Dr. Hazem Al-Mandeel, M.DAssistant Professor & ConsultantObstetrics & GynecologyCollege of MedicineKing Saud University

OB/GYN Rotation-course 481 GYN

1ry Amenorrhea: is the lack of onset of menses by age 16 in female with 2ry sexual characteristics

ORby age of 14 in female without 2ry sexual

development

2ry Amenorrhea: is the cessation of menses for a period of 6 months in a female who previously had initiation of menses

• Gonadal Failure 43%• Congenital Absence of the vagina 14%• Constitutional delay 10%

• Chronic anovulation 39%• Hypothyroidisim/Hyperprolactinemia 20%• Weight loss/anorexia 16%

Primary Sexual characteristics

Absent

Present

PE

5 -Reductase def.17-20 Desmolase def.17 Hydroxylase Def.(All XY Karyotype)

UterusAbsent

Normal

FSHHigh

Normal

•Kallman’s Syndrome•Physiologic Delay

Karyotype

•XX•Y line

•Turner (XO)

HCG+

Pregnancy

HCG -ve

Primary

No

Yes

PE

SecondaryR/O

Asherman’sCx Stenosis

Normal

TSH, PRL, FSH

Mullerian AbnAISTrue

Hemaphrodite

TSH, PRL, FSH

TSH

Normal

AbnormalHypoThyroidismHyperThyroidism

Prolactin High Hyperprolactenemia

Normal

FSH High•Ovarian Failure

•Radiation•Chemo•Infection•Autoimune

•Galacrosemia•Idiopathic

Normal

Estrogen

LowNormal

CNS Exam

PCOSIdiopathicOvarian NeoplasmsObesityCushing’sCAH

Pituitary Hypothalamic Lesions:

TumorsInfectionInfarctionFailure

Toxic

Chronic Disease

1-TURNER SYNDROME: 45XO2-Mosaicism of Turner’s: 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 Amenorrhea, & streak gonads

1ry amenorrhea No breast development Normal ♀♀ genital organs (external /internal)Streak gonads (ovaries are replaced by nonfunctioning tissue)Short statureWebbed neck (Short broad neck) with a low hair lineCubitus vulgusShield chest / Widely spaced nipplesHigh arched palateShort 4th metacarpalCoarctation of the aorta or VSDHorse shoe kidney or single kidneyLymphedema

4-Pure gonadal dysgenesis : 46XX, mutation in an autosomal gene accelerated germ cell loss streak gonads. Features: genetalia with normal mullerian ♀

structures

5- Pure gonadal dysgenesis : 46 XY. Features: normal ♀genitalia and mullerian structures with streak gonads ↑ risk of malignancy

6- 17-α hydroxylase deficiency (rare) ovarian synthesis of estrogens 1ry AmenSexual immaturity cortisol ↑ ACTH ↑ Na K ↑ BP ↑ Progestrone as it is not converted to cortisol

7- Galactosaemia (rare) galactosaemia is toxic to oocytes

Anosmia & Hypogonadotropic Hypogonadism X linked ----Mutation in the KAL geneMore common in > ♂ ♀

Midline defects Cleft lip & PalateSomatic defects color blindness, renal agenesis,

retinitis pigmentosa, neurosensory deafness Lack 2ry sexual chct & the ability to smellHT & bone age appropriate for age

CNS tumors GnRH pulses LH & FSH estradiol

Hypothalamic Lesions Craniopharyngioma granuloma, aqueduct stenosis , & encephalitis CNS tumors interfere with the –ve feedback of Dopamine on Prolactin ↑ Prolactin Other causes of HypoGonadotropic Amen

hypothyroidism

Functional GnRH deficiency May present with or without Breast developmentPhysical stress delay menarcheEach year of athelitic training before menarche

delayed menarche 5 MOsteoporosis could occur with prolonged periods of

Amenorrhea, low body Wt

1. HYPOTHALAMIC CAUSES: CNS lesions (tumors) Stress, Excessive exercise & low body Wt

2. PITUITARY CAUSES: Hyperprolactinemia Hypothyroidism ↑ TRH ↑ prolactin

3. OVARIAN CAUSES: Polycystic ovarian disease/syndrome

4. OUTFLOW TRACT OBSTRUCTION: Imperforate hymen Transverse vaginal septum

XY Karotype produce MIF Mullerian structures are absentComplete/ Partial absence of androgen receptorsX-linked recessive or dominant Female external genitalia with Short blind vaginaTestosterone normal range♂

Breast development due to peripheral conversion of androgens to estrogens

Sexual hair is absent due to absence of androgen receptorsGonadectomy after puberty ↑ risk of malignancy

(gonadoblastoma, dysgerminoma)

Autosomal recessive Formation of the external genitalia requires 5♂ α REDUCTASE testosterone dihydrotestosteroneFormation of the internal wolfiane structures respond directly

to testosteroneExternal genitalia with mild musculinization♀

Absent uterusAt puberty testosterone secretion virilization

Etiology ?Failure of mullerian duct development absence of the upper

vagina, cx & uterus (uterine reminants may be found)The ovaries & fallopian tubes are presentNormal 46XX with normal exrenal genitalia♀

Pt present with 1ry amenorroea47% have asociared urinary tract anomalies12% skeletal anomaliesRx psychological counseling surgical treatments: vaginoplasty, excision of utrine

reminant (if it has fuctioning endometrium)

The least common presentation of 1ry AmenorrheaAll patients are 46 XYTestosterone or NFSH/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 Insufficient estrogens for breast development

B. 17 α HYDROXYLASE DEFICIENCYSimilar to 17-20 desmolase deficiency. Cortisol synthesis also ↑ BP, hypernatraemia & hypokalaemia

C. AGONADISM Degeneration of the testes (in utero) after the production of

the MIF

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 ♀

mensesWHAT IS THE PREVELANCE OF AMENORRHEA?1.8-3%WHAT IS THE CLASSIFICATON OF 2RY AMENORRHEA?HypergonadotropicHypogonadotrpicEuogonadotrpicHperprolactinemiaAnatomic defects

Stress ↑ β-endorphins GnRH FSH LH EstrogensExercise Excessive streneous exercise e.g.: runners 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

persistent pulse frequency of “Luteal Phase ” 2ry to neurotransmitter abnormality of the CNS (? ↑

Opioid activity)

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

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 but less

than athletes with regular cyclesAnorexia nervosa Pt BMD (0.64)Anorexia nervosa Pt may have osteoporotic fractures

SHEHAN’S SYNDROMEPituitary failure following sever post partum

hemorrhageDeficiency of all pituitary hormonesFSH & LH Failure of ovarian follicular development estrogen AmenorrheaRx HRT

In training intensity to a level where regular menses resume

HRT Cyclic estrogen / progestrone; e.g.: Premarin continuously + Medroxyprogestrone acetate for 12 days

OCP better compliance Anorexia nervosa Psychiatric Rx + HRT Long term follow up Frequent relapses after attaining

ideal body wt.Functional Amennorhea HRT / ovulation induction

Polycystic Ovarian Disease / SyndromeAmenorrhea / anovulatory cyclesEnlarged polycystic ovariesInfertilityHyperinsulinemia / ObesityHyperandrogenism / hirsutism↑ LHAcyclic estrogen production / unopposed by

progesrtrone ↑ risk of endometrial hyperplasia/CaInheritable disorder with a complex inheritance pattern

WHAT IS PREMATURE OVARIAN FAILURE (POF) ?2ry Amenorrhea ↑ FSH & LH Estrogen Before the age of 40 yearsWHAT IS THE INCIDENCE OF POF ?1%WHAT IS THE CAUSE?Unknown / autoimmune / genetic factorsAssociated autoimmune disease 39%

WHAT ARE THE PATHOLOGICAL CHARACTERISTICS OF POF ?Ovarian sclerosis & lack of folliclesResistant ovary syndrome

HOW TO MANAGE POF?R/O other autoimmune diseases RH factor ANA, Antithyroid Antibodies, Antichromosomal Antibodies,

glucose, cortisol, Ca , Ph, TSHHRT to prevent osteoprosisSpontaneous pregnancy can occur in 8% of women with POF on HRT

The most common pituitary cause of 2ry AmenorrheaCauses -Pituitary adenoma -Idiopathic -Loss of inhibition by dopamine Hypothalamic or pituitary stalk lesions -Hypothyroidism -PCOS -Medications phenothiazines , haloperidol monoamineoxidase inhibitors, TCA, H2 receptors blockers

Galactorrhea 1/3 of Pt Amenorrhea/ Hyperprolactinemia Pt at risk of osteoporosis due to estrogenTREATMENT - 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

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 to normalize the

menstrual cycle

IDIOPATHIC HYPERPROLACTINEMIA Rx Dopamine agonist Bromocriptin or PergolideSide effects of dopamine agonists -Postural hypotension -Nausea -Headache -Nasal stuffinessStarting with a low dose & gradually ↑ it helps to avoid

the side effects

Uncommon cause of 2ry AmenorrheaAsherman’s Syndrome Hx of D/C for RPOC after

abortion / puerperium or previous uterine infectionIntrauterine AdhesionsNormal hormonesNegative progestrone chalange testDx HSG / HYSTROSCOPYRx Hystroscopic resection of the adhesions followed

by estrogen therapy