1. Menstrual Cycle
Bam

2. Anatomy

3. 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
Understanding the menstrual cycle is critical to the diagnosis and management of many reproductive problems. With the first part of the lecture, it is our objective then to summarize the physiologic and anatomic happenings during the female menstrual cycle

4. Menstrual Cycle
Coordinated interactions between the hypothalamus, anterior pituitary gland, ovaries and uterine endometrium
Normally is a day cycle
Typically lasts for 2 to 6 days
With a ml blood loss

5. RECALL: Menstrual Cycle Physiology
Ovarian cycle
Follicular phase
Luteal phase
Uterine cycle
Proliferative phase
Secretory phase

6. Menstrual Cycle

7. Ovarian Cycle Menarche to menopause
Monthly release of a single mature follicle
Number of oocytes:
Fetus: 6-7million by 20 weeks AOG
Birth: 1-2 million
Puberty: 300k-400k
Ovulation:
A dynamic process that continues from menarche to menopause
Allows for monthly recruitment of follicles, ultimately to release a single mature dominant follicle during ovulation
Mammalian females do not produce oocytes postnatally
Number of oocytes peaks in the fetus at 6 to 7 million by 20 weeks gestation
At birth, only 1 to 2 million oocytes remain
At puberty, only 300,000 – 400,000 oocytes are available
Only 400 to 500 will ultimately be released during ovulation

8. 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
Follicle-stimulating hormone (FSH) is secreted by the anterior pituitary gland. FSH secretion begins to rise in the last few days of the previous menstrual cycle and is highest and most important during the first week of the follicular phase. The rise in FSH levels recruits five to seven tertiary-stage ovarian follicles (this stage follicle is also known as a Graafian follicle or antral follicle) for entry into the menstrual cycle. These follicles then compete with each other for dominance.
FSH induces the proliferation of granulosa cells in the developing follicles, and the expression of luteinizing hormone (LH) receptors on these granulosa cells.
Under the influence of FSH, aromatase and p450 enzymes are activated, causing the granulosa cells to begin to secrete estrogen. This increased level of estrogen stimulates production of gonadotropin-releasing hormone (GnRH), which increases production of LH.[2][3] LH induces androgen synthesis by thecal cells, stimulates proliferation, differentiation, and secretion of follicular thecal cells and increases LH receptor expression on granulosa cells.[3]

9. 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

10. 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

11. Uterine Cycle Types of Decidua Decidua Functionalis Decidua Basalis
Superficial 2/3 of the endometrium
Zone that proliferates and shed each cycle
Two zones:Stratum spongiosum (deeper layer)
Stratum Compactum (superficial and compact layer)
Decidua Basalis
Deepest region of the endometrium
Does not undergo significant monthly proliferation
Source of endometrial regeneration after each menses

12. 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

13. Secretory Phase In a typical 28-day cycle, ovulation occurs on day 14
Within 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
This phase is characterized by the effect of progesterone together with estrogen  these changes are 1) progressive decrease in endometrial cell’s estrogen receptor 2) antagonized estrogen-enduced DNA synthesis and cellular mitosis
glycogen-containing subnuclear vacuoles- first sign of progesterone secretion

14. Secretory Phase By day 21 By day 24 2 days before menses
Progressive edema
Visible long and coiled spiral arteries
By day 24
Cuffing visible in perivascular stroma
2 days before menses
Increase in polymorphonuclear lymphocytes
Collapse of endometrial stroma and start of menstrual flow

15. Menses No more glandular secretion
Destruction of corpus luteum  Breakdown of decidua functionalis  menses
Prostaglandin (PGF-alpha)
In the absence of egg implantation, you have menses
Destruction of corpus luteum and its production of estrogen and progesterone leads to spiral artery vascular spasm  endometrial ischemia and break down of lysosomes which then lead to release of proteolytic enzymes that’s responsible for local tissue destruction
Another factor responsble for the flow of menses prostaglandin which is a potent vasoconstrictor; produces myometrial contractions, decrease in uterine blood flow and physically expel the sloughing endometrial tissue

16. Abnormal Uterine Bleeding
Nina

17. What is abnormal uterine bleeding?
Parameter
Normal menstrual flow
Abnormal 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
Vs. dysfunctional UB – No organic cause
No demonstrable organic cause
≠ Dysfunctional uterine Bleeding (DUB)

18. AUB forms INTERVAL DURATION AMOUNT Oligomenorrhea Infrequent bleeding
35 days to 6 months
scanty
Amenorrhea
Absent
No menses for at least 6 months
IntermenStrual or Intercyclic bleeDing
Regular
Variable
Menorrhagia=
HYPERMENORRHEA
>7 days
>80 ml
METRORRHAGIA
Irregular but infrequent
±prolonged
variable
MENO METRORRHAGIA
Irregular
prolonged
excessive
POLYMENORRHEA
<21 days
Black = Katz Comprehensive Gynecology
Orange = Novaks Gynecology

19. 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

20. ETIOLOGY Organic Causes Dysfunctional Causes Systemic Diseases
Reproductive Tract Diseases
Dysfunctional Causes

21. Organic Causes Systemic Diseases Blood Dyscrasias Liver Disease
Thyroid Problems
PCOS (Polycystic Ovarian Syndrome)
Medications

22. Organic Causes: Systemic Diseases
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
Von Willebrand factor
Major adhesion molecule that tethers the platelet to the exposed subendothelium  platelet adhesion  platelet aggregation

23. Organic Causes: Systemic Diseases
2. Liver Disease
Cirrhosis of the liver
Excessive bleeding
Reduced capacity of the liver to metabolize estrogens
Site of synthesis and clearance of most procoagulant and natural anticoagulant proteins and of essential components of the fibrinolytic system.
Liver failure
- Associated with a high risk of bleeding due to deficient synthesis of procoagulant factors and enhanced fibrinolysis

24. Organic Causes: Systemic Diseases
3. Thyroid problems
Hypothyroidism
Associated with menorrhagia
Intermenstrual bleeding
Hyperthyroidism
Usually not associated with menstrual abnormalities
Hypomenorrhea
Oligomenorrhea
Amenorrhea

25. Organic Causes: Systemic Diseases
4. 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
Polycystic ovary syndrome (PCOS). PCOS is a condition in which the ovaries become filled with tiny cysts and enlarge. The problem occurs when the pituitary gland produces too much of a hormone called luteinizing hormone (LH). The hormonal imbalance that results creates an overabundance of uterine lining that makes bleeding irregular.

26. Organic Causes: Systemic Diseases
5. Medications
Hormonal medications
Anticoagulants, platelet inhibitors
Androgens, spironolactones
Oral and injectable steroids
Psychotropic drugs
May present with menorrhagia
Abnormal intracycle (in between cycles) bleeding

27. Reproductive Tract Disease
Pregnancy-related problems
Cervical problems
Uterine problems
Ovarian tumors
Infection
Carcinomas

28. 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

29. 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.

30. Cervix Bleeding occurs after coitus Cervicitis Endocervical Polyp
Foul smelling discharge
Spotted cervix
Endocervical Polyp
Round protruding mass
Cervical Cancer
Abnormal pap smear
Multiple sexual partners
Early age of coitus

31. Uterus Myoma Endometrial Polyp Endometrial Carcinoma Subserous
Intramural
Submucous (presents w/ abnormal bleeding)
Endometrial Polyp
Endometrial Carcinoma
Transvaginal ultrasound, hysteroscopically guided biopsy, fractional dilatation and curettage

32. Ovary Polycystic ovary syndrome (PCOS) Ovarian cyst or tumor
Irregular menses
Signs of androgen excess (hirsutism)
Evidence of polycystic ovaries by ultrasound
“string of pearls”
Ovarian cyst or tumor
Endometriosis

33. Infection Pelvic Inflammatory Disease Abdominal pain Vaginal discharge
Vaginal bleeding
Fitz-Hugh-Curtis Syndrome

34. 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

35. Diagnosis History and Physical Exam Laboratory Exam & Radiologic Test
Organic or dysfunctional in origin
Family history (ex. blood dyscrasia)
Laboratory Exam & Radiologic Test
Pregnancy test
CBC
Coagulation profile
Ultrasound
Procedures
Dilatation and Curettage
Hysteroscopy

36. IV. Management - AUB
Mac

37. Outline
IV. Management
A. Goals
B. Medical
C. Surgical

38. 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

39. Medical Management attempted before surgical management Estrogens
Progesterones
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Antifibrinolytic Agents
Gonadotropin-releasing hormone (GnRH) agonists

40. 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
causes rapid growth of endometrial tissue over denuded and raw surface
stabilizes it
for patchy (anovulatory) bleeding – give estrogen to regenerate the lining
2 forms of estrogen: oral or IV with SAME efficacy  both within 24 hours of action
beneficial if the endometrium is thin < 5 mm
conjugated equine estrogen, 10 mg per day in 4 divided doses
bleeding usually ceases after 24 hours
after bleeding stops, estrogen is continued, along with a progestin for another 7 to 10 days
withdrawal bleed
to allow complete and even sloughing of the endometrium
maintain cycles using OCPs

41. 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
Stops endometrial growth  allows sloughing off after the cessation of bleeding
After 10 days, it promotes sloughing off
In anovulatory cycles, in the absence of progesterone, what is decreased? PGF2alpha
Supports and organizes the endometrium
Organized sloughing of endometrium after its withdrawal
Allows rapid cessation of bleeding
Stimulates arachidonic acid production
Increased PGF2α /PGE2 ratio
Progesterone IUD - medicated IUD
Local action of progesterone in the uterus  where it’s needed
Extended use up to 5 years
80% reduction in menstrual blood loss
Effective in women with ovulatory DUB, fibroids, adenomyosis

42. 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 day
Meclofenamate sodium 100 mg 3x a day
Naproxen sodium 275 mg 4x a day
Given on the first 3 days of menses
Prostaglandin synthetase inhibitors
Inhibit biosynthesis of cyclic endoperoxides which convert arachidonic acid to prostaglandins
Blocks the action of prostaglandins by interfering directly at their receptor sites
Reduces menstrual blood loss by 50%
Mefenamic acid 500 mg 3x a day
Ibuprofen 400 mg 3x a day
Meclofenamate sodium 100 mg 3x a day
Naproxen sodium 275 mg 4x a day
Given on the first 3 days of menses
efficacious even before period starts  bleeding would be less and pain-free

43. 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
To prevent further bleeding
Not primary meds; just ADJUNCT to decrease blood loss
Beneficial to patients who are ovulating and have menorrhagia
Para-Aminomethylbenzoic acid
Potent inhibitors of fibrinolysis
Decreases blood loss among women who experience menorrhagia and ovulatory

44. Antifibrinolytic Agents
Side effects:
Nausea
Dizziness
Diarrhea
Headache
Abdominal pain
Allergic manifestation
Contraindicated in patients with renal failure
To prevent further bleeding
Not primary meds; just ADJUNCT to decrease blood loss
Beneficial to patients who are ovulating and have menorrhagia
Para-Aminomethylbenzoic acid
Potent inhibitors of fibrinolysis
Decreases blood loss among women who experience menorrhagia and ovulatory

45. 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
Put patient in pseudomenopausal state ~ no more cycle, won’t have menses
Not curative or permanent effort – only temporary relief
For Jehovah’s witness, give GnRH agonist and iron (to have extra reserves when they undergo surgery)
Can’t give this for a long time because after 3 months, they’re in pseudomenopausal state, they feel the symptoms (hot flushes, decrease libido, decrease lubrication during intercourse, etc)

46. Surgical Management
should be reserved for situations in which medical therapy has been unsuccessful or is contraindicated
Dilatation and curettage (D and C)
Endometrial Ablation
Hysterectomy

47. Dilatation and curettage (D and C)
to denude lining
Diagnostic 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
Diagnostic - send for histopathological exam (ex. Polyp or carcinoma)

48. Endometrial Ablation It destroy endometrium Techniques
roller ball technique: burns the lining
thermal balloon: scald the lining
microwave ablation: fry the lining
Cryoablation
Amenorrhea in 25% to 60%
destroy endometrium
Techniques:
Roller ball technique - burn the lining
Thermal balloon - scald the lining
Microwave ablation - fry the lining
Cryoablation
Done for patients who are premenopausal, postemenopausal
Permanent effect! Not done for reproductive age group
Loses function but uterus is still there (compared to a hysterectomy)
Amenorrhea in 25% to 60%
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

49. 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
destroy endometrium
Techniques:
Roller ball technique - burn the lining
Thermal balloon - scald the lining
Microwave ablation - fry the lining
Cryoablation
Done for patients who are premenopausal, postemenopausal
Permanent effect! Not done for reproductive age group
Loses function but uterus is still there (compared to a hysterectomy)
Amenorrhea in 25% to 60%
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

50. Hysterectomy Last resort after failed medical treatment
Other indications for hysterectomy
Leiomyomas
Uterine prolapsed
Adenomyosis
Last resort after failed medical treatment
For people who have fibroids, adenomyosis or polyp  depends on the depth of the problem
Only if patient completed their family size and she has a myoma or ovarian tumor ~ do hysterectomy
With other indications for hysterectomy
Leiomyomas
Uterine prolapsed
Adenomyosis  for hysterectomy