Amenorrhea

Jean Amoura, MD, MSc

AmenorrheaPrimary

Absence of menses by age 16 with normal secondary sexual characteristics

Absence of menses by age 14 without secondary sexual development

Secondary Absence of menses for 6 months in a

previously menstruating female

Events of Puberty Thelarche (breast development)

Requires estrogen Pubarche/adrenarche (pubic hair development)

Requires androgens

Menarche Requires: GnRH from the hypothalamus FSH and LH from the pituitary Estrogen and progesterone from the ovaries Normal outflow tract

Are there secondary sexual characteristics?

Primary Amenorrhea Is there normal development of

secondary sexual characteristcs?

NO

Think hypogonadism or hypogonadotropism

Amenorrhea with Immature Secondary Characteristics

FSH Serum level

Low / normal

High

Hypogonadotropichypogonadism

Gonadal dysgenesis

Primary Amenorrhea Hypogonadism

30% have genetic abnormality Gonadal dysgenesis, Turner’s syndrome, mosaicism

Enzyme deficiencies Kallmann’s syndrome, CNS tumors Irradiation Chemotherapy Galactosemia

Primary Amenorrhea with Immature Sexual Characteristics

Hypogonadism (gonadal failure) Gonadal dysgenesis Irradiation Chemotherapy Galactosemia

Note: gonadotropins (FSH/LH) will be high, similar to menopause

Gonadal Dysgenesis Chromosomally abnormal - Classic turner’s syndrome (45XO) - Turner variants (45XO/46XX),(46X-abnormal X) - Mixed gonadal dygenesis (45XO/46XY) Chromosomally normal - 46XX (Pure gonadal dysgeneis) - 46XY (Swyer’s syndrome)

Primary Amenorrhea with Immature Sexual Characteristics

Hypogonadotropism Hypothalamic dysfunction

Kallmann syndrome Anorexia nervosa Space-occupying lesion of CNS Marijuana use

Pituitary damage (surgery/radiation) Constitutional delay

Are there secondary sexual characteristics?

Primary Amenorrhea Is there normal development of

secondary sexual characteristics?

YESThink

Pregnancy Mullerian anomaly Androgen insensitivity

Primary Amenorrhea with Normal Secondary Characteristics

Mullerian Anomalies Mullerian agenesis (Mayer-Rokitansky-

Kuster-Hauser syndrome) Imperforate hymen Transverse vaginal septum

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

15% of primary amenorrhea Normal secondary

development & 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

Imperforate Hymen

Androgen Insensitivity 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

Primary AmenorrheaEvaluation

Pregnancy test Physical exam to determine presence of

uterus FSH Karyotype

Primary AmenorrheaTreatment

Cyclic estrogen/progestin Remove gonadal streaks if XY or mosaic

Increased (52%) risk of gonadoblastomas, dysgerminomas, and yolk sac tumors

Pulsatile GnRH for ovulation induction in select patients

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

Secondary Amenorrhea Pregnancy! CNS disorders Pituitary gland Thyroid Ovary Uterus Systemic disorders

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

Secondary AmenorrheaCNS disorders

Chronic hypothalamic anovulation Stress Increased exercise levels Anorexia nervosa

Head trauma Space-occupying lesions

Secondary Amenorrhea Pituitary disorders

Hyperprolactinemia Prolactinoma Medications PCOS Renal failure

Hypoprolactinemia Pituitary resection Sheehan’s syndrome

Thyroid disorders Hyper- or hypothyroidism

Secondary Amenorrhea Ovulation disorders

Polycystic ovarian syndrome Premature ovarian failure

Uterine abnormalities Asherman’s syndrome Cervical stenosis

Drug-induced amenorrhea Hormonal contraceptives GnRH analogues

Asherman’s Syndrome

Secondary AmenorrheaHistory

Nutrition/exercise habits, weight change Sexual/contraceptive practice History of uterine/cervical surgery

Physical exam Height/weight Hirsutism Galactorrhea Estrogen status of tissues

Laboratory BhCG PRL & TSH progesterone challenge FSH if

high karyotype

Negative Pregnancy.test

TSH ,PROLACTIN, Progesterone challenge test

withdrawal bleeding

without withdrawal bleeding

hypoestrogenic compromised outflow tract

+ve.est/progest challenge test

-ve.est/progest challenge test

FSH>30-40Normal FSH

HSG OR hysteroscopy Asherman’s

FSH norm.

repeatRepeat+serum estrogen level

PreOvFailure

hypothalamic-pituitary failure

anovulation

Secondary AmenorrheaTreatment goals

Discovery and treatment of underlying disorder

Hormone replacement Menses every 1-3 months Pregnancy

Ovulation induction GnRH pump FSH/LH

Amenorrhea26 yo Gravida 0 with menarche at age

14 presents with one-year history of amenorrhea.

AmenorrheaSexually active, using condomsNo recent change in weight, skin, hairOccasional heat intoleranceNo cyclic painNo gynecologic surgeryRegular menses (every 28-30 days)

prior to past year

Amenorrhea Exam

Overweight No galactorrhea Normal hair distribution Normal pelvic exam

Pregnancy test Progestin challenge, TSH, serum prolactin Estrogen/progestin cycle, FSH