Todays Quranic verse

For, Believers are those who, when God is

mentioned, feel a tremor in their hearts, and
when they hear His signs rehearsed, find their
faith strengthened, and put (all) their trust in
their Lord; [008:002]

REPRODUCTIVE SYSTEM-1
NORMAL & ABNORMAL VAGINAL BLEEDING
Dr. Khurshid Anwar
https://www.facebook.com/pages/Human-Pathology/169869373198364

Phases of the Menstrual Cycle

Reproductive Cycle
Follicular (14 days) varies
Begins with Menses ends with luteinizing (LH) hormone surge

Ovulation (30-36 hours)

Begins with LH surge and ends with ovulation

Luteal (14 days) constant

-- Begins with the end of the LH surge and ends with onset of
menses

How does Ovulation happen?

Positive feedback to pituitary from estradiol

LH surge
Ovulation triggered
Granulosa and theca cells now produce progesterone
Oocyte expelled from follicle
Follicle converts to corpus luteum

Proliferative
Endometrium

Proliferative endometrium begins with day 4 following menses (d

1-4).

The glands are straight tubules lined by pseudostratified columnar

cells.
Mitotic figures are numerous.
Stroma is compact

Estrogen dominant phase.

Follicle maturation in the ovary triggers this phase.

Secretory Endometrium

Begins 14 days after the start of menses.

Single layer of cells lining tortuous glands.

Glandular cells show basal and supranuclear vacoulation
and cells margins are serrated in late stage.
Stroma is loose and edematous

Triggered by ovulation.
Progesterone dominant from the corpus luteum.

Menstrual Endometrium

The stroma breaks down- making

clusters of stroma only and
fragmented glands.
Inflammatory cells including
neutrophils are present.
Blood is present

Postmenopausal Endometrium

Inactive/Atrophic
Grossly thinned, fragile
Cuboidal epithelium, little
stroma
Tubular glands with no
mitoses, minimal
pseudostratification
Inactive with cystic change

DECIDUAL TISSUE

Hypersecretory
Ferning glands lined by
enlarged cells with clear or
eosinophilic cytoplasm
Decidualized stroma
Epithelioid-looking, pink
Prominent cell borders
Arias-Stella
Scary looking
Very big cells, with enlarged
nuclei and cytoplasm
Hyperchromatic, irregular
chromatin
May show hobnailing

Gestational Endometrium

ARIAS STELLA REACTION

Normal Menstrual Period

Blood loss 30- 80 ml (< 80 ml)

Duration of flow 3-8 days
Cycle length 21 - 35 days
(28 days +/- 7 days)

(average 30-35 ml)

(average 4 days)
(average 28 days)

New Classification of abnormal menstrual bleeding 2009

ABNORMAL VAGINAL BLEEDING

Abnormal vaginal bleeding is any vaginal bleeding unrelated to normal menstruation.
This type of bleeding may include spotting of small amounts of blood between periods
or extremely heavy periods in amount, duration or both.
ORGANIC CAUSES DUE TO IDENTIFIABLE DISEASES OF GENITAL TRACT
DYSFUNCTIONAL UTERINE BLEEDING

Abnormal Uterine Bleeding

( Definitions)
Menorrhagia
Heavy or prolonged uterine bleeding that occurs at regular intervals. Some sources define further as
the loss of 80 mL blood per cycle or bleeding > 7 days.

Hypomenorrhea
Periods with unusually light flow, often associated with hypogonadotropic hypogonadism (athletes,
anorexia). Also may be associated with Ashermans syndrome

Metrorrhagia
Irregular menstrual bleeding at frequent interval or bleeding between periods

Menometrorrhagia
Prolonged uterine bleeding occurring at irregular intervals.
(Metrorrhagia associated with > 80 mL)

Polymenorrhea
Frequent menstrual bleeding, strictly, menses occur 21 days or less

Oligomenorrhea
Menses are > 35 days apart (35 days-6 months)
Most commonly caused by PCOS, pregnancy, and anovulation

Amenorrhea
(Absence of a menstrual period in a woman of reproductive age)-Primary/Secondary

Abnormal Uterine Bleeding

ORGANIC CAUSES DUE TO IDENTIFIABLE DISEASES OF GENITAL TRACT
Pregnancy related irregularity
(Abortion, Ectopic pregnancy, Placental abnormalities, Molar pregnancy, Trauma etc )

IUCD Related Irregularity

Benign Conditions
(Polyps, Fibroids, Adenomyosis, Endometriosis)

Malignant Lesions
(Endometrial, Cervical, Vaginal, Ovarian)

Systemic Causes
(Coagulation disorder , thyroid and liver disease)

ECTOPIC PREGNANCY

1.
2.
3.
4.
5.
6.

Complication of pregnancy where fertilized ovum implants outside the uterine cavity.
Most of ectopic pregnancies are not viable.
Localizations of ectopic pregnancy: Fallopian tube 95% (ampullary section 80%)
cervix, ovaries abdomen etc
Clinically characterized by abdominal pain & vaginal bleeding
Risk factors; IUD, PID, previous ectopic pregnancy, endometriosis, tubal ligation, tubal surgery,
smoking, etc.
Diagnosis:
-ultrasound - the most reliable method of verification of ectopic pregnancy
-levels of -hCG - more often levels are lower than in normal pregnancy
-laparascopy
-laparatomy

Abnormal Uterine Bleeding

DYSFUNCTIONAL UTERINE BLEEDING
Defined as abnormal bleeding from genital tract without any demonstrable
organic cause.
Anovulatory cycles
Inadequate luteal phase
Contraceptive induced bleeding
Postmenopausal bleeding
(Pathophysiology of bleeding; altered Hypothalamus-pituitary-ovarian-function/ altered endometrial
response to sex hormones/ altered proportion of estrogen and progesterone production and their
effect on endometrial phasing)

Diagnosis is made by excluding organic cause .

Normal Ovulatory Cycle

Follicular development
Ovulation (d14)
Corpus luteal function
Luteal regression
Menses

Endometrium is exposed to
Ovarian production of estrogen Proliferation
Combination of estrogen and progesterone Secretory phase
Estrogen and progesterone withdrawal Desquamation and repair)

ANOVULATION
Anovulatory cycles are very common at both ends of reproductive life, due to
(1)hypothalamic-pituitary axis, adrenal, or thyroid dysfunction;
(2)functional ovarian lesions producing excess estrogen;
(3)malnutrition, obesity, or debilitating disease;
(4)severe physical or emotional stress.

Ovulatory failure results in an excess of oestrogen relative to progesterone as corpus

luteum is not produced

Endometrium goes through a proliferative phase that is not followed by the normal
secretory phase.

Endometrial glands may develop mild cystic changes or appear disorderly, while the
endometrial stroma, which requires progesterone for growth, may be scarce.

Endometrium becomes excessively vascular without stromal support, gets fragile and
prone to breakdown

Irregular and abnormal endometrial bleeding

Anovulatory Bleeding

Adolescents (13-18 years)

Mostly physiological, Screening for coagulation disorders etc.

Adolescents (19-39 years)

6-10% of women have hyperandrogenic chronic anovulation (i.e. PCOS), characterized by
noncyclic bleeding, hirsutism, obesity (BMI 25)

Later Reproductive Age (40-Menopause)

Due to declining ovarian function or iatrogenic.

INADEQUATE LUTEAL PHASE

The corpus luteum may fail to mature normally or may regress prematurely leading to
a relative lack of progesterone.
The endometrium under these circumstances fails to show the expected secretory
changes.

CONTRACEPTIVE INDUCED BLEEDING

Older oral contraceptives containing synthetic estrogens and progestin induced a
variety of endometrial responses, including a lush, decidua-like stroma and inactive,
nonsecretory glands.

Endometrial hyperplasia
Epidemiology and pathogenesis
Prolonged estrogen stimulation
Early menarche or late menopause, Nulliparity , Obesity, Increased aromatization of
androgens to estrogen, PCOS, Granulosa cell tumor of ovary, Prolonged taking estrogen
without progesterone, Anovulatory menstrual cycles, Hereditary NPCC

Diagnosis
Endometrial biopsy

Classification

Simple hyperplasia without atypia

Increased number of cystically dilated glands
Simple hyperplasia with atypia
Complex hyperplasia without atypia
Increased number of dilated glands with branching & glandular crowding
Complex hyperplasia with Atypia (Atypical hyperplasia)
Clinically Glandular crowding and dysplastic epithelium & greatest risk for endometrial cancer
(20-50%)
Menorrhagia,
metrorrhagia, In a significant number of cases, the hyperplasia is associated with inactivating mutations in thePTEN tumor
suppressor gene, an important brake on signaling through the PI-3-kinase/AKT signaling pathway
menometrorrhag
ia
postmenopausal
bleeding

Simple Hyperplasia

Complex Hyperplasia

Atypical Hyperplasia

Atypical Hyperplasia

Abnormal Uterine Bleeding

(Workup)

History
Timing of bleeding, quantity of bleeding, menstrual hx including menarche and recent
periods, associated sxs, family hx of bleeding disorders

Physical
R/o vaginal or cervical source of bleeding. Bimanual may reveal bulky uterus/discrete
fibroids
Assess for obesity, hirsutism, stigmata of thyroid disease (hypothyroidism associated
with anovulation), signs of hyperprolactinemia (visual field testing, galactorrhea)
Pap smear
Endometrial biopsy, if appropriate

Pregnancy Test
Imaging
Pelvic ultrasound
Sonohystogram or hysterosalpingogram

Surgical
Hysteroscopy
D&C

THANKS

Abnormal Uterine Bleeding

(Differential Diagnosis)
Structural
Cervical or vaginal laceration
Uterine or cervical polyp
Uterine leiomyoma
Adenomyosis
Cervical stenosis/Ashermans (hypomenorrhea)

Hormonal
Anovulatory bleeding
Hypogonadotropic hypogonadism
Pregnancy
Hormonal Contraception (i.e. OCPs, Depo-Provera)

Malignancy
Uterine or Cervical cancer
Endometrial hyperplasia (potentially pre-malignant)

Bleeding disorders
von Willebrands Disease, Hemophilia/Factor deficiencies, platelet disorders