The abbreviation AUB refers to abnormal uterine bleeding, The bleeding may be either excessive or reduced in frequency and volume. AUB is inclusive of many possible underlying causes. It is reflective of a symptom or sign with many possible etiologic bases. When AUB cannot be attributed to an anatomic, organic, or systemic lesion or disease, it has traditionally been referred to as dysfunctional uterine bleeding (DUB). However, “anovulatory uterine bleeding” is a more descriptive term, reflecting the fact that many of these women suffer from chronic anovulation or oligoovulation. Anovulatory uterine bleeding is a relatively narrow and exclusive term; it is a diagnosis made by excluding all other possible causes, such as leiomyomas, polyps, malignancy, coagulopathies, etc. Anovulatory uterine bleeding is usually discussed in terms of an endocrinologic derangement associated with anovulation in the absence of the influence of cyclic estrogen and progesterone upon the endometrium.
The impact of abnormal uterine bleeding on the patient is significant, resulting in diminished quality of life. Excessive and unpredictable uterine bleeding may cause the woman much anxiety and interfere with her social activities, employment, sexuality, and fertility. Excessive bleeding may also result in iron-deficiency anemia and attendant fatigue.
Approximately one-third of all outpatient gynecologic visits annually are for the evaluation of AUB. Among adolescents, AUB is the most frequent cause of urgent admission to the hospital. Worldwide, AUB affects about 50% of menstruating women. The majority of cases of AUB occur in the 5 to 10 years prior to menopause or after menarche, when the ovaries are in an unstable responsive state.
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.
In addition to the terms abnormal uterine bleeding (AUB) and anovulatory uterine bleeding, several other terms have traditionally been associated with menstruation. These traditional terms are shown on this slide.
Normal human menstrual function is dependent upon an intricate series of hormonal actions linking the neuronal nuclei of the hypothalamus to the pituitary gland, which subsequently stimulates the ovaries to produce sex-steroids that act upon the endometrial lining of the uterus. This pathway is known as the hypothalamic-pituitary-ovarian (HPO) axis. Along the HPO axis there is a complex system of positive and negative feedback signals that allow the end-organs to communicate with the higher centers. Late in the menstrual cycle, the arcuate nucleus of the hypothalamus generates carefully timed pulses of gonadotropin-releasing hormone (GnRH), which stimulates cells of the anterior pituitary gland to produce follicle-stimulating hormone (FSH) and, to a smaller extent, luteinizing hormone (LH). In the right proportion, FSH will recruit a cohort of ovarian follicles for development. At the same time, pituitary FSH/LH circulates back to the hypothalamus, exerting a negative feedback control on pulses of GnRH to limit recruitment of additional follicles. From this cohort of ovarian follicles, a dominant follicle is selected by the seventh day of the next menstrual cycle. This one follicle matures and proceeds to ovulation, usually on the 14 th day. While maturing, the dominant follicle secretes increasing amounts of estradiol, which initiates ovulation through positive feedback by causing a massive and sudden release of LH from the pituitary (LH surge). In the endometrial lining, rising levels of estradiol produced by the follicle stimulate proliferative growth of epithelial and stromal elements. This phase of growth is termed the proliferative phase and, under the influence of estradiol, the endometrium grows in height and becomes rich in progesterone-receptors. Once the LH-surge occurs, the ovum is released, and the follicle collapses to become the corpus luteum. The corpus luteum is a sub-organ within the ovary with a lifespan of approximately 10 days that produces large amounts of progesterone. Under this progestagenic influence the endometrium enters the secretory phase. Endometrial growth stops, and the stroma becomes more compact and stable. The glandular epithelium develops glycogen vacuoles to prepare for implantation of an embryo. If implantation fails to occur, then the corpus luteum undergoes involution and production of progesterone is withdrawn. Upon progesterone-withdrawal, the endometrial lining collapses, resulting in menstruation. Once levels of progesterone and estradiol decline, the hypothalamus and pituitary escape the influence of negative feedback, and FSH values rise again for the subsequent cycle.
Hormonal, Ovarian, endometrial, and basal body temperature changes and relations throughout the normal menstrual cycle. (From Carr BR, Wilson JD. Disorders of the ovary and female reproductive tract. In: Braunwald E, Isselbacher KJ, Petersdorf RG, et al, eds. Harrison's Principles of Internal Medicine . 11th ed. New York: McGraw-Hill, 1987: 1818-1837.
Anovulatory uterine bleeding is usually caused by one of three hormonal imbalances: estrogen-withdrawal, estrogen-breakthrough, or progesterone-breakthrough. Bleeding due to estrogen-withdrawal results from an unexpected decrease in levels of estrogen. The causes are often iatrogenic, such as cessation of estrogen therapy. This type of bleeding is usually isolated, self-limited, and not likely to recur if levels of estrogen remain low. Some women experience recurrent midcycle bleeding or spotting just before ovulation during the normal menstrual cycle due to a pronounced dip in levels of estradiol at that time. Anovulatory women may also experience periodic fluctuation of levels of estradiol that results in withdrawal bleeding, but anovulatory uterine bleeding is usually caused by estrogen breakthrough. Estrogen-breakthrough bleeding occurs with chronic and unopposed estrogenic stimulation of the endometrium. The classic example is observed in women with anovulation due to polycystic ovarian syndrome (PCOS). Without ovulation, there is no influence from progesterone on the proliferating endometrium. Eventually, the unabated proliferation leads to insufficient structural support, and parts of the endometrium slough at irregular, unpredictable intervals, causing bleeding. The bleeding is often not only irregular, but excessive. Progesterone-breakthrough bleeding occurs when the progesterone-to-estrogen ratio is relatively high. This usually occurs with the use of progesterone-only contraceptives. The endometrium atrophies and ulcerates due to the lack of estrogen and is prone to frequent irregular bleeding.
Abnormal uterine bleeding without any attributable anatomic, organic, or systemic cause but associated with regular ovulation is not a common finding. It is loosely named ovulatory AUB and is generally observed with regular progesterone-withdrawal menses every 24-35 days but with excessive blood loss. This uncommon form of ovulatory AUB occurs when there is loss of local endometrial hemostasis. The woman experiences regular and predictable menstruation, and usually retains existing premenstrual symptoms associated with ovulation such as dysmenorrhea, midcycle pain, breast tenderness, bloating, and irritability. Although exact mechanisms of ovulatory AUB are unknown, possible causes have been proposed. The ratio of PGE 2 : PGF 2 and level of PGI 2 are increased in women with menorrhagia. In addition, fibrinolytic activity is significantly elevated in most women with ovulatory AUB.
Anovulatory uterine bleeding is defined as noncyclic menstrual blood flow that may range from spotty to excessive, is derived from the uterine endometrium, and is due to anovulatory production of sex-steroids, specifically excluding an anatomic lesion. It is typically caused by estrogen-withdrawal or estrogen-breakthrough bleeding and occurs in the absence of the cyclic production of ovarian progesterone. This may occur with the sustained levels of unopposed estrogen associated with PCOS, obesity, immaturity of the hypothalamic-pituitary-ovarian (HPO) axis, and late anovulation (eg, women in their late 30s and 40s). The mechanisms involved in anovulatory uterine bleeding are uniquely different from those with ovulatory AUB. In the absence of cyclical progesterone and periodic menstruation, the endometrium hyperplastic without the necessary structural support. The hyperplastic, unstructured endometrium is fragile and prone to localized breakage and bleeding. As one site of breakage heals, a different site may break down and bleed. The resulting bleeding is usually erratic—in both timing and volume of blood loss—with alternating periods of amenorrhea. In addition, local hemostatic mechanisms are hampered due to the absence of cyclical progesterone and the associated synthesis of prostaglandins and other substances necessary to control 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.
The most likely causes of AUB and pathologic findings in the endometrium relate to the woman’s reproductive age. Anovulatory uterine bleeding is a diagnosis of exclusion, and other possible causes of uterine bleeding must be ruled out before establishing a diagnosis of anovulatory uterine bleeding. This slide summarizes possible causes of abnormal uterine bleeding. Complications from pregnancy may include intrauterine pregnancy, ectopic pregnancy, spontaneous abortion, gestational tophoblastic disease, placenta previa, and retained products of conception. Infections may include cervicitis, endometritis, and pyosalpinx. Trauma, such as lacerations/abrasions or foreign bodies, and gynecologic cancers can also cause bleeding. Benign pelvic pathology that may cause bleeding includes submucosal fibroids (seen on next slide), cervical polyps, endometrial polyps (seen on following slide), leiomyoma, adenomyosis, and endometrial hyperplasia. Many systemic disease may cause abnormal uterine bleeding, including hepatic disease, renal disease, coagulopathies, endocrinopathies, thrombocytopenia, and leukemia. Certain medications can cause AUB, including hormones (OCs, estrogen, progesterone), steroids, and dilantin. Intrauterine devices (IUDs), stress (emotional, excessive exercise), and cigarette smoking may also cause abnormal uterine bleeding.
This slide shows a transvaginal saline infusion sonography (SIS) of a submucosal fibroid. The fibroid can be clearly delineated and seen to be protruding into the endometrial cavity.
This slide shows an SIS image of endometrial polyps. Slide courtesy of Linda Darlene Bradley, MD.
This slide shown an algorithm for the evaluation of AUB in premenopausal women. If the reproductive-age woman is not pregnant and has a normal physical examination, then anovulatory uterine bleeding is the most likely diagnosis. For women of reproductive age, the first step is to determine whether the bleeding is anovulatory or ovulatory. Menstrual cycles can be quite variable. Patients can have alternating anovulatory cycles interspersed with ovulatory cycles. In addition, intracavitary pathologic conditions can co-exist in the uterus with these problems. Anovulation is the most common cause of AUB in premenopausal women, and is especially common in adolescents during the first few years after menarche. Tests for TSH and prolactin can help rule out pituitary dysfunction as a cause of the anovulation. Other factors may also be associated with hypothalamic-based anovulation, including weight loss, eating disorders, stress, chronic illness, or excessive exercise. A common cause of anovulation in women of reproductive age that must be ruled out before making a diagnosis of anovulatory uterine bleeding is PCOS. Ovulatory AUB is less common in premenopausal women than anovulatory uterine bleeding, but it may occur. Ovulatory AUB manifests as regular cyclic bleeding. Although extensive laboratory testing for ovulation is costly and sometimes impractical, the typical patient who ovulates notes changes in vaginal secretions, premenstrual tension syndrome, and premenstrual breast tenderness. The clinical history of a regular menstrual cycle with characteristic premenstrual symptoms often correlates with an ovulatory menstrual cycle. The ovulatory patient with abnormal bleeding should be thoroughly evaluated for uterine pathology (eg, leiomyomas, adenomyosis, or endometrial polyps) and coagulation disorders. Ovulatory AUB without any attributable anatomic, organic or systemic disease is uncommon.
This slide shows an algorithm for the evaluation of AUB in perimenopausal women. As women approach menopause, the cycles shorten and may become intermittently anovulatory. The risk of endometrial cancer is low ( <1%) in women under 40 years of age. In these women, the most common causes of bleeding will not be endometrial cancer or even endometrial hyperplasia, but intracavitary pathologic conditions, including endometrial polyps or submucosal fibroids. However, all perimenopausal women with persistent abnormal uterine bleeding should be evaluated for endometrial hyperplasia or cancer. Techniques for evaluating endometrial pathologic conditions include biopsy, transvaginal ultrasonography (TVS), hysteroscopy, and saline infusion sonography (SIS).
This slide shows an algorithm for the evaluation of AUB in postmenopausal women. The most common cause of postmenopausal bleeding is endometrial atrophy, followed by iatrogenic bleeding often due to hormone replacement therapy (HRT). Women receiving sequential HRT may experience midcycle breakthrough-bleeding caused by missed pills, drug interactions, or malabsorption. Up to 40% of women receiving continuous combined HRT have irregular bleeding the first 4 to 6 months of therapy. The traditional recommendation has been to wait for 6 to 9 months of bleeding before performing a formal workup. This, however, will often lead to cessation of HRT, because of the inconvenience, annoying bleeding, and fear of endometrial cancer. Therefore, a more circumspect approach is advocated, in order to keep the patient compliant with therapy. Further evaluation may also be considered if the bleeding does not stop within 3 weeks after the cessation of HRT. Hysteroscopy and transvaginal ultrasonography (TVS) are very useful in the evaluation of postmenopausal bleeding, and may eliminate the need for endometrial biopsy. Endometrial cancer and endometrial hyperplasia are less common causes of postmenopausal bleeding. Of all postmenopausal women with bleeding, up to 10% may have endometrial cancer. Other causes of AUB in the postmenopausal woman may include cervical lesions, ovarian cancer, tubal cancer, and pathologic tissue in the vagina.
This slide lists diagnostic techniques useful for the evaluation of AUB. These will be reviewed in more detail on the following slides.
Endometrial biopsy is a safe, relatively simple procedure that can be performed during the initial office visit. It is widely used for excluding endometrial cancer, especially in peri- and postmenopausal women. A biopsy may also be used to determine if the bleeding is ovulatory or anovulatory. A drawback to the utility of endometrial biopsy is that it is not a sensitive technique for detecting structural abnormalities, such as polyps or fibroids. Several techniques may be used to obtain endometrial samples. Unfortunately, hospital-based D&C is still performed—even though it should be discouraged. It is no longer considered the gold standard for evaluation of abnormal bleeding, except in patients who have had a miscarriage. A diagnostic D&C is highly inaccurate, resulting in missed diagnoses and incomplete removal of intracavitary pathologic tissue, and is associated with a high false-negative rate. A recently reported retrospective study demonstrated that D&C failed to detect intrauterine disorders in 248 of 397 (62.5%) women. Office-based sampling techniques have been shown to be at least equivalent to D&C in sensitivity and rate of positive diagnosis/effectiveness, while being less intrusive and more cost-effective. Several sampling devices are available for office-based endometrial biopsy, including disposable devices (eg, Pipelle, Tis-u-Trap, Accurette, Z-sampler) and reusable instruments (eg, Novak Curette, Randall Curette, Vabra Aspirator).
The results of most endometrial biopsies fall into one of several categories, shown on this slide. Atypia is the most important risk factor for endometrial cancer. Approximately 25% of patients with atypia have been reported to develop endometrial cancer, compared with only 2% of patients without atypia. A finding on biopsy of normal secretory endometrium indicates that the patient is having ovulatory cycles, and abnormal uterine bleeding is therefore most likely due to a cause other than anovulation.
TVS is inexpensive, noninvasive, and a convenient technique for indirectly visualizing the endometrial cavity, myometrium, and adnexa, and measuring endometrial thickness. It may be used to identify possible abnormal endometrial conditions, such as atrophy, hyperplasia, cancer, leiomyomas, and polyps. Normally, the postmenopausal endometrial echo measures less than 5 mm. Fewer than 0.5% of women with an endometrial echo less than 5 mm will have endometrial cancer. Thicknesses greater than 5 mm are associated with endometrial hyperplasia, polyps, submucosal fibroids, and endometrial cancer. Even through the endometrium is thicker in women receiving HRT, a thin endometrial echo has high negative predictive value for endometrial cancer. Limitations of TVS may include problems associated with poor body habitus, skill of the operator, low signal-to-noise ratio, and lack of tissue-characterization. TVS may not always distinguish among a submucosal fibroid, endometrial polyp, or adenomyosis.
This slide shows a TVS image of a posterior fibroid. Slide courtesy of Linda Darlene Bradley, MD.
Hysteroscopy with biopsy allows visualization of the endometrial cavity, and this technique has been regarded as the “gold standard” for endometrial assessment. Most hysteroscopies are performed to evaluate abnormal uterine bleeding—up to 60% in one author’s experience. Diagnostic hysteroscopy can now be performed easily in an office setting, requires minimal anesthesia or sedation, and allows detection of endometrial myomas, polyps, and other lesions that may cause bleeding. Diagnostic hysteroscopy is particularly useful in the diagnosis of intrauterine lesions in women of reproductive age with ovulatory AUB. Office-based diagnostic hysteroscopy has been associated with a low ( <1%) incidence of complications when performed by physicians skilled in the technique. Complications may include uterine perforation, infections, excessive bleeding, and complications related to the distending medium (eg, CO 2 embolus). The major disadvantages of office-based hysteroscopy include the cost and maintenance of expensive equipment (eg, camera, insufflator, hysteroscope, video equipment), the skill and training required to perform the procedure, and the cost of the procedure.
This slide shows four hysteroscopic images of endometrial polyps. Slide courtesy of Linda Darlene Bradley, MD.
This slide shows a hysteroscopic image of the endometrial polyps seen on the SIS in the previous slide. Slide courtesy of Linda Darlene Bradley, MD.
This slide shows multifocal endometrial hyperplasia. Slide courtesy of Linda Darlene Bradley, MD.
Saline infusion sonography (SIS) is a relatively new technique that involves the infusion of saline into the endometrial cavity to enhance the detection of abnormalities. This technique is very useful for the evaluation of abnormal bleeding in pre-, peri-, and postmenopausal women. It has been reported that SIS is superior to TVS alone for evaluating the uterine cavity in patients with abnormal uterine bleeding. When used in conjunction with endometrial biopsy for the evaluation of postmenopausal women with abnormal uterine bleeding, SIS may have a sensitivity of 95% to 96.2% and a specificity of 65.7% to 98% for the detection of abnormal endometrial tissue. A reported disadvantage of SIS is that small irregularities caused by blood clots or endometrial protrusions have been frequently misinterpreted as polyps.
This slide shows a SIS image of a posterior Class 3 fibroid abutting the posterior endometrium. Slide courtesy of Linda Darlene Bradley, MD.
MRI is a powerful and noninvasive technique for visualizing the endometrial cavity and uterine abnormalities. It is gaining widespread acceptance and is cost-effective in many instances for the evaluation of abnormal uterine bleeding. It reliably differentiates uterine anatomy, localizes pelvic pathologic conditions, and estimates the size of lesions. MRI can reliably distinguish between adenomyosis and leiomyomata, and it is more sensitive and accurate than TVS and SIS for these conditions. However, MRI may not be superior to SIS and hysteroscopy in overall diagnostic potential of morphology in the uterine cavity, primarily because MRI has failed to be reliable in diagnosing endometrial abnormalities such as polyps.
This slide lists medical treatments available for the management of AUB. These will be reviewed in more detail on the following slides. Medical therapy is preferred over surgical therapy for the treatment of AUB, especially if the woman desires future fertility and has no anatomic, organic, or systemic cause for the bleeding. In the absence of pregnancy and anatomic pathology requiring surgical treatment, women with AUB, and especially anovulatory uterine bleeding, should be encouraged to try medical therapy as the primary option for controlling the bleeding.
The average woman in North America ingests enough dietary iron to replace that lost in menstrual blood volumes up to 60 mL per month. Menstrual volumes that exceed 60 mL per month may lead to iron-deficiency anemia. In may women with AUB, the primary symptom is fatigue secondary to anemia. The anemia may be successfully treated with daily doses of 60-180 mg of iron, an essential component of medically managing the patient with AUB. In some cases, administration of iron may be the only treatment necessary.
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.
Prostaglandins play a central role in normal menstrual hemostasis and may be involved in the pathogenesis of AUB. Within the endometrium, COX converts arachidonic acid into prostaglandins, and COX-inhibitors such as NSAIDs have therefore been evaluated in the treatment of AUB. NSAIDs that have been shown to be effective in the treatment of menorrhagia include mefenamic acid, diclofenac, flurbiprofen, ibuprofen, indomethacin, naproxen, and naproxen sodium. However, controlled comparative trials have shown that other medical therapies, such as the antifibrinolytic TA, may be superior to NSAIDs in the treatment of menorrhagia.
Progestin are commonly administered for the treatment of AUB. In North America, the agent of choice seems to be medroxyprogesterone acetate, and norethindrone is commonly prescribed in the rest of the world. Progestins may be administered cyclically (usually on a monthly schedule), continuously, or locally through progestin-impregnated IUDs. For women with ovulatory AUB (ie, menorrhagia), several trials demonstrated little benefit from the cyclic administration of norethindrone (10-15 mg/day during the luteal phase). Since ovulatory women already experience regular menses, cyclic progestin therapy offers few advantages. Continuous administration of progestins alone (i.e., without estrogens) may be more effective in the treatment of ovulatory AUB, but there are no published data evaluating this approach. Women with anovulatory uterine bleeding, with absence of the post-ovulatory progestagenic luteal phase, are more likely to benefit from the administration of cyclic progestins. In trials comparing the efficacy of progestin IUDs with other medical and surgical therapies for AUB, patients who received the IUDs experienced reductions in volume of bleeding of 79% to 94%. In other studies, 64.3% to 82% of women who received the IUDs but were also scheduled for hysterectomies elected to cancel the surgeries due to satisfaction with the IUDs.
Oral contraceptives (OCs) are effective for the treatment of both ovulatory AUB and anovulatory uterine bleeding. In the US, combination OCs are the most commonly prescribed medical treatment for AUB in women of reproductive age, especially for anovulatory uterine bleeding. Combination OCs are also effective in adolescents with excessive uterine bleeding. For patients with AUB, it may be clinically prudent to choose a pill containing 30-35 g of ethinyl estradio, rather than one containing 20 or 50 g. Low-dose OCs may also be effective as add-back therapies for women taking GnRH agonists for the treatment of AUB.
Conjugated equine estrogens (CEEs), administered by intramuscular (IM) injection or intravenous (IV) infusion, are the most widely prescribed emergent medical treatment for acute, excessive, and rapid uterine bleeding. Evidence suggests that parenteral estrogens may be effective in the treatment of both ovulatory AUB and anovulatory uterine bleeding. In one randomized controlled trial, IV administration of conjugated estrogens stopped the bleeding in 71% of women with AUB, compared with 38% of those who received placebos. Acute bleeding in adolescent girls usually results from anovulation and inadequate stimulation of the endometrium by estrogen—after pregnancy is ruled out. For severe bleeding resulting in adverse complications (ie, anemia or hypotension), initial treatment with high-dose estrogens may be effective. The administration of high-dose IV CEEs (25 mg IV every 4 hours) will usually result in rapid reduction of uterine bleeding. For adolescents with less serious bleeding, low-dose CEEs (2.5 mg administered orally every 4 to 6 hours for 14 to 21 days) may be appropriate. Once bleeding has stopped, progestins should be administered for 7 to 10 days.
Danazol, a synthetic testosterone derivative, has been used successfully to reduce menstrual bleeding in women with ovulatory AUB, with higher doses (eg, 200-400 mg/day) generally being more effective than lower doses (eg, 100 mg/day). Two trials compared the efficacy of danazol with that of cyclic norethindrone in women with ovulatory AUB. Danazol decreased menstrual volume in about half of the women, while norethindrone was not effective. Danazol has also been shown to be more effective than mefenamic acid (an NSAID) in women with ovulatory AUB. However, many women may find the adverse effects associated with danazol (eg, weight-gain, oily skin, acne, and deepening of the voice) sufficiently unpleasant to make long-term therapy with this agent undesirable.
GnRH agonists, which create a reversible hypogonadotropic state by down-regulating GnRH-receptors, dramatically decrease production of gonadotropin by the anterior pituitary. They have been evlauated primarily for stopping bleeding associated with leiomyomas, but may be effective for bleeding associated with both ovulatory AUB and anovulatory uterine bleeding. GnRH agonists induce amenorrhea by shrinking total uterine volume by about 40% to 60%. Administration of agonists has been associated with a gonadotropin “flare,” which may induce bleeding in the second week after starting therapy. Cost and significant side effects (eg, osteopenia) may limit the suitability of GnRH agonists for the treatment of AUB. As a result, physicians in the U.S. often view GnRH agonists as a treatment of last resort. GnRH antagonists may also create a hypogonadotropic state and may be effective for treating bleeding associated with both ovulatory AUB and anovulatory uterine bleeding. Antagonists, however, would not be associated with the gonadotropin flare associated with agonists.
Mifepristone is an antiprogestational agent, and a dosage of 50 mg/day has been reported to induce amenorrhea in subjects with leiomyomas. Administration of the agent has been shown to reduce the number of progesterone-receptors in the myometrium, but not the number of estrogen-receptors. This suggests that its ability to induce amenorrhea is a result of its antiprogestational activity.
Women with ovulatory AUB have a number of medical options for treatment. If contraception is desired, combination OCs reduce menstrual blood loss by about 50% and would be a good initial therapy. Progestin IUDs, which reduce menstrual blood loss by 80% to 90%, would be another good choice. For women who desire fertility, the use of NSAIDs would be effective at reducing menstrual blood loss, but not quite as effective as use of tranexamic acid (TA). Use of NSAIDs would, however, also be effective for reducing dysmenorrhea. The antifibrinolytic agent tranexamic acid (TA) would be an effective and apparently safe treatment, although it is rarely used in the U.S. A dosage of 1 g four times daily for days 1 through 4 of the menses reduces menstrual bleeding by about 50%. Such a regimen would be particularly attractive for women who desire to limit treatment to a few days per month. Use of GnRH agonists may also be an effective treatment for women with ovulatory AUB. In one study, a GnRH agonist was combined with add-back treatment (cyclic estrogen-progestin) for vasomotor symptoms and prevention of osteopenia. The women in this study experienced a significant reduction in bleeding volume, and 90% were willing to continue therapy beyond 12 months. However, as previously mentioned, the cost and significant side-effects (osteopenia) associated with GnRH agonists may limit their suitability as a first-line treatment for AUB.
Because the mechanisms involved in anovulatory uterine bleeding are unique, the strategies for medical treatment for these women differ significantly from those for women with ovulatory AUB. If possible, the cause of anovulation should be identified and treated, which would allow ovulation and regular menses to resume. Cyclic progestins and combination OCs are usually effective in women with anovulatory uterine bleeding, because these agents ameliorate the basic deficit of luteal-phase progesterone. Cyclic progestins may be ideal for those patients with contraindications to use of combination OCs, such as women over the age of 35 who smoke, those with other cardiovascular risk factors, or those with a history of recurrent deep-vein thrombosis. Use of GnRH-agonists is an effective—but expensive—treatment for anovulatory uterine bleeding. Women with anovulatory uterine bleeding are less likely to benefit from antifibrinolytics and NSAIDs than women with ovulatory AUB, because these agents target mechanisms specific to ovulatory women. Progestin IUDs and continuous systemic progestins could be expected to cause troublesome breakthrough-bleeding.
The main surgical treatments for AUB are hysterectomy, hysteroscopic endometrial ablation, and nonhysteroscopic endometrial ablation. We will review these techniques in more detail on the following slides. As stated previously, D&C is now considered obsolete for the evaluation of AUB, and it is also obsolete as a treatment for AUB.
Hysterectomy is the most common surgical treatment for AUB. Of the approximately 550,000 hysterectomies performed each year in the US, up to 40% of them may be performed for the treatment of AUB. Moreover, up to 50% of the uterine specimens demonstrate no histologic abnormality. Three techniques are used to perform hysterectomies: abdominal hysterectomy (AH), vaginal hysterectomy (VH), and laparoscopically assisted vaginal hysterectomy (LAVH). Abdominal hysterectomy generally costs more and is associated with greater morbidity than vaginal hysterectomy. The LAVH technique was developed to reduce the costs and morbidity associated with AH. Compared with AH, the LAVH technique results in fewer inpatient days, but increased costs overall, largely due to the use of disposable rather than nondisposable surgical supplied.
Use of the hysteroscope has been incorporated into several techniques for endometrial ablation, which appear to be the surgical treatments of choice for managing AUB. These techniques, however, require specialized training and surgical expertise, and they involve a significant learning curve. These techniques have also been associated with serious adverse effects, including fluid overload, uterine perforation, infection, hemorrhage, thermal injuries, and death. The first hysteroscopic ablative techniques employed the Nd:YAG laser, in which laser energy is transmitted to the endometrium through a flexible quartz fiber passed through the hysteroscope. Tissue necrosis reaches a depth of 4-5 mm. The vast majority of patients ( >90%) experienced a significant reduction in uterine blood flow. In clinical practice, electrosurgical techniques of hysteroscopic endometrial ablation have superseded the laser technique. In rollerball ablation, an electrode with a large surface area is passed over the endometrium to coagulate the tissue. In another technique, an electrosurgical loop electrode is used to resect endometrial tissue. Potential advantages of this technique include availability of tissue for histologic analysis and a lower risk of concealed endometrial hyperplasia or carcinoma. Electrosurgical vaporization is a relatively new technique, in which a fairly large electrode with multiple edges is used to vaporize endometrial tissue. For all three electrosurgical techniques, clinical outcomes are equally high, with about 90% of patients experiencing a significant reduction in bleeding volume. However, these techniques require the use of an electrolyte-free, low-viscosity distention solution. In rare cases, long-term morbidity and death due to fluid overload have been reported. Thus, rigorous fluid management is critical for the safety of electrosurgical endometrial ablation. A newer hysteroscopic technique known as hydrothermablation involves the use of heated free fluid. The procedure requires that the hysteroscope be inserted to visualize the endometrial cavity during the procedure. One device, the Hydro ThermAblator® Endometrial Ablation System, is currently approved by the FDA for clinical use. Preliminary results from one study suggested that efficacy of hydrothermablation was similar to that achieved with rollerball electrosurgical endometrial ablation. Hysteroscopic endometrial ablation techniques are about 50% less costly (direct hospital costs) than hysterectomy. The economic savings associated with endometrial ablation may be even greater if indirect costs, such as reduced morbidity and faster return of the patient to work, are considered.
Hysteroscopic view of electrosurgical endometrial resection. The resection loop is seen in distance. Normal endometrium is on the the right and a recently resected section is on the left.. Slide courtesy of Raymond W. Ke, MD.
Nonhysteroscopic endometrial ablation techniques are attractive for several reasons. First, they require relatively little skill and experience to perform successfully and safely. The nonhysteroscopic techniques, because they don’t require distention solution, obviate the risk of fluid overload. Additionally, these techniques may be performed relatively quickly in the office or clinical environment. The balloon technique (see next slide) is a thermal ablative system that utilizes a silicone intrauterine balloon filled with a solution of dextrose and water, which is heated to 87 degrees C for 8 minutes. Clinical outcomes have been reported to be similar to those achieved with rollerball electrosurgical ablation and hysteroscopic endometrial resection. The ThermaChoice ® Uterine Balloon Therapy System is approved for use in the US. Cryotherapeutic endometrial ablative techniques are currently undergoing investigation. One device, the Her Option™ Uterine Cryoablation Therapy™ System, was approved by the FDA for clinical use in April 2001. Preliminary data indicate that cryoablation is safe and effective for the treatment of AUB and requires less anesthesia than rollerball electrosurgical ablation. The radiofrequency probe employs an intrauterine probe that delivers ultrahigh-radiofrequency alternating current. The technique has been reported to have satisfactory reduction in menstrual bleeding in 93% of patients enrolled in clinical trials, including 42% of patients with resulting amenorrhea and 51% with reduced menses. A number of women, however, developed vesicovaginal fistulas, an adverse effect that precludes use of this technique. One unipolar electrode device, the Vesta system, is composed of a balloon covered with electrodes. When inserted into the endometrial cavity, the balloon is inflated and the electrodes contact the endometrial surface. Activation of the electrodes causes controlled desiccation and coagulation of the endometrium. Preliminary data show the device to be equally effective as hysteroscopic resection and electrocoagulation. One bipolar device, the NovaSure™ System, employs electrodes utilizing a combination of electrosurgical vaporization and desiccation/coagulation. Suction is required to remove steam and vapor from the endometrial cavity. Therapy with the device reportedly lasts for less than 3 minutes on average, and it has been approved by the FDA for clinical use.
This slide shows a schematic of the balloon thermal ablative technique.
This slide presents data reported for the ThermaChoice® Uterine Balloon Therapy System, Hydro ThermAblator® Endometrial Ablation System, Her Option™ Uterine Cryoablation Therapy™ System, and the NovaSure™ System. The data presented here were collected for intent-to-treat groups from separate studies as reported in FDA Summary of Safety and Effectiveness Data (SSED) for each device. These data do not reflect head-to-head comparison of the devices, so caution should be used when comparing efficacy of the devices based on these data.
AUB is a significant gynecologic health problem that affects adolescents, women of reproductive age, and postmenopausal women. Approximately one-third of all outpatient gynecologic visits annually are for the evaluation of AUB. Among adolescents, AUB is the most frequent cause of urgent admission to the hospital. The differential diagnosis of AUB includes complications of pregnancy, infection, trauma, gynecologic cancer, systemic disease, adverse effects of drugs, and iatrogenic cuases. Anovulatory uterine bleeding is a diagnosis of exclusion, and other causes of uterine bleeding must first be ruled out. The most likely causes of AUB relate to the woman’s reproductive age. A detailed menstrual history and physical examination can determine the woman’s ovulatory status and possible cause of the bleeding, such as pathologic uterine conditions or systemic disease. Laboratory testing can help in the evaluation of suspected coagulopathies and endocrinopathies. Pathologic uterine conditions can be evaluated by several diagnostic techniques, including endometrial biopsy, transvaginal ultrasound (TVS), hysteroscopy, saline infusion sonography (SIS), and magnetic resonance imaging (MRI). AUB may be managed medically or surgically, and a variety of effective options exist in both treatment modalities. Medical therapy is generally preferred over surgery, especially if the woman desires future fertility and has no anatomic, organic, or systemic cause for the bleeding. Available medical treatments include supplemental iron, antifibrinolytics, COX-inhibitors (including NSAIDs), hormonal agents (including OCs), GnRH agonists/antagonists, and antiprogestational agents. Surgical treatment for AUB include removal of the anatomic lesion, hysterectomy, hysteroscopic endometrial ablation/resection, free fluid ablation, and nonhysteroscopic endometrial ablation. Hysterectomy remains the most common surgical treatment for AUB.
Management of Abnormal Uterine Bleeding Modified from: APGO Educational Series on Women’s Health Issues
AUB vs. Anovulatory Uterine Bleeding <ul><li>Abnormal uterine bleeding (AUB): fairly broad term referring to bleeding that occurs outside of normal cyclic menstruation </li></ul><ul><li>Anovulatory uterine bleeding: abnormal bleeding that cannot be attributed to an anatomic, organic, or systemic lesion or disease </li></ul><ul><li>The term “dysfunctional uterine bleeding” is no longer in favor and has been replaced by AUB </li></ul>
AUB Affects . . . <ul><li>>10 million women in the U.S. </li></ul><ul><li>Impacts daily activities and quality of life </li></ul><ul><li>May cause anxiety </li></ul><ul><li>May lead to iron-deficiency anemia/fatigue </li></ul>
AUB Affects . . . <ul><li>Adolescents </li></ul><ul><li>Women of reproductive age </li></ul><ul><li>Peri- and postmenopausal women </li></ul>
Definitions <ul><li>Amenorrhea: absence of menstruation for at least three usual cyclic lengths </li></ul><ul><li>Oligomenorrhea: cyclic length >35 days </li></ul><ul><li>Polymenorrhea: cyclic length <24 days </li></ul><ul><li>Menorrhagia: regular, normal intervals with excessive volume and durations of flow </li></ul><ul><li>Metrorrhagia: irregular intervals with normal or reduced volume and duration of flow </li></ul><ul><li>Menometrorrhagia: irregular interval and excessive volume and duration of flow </li></ul>
Regulation of Normal Menstruation <ul><li>Hypothalamic-pituitary-ovarian (HPO) axis </li></ul><ul><li>GnRH pulses stimulate FSH and LH </li></ul><ul><li>Dominant follicle matures to ovulation and provides negative feedback to stop recruitment </li></ul><ul><li>Estradiol initiates ovulation via LH surge through a positive feedback </li></ul><ul><li>Proliferative phase of the endometrium </li></ul><ul><li>Corpus luteum and progesterone influences the secretory phase of the endometrium </li></ul><ul><li>If implantation fails: progesterone withdrawal, endometrial collapse, and menstruation </li></ul>
Etiologic Basis of Anovulatory Uterine Bleeding <ul><li>Estrogen-withdrawal bleeding (e.g. iatrogenic with cessation of therapy) </li></ul><ul><li>Estrogen-breakthrough bleeding (e.g. anovulation) </li></ul><ul><li>Progesterone-breakthrough bleeding (e.g. OCP administration) </li></ul>
Ovulatory AUB <ul><li>AUB without any attributable anatomic, organic, or systemic cause but associated with regular ovulation </li></ul><ul><li>Uncommon </li></ul><ul><li>Regular progesterone-withdrawal menses every 24-35 days—but excessive blood loss </li></ul><ul><li>Loss of local endometrial hemostasis </li></ul><ul><li> Ratio of PGE 2 : PGF 2 </li></ul><ul><li> Level of PGI 2 </li></ul><ul><li> Fibrinolytic activity </li></ul>
Anovulatory Uterine Bleeding <ul><li>Noncyclic menstrual blood loss due to anovulatory productions of sex steroids </li></ul><ul><li>Estrogen-withdrawal or estrogen-breakthrough bleeding in the absence of cyclic progesterone </li></ul><ul><li>Characterized by a hyperplastic, fragile endometrium prone to localized breakage and bleeding </li></ul><ul><li>Erratic in both timing and volume </li></ul>
Usual Causes of AUB Throughout a Woman’s Lifetime
Differential Diagnosis of AUB In Reproductive Age Women <ul><li>Complications from pregnancy </li></ul><ul><li>Infection </li></ul><ul><li>Trauma </li></ul><ul><li>Cancer </li></ul><ul><li>Pelvic pathology (benign) </li></ul><ul><li>Systemic disease </li></ul><ul><li>Medications/iatrogenic causes </li></ul>
Submucosal Fibroid Slide courtesy of Raymond W. Ke, MD.
Endometrial Polyps Slide courtesy of Linda Darlene Bradley, MD.
Endometrial Biopsy <ul><li>Safe, relatively simple procedure useful in perimenopausal or high risk women </li></ul><ul><li>Not sensitive for detecting structural abnormalities (eg, polyps or fibroids) </li></ul><ul><li>Office-based techniques (gold standard replacing D&C </li></ul><ul><ul><li>Disposable devices (eg, Pipelle, Tis-u-Trap, Accurette, Z-sampler) </li></ul></ul><ul><ul><li>Reusable instruments (eg, Novak Curette, Randall Curette, Vabra Aspirator) </li></ul></ul>
Possible Endometrial Biopsy Findings <ul><li>Proliferative, secretory, benign, or atrophic endometrium </li></ul><ul><li>Inactive endometrium </li></ul><ul><li>Tissue insufficient for analysis </li></ul><ul><li>No endometrial tissue seen </li></ul><ul><li>Simple or complex (adenomatous) hyperplasia without atypia </li></ul><ul><li>Simple or complex (adenomatous) hyperplasia with atypia </li></ul><ul><li>Endometrial adenocarcinoma </li></ul>
Transvaginal Ultrasonography (TVS) <ul><li>Inexpensive, noninvasive, and convenient </li></ul><ul><li>Indirect visualization of the endometrial cavity, myometrium, and adnexa </li></ul><ul><li>Measurement of endometrial thickness ( <5 mm vs. >5 mm) </li></ul><ul><li>May be used to increase index of suspicion for endometrial atrophy, hyperplasia, cancer, leiomyomas, and polyps </li></ul><ul><li>May not always distinguish among submucosal fibroid, polyp, or adenomyosis </li></ul>
Posterior Fibroid Slide courtesy of Linda Darlene Bradley, MD.
Hysteroscopy <ul><li>Hysteroscopy + biopsy = “gold standard” </li></ul><ul><li>Most are performed to evaluate AUB </li></ul><ul><li>Diagnostic hysteroscopy easily performed in the office setting—although it requires skill </li></ul><ul><li>Particularly useful in the diagnosis of intrauterine lesions in women of reproductive age with ovulatory AUB </li></ul><ul><li>Complications ( <1%) may include uterine perforation, infections, excessive bleeding, and those related to distending medium </li></ul>
Endometrial Polyps Slide courtesy of Linda Darlene Bradley, MD.
Endometrial Polyps Slide courtesy of Linda Darlene Bradley, MD.
Endometrial Hyperplasia Slide courtesy of Linda Darlene Bradley, MD.
Saline Infusion Sonography (SIS) <ul><li>Relatively new technique </li></ul><ul><li>Very useful for evaluation of AUB in pre-, peri-, and postmenopausal women </li></ul><ul><li>May be superior to TVS alone (94.1% vs. 23.5% for detection of focal intrauterine pathology) </li></ul><ul><li>SIS + biopsy: 96.2% sensitivity and 98% specificity </li></ul><ul><li>Disadvantage: small irregularities may be misinterpreted as polyps </li></ul><ul><li>Able to determine penetration depth of uterine fibroids </li></ul>
Posterior Class 3 Fibroid Slide courtesy of Linda Darlene Bradley, MD.
Magnetic Resonance Imaging (MRI) <ul><li>Powerful, noninvasive technique for visualizing the endometrial cavity and uterine abnormalities </li></ul><ul><li>Reliably differentiates uterine anatomy, localizes pelvic pathologic conditions, and estimates the size of lesions </li></ul><ul><li>Can reliably distinguish between adenomyosis and leiomyomata—more sensitive than TVS and SIS </li></ul><ul><li>May not be superior to SIS and hysteroscopy in overall diagnostic potential </li></ul><ul><li>Able to determine penetration depth of uterine fibroids </li></ul>
Medical Treatment of AUB <ul><li>Iron </li></ul><ul><li>Antifibrinolytics </li></ul><ul><li>Cyclooxygenase inhibitors </li></ul><ul><li>Progestins </li></ul><ul><li>Estrogens + progestins (OCs) </li></ul><ul><li>Parenteral estrogens (CEEs) </li></ul><ul><li>Androgens </li></ul><ul><li>GnRH agonists and antagonists </li></ul><ul><li>Antiprogestational agents </li></ul>
Iron <ul><li>Menstrual volume >60 mL—iron-deficiency anemia </li></ul><ul><li>Primary symptom is fatigue </li></ul><ul><li>Daily doses of 60-180 mg of iron </li></ul><ul><li>In some cases, may be the only treatment necessary </li></ul>
Antifibrinolytics <ul><li>Fibrinolysis—endometrial hemostasis </li></ul><ul><li>Tranexamic acid (TA) and precursors effective in reducing menstrual blood loss </li></ul><ul><li>TA reduced blood loss by up to 54% </li></ul><ul><li>Rarely administered in North America, but a mainstay treatment elsewhere </li></ul><ul><li>Concern about thromboembolic events may be unwarranted based on retrospective data </li></ul>
COX Inhibitors <ul><li>Prostaglandins: central role in menstrual hemostasis </li></ul><ul><li>NSAIDs have been shown to be effective in the treatment of menorrhagiaMefenamic acid, diclofenac, flurbiprofen, ibuprofen, indomethacin, naproxen, meclofenamate sodium, and naproxen sodium </li></ul><ul><li>New COX 2 drugs may have a role in alternate pathways </li></ul>
Progestins <ul><li>Medroxyprogesterone acetate: North America </li></ul><ul><li>Norethindrone: worldwide </li></ul><ul><li>Cyclic, continuous, or local administration </li></ul><ul><li>Ovulatory AUB: continuous progestins may be better than cyclic progestins </li></ul><ul><li>Anovulatory uterine bleeding: cyclic progestins more effective </li></ul><ul><li>Local (IUD) progestins: reductions in bleeding volume of 79% to 94%; up to 82% of women elected to cancel hysterectomies </li></ul>
Estrogens + Progestins (OCs) <ul><li>Effective for ovulatory AUB and anovulatory uterine bleeding—most commonly prescribed treatment in the U.S. </li></ul><ul><li>Effective in adolescents with excessive bleeding </li></ul><ul><li>For AUB: choose an OC containing 30-35 g of ethinyl estradiol </li></ul><ul><li>Low-dose OCs may be effective add-back therapy for women taking GnRH agonists </li></ul>
Parenteral Estrogens (CEEs) <ul><li>IV or IM conjugated equine estrogens (CEEs): most widely prescribed emergent treatment for acute, rapid, and excessive uterine bleeding </li></ul><ul><li>May be effective for both ovulatory AUB and anovulatory uterine bleeding: 71% bleeding cessation vs. 38% for placebo </li></ul><ul><li>High-dose CEEs (25 mg IV every 4 hrs) effective in adolescents with acute bleeding </li></ul>
Androgens <ul><li>Danazol (synthetic testosterone derivative) has reduced bleeding volume in 50% of women with ovulatory AUB </li></ul><ul><li>More effective than cyclic progestins and NSAIDs for women with ovulatory AUB </li></ul><ul><li>Adverse effects associated with androgen therapy may make long-term treatment undesirable for many women </li></ul>
GnRH Agonists/Antagonists <ul><li>May be effective for the treatment of both ovulatory AUB and anovulatory uterine bleeding </li></ul><ul><li>Agonists induce amenorrhea by shrinking total uterine volume by 40% to 60% </li></ul><ul><li>Gonadotropin “flare” associated with agonists may induce bleeding in 2 nd week of treatment (not associated with antagonists) </li></ul><ul><li>Cost and adverse effects (eg, osteopenia) may limit utility in women with AUB, and physicians in the U.S often regard GnRH agonists as a treatment of last resort </li></ul>
Antiprogestational Agents <ul><li>Mifepristone 50 mg/day reported to induce amenorrhea in women with leiomyomas </li></ul><ul><li>Reduces the number of progesterone-receptors in the myometrium, but not the number of estrogen-receptors </li></ul><ul><li>May reduce uterine size in leiomyoma patients ( Obstet Gynecol 2/03 ) </li></ul>
Medical Therapy: Ovulatory AUB <ul><li>If contraception desired: combination OCs or progestin IUDs are good initial treatment </li></ul><ul><li>If fertility desired: NSAIDs or tranexamic acid (rarely used in the U.S.) would reduce bleeding volume </li></ul><ul><li>GnRH agonists may be effective as second-line treatment </li></ul>
Medical Therapy: Anovulatory Uterine Bleeding <ul><li>Cause of anovulation should be identified and treated </li></ul><ul><li>Cyclic progestins and combination OCs are usually effective—cyclic progestins may be ideal for women with contraindications to OCs (eg, smokers >35, hypertension) </li></ul><ul><li>GnRH agonists are effective, but expensive </li></ul><ul><li>Less likely to benefit from antifibrinolytics, NSAIDs, progestin IUDs, or continuous progestins </li></ul>
Endometrial Ablation Techniques: Reported Data
Summary <ul><li>AUB is a significant gynecologic health problem </li></ul><ul><li>Anovulatory uterine bleeding is a diagnosis of exclusion </li></ul><ul><li>Uterine pathology can can be evaluated by: biopsy, TVS, hysteroscopy, SIS, and MRI </li></ul><ul><li>Medical therapy is generally preferred </li></ul><ul><li>Surgical treatments for AUB include removal of the anatomic lesion, hysterectomy, hysteroscopic endometrial ablation/resection, free fluid ablation, and nonhysteroscopic endometrial ablation </li></ul>