsutism with ovulatory disorders comes mostly

to gynecologistto gynecologistHirsutism with virilization requires immediate Hirsutism with virilization requires immediate

work-upwork-up

Evaluation of a patientEvaluation of a patient HistoryHistory

Time of onsetTime of onset :: Puberty, PregnancyPuberty, Pregnancy

DurationDuration :: Rapid/slow growthRapid/slow growth

SymptomsSymptoms :: Headache, Visual Headache, Visual disturbances, pain abdomen, lump disturbances, pain abdomen, lump abdomen, galactorrhoea.abdomen, galactorrhoea.

Other endocrinopatiesOther endocrinopaties :: Hypothyroidism, HyperprolactinemiaHypothyroidism, Hyperprolactinemia

Family historyFamily history :: CAH, IdiopathicCAH, Idiopathic

DrugsDrugs :: Androgens, danazol, 19-nor progesterone, Androgens, danazol, 19-nor progesterone, Minoxidil.Minoxidil.

ExaminationExamination

Thyroid, galactorrhoeaThyroid, galactorrhoea

Acne/seborrhaea/alopecia, Hirsutism scoring Acne/seborrhaea/alopecia, Hirsutism scoring (FG Score)(FG Score)

Abdomen/ pelvic examAbdomen/ pelvic exam

Other signs of virilization- clitoromegalyOther signs of virilization- clitoromegaly

Hirsutism scoringHirsutism scoring ((Ferriman Gallwey Ferriman Gallwey score)score)

Body area Body area ScoreScore Upper lipUpper lip All graded from 0-4All graded from 0-4 ChinChin 0=no hisutism0=no hisutism ChestChest 4= severe4= severe Upper abdomenUpper abdomen Score>8= hirsutismScore>8= hirsutism Lower abdomenLower abdomen Upper armUpper arm ThighsThighs Upper backUpper back Lower backLower back

Lab evaluation Lab evaluation

Normal valuesNormal values HirsutismHirsutism

TestosteroneTestosterone 20-80 mg/dl20-80 mg/dl (N) to (N) to > 200-tumor> 200-tumor

Free testosteroneFree testosterone 0.6-6.8 pg/ml0.6-6.8 pg/ml SHBGSHBG 18-114 n mol/L18-114 n mol/L

DHEASDHEAS 100-350µg/dl100-350µg/dl (N) to (N) to > 700-Adrenal> 700-Adrenal

170HP170HP 30-200mg/dl30-200mg/dl -CAH-CAH

Work- upWork- upS-Testosterone S-Testosterone

<2000ng/dL<2000ng/dL >2000ng/dL>2000ng/dL

TumourTumour LH/FSHLH/FSH TSH TSH DHEASDHEAS ProlactinProlactin USG USG

OvaryOvary AdrenalAdrenal

-- Imaging / USG / CT / MRIImaging / USG / CT / MRI-- Selective venous angiographySelective venous angiography-- Laparoscopy / laparotomyLaparoscopy / laparotomy

Work- upWork- up17- OHP17- OHP

<200ng/dl<200ng/dl >200ng/dl>200ng/dl

CAH excludedCAH excluded

ACTH stimulation testACTH stimulation test

NormalNormal AbnormalAbnormal

21-hydroxylase21-hydroxylase CAH CAHdef.excludeddef.excluded

Work- upWork- up

Idiopathic hirsutismIdiopathic hirsutism

– (N) menstrual cycles(N) menstrual cycles

– (N) lab evaluation(N) lab evaluation

Etiology ? Etiology ? Sensitivity to androgensSensitivity to androgens

Management of hirsutismManagement of hirsutism Treatment of etiological causeTreatment of etiological cause -- AnovulationAnovulation

-- CAHCAH-- Adrenal tumorAdrenal tumor-- Ovarian tumorOvarian tumor

Idiopathic hirsutismIdiopathic hirsutism Pharmacologic therapyPharmacologic therapy Non- pharmacologic adjunctsNon- pharmacologic adjuncts

-- Weight reduction ( in obese women)Weight reduction ( in obese women)-- Cosmetic therapyCosmetic therapy-- Depilatory creamDepilatory cream- - BleachBleach- - Electrolysis/laserElectrolysis/laser- - ShavingShaving

Management of hirsutismManagement of hirsutism Ovarian causeOvarian cause -- OCPOCP

-- Progesterone therapyProgesterone therapy -- Insulin sensitisers (Metformin)Insulin sensitisers (Metformin)

-- GnRH a with add back therapyGnRH a with add back therapy Adrenal cause- steroids to suppress adrenalAdrenal cause- steroids to suppress adrenal

Anovulation with desire of conception-Anovulation with desire of conception- Induction of ovulationInduction of ovulation

-- Pharmacologic (clomiphene, letrrozole, gonadotrophins)Pharmacologic (clomiphene, letrrozole, gonadotrophins)-- Surgical- ovarian drillingSurgical- ovarian drilling

OCPsOCPs E2 component - E2 component - SHBGSHBG free T free T

LHLH P Component- Cycle controlP Component- Cycle control

Prevents endometrial hyperplasiaPrevents endometrial hyperplasia E2+P- contraceptionE2+P- contraception Advantage Advantage

-- ContraceptionContraception

-- Cycle regulationCycle regulation

-- Reduce menstrual blood lossReduce menstrual blood loss

Anti-androgensAnti-androgens SpironolactoneSpironolactone Cyproterone acetate (CPA)Cyproterone acetate (CPA) FinasterideFinasteride FlutamideFlutamide Other drugs with antiandrogenic actionOther drugs with antiandrogenic action

-- Cimetidine- weak antiandrogen Cimetidine- weak antiandrogen

-- KetoconazoleKetoconazole

Contraindicated in women desirous of conceptionContraindicated in women desirous of conception

Peripheral action of Peripheral action of antiandrogensantiandrogens

55 reductase reductase

Testosterone Testosterone DHT DHT Androgen receptor Androgen receptor

Finasteride Finasteride SironolactoneSironolactone

Ketoconozol Ketoconozol CPACPA

FlutamideFlutamide

Surgical managementSurgical management In PCOSIn PCOS

-- Wedge resection?Wedge resection?-- Ovarian drillingOvarian drilling

In tumour In tumour -- Adrenal tumour excisionAdrenal tumour excision-- Ovarian tumour excisionOvarian tumour excision

Androgen secreting ovarian tumorsAndrogen secreting ovarian tumors ThecomasThecomas Sertoli-leydig cell tumors (Androblastoma)Sertoli-leydig cell tumors (Androblastoma) Sclerosing stromal tumorSclerosing stromal tumor LuteomaLuteoma GynandroblastomasGynandroblastomas Stromal hyperplasia/hyperthecosisStromal hyperplasia/hyperthecosis Management - Surgical (conservative) Management - Surgical (conservative)