Dub gynae seminar

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dysfunctional uterine bleeding

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  • 1. This stasis is initiated by constriction of the coiled arteries. 2. This is because there is usually a lack of orderly exposure to estrogen and progesterone.
  • 1. Platelets first adhere to the subendothelium of the damaged vessel wall. Occlusion of the site of injury by aggregation Initiates release of proaggregatory compounds such as thromboxane which accelerates aggregation and initiates coagulation This is an important interaction because vWF serves as the bridge between platelets and the damaged endothelium. This is important when considering DUB in perimenarchal adolescents. 2. Vascular occlusion by both methods is never total so blood leakage occurs until endometrial regeneration is completed.
  • Normal menstrual bleeding due to postovulatory estrogen-progesterone withdrawal is stable and precisely regulated. It is generally agreed that the normal menstrual cycle will be between 24 and 35 days in length, measured from the first day of menstrual flow of once cycle to the first day of the next cycle. The usual duration of menstrual flow is 4-6 days, but many women may have a flow for as little as 2 days or as much as 7 days. Normal menstruation also tends to be consistent in the amount of blood that is lost. The usual volume of menstrual blood loss is 30 mL, and a menstrual flow greater than 80 mL is considered abnormal. In practice, however, it is virtually impossible for either the patient or her clinician to estimate menstrual volume of blood loss accurately.
  • 1. Diagnosis arrived at after pregnancy, benign and malignant dz of the reproductive tract, systemic illness, and iatrogenic causes are ruled out.
  • 1. This gives rise to continuously proliferating endometrium which may outgrow its blood supply or lose nutrients with varying degrees of necrosis. Asynchronous development of stroma, glands, and blood vessels as well as overdevelopment of Golgi-lysosomal complexes may occur. Uniform slough to the basalis layer does not occur, which leads to excessive and irregular uterine blood flow. Overactivity of the fibrinolytic system may be present as well, but this relationship is not well studied.
  • Medical management is the preferred initial treatment, especially if the woman desires future fertility and there is no associated pelvic pathology Selection of treatment depends primarily on whether it is used to stop acute heavy bleeding or to control recurrent episodes
  • Acute bleeding can be managed by estrogen which promotes rapid regrowth of the endometrium over denuded epithelial surfaces. It also causes proliferation of the endometrial ground substance and stabilizes lysosomal membranes. There are no studies that indicate IV estrogen acts quicker or is more effective than high dose oral estrogen. After treatment is finished, all medications are stopped and the patient is allowed to have withdrawal bleeding. This can be heavy so warn patients, but it is rarely prolonged
  • A third option is high dose estrogen-progestin therapy This is the preferred method for many physicians One study suggested progestins may not be as successful because simultaneous use of a progestin can inhibit the synthesis of estrogen receptors and increase Estradiol dehydrogenase in the endometrial cell. The actions of progestins serving to interfere with the rapid growth-promoting effects of unopposed high dose estrogen. Once the bleeding episode has been controlled, you can continue standard dose OCP regimens using one tablet per day for 21 days or medroxyprogesterone acetate, 10 mg each day for the first 10 days of each month.
  • Because fibrinolysis plays an important role in hemostasis of the bleeding menstrual endometrium, the use of antifibrinolytics has been evaluated in the treatment of women with AUB. In particular, tranexamic acid (TA) and its precursors have been found to be particularly effective in reducing menstrual blood loss. In clinical trials, TA reduced menstrual blood loss by 45% to 54%. In light of such favorable data, it is easy to see why antifibrinolytics are a mainstay for treatment of ovulatory AUB in most of the world, but it is puzzling to understand why these agents are rarely administered in North America. One author proposed that North American physicians may be mistakenly concerned about an increased risk of thromboembolic events in women receiving antifibrinolytics. This concern is largely unwarranted, and one retrospective study in a large cohort of women at enhanced risk for thromboembolic disease failed to show an associated between administration of TA and thromboembolic events.
  • The progesterone IUD has been used successfully to treat women with ovulatory DUB. Bergqvist et al. Reported a decrease in MBL from an average of 138ml to 49 ml in 12 women with one year of IUD usage. Milson et al. used the levonorgestral IUD to treat DUB and reported an 80% reduction in the MBL at 3 months and 100% reduction at the end of the first year of use. It has a duration of action of 7 years or more.
  • Acute bleeding episodes are best controlled by high dose estrogen therapy; recurrent episodes by progestin therapy. Progestin therapy may be the first choice for chronic anovulatory DUB and it has been used to manage ovulatory DUB. However MBL usually is reduced by only 15% or less in these patients. There are other options for patients with ovulatory DUB. NSAIDs Prostacyclin is a vasodilator that inhibits platelet aggregation. The precise mechanism is unclear as NSAIDS generally inhibit thromboxane formation as well. Ideally, to control bleeding, inhibiting the synthesis of prostacyclin without altering thromboxane formation is desired. Currently no NSAID possesses this unique activity. Naproxen, ibuprofen, mefenamic acid, and meclogenamite sodium all studied. Most effective in women with the greatest amount of pretreatment blood loss. (decrease 20 to 50%) Treatment results in a sustained reduction in blood loss and an increase in ferritin indicating increased iron stores Usually added to hormonal therapy to achieve a greater decrease in blood loss.
  • The usual causes of AUB vary over a woman’s lifetime, as shown on this slide. Anovulatory uterine bleeding and irregular periods are common during the first few years after menarche. This primarily due to immaturity of the HPO axis, which renders it incapable of naturally responding to estrogen with a LH surge. Regular ovulatory bleeding is usually established within 2-3 years after menarche, and persistence of irregular periods beyond this time warrants further investigation. Coagulation disorders are not uncommon in adolescent women. Such disorders may be noted by unusual bleeding from the gums, prolonged bleeding after minor cuts, and easy bruising. In one study, 19% of adolescent patients evaluated for AUB were found to have coagulation disorders. This incidence was even higher if the hemoglobin was <10 g/dL (in approximately 25%) or if hospitalization was required (approximately 50%). Coagulation disorders in the adolescent may include von Willebrand disease, thalassemia major, Fanconi anemia, prothrombin deficiency, and other disorders. In addition, psychosocial stress, including that associated with eating disorders, may contribute to irregular periods in adolescents. It is common for women of reproductive age to suffer from occasional and self-limited AUB. The reasons are unclear, but the process of normal menstruation is complex and easily deranged. Pregnancy and related complications are a common cause of bleeding in women of reproductive age and must not be overlooked. Sexually transmitted diseases can cause pelvic infections associated with vaginal bleeding. Abnormal bleeding can also be caused by endometrial polyps or submucous myomas. Although the cause of abnormal bleeding in women of reproductive age is often benign, malignancy is always a possibility, particularly if the woman is obese or has a history of chronic oligoovulation or anovulation. Anovulatory uterine bleeding is also common in women of reproductive age and may be due to various causes. By far, the most common endocrinopathy is PCOS, affecting 6% of all women of reproductive age. Perimenopausal women have an increased incidence of anovulatory cycles due to depletion of the store of ovarian oocytes. With aging, endometrial hyperplasia, cancer, polyps, or submucosal fibroids become more prevalent, and pathologic endometrial tissue should be suspected in the perimenopausal woman with abnormal bleeding. Risk factors such as obesity, hypertension, diabetes mellitus, and chronic anovulation are significantly associated with cancer in perimenopausal women. Any vaginal bleeding in menopausal women should be considered abnormal. Up to 10% of these women have been found to have cancer. A large percentage of postmenopausal women (up to 80%) may have endometrial pathology such as hyperplasia, polyps, or submucous fibroids, particularly if the bleeding occurs after 1 year of amenorrhea or persists with hormone replacement therapy.
  • Dub gynae seminar

    1. 1. Roziana Ramli MD, Mmed(OBGYN) HSNZ
    2. 2. •Estrogen causes increased blood flow to the endometrium •Normal menses results from fluctuations in the circulating levels of estrogen and progesterone.
    3. 3. NORMAL MENSES • Estradiol and progesterone levels decrease several days prior to the onset of menses. • Endometrial blood flow decreases • Endometrial height decreases and vascular stasis occurs. • Tissue ischemia occurs. • Arterial relaxation • Sloughing of the endometrium. • Uterine bleeding occurs
    4. 4. CESSATION OF MENSES • Two main mechanisms: • Formation of the platelet plug • important in the functional endometrium • Prostaglandin dependent vasoconstriction • important in the basalis layer
    5. 5. CHARACTERISTICS OF NORMAL MENSES
    6. 6. NORMAL MENSTRUATION • Life Cycle • Menarche • 5-7 years of relatively long cycles • Increasing regularity of cycles • In the 40’s cycles begin to increase in length with increasing episodes of anovulation (2-8 years “perimenopause”) • Menopause (average age = 51) • Characteristics • By age 25, 40% of women have cycles between 25-28 days • Age 25-35, 60% of women have 25-28 day cycles. • Overall 15% have 28 day cycles • 5% have cycles < 21days • 9% have cycles >35 days
    7. 7. •Dysfunctional uterine bleeding (DUB) is defined as ABNORMAL uterine bleeding that occurs in the absence of any pathology, pregnancy or medical illnesses. •Diagnosis of EXCLUSION •Abnormal bleeding: (excessively heavy or light, prolonged, frequent, or random) •DUB occurs most often shortly after menarche and at the end of the reproductive years. –20% of cases are adolescents –50% of cases in 40-50 year olds DUB
    8. 8. • Two types: anovulatory and ovulatory • Most women with DUB do not ovulate (ANOVULATION) • Most common: either ESTROGEN BREAKTHROUGH bleeding OR ESTROGEN WITHDRAWAL bleeding • Ovulatory DUB occurs most commonly after the adolescent years and before the perimenopausal years. • Incidence in these patients may be as high as 10% WHAT WENT WRONG IN DUB?
    9. 9. ESTROGEN BREAKTHROUGH BLEEDING Anovulatory cycles: • NO corpus luteum, therefore NO progesterone • UNOPPOSED estrogen causes continuous endometrial proliferation • endometrium may then OUTGROW its blood supply resulting in areas of necrosis • endometrial shedding will be irregular manner without uniform sloughing of the basalis layer • subsequent endometrial healing: irregular and dyssynchronous • RESULT: EXCESSIVE AND IRREGULAR UTERINE BLEEDING
    10. 10. ESTROGEN WITHDRAWAL BLEEDING • Frequently: at the end of reproductive life. • SHORT CYCLE due to aberrant follicular recruitment • LESS ESTRADIOL causing insufficient endometrial proliferation and irregular menstrual shedding. • RESULT: LIGHT, IRREGULAR SPOTTING
    11. 11. OVULATORY DUB • DUB without any attributable anatomic, organic, or systemic cause BUT associated with regular ovulation (uncommon) • Regular withdrawal menses every 24-35 days—BUT excessive blood loss • Loss of local endometrial hemostasis • ↑ Ratio of PGE2α : PGF2α • ↑ Level of PGI2 • ↑ Fibrinolytic activity
    12. 12. SO WHAT?? • (Too MUCH): Ward admission, fluid management, transfusion, Rx • (Too FREQUENT): Iron deficiency anemia (30%). Mainly adolescents (20% might have a disorder of hemostasis) • (Too LONG): Chronic unopposed estrogenic stimulation of the endometrial lining increases the risk of both endometrial hyperplasia and endometrial carcinoma. (1-2% of women with improperly managed anovulatory bleeding) • (Too BAD): Infertility associated with chronic anovulation,
    13. 13. WHAT DO WE DO NEXT??
    14. 14. PHYSICAL EXAMINATION •Assess hemodynamic stability (vital signs) and proceed with evaluation of the following: • Obesity (BMI) • Signs of androgen excess (hirsutism, acne) • Goitre or manifestations of hyper/hypothyroidism • Galactorrhea (may suggest hyperprolactinemia) • Ecchymosis, purpura (signs of bleeding disorder) • Signs of anemia or chronic blood loss
    15. 15. • VAGINAL EXAMINATION and Pap smear • The hallmark of DUB: -ve pelvic examination despite the clinical history • Rule out uterine fibroids or polyps • Rule out endometrial hyperplasia or carcinoma PHYSICAL EXAMINATION
    16. 16. INVESTIGATIONS (CASE TO CASE BASIS) • UPT / HCG • Complete blood count . • Pap smear • Endometrial sampling • Thyroid function tests and prolactin • Coagulation factors • Other hormone assays as indicated for PCOS, 21 hydroxylase deficiency, or ovarian or adrenal tumors • Ultrasound • Women in menopausal transition usually can be followed without an extensive hormonal evaluation.
    17. 17. HOW TO TREAT DUB?
    18. 18. • NSAID’s • estrogens, progestins, or both • antifibrinolytic agents • GnRH agonists TREATMENT OF DUB Medical management Surgical management • Ablative therapy • Endometrial resection • Hysterectomy
    19. 19. TREATMENT OF DUB ACUTE BLEEDING • Estrogen therapy promotes rapid regrowth of the endometrium over denuded epithelial surface, exerts vasospastic action on capillary bleeding by affecting the level of fibrinogen, factor IV, and factor X in blood, as well as platelet aggregation and capillary permeability. • Oral conjugated equine estrogens • 10mg a day in four divided doses • treat for 21 to 25 days • medroxyprogesterone acetate, 10 mg per day for the last 7 days of the treatment estrogen induces formation of progesterone receptors, making subsequent treatment with progestins more effective. • if bleeding not controlled, consider organic cause OR • 25 mg IV every 4 to 12 hours for 24 hours, then switch to oral treatment as above. • Bleeding usually diminishes within 24 hours
    20. 20. TREATMENT OF DUB ACUTE BLEEDING • Acute bleeding (continued) • High dose estrogen-progestin therapy • use combination OCP’s containing <=35 mics of ethinylestradiol • four tablets per day • treat for one week after bleeding stops • may not be as successful as high dose estrogen treatment
    21. 21. ANTI-FIBRINOLYTICS • Fibrinolysis-endometrial hemostasis • Tranexamic acid (TA) and precursors effective in reducing menstrual blood loss (54%) • Concern about thromboembolic events may be unwarranted based on retrospective data
    22. 22. PROGESTINS • Drug of choice in anovulatory DUB. • Can be used alone after acute bleeding episode, in pts with adequate amounts of endogenous estrogen to cause endometrial growth. • Progestin therapy in adolescents produces regular cyclic withdrawal bleeding until positive feedback system matures. • Occasional anovulatory bleeding that is not profuse or prolonged can be treated with progestins.
    23. 23. PROGESTINS • Progestins inhibit estrogen receptor replenishment and activate 17- OHsteroid dehydrogenase in endometrial cells, converting estradiol to the less active estrone. • Stops endometrial cell proliferation, allowing organized sloughing of cells after withdrawal.
    24. 24. PROGESTINS • Synthetic progestins have an antimitotic effect, allowing the endometrium to become atrophic if administered continuously (effective in cases of endometrial hyperplasia) • Some perimenopausal patients will not respond well to progestin therapy because of an inherent estrogen deficiency. • Also, patients with thin, denuded endometrium occurring after several days of chronic bleeding might require induction of new endometrial proliferation by estrogen therapy first.
    25. 25. PROGESTIN • Recurrent bleeding episodes • Progesterone releasing IUD (Levonorgestrel IUD) • Avoids systemic side effects • 80% reduction of blood loss at 3 months • 100% reduction at 1 year • found to be superior to antifibrinolytic agents and prostaglandin synthetase inhibitors
    26. 26. COCP • Oral contraceptive pills (OCPs) suppress endometrial development, reestablish predictable bleeding patterns, decrease menstrual flow, and lower the risk of iron deficiency anemia. • Acute episodes of heavy bleeding suggest an environment of prolonged estrogenic exposure and buildup of the lining. • Prolonged uterine bleeding suggests the epithelial lining of the cavity has become denuded over time. In this setting, a progestin is unlikely to control bleeding. Estrogen alone will induce return to normal endometrial growth rapidly • OCPs can be used effectively in a cyclic or continuous regimen to control DUB.
    27. 27. COCP • Bleeding usually is controlled within the first 24 hours, as the overgrown endometrium becomes pseudodecidualized. • Contraceptive pills containing estrogen and progestin have been advocated for patients with DUB who desire contraception. • When progestin is present it takes longer to induce endometrial proliferation. • In long-term management of DUB, combination oral contraceptives are very effective.
    28. 28. • Cyclooxygenase inhibitor, inhibits prostacyclin formation(accelerates platelet aggregation and initiates coagulation) • Administered t/out the duration of bleeding/first 3/7 of menses • Most effective: menorrhagia in ovulatory cycles, not effective for the DUB • Used for relief of mild to moderate pain. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
    29. 29. GNRH AGONISTS • Reduce concentration of GnRH receptors in the pituitary • Initial gonadotropin release associated with rising estradiol, gonadotropin levels fall to castrate levels, with resultant hypogonadism. • Very effective in inducing amenorrhea • Prolonged therapy: osteoporosis and other postmenopausal side effects • Expensive, not used as a first line approach but for short-term relief, particularly in patients with renal failure or blood dyscrasia.
    30. 30. SURGICAL MANAGEMENT •Surgical measures including Hysterectomy: when medical therapy has failed, symptomatic anemia, and a disruption in the quality of life from persistent, unscheduled bleeding. •D&C is an appropriate diagnostic (not therapeutic as not shown to be efficacous) step in a patient who fails to respond to hormonal management. • The addition of hysteroscopy will aid in the treatment of endometrial polyps or the performance of directed uterine biopsies.
    31. 31. SURGICAL MANAGEMENT • Endometrial ablation: alternative to avoid hysterectomy or pt not fit for major surgery. • Ablation techniques: laser, rollerball, resectoscope, or thermal destruction • Pretreat with agent to thin the endometrium. • Shorter recovery time. • May fail treatment • HYSTERECTOMY
    32. 32. ESSENTIAL UPDATE: NEW ACOG TREATMENT GUIDELINES FOR ABNORMAL UTERINE BLEEDING •Either low-dose COCP or progestin therapy is generally effective in women aged 19-39 years; high-dose estrogen may benefit patients with an extremely heavy menstrual flow or hemodynamic instability •Medical treatment for women >=40 can, prior to menopause, consist of cyclic progestin therapy, low-dose oral contraceptive pills, the LNGIUS, or cyclic hormone therapy •If medical therapy fails, patients should undergo further testing (eg, imaging or hysteroscopy) •An in-office endometrial biopsy is preferable to (D&C) when examining a patient for endometrial hyperplasia or cancer •If medical therapy fails in a woman in whom childbearing is complete, hysterectomy may be considered
    33. 33. •Surgery only in patients in whom medical treatment has failed, cannot be tolerated, or is contraindicated •Endometrial ablation is not acceptable as a primary therapy, because the procedure can hamper the later use of other common methods for monitoring the endometrium •Regardless of patient age, progestin therapy with the levonorgestrel intrauterine device should be considered; contraceptives containing a combination of estrogen and progesterone also provide effective treatment •Low-dose combination hormonal contraceptive therapy (20-35 μg ethinyl estradiol) is the mainstay of treatment for adolescents up to age 18 years ESSENTIAL UPDATE: NEW ACOG TREATMENT GUIDELINES FOR ABNORMAL UTERINE BLEEDING
    34. 34. USUAL CAUSES OF BLEEDING THROUGHOUT A WOMAN’S LIFETIME
    35. 35. • Must rule out Hyperplastic Endometrium/Ca • Minimum req: ultrasound for endometrial thickness and pelvic pathology • ENDOMETRIAL SAMPLING • Unlikely cancerous, Unlikely pelvic pathology related • Treat only when DUB disturbs life (pt’s wishes, menses TOO LONG, TOO MUCH, TOO FREQUENT) • REASSURANCE TAKE HOME Adolescent Older adult
    36. 36. • Reassure: • Menses at least 3-4x/year • Counsel: • Fertility • DM,IHD • Ca endometrium • Use ovulation induction drugs to prevent anovulation PCOS? FERTILITY ISSUES?
    37. 37. THANK YOU ….

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