Transcript Amenorrhea
AMENNORHEA SALWA NEYAZI COSULTANT OBSTETRICIAN GYNECOLOGIST PEDIATRIC & ADOLESCENT GYNECOLOGIST AMENORRHEA WHAT IS 1RY AMENORRHEA? Lack of the onset of menses by the 16 Y in a ♀ with 2ry sexual chct or by the age of 14 Y in ♀ without 2ry sexual development WHAT IS 2RY AMENORRHEA? Cessation of menses for a period of 6 months in a ♀ who previously had initiation of menses CLASSIFICATION OF 1RY AMENORRHEA A-BREAST ABSENT UTERUS PRESENT GONADAL DYSGENESIS 1-TURNER SYNDROME 45XO Variations of Turner ‘s syndrome 2-Mosaicism XO/XX not always short They will have menses , get pregnant then develop premature menopause 3-Structural abnormalities of the X chromosome Deletion of the short arm of the X chromosome Short stature Deletion of the long arm normal HT, 2ry Amen, streak gonads TURNER SYNDROME FEATURES 1ry amenorrhea No breast development Normal ♀ genital organs (external /internal) Streak gonads (ovaries are replaced by white nonfunctioning tissue) Short stature Webbed neck (Short broad neck) with a low hair line Cubitus vulgus Shield chest / Widely spaced nipples High arched palate Short 4th metacarpal Coarctation of the aorta or VSD Horse shoe kidney or single kidney Lymphedema GONADAL DYSGENESIS 4-Pure gonadal dysgenesis 46XX Mutation in an autosomal gene Accelerated germ cell loss Streak gonads ♀ genetalia , normal Mullerian structures Rarely Turner’s Stigmata 5- Pure gonadal dysgenesis 46 XY ♀ genitalia Streak gonads ↑ risk of malignancy N Mullerian structures GONADAL DYSGENESIS 6- 17-α hydroxylase deficiency (rare) ovarian synthesis of estrogens 1ry Amen Sexual immaturity cortisol ↑ ACTH ↑ Na K ↑ BP ↑ Progestrone as it is not converted to cortisol 7-Galactosaemia (rare) galactosaemia is toxic to oocytes HYPOTHALAMIC FILURE 8-Isolated GnRH deficiency (Kalman’s Syndrome) Anosmia & Hypogonadotropic Hypogonadism X linked ----Mutation in the KAL gene More common in ♂ > ♀ Midline defects Cleft lip & Palate Somatic defects color blindness, renal agenesis, retinitis pigmentosa, neurosensory deafness Lack 2ry sexual chct & the ability to smell HT & bone age appropriate for age HYPOTHALAMIC FILURE 9-Hypogonadotropic Amenorrhea CNS tumors GnRH pulses LH & FSH estradiol Hypothalamic Lesions Craniopharyngioma granuloma, aqueduct stenosis , & the sequelae of encephalitis CNS tr interfere with the –ve feedback of Dopamine on Prolactin ↑ Prolactin Other causes of HypoGonadotropic Amen hypothyroidism Prader Willi & Laurence Moon Biedl syndromes HYPOTHALAMIC FILURE 10-Anorexia Nervosa, Malnutrition, Excessive Exercise & Chronic Illness Functional GnRH deficiency May present with or without Breast development Physical stress delay menarche Each year of athelitic training before menarche delayed menarche 5 M Osteoporosis could occur with prolonged periods of Amenorrhea, low body Wt B-BREAST PRESENT , UTERUS PRESENT 1-HYPOTHALAMIC CAUSES CNS lesions (tumors) Stress, Excessive exercise & low body Wt 2-PITUITARY CAUSES Hyperprolactinemia Hypothyroidism ↑ TRH ↑ prolactin 3-OVARIAN CAUSES PCO 4-OUTFLOW TRACT OBSTRUCTION Imperforate hymen Transverse vaginal septum C-BREAST PRESENT , UTERUS ABSENT 1-Testicular feminization/ Androgen insensitivity XY Karotype produce MIF Mullerian structures are absent Complete/ Partial absence of androgen receptors X linked recessive or dominant Female external genitalia with Short blind vagina Testosterone normal ♂ range Breast development due to periferal conversion of androgens to estrogens Sexual hair is absent due to absence of androgen receptors Gonadectomy after puberty ↑ risk of malignancy (gonadoblastoma, dysgerminoma) C-BREAST PRESENT , UTERUS ABSENT 2- 5 α reductase deficiency Autosomal recessive Formation of the ♂ external genitalia requiers 5α REDUCTASE testosterone dihydrotestosterone Formation of the internal wollfiane structures respond directly to testosterone External genitalia ♀ with mild musculinization Absent uterus At puberty testosterone secretion virilization C-BREAST PRESENT , UTERUS ABSENT 3-Mulerian Agenesis/ Mayer –Rokitansky-Kuster-Huser syndrome Etiology ? Failure of mullerian duct development absence of the upper vagina, cx & uterus (uterine reminants may be found) The ovaries & fallopian tubes are present Normal 46XX ♀ with normal exrenal genitalia Pt present with 1ry amenorroea 47% have asociared urinary tract anomalies 12% skeletal anomalies Rx psychological counseling surgical - vaginoplasty - excision of utrine reminant (if it has fuctioning endometrium) -vaginal dilators D-BREAST ABSENT, UTERUS ABSENT The least common presentation of 1ry Amen All Pt are 46 XY Testosterone or N FSH/LH ↑ A- 17-20 DESMOLASE DEFICIENCY The enzyme required for the synthesis of Androgens Androgens estrogen The testes produce MIF therefore no Mullerian structures ♀ external genitalia Insufecient estrogens for breast development D-BREAST ABSENT, UTERUS ABSENT B- 17 α HYDROXYLASE DEFICIENCY Similar to 17-20 desmolase def Cortisol synthesis also ↑ BP, hypernatraemia & hypokalaemia C-AGONADISM Degeneration of the testes (in utero) after the production of the MIF INVESTIGATIONS & TREATRMENT Hx & Physical examination to place the Pt in one of the four categories 1-BREAST ABSENT UTERUS PRESENT ↑↑FSH FSH Kallman’s Syndrome Wt Wt ↑Exercise ↑Exercise Stress Stress CNS / HP DISORDER 17α hydroxylase deficiency Gonadal Dysgenesis ↑Na K ↑Progestrone ↑TSH ProlactinN TSHN PROLACTIN ↑ /N XX Karyotype Hypothyroidism CNS TUMORS CT / MRI HEAD XY XO Gonadectomy TREATMENT 1-BREAST ABSENT UTERUS PRESENT Hypothyroidism Thyroxin Gonadal Dysgenesis Wt ↑Exercise Stress 17αOH-Dif Cortisol XX XO XY CNS Tmr Psychiatric Help Treat thecause Kallman’s Syndrome Gonadectomy Treat accordingly Estrogen Progestrone Replacement Estrogen Progestrone Replacement Breast development / Menses Improve Bone Min Density 2-BREAST PRESENT UTERUS PRESENT ↑↑ TSH TSH Hypothyroid Hypothyroid Karyotyping ↑FSH ↑Prolactin ↑Prolactin TSHN TSHN Prolactin N TSH N Ovarian Failure -Progestrone chalange Out flow Tract Obstruction MRI/CT R/O CNS TMR MRI/CT Pituitary FSH +Progestrone chalange Hypoth/ pituit Failure Anovulatory cycle TREATMENT 2-BREAST PRESENT UTERUS PRESENT ↑ TSH Hypothyroid Out flow Tract Obstruction ↑Prolactin TSHN Anovulatory cycle Ovarian Failure Hypoth/ pituit Failure Thyroxin Bromocriptin Surgery HRT Progestin D16-25 3-BREAST PRESENT UTERUS ABSENT ↑Testosterone N♂ Karyotyping XY Testicular Feminization Testosterone N♀ Karyotyping XX Mullerian Agenesis Gonadectomy U/S Pelvis U/S MRI Gonads U/S Pelvis U/S KIDNEY IVP 3-BREAST PRESENT UTERUS ABSENT XX XY Testicular Feminization Mullerian Agenesis HRT Vaginoplasty Gonadectomy Vaginal dilators 4-BREAST ABSENT UTERUS ABSENT All 46 XY Pysical Exam U/S MRI for Gonads Gonadectomy HRT 2RY AMENORRHEA 2RY AMENORRHEA WHAT IS 2RY AMENORRHEA? Cessation of menses for a period of 6 months or 3 consecutive menstrual cycles in a ♀ who previously had initiation of menses WHAT IS THE PREVELANCE OF AMENORRHEA? 1.8-3% WHAT IS THE CLASSIFICATON OF 2RY AMENORRHEA? Hypergonadotropic CNS / Hypothalamic Hypogonadotrpic Pituitary Euogonadotrpic Ovarian Hperprolactinemia Outflow Uterine Cx Anatomic defects Vaginal HYPOGONADOTROPIC AMENORRHEA “CNS / HYPOTHALAMIC ” Stress ↑ β-endorphins GnRH FSH LH Estrogens Exercise Excessive streneous exercise Runners & Ballet dancers Mechanism Similar to stress Wt loss “Anorexia nervosa” More frequent in adolescent & young adults 0.5-1% of women aged 15 –30 years 15% < Ideal body Wt Functional “Non of the above causes” No LH pulses or Persistant pulse frequency of “luteal phase ” 2ry to neurotransmitter abnormality of the CNS (? ↑ Opioid activity) HYPOGONADOTROPIC AMENORRHEA IS IT OF ANY CONCERN IF THESE YOUNG WOMEN BECOME AMENORRHEIC ? HYPOESTROGENISM is the main concern WHY IS IT MORE WORRYING THAN THE MENOPAUSAL WOMEN ? During adolescence estrogen plays a critical role in determining PEAK BONE DENSITY which reached in the 2nd decade of life HYPOGONADOTROPIC AMENORRHEA IS THERE ANY EVIDENCE OF ITS EFFECT ON THE BONES? Amenorrheic Athletes Bone Mineral Density (BMD) in lumbar spines, femur, tibia Athletes with menstrual irregularities BMD < athletes with regular cycles Anorexia nervosa Pt BMD (0.64) < Normal controls (0.72) Anorexia nervosa Pt may have osteoporotic fractures HYPOGONADOTROPIC AMENORRHEA SHEHAN’S SYNDROME Piuitary failure following sever post partum hemorrhage Deficiency of all pituitary hormones FSH & LH Failure of ovarian follicular development estrogen Amenorrhea Rx HRT hMG for ovulation induction TREATMENT OF HYPOGONADOTROPIC AMENORRHEA In training intensity to a level where regular menses resume HRT Cyclic estrogen / progestrone Premarin 1.25 mg continuously Medroxyprogestrone acetate 5 mg /D for 12 D each cycle OCP better compliance Anorexia nervosa Psychiatric Rx Meanwhile HRT Long term follow up Frequent relapses after attaining ideal body Wt Functional HypoGt Amen HRT / ovulation induction EUOGONADOTROPIC AMENORRHEA PCO Amenorrhea / anovulatory cycles Enlarged polycystic ovaries Infertility Hyperinsulinemia / Obesity Hyperandrogenism / hirsutism ↑ LH Acyclic estrogen production / unopposed by progesrtrone ↑ risk of endometrial hyperplasia/Ca Inheritable disorder with a complex inheritance pattern TREATMENT OF PCO Infertility Amenorrhea Irrigular cycles Hirsutism Hyperinsulinism Obesity Clomid Gluco phage Cyclic progest OCP OCP hMG Ovarian drilling Anti + androgens Ovarian Androgen ↑SHBG -Protect endometrium -Regulate cycle -menorrhagia Wt Sprinolactone Cyproterone acetate Flutamide Bind androgen receptors Androgens 5αreductase activity Ovulation 70% Pregnancy 40% Ovulation 92% Pregnancy 70% HYPERGONADOTROPIC AMENORRHEA WHAT IS PREMATURE OVARIAN FAILURE (POF) ? 2ry Amenorrhea ↑ FSH & LH estrogen Before the age of 40 Y WHAT IS THE INCIDENCE OF POF ? 1% WHAT IS THE CAUSE? Unknown / autoimmune / genetic factors Associated autoimmune disease 39% POF WHAT ARE THE PATHOLOGICAL CHCT OF POF ? TWO TYPES Ovarian sclerosis & lack of follicles Resistant ovary syndrome HOW TO MANAGE POF? R/O other autoimmune diseases RH factor ANA, Antithyroid Antibodies, Antichromosomal Antibodies, glucose, cortisol, Ca , Ph, TSH HRT to prevent osteoprosis Spontaneous pregnancy can occur in women with POF on HRT 8% hMG/HCG glucocorticoids have been cliamed to give better pregnancy rates HYPERPROLACTINEMIA The most common pituitary cause of 2ry Amenorrhea Causes -Pituitary adenoma -Idiopathic -Loss of inhibition by dopamine Hypothalamic or pituitary stalk lesions -Hypothyroidism -PCOS -Medications phenothiazines , haloperidol monoamineoxidase inhibitors, TCA, H2 receptors blockers HYPERPROLACTINEMIA Galactorrhea 1/3 of Pt Amenorrhea/ Hyperprolactinemia Pt at risk of osteoporosis due to estrogen TREATMENT - Hypothyroidism L-Thyroxin If still amenorrheic after RX Parlodel + Thuroxin -If no substitute for the medications that cause hyperprolactinemia HRT -Hypothalamic or pituitary stalk lesions Surgical excision TREATMENT OF HYPERPROLACTINEMIA PITUITARY ADENOMA (PROLACTINOMA) *Macroadenoma > 10 mm Respond to medical Rx Dopamine agonist (bromocriptin) size of the tumor & prolactin level Pt not responding to medical Rx or not tolerating it Surgery/ Irradiation *Microadenoma < 10mm remain stable in size Rx Bromocriptin prolactin level Normalize the menstrual cycle TREATMENT OF HYPERPROLACTINEMIA IDIOPATHIC HYPERPROLACTINEMIA Rx Dopamine agonist Bromocriptin or Pergolide Side effects of dopamine agonists -Postural hypotension -Nausea -Headache -Nasal stuffiness Starting with a low dose & gradually ↑ it helps to avoid The side effects ANATOMICAL CAUSES Uncommon cause of 2ry Amenorrhea Asherman’s Syndrome Hx of D/C for RPOC after abortion / puerperium or previous uterine infection Intrauterine Adhesions Normal hormones -ve progestrone chalange test Dx HSG / HYSTROSCOPY Rx Hystroscopic resection of the adhesions followed by estrogen therapy