Amenorrhea

Definition Of Amenorrhea Is complete absence of menstruation in the childbearing period.

Definition Of Amenorrhea ORIGIN from Greek A = without Meno = relating to menstruation rrhea = discharge, flow Absence of menstruation.

Background Understanding normal menstruation. Classification of amenorrhea. Amenorrhea is a Symptom not a disease, so the final diagnosis should be pathological .

Pre-requisities for normality of menstruation Coordinated Neuro endocrine Axis. Responsive ,patent Utero vaginal canal. Good general health .

Coordinated pituitary- ovarian –uterine Axis VARIABLE CONSTANT

Classifications Of Amenorrhea According to the onset: Primary amenorrhea. Secondary amenorrhea. According to the cause: Physiological. Pathological According to Hidden or apparant: False amenorrhea (Crypto menorrhea). True amenorrhea. These are complementary to each other

Primary & Secondary Secondary Primary

pubertal changes - Marshall & Tanner Regular sequence of events between ages of 10-16 yrs in girls GROWTH SPURT 8 - 14 yrs (9 yrs) 6 - 10 cm / yr peak 2.5 yrs duration BREAST GROWTH (Thelarche) 8 - 13 yrs (11 yrs) PUBIC HAIR (Pubarche) 9 - 13 yrs 1st Pubertal Sign in 25% AXILLARY HAIR (Adrenarche) 9.5 - 15 yrs may follow menarche MENSTRUATION (Menarche) 10 - 16 yrs (13 yrs) 9

According to cause Physiological. Before puberty. During pregnancy. During lactation . During menopause Pathological: Primary: True ( physiologic & pathologic) False Secondary:

Hidden or true : Crypto menorrhea = Obstruction of outflow tract below internal OS : Primary: Cervical atresia . Vaginal aplasia. Transverse vaginal septum Imperforate hymen Secondary: Cervical Cauterization. Cervical conization ( Leep diathermy) . Vaginal synechiae

Workup FOR DIAGNOSIS Exclude physiologic causes Exclude anatomical. Clinical workup

Exclude physiologic causes

Crypto menorrhea - Possible difficulty with micturition - Intermittent abdominal pain - Possible difficulty with micturition - Possible lower abdominal swelling Bulging bluish membrane at the introitus or absent vagina (only dimple)

False (crypto menorrhea) hematocolpos hematometra 15

Four phenotypes (Breast & uterus ) Clinical workup Four phenotypes (Breast & uterus ) 1. Absent breast + presence of uterus 2. Presence breast + absence uterus 3 Absence breast + absence uterus 4. Presence breast + presence uterus

Breast is absent in cases with Hypogonadism

Absent breast + presence of uterus (Hypogonadism) Serum FSH LOW (less than 5 IU/l.) HIGH (more than 20 IU/l) Hypothalamo - pituitary PRIMARY OV. FAILURE GnRH challenge . LOW FSH HIGH FSH Gonadal dysgenesis KARYOTYPE Gonadal biopsy PITUITARY HYPOTHALAMIC History , exam & investigation

Gonadal dysgenesis (Turner’s syndrome) • Sexual infantilism and short stature. • Associated abnormalities: webbed neck, cubitus valgus coarctation of the aorta, high-arched palate, broad shield-like chest with widely spaced nipples, short metacarpal bones Renal anomalies. • Bilateral streaked gonads. • Karyotype - 80 % 45, X0 - 20% mosaic forms (46XX/45X0) • Treatment: HRT

Gonadal Dysgenesis (Turner’s syndrome)

Causes of hypothalmo - pituitary Congenital Traumatic Inflammatory Neoplastic Miscellaneous

Hypothalamus & Pituitary (Hypogonadotropic ) Stress Weight changes :anorexia nervosa ,bulimia Exercise Psuedocyesis Syndromes Pituitary : Craniopharyngioma. Adenomas. syndromes . e.g. Sheehan's syndrome

Emotional stress Emotional shock Stress Endorphins Gn Rh

Weight changes Excess weight gain : Diet regimen Anorexia nervosa Weight loss (15% of ideal wt for age) whether By: Diet regimen Anorexia nervosa Excess weight gain : simple overeating Bulimia nervosa. 24

Kallmann Syndrome Deficient secretion of GnRH + anosmia. Possible co-existing features include: Bone anomalies. Renal anomalies. Cleft lip and palate. Color blindness. .

Frolich syndrome Primary amenorrhea. Hypogonadism. Trunkal obesity.

Laurence-Moon -Biedle syndrome As Frolich syndrome with: Polydactyl. Syndactly. Mental retardation. Retinitis pigmentosa.

Craniopharyngioma Arises from remnants of Rathke's pouch Compresses the hypothalamus Suppress GnRH secretion . Interrupt portal flow of GnRH in the pituitary stalk. Calcifications may be apparent on radiography of the sella turcica. Frequent manifestations include visual field defects and blurring vision.

Galactorrhoea + amenorrhea. Chiari-Frommel syndrome It occurs after delivery: due to persistent Prolactin secretion. Delcastello syndrome: It is not preceded by delivery.

Levi- Lorian Syndrome (Pituitary infantilism) Amenorrhea. Hypogonadism. Short stature (Dwarfism).

Sheehan's syndrome &Simmonds Postpartum hge. Failure of gonadotrphic function + failure of lactation. More extensive damage lead to : Simmonds : (Destruction of the anterior pituitary gland due to septic emboli due to puerperal sepsis.)

Pituitary Adenoma Evaluation of the sella turcica with (MRI) + radiography is necessary. Vary in size. Micro adenomas (less than 10 mm). Macro adenomas (more than 10 mm). May be associated with: Visual changes. Galactorrhoea. Hypothyroidism. Amenorrhea

Work up for : hypothalamic- pituitary History Exam Investigation… Then: Categorize as primary or secondary Categorize cause……..

History in primary amenorrhea Developmental milestones (age of growth spurt ,age of thelarche, adrenarche) Chronic illness (CRI ,TB, Bl disease). Weight changes Excessive exercise History of anosmia

Examination General condition Height BMI 2ndary sex characters

Investigations Bed –side: Laboratory: Imaging: Instrumental: Visual field in suspected pituitary adenoma Laboratory: BHCG: to exclude pregnancy Serum prolactin TSH Imaging: Ultrasound : prove presence or absence of uterus, measure its size CT MRI Instrumental: Hysteroscopy: uterine synechia Laparoscopy

2. Presence breast + absence uterus Sexual hair & Karyotype 46-XY 46-XX Andogen Insenitivity (TSF syndrome) Mullerian Agenesis (MRKH syndrome) Absent sexual hair Presence of sexual hair

Utero-vaginal Agenisis Mayer- Rokitansky- Kuster-Hauser syndrome Normal breasts. N. sexual hair development . Normal looking external female genitalia Normal female range testosterone level Absent uterus and upper vagina Normal ovaries Karyotype 46-XX 15-30% renal, skeletal and middle ear anomalies. Treatment : STERILE? Vaginal creation : Dilatation & Vaginoplasty) 38

Testicular feminization syndrome Normal breasts but no sexual hair Normal looking female external genitalia Absent uterus and upper vagina Karyotype 46, XY Male range testosterone level Treatment : gonadectomy after puberty + HRT ? Vaginal creation (Vaginoplasty ) 39

Vaginal Agenesis: Comparison of Two Syndromes Mullerian Agenesis Androgen Insensitivity Syndrome Vagina absent Pubic hair present Breasts Present Gonads ovaries Testes Uterus Absent Testestrone level Female level Male level Karyotype 46 XX 46 XY

3. absence breast + absence uterus 17, 20 desmolase deficiency 17 a hydroxylase deficiency Agonadism Very rare All are 46 XY

Degeneration of the testes (in utero) after the production of the MIF AGONADISM Degeneration of the testes (in utero) after the production of the MIF

4. Presence breast + presence uterus (Like secondary amenorrhea) PREGESTERONE BLEEDING NO BLEEDING CHRONIC ANOVULATION e.g PCOS COMBINED OESTROGEN & PROGESTERONE BLEEDING NO BLEEDING OVARIAN FAILURE ( Non dysgenetic) UTERINE FACTOR ( Ashermann syndrome) SERUM FSH

Summary of Sub-phenotypes Amenorrhea Breast – Absent Uterus Absent Uterus Present 17, 20 desmolase deficiency 1. Gonadal failure turner 45X 17 a hydroxylase deficiency 46xy Gonadal dysgenisis Agonadism 17 a hydroxylase deficiency with 46XX 2. Hypothalamic failure 3. Pituitary failure Breast – Present AIS (T.F.) Hypothalamic, pituitary, ovarian & uterine etiology Mullerian agenesis

General Principles of management Try causative Treatment. Do not forget general factors Remember stress is common cause in adolescents Pregnancy is the commonest cause of secondary amenorrhea

General Principles of management . HRT: (estrogen and progesterone) In hypo-estrogenic amenorrheic women (to prevent osteoporosis) . Periodic progestogen: In euestrogenic amenorrheic women (to avoid endometrial cancer) . If Y chromosome is present: gonadectomy is indicated . Many cases require frequent re-evaluation

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