Bam. It’s a girl thing Understanding the mechanism is critical to diagnosis and management of reproductive problems Physiologic and anatomic changes.

MENSTRUAL CYCLE

Bam

ANATOMY

MENSTRUAL CYCLE It’s a girl thing Understanding the mechanism is critical

to diagnosis and management of reproductive problems

Physiologic and anatomic changes within the cycle

MENSTRUAL CYCLE Coordinated interactions between the

hypothalamus, anterior pituitary gland, ovaries and uterine endometrium

Normally is a 21- 35 day cycle Typically lasts for 2 to 6 days With a 20- 60 ml blood loss

RECALL: MENSTRUAL CYCLE PHYSIOLOGY Ovarian cycle

Follicular phaseLuteal phase

Uterine cycleProliferative phaseSecretory phase

MENSTRUAL CYCLE

OVARIAN CYCLE

Menarche to menopause

Monthly release of a single mature follicle

Number of oocytes:Fetus: 6-7million by 20

weeks AOGBirth: 1-2 millionPuberty: 300k-400kOvulation: 400-500

FOLLICULAR PHASE FSH secretion recruit 5-7 Graafian follicle FSH proliferation of granulosa cells and

expression of LH receptors Aromatase and p450 activation

granulosa cells secrete estrogen increase in GnRH increase in LH androgen synthesis proliferation, differentiation, secretion follicular thecal cells

High levels of LH results in the luteinization of the granulosa cells, production of progesterone and initiation of ovulation

LUTEAL PHASE: CORPUS LUTEUM• Primary regulator of the luteal phase• Active secretory structures that produce

progesterone• Estrogen and Inhibin A are also produced• Corpus luteum steroids provide negative

feedback and cause decrease in FSH and LH

• Inhibin secretion potentiates FSH withdrawal

• Production of progesterone inhibits further development and recruitment of additional follicles

LUTEAL PHASE• Continued corpus luteum function depends

on continued LH production• Corpus luteum regresses after 12 to 16

days in the absence of stimulation and form: corpora albicans

• As the corpus luteum regresses, progesterone and estrogen levels wane and allows FSH and LH levels to rise again and recruit follicles

• And the cycle begins again

UTERINE CYCLE

Types of DeciduaDecidua FunctionalisDecidua Basalis

PROLIFERATIVE PHASE Progressive mitotic growth of

decidua functionalis Early endometrium is thin (1-2mm) Straight, narrow, short endometrial

glands Low columnar during early proliferative

phase Pseudostratified pattern before

ovulation Dense complex stroma Infrequent vascular structures

SECRETORY PHASE In a typical 28-day cycle, ovulation

occurs on day 14 Within 48-72 hours, onset of

progesterone secretion produces a change in the histologic appearance in the endometrium

Characterized by cellular effects of Progesterone in addition to Estrogen

Presence of glycogen-containing subnuclear vacuoles

SECRETORY PHASE By day 21

Progressive edemaVisible long and coiled spiral arteries

By day 24Cuffing visible in perivascular stroma

2 days before menses Increase in polymorphonuclear lymphocytesCollapse of endometrial stroma and start of

menstrual flow

MENSES No more glandular secretion Destruction of corpus luteum

Breakdown of decidua functionalis menses

Prostaglandin (PGF-alpha)

ABNORMAL UTERINE

BLEEDINGNina

WHAT IS ABNORMAL UTERINE BLEEDING?Parameter Normal menstrual

flowAbnormal uterine bleeding

Mean interval between menses

28 days (±7 days) <21 days

Mean duration 4 days >7 days (menorrhagia)

Mean blood loss between 35-80ml (depends on source)

>80ml (hypermenorrhea)

•Excessive uterine bleeding with a demonstrable organic cause•Genital or extragenital

≠ Dysfunctional uterine Bleeding (DUB)

No demonstrable organic cause

AUB FORMSINTERVAL DURATION AMOUNT

OLIGOMENORRHEA Infrequent bleeding 35 days to 6

months scanty

AMENORRHEA Absent No menses for

at least 6 months

Absent

INTERMENSTRUAL or Intercyclic BLEEDING Regular Variable

MENORRHAGIA=HYPERMENORR

HEA Regular >7 days >80 ml

METRORRHAGIA Irregular but infrequent ±prolonged variable

MENO METRORRHAGIA Irregular prolonged excessive

POLYMENORRHEA Regular <21 days

QUANTIFYING MEAN BLOOD LOSS (MBL)• Subjective– Subjective judgment– Number of sanitary pads– Passage of blood clots – Degree of inconvenience

• Objective– Radioisotopic labeling of RBCs– Photometric measurement: most common

• ALKALINE HEMATIN test – very accurate

ETIOLOGY Organic Causes

Systemic DiseasesReproductive Tract Diseases

Dysfunctional Causes

ORGANIC CAUSES Systemic Diseases

1. Blood Dyscrasias 2. Liver Disease3. Thyroid Problems 4. PCOS (Polycystic Ovarian Syndrome) 5. Medications

ORGANIC CAUSES: SYSTEMIC DISEASES1. Blood Dyscracias– Von Willebrand’s disease

Inherited disorder of platelet dysfunction Most common inherited bleeding disorder menorrhagia

– Disorders of blood coagulation • Prothrombin deficiency

– Platelet deficiency• Leukemia• Severe sepsis• Idiopathic thrombocytopenic purpura• Hypersplenism

ORGANIC CAUSES: SYSTEMIC DISEASES2. Liver Disease

Cirrhosis of the liver Excessive bleeding Reduced capacity of the liver to metabolize

estrogens

ORGANIC CAUSES: SYSTEMIC DISEASES3. Thyroid problems

Hypothyroidism Associated with menorrhagia Intermenstrual bleeding

Hyperthyroidism Usually not associated with menstrual

abnormalities Hypomenorrhea Oligomenorrhea Amenorrhea

ORGANIC CAUSES: SYSTEMIC DISEASES4. Polycystic Ovarian Syndrome

(PCOS)– Common cause of abnormal bleeding in the

adolescent– Diagnosis is based upon clinical and

biochemical criteria• Obesity• Menstrual irregularity• Insulin resistance• Hyperandrogenism– Hirsutism – excessive hair growth– Acne– Clitoromegaly

ORGANIC CAUSES: SYSTEMIC DISEASES5. Medications

Hormonal medicationsAnticoagulants, platelet inhibitorsAndrogens, spironolactonesOral and injectable steroidsPsychotropic drugsMay present with menorrhagiaAbnormal intracycle (in between cycles)

bleeding

REPRODUCTIVE TRACT DISEASE Pregnancy-related problems Cervical problems Uterine problems Ovarian tumors Infection Carcinomas

PREGNANCY Always rule out pregnancy in women of

reproductive age!Serum B-HCG test

Ectopic Pregnancy 1st trimester:

Spontaneous Abortion Complete, Threatened, Incomplete

3rd trimester:Abruptio Placenta vs. Placenta Previa

Abruptio Placenta Placenta Previa

Pathophysiology Separation of normally implanted placenta from attachment to uterus.

Abnormal implantation of placenta near or at cervical os.

Symptoms Painful vaginal bleeding that usually does not spontaneously cease.Abdominal pain.

Painless bright red bleeding that often stops within 1-2 hours.

CERVIX Bleeding occurs after coitus Cervicitis

Foul smelling dischargeSpotted cervix

Endocervical PolypRound protruding mass

Cervical CancerAbnormal pap smearMultiple sexual partnersEarly age of coitus

UTERUS Myoma

Subserous IntramuralSubmucous (presents w/ abnormal

bleeding) Endometrial Polyp Endometrial Carcinoma

Transvaginal ultrasound, hysteroscopically guided biopsy, fractional dilatation and curettage

OVARY

Polycystic ovary syndrome (PCOS) Irregular mensesSigns of androgen excess

(hirsutism)Evidence of polycystic ovaries

by ultrasound “string of pearls”

Ovarian cyst or tumor Endometriosis

INFECTION Pelvic Inflammatory

DiseaseAbdominal painVaginal dischargeVaginal bleeding

Fitz-Hugh-Curtis Syndrome

DYSFUNCTIONAL UTERINE BLEEDING (DUB)

No organic, systemic, iatrogenic cause Disruption in menstrual cycle

Ovulatory Anovulatory

•Increase in amount of PGF2α and PGE2•Increase in endometrial pGF2α/PGE2 ratio from midcycle to menses•Promotes vasoconstriction

•No progesterone production•Reduced (vasoconstriction) PGF2α concentration•PGE2 levels are normal•Decreased PGF2α/PGE2 ratio•Promotes vasodilatation•Why medical treatment works•Heavier or more prolonged bleeding

DIAGNOSIS History and Physical Exam

Organic or dysfunctional in originFamily history (ex. blood dyscrasia)

Laboratory Exam & Radiologic TestPregnancy testCBCCoagulation profileUltrasound

ProceduresDilatation and CurettageHysteroscopy

IV. MANAGEMENT -

AUBMac

OUTLINEIV. Management

A. Goals B. Medical C. Surgical

GOALS Establish or maintenance of

hemodynamic stability Correction of acute or chronic anemia

Treat what is pressing at the moment! Return to a pattern of normal menstrual

cycles Prevention of recurrence Prevention of long-term consequences

MEDICAL MANAGEMENT attempted before surgical management

EstrogensProgesteronesNonsteroidal Anti-inflammatory Drugs

(NSAIDs)Antifibrinolytic Agents Gonadotropin-releasing hormone (GnRH)

agonists

ESTROGENS• for acute management• causes rapid growth of endometrial tissue

over denuded and raw surface• promotes platelet adhesiveness• beneficial if the endometrium is thin < 5 mm • after bleeding stops, estrogen is continued,

along with a progestin for another 7 to 10 days

• regularize menses and also to better the skin

PROGESTERONES Stops endometrial growth allows

sloughing off after the cessation of bleeding

Organized sloughing of endometrium after its withdrawal

Stimulates arachidonic acid production Progesterone IUD

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

Prostaglandin synthetase inhibitors Reduces menstrual blood loss by 50%

Mefenamic acid 500 mg 3x a day Ibuprofen 400 mg 3x a dayMeclofenamate sodium 100 mg 3x a dayNaproxen sodium 275 mg 4x a day

Given on the first 3 days of menses

ANTIFIBRINOLYTIC AGENTS • To prevent further bleeding– not primary meds; just ADJUNCT to

decrease blood loss– beneficial to patients who are ovulating and

have menorrhagia• Examples:– ε–Aminocaproic acid (EACA)– Tranexamic acid (AMCA)– Para-Aminomethylbenzoic acid

ANTIFIBRINOLYTIC AGENTS • Side effects:– Nausea– Dizziness– Diarrhea– Headache– Abdominal pain– Allergic manifestation

• Contraindicated in patients with renal failure

GONADOTROPIN-RELEASING HORMONE (GNRH) AGONISTS

Inhibits ovarian steroidogenesis Cessation of menses Allows temporary management of

bleeding and correction of anemia prior to definitive procedure

• Cannot be used for extended treatment because of risk of osteoporosis

SURGICAL MANAGEMENT should be reserved for situations in

which medical therapy has been unsuccessful or is contraindicatedDilatation and curettage (D and C)Endometrial Ablation Hysterectomy

DILATATION AND CURETTAGE (D AND C)

to denude liningDiagnostic and therapeutic Immediate management of severe bleeding

episode Indicated for hypovolemic women who are

actively bleeding and for older women who are at higher risk of having endometrial hyperplasia

ENDOMETRIAL ABLATION

It destroy endometrium Techniques

roller ball technique: burns the lining thermal balloon: scald the liningmicrowave ablation: fry the liningCryoablation

Amenorrhea in 25% to 60%

ENDOMETRIAL ABLATION

Used for women without uterine lesions who are unresponsive to medical therapy

Alternative to hysterectomy, for patients who are not good candidates for surgery

For patients who do not want to keep their reproductive capacity

HYSTERECTOMY Last resort after failed medical

treatment Other indications for hysterectomy

LeiomyomasUterine prolapsedAdenomyosis