Menstrual Abnormalities
Menstrual Abnormalities
Authors: Edward Onusko, MD, Assistant Clinical Professor, Department of Family Medicine, University of Cincinnati College of Medicine; and Rancie Hannah, MD, Chief Resident, Clinton Memorial Hospital Family Practice Residency Program.
Peer Reviewers: Sarina Schrager, MD, Assistant Professor, Department of Family Medicine, University of Wisconsin, Madison, WI; and Leon Speroff, MD, Professor of Obstetrics and Gynecology, Oregon Health Sciences University, Portland.
Editor’s Note—Abnormal uterine bleeding is a common complaint in most primary care practices. An average human female will have as many as 400 menstrual cycles during her reproductive years. As many as 31 per 1000 consults annually to a practice1 or 20% of women at some time in their lives2 will present to their physicians with the complaint of abnormal periods. The prevalence of numerous possible etiologies that can give rise to abnormal uterine bleeding varies based on the age and reproductive status of the patient. Anovulatory menstrual cycles and hormonal imbalances are common, especially at the extremes of a woman’s reproductive life cycle (< 20 and > 40 years old). The term dysfunctional uterine bleeding (DUB) is used to describe the syndrome of abnormal menstrual patterns caused by a variety of hormonal imbalances. In approximately one-quarter of cases of menstrual abnormalities, an organic or pathologic etiology such as pregnancy (or complications thereof), neoplasm (either benign or malignant), infection, or secondary disease conditions (such as a coagulation disorder) can account for the abnormality.3 Accurate diagnosis of abnormal uterine bleeding can be challenging. A careful history and physical exam are indispensable in the evaluation, since many cases provide no sensitive physical abnormalities or useful laboratory findings to complement the clinician’s diagnostic acumen. Evaluation of amenorrhea will not be included in the scope of this article.
Normal Menstrual Physiology
The physiologic mechanisms of the normal menstrual cycle are not completely understood, but a basic comprehension of the cyclic hormonal variations and end organ responses is important for understanding the pathologic processes that result in abnormal conditions (see Figure 1).
Menstruation is the physiologic shedding of the inner lining of the uterus, or endometrium, which occurs on average once per month. Cycles are considered normal if they occur at 28-day intervals, give or take seven days. Pubertal females tend to have a greater variability of cycle length secondary to immaturity of neuroendocrine controls. Uterine bleeding usually lasts from two to seven days, resulting in a blood loss averaging 35 mL (range, 15-50 mL). Blood loss greater than 80 mL per cycle is considered to be abnormal and can with time result in considerable iron deficiency. Subjective estimations by patients of the volume of vaginal blood lost or number of sanitary pads used are notoriously insensitive markers for actual uterine blood loss but may allow for a rough approximation of flow. Ten to fifteen pads or tampons would be consistent with a uterine blood loss of around 60 mL.
Menarche occurs when the hypothalamus signals the pituitary gland to begin manufacturing the gonadotropic hormones FSH (follicle-stimulating hormone) and LH (luteinizing hormone). This is accomplished by the action of hypothalamic GnRH (gonadotropin-releasing hormone), which is released in pulsatile fashion through the hypothalamic-pituitary portal system. FSH action at the ovaries allows the maturation of a cohort of primordial follicles. This period of the cycle is known as the follicular phase. The largest follicle that contains the most FSH receptors is responsible for production of increasing amounts of estradiol, the most physiologically potent estrogenic compound, from androgen precursors. Estradiol along with inhibin, a glycoprotein also produced by the developing follicle, serve as both positive and negative feedback mechanisms at the level of the pituitary.
First, in response to increasing amounts of estradiol and inhibin, FSH levels begin to fall and the remaining follicles in the cohort undergo atresia. With the dominant follicle remaining and estradiol concentrations greater than a critical level for 2-3 days, the pituitary is triggered to release a surge of LH, leading to rupture of the dominant follicle and ovulation. Following ovulation, the follicle proceeds into the luteal phase with production of progesterone by the granulosa cells that remain. If not supported by rising concentrations of BHCG from a fertilized ovum, the corpus luteum regresses and progesterone levels fall.
During follicular development, the endometrial tissue, responding to increasing levels of estrogens, begins to grow during what is termed the proliferative phase of the uterine cycle. Estrogen serves to stimulate the production of endometrial growth factors that permit replication of both endometrial glandular and supportive stromal elements. The endometrial thickness increases to approximately 8-9 mm (post-menses thickness is approximately 1-2 mm). High estrogen concentrations also allow for an up-regulation of additional estrogen receptors and progesterone receptors on endometrial cells. With unopposed and continuous estrogen available, the endometrium will continue to proliferate.
The secretory phase of the endometrial cycle begins with ovulation and the development of the corpus luteum from the remaining elements of the dominant follicle. The rising concentration of progesterone from the corpus luteum exerts an anti-estrogenic effect on the endometrium that causes an arrest of the proliferative phase by down-regulation of both estrogen and progesterone receptors. Progesterone serves to induce endometrial glandular cell differentiation and to organize stromal elements in preparation for possible implantation of a fertilized ovum. Endometrial prostaglandins are also altered by the concentration of progesterone. PGF2a and thromboxane are the major vasoconstrictive agents and PGE exerts a vasodilatory effect. Progesterone withdrawal causes an increase in the ratio of PGF2a to PGE, with a resultant constriction of the spiral arteries of the uterus and local ischemia of the endometrium with the onset of menses. Completion of menses requires clot formation at the spiral arteries secondary to the action of thromboxane and regeneration of the basal layer of the endometrium through the effect of estrogen.
| Table 1. Defining Abnormal Bleeding | |
| Menorrhagia | Regularly occurring menses with excessive or prolonged flow |
| Metrorrhagia | Irregularly occurring menses |
| Menometrorrhagia | Irregularly occurring menses with excessive or prolonged flow |
| Polymenorrhea | Regular menses at intervals less than 21 days |
| Oligomenorrhea | Regular menses at intervals greater than 35 days |
Etiologies
There are a wide variety of causes of abnormal vaginal bleeding (see Table 2). It is useful to view this subject from the perspective of what phase of the female reproductive life cycle the patient is in. For example, the usual causes of abnormal vaginal bleeding in a postmenopausal female are much different from the usual causes in an adolescent.
Causes of Abnormal Bleeding—Preadolescent
Although urogenital bleeding in prepubertal females is uncommon, some causes are worth mentioning. Hormonal causes may be the result of exogenous estrogens in the form of prescription medications such as oral contraceptives that may be ingested or topically applied by unsuspecting children. If a sufficient dosage is taken, the endometrium may be stimulated to proliferate and withdrawal of the estrogen source may cause bleeding. Newborn females may have a sanguineous discharge or frank bleeding secondary to withdrawal of maternal estrogens transferred in utero.4 No specific therapy is necessary and bleeding usually stops within 10 days. More likely causes of bleeding in children are localized disorders of the urogenital tract secondary to trauma, abuse, foreign bodies, urethral prolapse, or infection.
Causes of Abnormal Bleeding—Adolescents
Abnormal uterine bleeding becomes a significant and common presenting complaint once a female reaches the pubertal age. Approximately 90% of cases in nonpregnant adolescents are secondary to DUB.5 True DUB is defined as excessive, prolonged, unpatterned bleeding from the endometrium that is unrelated to secondary disease states or anatomic abnormality. On a physiologic level, DUB in adolescents is caused by immaturity of the hypothalamic-pituitary-ovarian endocrine axis; therefore, ovulatory cycles do not always occur. FSH from the pituitary acts on the ovarian cells, producing estrogen. However, critical estradiol concentrations are not achieved for positive feedback stimulation of LH release (or hypothalamic-pituitary controls fail to initiate the LH surge). The net result is failure of adequate LH to induce ovulation in a developing follicle, absence of ovarian luteal-phase progesterone, and a prolonged proliferative phase of the endometrium. Without the presence of regularly cycling progesterone concentrations, the endometrium grows to excessive and unstable thickness. Eventually, secondary to either abrupt estrogen withdrawal or insufficient blood supply for the excessive endometrial tissue, patchy sloughing of the endometrium occurs. Bleeding is usually prolonged due to the lack of coordination of the shedding process and lack of appropriate local control of the event by chemical mediators (prostaglandins and thromboxane). Establishment of regular ovulatory cycles usually occurs with time. On average, the younger the age at menarche, the less time is required to establish a majority of ovulatory cycles.6
Despite the absence of ovulation, most postmenarchal cycles do not differ significantly in length from normal limits due to an intact negative feedback system, whereby rising estrogen concentrations inhibit further FSH release, which, in turn, inhibits estrogen production by ovarian follicles. This cyclical pattern is responsible for maintaining the rather regular pattern of menses, as the resultant estrogen withdrawal bleeding prevents excessive endometrial thickening between cycles.7
DUB may also occur with ovulatory cycles as a result of insufficiency of the corpus luteum ("luteal phase defect"). Periods are usually regular in timing but duration of menses is increased. Resultant blood loss may be excessive.8 This is less common in adolescents than in older women.
Disorders of hemostasis should be considered as a cause of abnormal or excessive uterine bleeding. These include diseases that affect platelet number or function (such as idiopathic thrombocytopenic purpura, von Willebrand’s disease, or leukemia), as well as disruption of intrinsic coagulation factors (hereditary coagulopathies, hepatic or renal failure). Medications such as aspirin or warfarin may also contribute to problem bleeding. In one retrospective case series, 3% of adolescents presenting with abnormal uterine bleeding were diagnosed with a new hematologic disorder. Several others were known to have pre-existing coagulopathies.9
Polycystic Ovary Syndrome (PCOS)
The classic syndrome complex of oligomenorrhea, hirsutism, obesity, and polycystic ovaries was first described in 1935 by Stein and Leventhal. It is now appreciated that there is a clinical spectrum of related androgen excess syndromes in many women with anovulatory cycles, in which any of these four signs may be minimal or absent.10 Although these syndromes are still incompletely understood, a possible underlying mechanism may be hypersecretion of LH. The consequences of high baseline LH levels include:
• stimulation of ovarian theca cell conversion of cholesterol to androgens (i.e., hyperthecosis);
• suppression of FSH, which a) limits ovarian granulosa cell aromatization of androgens to estrogens, and b) prevents normal development of ovarian follicles;
• subsequent systemic androgenic effects of hirsutism, acne, unfavorable lipid profiles, male-pattern adipose distribution;
• conversion of excess androgens to estrogens by adipose tissue, which stimulates the endometrium; and
• chronic anovulation, which prevents the protective effect of cyclic progesterone on the endometrium.2
Chronic anovulation from many different etiologies can cause negative effects from both androgen and estrogen excess. Associated pathologies include insulin resistance syndromes, cardiovascular disease, and structural abnormalities of the ovaries. Which of these are the primary disorders and which are secondary results is often unclear.
Causes of Abnormal Bleeding—Reproductive Age
Pregnancy-related complications must always be an initial consideration in this population. These can often be easily ruled out with measurement of urine or serum B-HCG levels. Ectopic pregnancy, spontaneous or threatened abortion, and gestational trophoblastic disease are all considerations.
Hormonal abnormalities (DUB) are still the most common causes of abnormal bleeding in this age group. Low levels of estrogen provide inadequate support to the endometrium and cause irregular, prolonged, but usually light bleeding patterns (estrogen withdrawal bleeding). Sustained levels of excess estrogen, which may result from anovulation, cause periods of amenorrhea followed by acute, heavy bleeding (estrogen breakthrough bleeding).
Other endocrine disorders include hypothyroidism (menorrhagia), hyperthyroidism (oligo- or amenorrhea and elevated estrogen levels), diabetes mellitus (anovulation, obesity, insulin resistance, androgen excess), and androgen excess disorders.
Exogenous hormones (oral contraceptives) are a common cause of abnormal vaginal bleeding. Because of the relatively low-dose pills currently in use, missing a single day’s dose, or even taking the day’s dose later than usual, may result in intermenstrual bleeding. Even though oral contraceptive pills are often prescribed to correct anovulatory bleeding patterns, the balance of estrogenic and progestational effects of combination pills prescribed for contraception may not be right for an individual patient and may result in bleeding irregularities. Long acting hormone preparations such as depo-medroxyprogesterone acetate (Depo-Provera) may cause abnormal vaginal bleeding.
Certain medications have also been associated with abnormal uterine bleeding. Obviously, any anticoagulant (coumadin, heparin, aspirin) has the potential to alter platelet function or clotting factors. Phenytoin, phenothiazines, steroids, tricyclic antidepressants, and lithium may also contribute to abnormal menses by interfering with normal hormonal balance.
Anatomic (structural) lesions are much more common in this age group vs. adolescents. Endometrial (or cervical) polyps and submucosal leiomyomata (fibroids) are treatable causes of vaginal blood loss.11
Endometrial hyperplasia and endometrial carcinoma are significant concerns that must be considered in any adult woman with a vaginal bleeding disorder. Age older than 35-40 years is typically used as an indicator of risk, since only 2-5% of cases of endometrial cancer occur in women younger than 40 years.12 Other risk factors for significant endometrial pathology include hypertension, obesity, impaired carbohydrate metabolism, late onset of menopause, nulliparity, irregular menses, and unopposed exogenous estrogen. Ash et al suggest that patients with a pattern of predominantly irregular menstrual cycles in the preceding 12 months are at highest risk of abnormal endometrial histology, regardless of age.12
Smoking more than 16 cigarettes per day is associated with a threefold greater risk of abnormal bleeding patterns, probably due to the anti-estrogenic effects of nicotine.
Sexually transmitted diseases are a common cause of vaginal bleeding. For example, chlamydia is a common cause of cervicitis, which may result in intermenstrual vaginal spotting.
Causes of Abnormal Vaginal Bleeding—Perimenopausal
As women near the end of their reproductive years, the hypothalamic-pituitary axis tends to remain intact, but the aging ovary is less responsive to gonadotropins and produces less active follicles. Decreased production of estrogen from these follicles fails to trigger the LH surge required for ovulation and corpus luteum formation, resulting in more anovulatory cycles. Menopause may be defined clinically as the absence of menses for one year.13 Cycles tend to shorten (due to a shortened follicular phase) or become intermittently anovulatory. One study found the median age for the beginning of menopause to be 47.5 years, age at menopause 51.3 years, with a perimenopausal duration of 4-5 years.14 Eight percent of women become menopausal before age 40.
In this relatively older population of women, endometrial carcinoma must be carefully considered as a cause of abnormal bleeding patterns. However, loss of ovarian function with a resultant change in menstrual patterns is an inevitable result of normal aging, and every woman does not need to necessarily undergo diagnostic intervention at the time of menopause. Each patient needs to have individualized counseling and risk factor assessment.
Structural lesions (such as fibroids) and medical conditions that result in abnormal bleeding patterns (such as hepatic or renal failure) occur more frequently with aging.
Causes of Abnormal Bleeding—Postmenopausal
In the absence of hormone therapy, any vaginal bleeding after menopause should undergo evaluation for a neoplastic lesion.15 Other common causes of postmenopausal bleeding include exogenous estrogens, atrophic vaginitis/endometritis, endometrial or cervical polyps, and endometrial hyperplasia.
Despite the fact that in the majority of postmenopausal patients the benefits of hormone replacement therapy (osteoporosis reduction and favorable effect on the lipid profile) probably outweigh the adverse risks (thrombotic events and carcinoma of the breast), 1) less than 20-30% of eligible women take it long term,16 and 2) about 70% of women who are started on replacement therapy stop it within a year, most often secondary to unwanted vaginal bleeding.17 There is no clear definition of "abnormal bleeding" in postmenopausal women who are taking hormone replacement therapy.
Diagnostic Evaluation
A careful history and physical examination should allow the practitioner to formulate a focused diagnostic plan based on age, risk factors for neoplastic disease, fertility vs. contraceptive concerns, etc. Age of menarche, detailed description of the pattern of bleeding (menstrual diaries may be useful), current medications, previous OB/GYN history, family history, desire for contraception, review of systems to screen for associated medical problems, risk factors for sexually transmitted diseases, and tobacco use are all important aspects of the patient’s history. A complete physical exam including breast and pelvic exams should be done. Signs of androgen excess (hirsutism, acne, etc.), structural pelvic lesions (e.g., fibroids), thyromegaly, and many other physical findings may suggest an etiology for the bleeding abnormalities. Acanthosis nigricans (hyperpigmentation of the neck, axillae, and inguinal region) suggests a state of hyperinsulinemia.18
Pregnancy should be ruled out as the cause of abnormal vaginal bleeding in any woman of reproductive age. Bleeding disorders may be screened by coagulation studies (PT/PTT) and platelet count. Von Willebrand’s disease should be suspected with excessive bleeding at menarche. It may be diagnosed by an abnormal bleeding time and abnormal quantitative or functional assays for von Willebrand’s factor. Diagnostic studies for systemic diseases such as hypothyroidism, hyperthyroidism, renal disease, hepatic injury, malnutrition, etc., may be used as clinically indicated.19 Testing for sexually transmitted diseases may be indicated in sexually active women.
The traditional method for evaluation of women at risk for endometrial carcinoma is endometrial biopsy. Endovaginal ultrasound may be useful in selecting out a low-risk subpopulation of peri- or postmenopausal women (endometrial thickness less than 5 mm) who do not require further diagnostic intervention.20-22 Infusion of saline into the uterine cavity may improve diagnostic accuracy of ultrasound.23 Although the high negative predictive value of transvaginal ultrasonography makes it a useful test to screen for low-risk patients, the positive predictive value is poor.24 Office hysteroscopy (direct visualization of the endometrium via saline infusion and insertion of a flexible scope) is useful for diagnosing endometrial polyps and directing biopsy of suspicious-appearing lesions.25 A Pap test should always be considered as well, although it will be diagnostic in only about 50% of cases of endometrial carcinoma.
The diagnosis of anovulatory disorders is usually made by putting together the overall clinical picture rather than by a single diagnostic test. In PCOS, a properly timed LH:FSH ratio (> 2:1) is usually present, along with clinical and/or laboratory findings of hyperandrogenism (elevated free testosterone levels) and chronic anovulation (in the absence of secondary causes such as hyperprolactinemia, adult-onset congenital adrenal hyperplasia, and neoplasm). The ovaries may be structurally normal; therefore, the diagnosis cannot be excluded on the basis of imaging or direct observation of them. DUB is primarily a diagnosis of exclusion, implying an imbalance in the hypothalamic-pituitary-ovarian endocrine axis.26
Therapeutic Interventions
Abnormal vaginal bleeding found to be secondary to a specific etiology should be treated by correction of the underlying abnormality. Examples would be thyroid hormone replacement in hypothyroidism, or hysterectomy for endometrial carcinoma.
Women taking exogenous female hormones (either oral contraceptives or postmenopausal hormone replacement therapy) may benefit from a change in their regimen. There are a large number of hormone preparations (including all the oral contraceptive pills [OCPs]) available, with varying estrogen and progestin potency, in multiple combinations. If there is a clear pattern of hormonal abnormality, such as estrogen breakthrough bleeding (i.e., bleeding early in the cycle), a specific change in the content of the hormone prescription may be indicated (e.g., increase the pill’s estrogenic potency early in the cycle). There are few definitive, evidence-based data on therapeutic manipulation of estrogen/progestin preparations, however, and the patient’s bleeding does not often follow a specific pattern. Therefore, a trial of simply changing to a different estrogenic or progestational preparation may result in a more satisfactory menstrual pattern. A complete discussion of the use of OCPs and postmenopausal hormone replacement therapy is beyond the scope of this article.
Management of DUB may be based on age and other factors. In the adolescent population, anovulatory cycles may simply be observed while awaiting maturation of the endocrine axis. Regular cycling with a progestational agent, or combination oral contraceptives (particularly if contraception is desired), may be used to regulate the menses. The adult, reproductive-age patients with DUB are more at risk for adverse effects of chronic anovulation such as development of abnormal endometrial histology. Cycling with 5-10 days of progestin each month should prevent these complications. Estrogen/progestin oral contraceptive combinations may also be used, though the thromboembolic risks of estrogen supplementation increase with advancing age. Perimenopausal women may be cycled with progestin until they complete menopause, at which time chronic hormone replacement therapy may be initiated.14
Acute, heavy bleeding episodes of some urgency should be treated with high-dose estrogen therapy.11 The estrogen may be given either orally (conjugated equine estrogens 10 mg every 6 hours) or intravenously (25 mg every 2-4 hours). Usually, the bleeding is controlled within 24 hours and the patient is switched to oral maintenance estrogen of 10 mg per day for 21-25 days, with oral medroxyprogesterone acetate 10 mg per day given with the last 7-10 days of estrogen. Normal menses should then follow the withdrawal of both hormones. An alternative is to start treatment with combination estrogen/progestin preparations (i.e., birth control pills) 3-4 tablets per day with eventual tapering of the dose over 3-4 weeks. Urgency of treatment is suggested by hemodynamic instability (postural hypotension), marked anemia (hemoglobin < 7 g/dL), or prominent symptomatology (lightheadedness). Visual evaluation of blood loss by the patient is often not a reliable indicator of the objective severity of blood loss.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce vaginal bleeding via antiprostaglandin effects.11 They may be used alone or in combination with hormonal manipulation, particularly for the treatment of DUB. Use may be throughout the period of menses or limited to the first three days. Ibuprofen, mefamanic acid, meclofenamate sodium, and naproxen have all been successfully used for this indication. NSAIDs have the additional benefit of relieving other symptoms of dysmenorrhea, such as cramps.
Danazol is a synthetic agent with antiestrogenic and weak androgenic actvities.27 It has been useful for the treatment of endometriosis, as well as in reducing the severity of unexplained menorrhagia.28 It has a high incidence of unpleasant side effects and results in infertility secondary to suppression of ovulation, which limits its clinical usefulness.
Gonadotropin-releasing hormone agonists work by disrupting the pulsatile, physiologic release of hypothalamic GnRH. These agents include leuprolide (Lupron), nafarelin (Synarel), goserelin (Zoladex), and histrelin (Supprelion). Their antigonadotropin action results in induction of amenorrhea or reduction of menorrhagia. Unpleasant side effects (nausea, etc.), expense, and loss of bone density with long-term use also limit the usage of these agents as treatments for abnormal vaginal bleeding. Their endocrine effects (anti-gonadotropin) make them useful agents in the treatment of endometriosis, prostate cancer, breast cancer, induction of endometrial thinning prior to endometrial ablation, uterine leiomyomas, and precocious puberty.29
If the primary goal of treatment of an anovulatory syndrome is the restoration of fertility, ovulatory agents such as clomiphene (Clomid, Serophene) may be used. This drug appears to act on the hypothalamic-pituitary axis in anovulatory women via modification of intracellular estrogen receptors, with resultant induction of ovulation.
Surgical options include hysterectomy or hysteroscopic endometrial ablation (using laser, "rollerball" electrocoagulation, etc.).27 Dilatation and curettage may be necessary to achieve control of a single serious bleeding episode unresponsive to hormonal treatment but does not particularly result in long-term improvement in patterns of abnormal bleeding.
Weight loss in cases of PCOS may be effective in reducing insulin resistance, decreasing free testosterone, and restoring ovulation.30
Summary
A review of the basic hormonal mechanisms behind normal and abnormal menstrual cycles has led us to explore the various diagnostic and treatment options available for women at various stages in the life cycle. Thoughtful review of an individual patient’s clinical presentation and risk factor profile is necessary to direct appropriate management decisions.
The authors wish to thank Marsha Tomlin and her staff for their assistance in the preparation of this manuscript.
References
1. Chen BH, Giudice LC. Dysfunctional uterine bleeding. West J Med 1998;169(5):280-284.
2. Nelson AL. A practical approach to dysfunctional uterine bleeding. Fam Pract Recertification 1997;19(8):14-40.
3. Smith CB. Pinpointing the cause of abnormal uterine bleeding. Womens Health Prim Care 1998;1(10):835-844.
4. Hoekelman RA, et al. Primary Pediatric Care. 3rd ed. St. Louis, MO: Mosby; 1997:1140-1143.
5. Dealy MF. DUB in adolescents. Nurse Pract 1998;23(5):12-25.
6. Apter D, Vihko R. Early menarche, a risk factor for breast cancer, indicates early onset of ovulatory cycles. J Clin Endocrinol Metab 1983;57(1):82-86.
7. Goldfarb AF. Clinical Problems in Pediatric and Adolescent Gynecology. New York, NY: Chapman and Hall; 1996:61-68.
8. Lavin C. DUB in Adolescents. Curr Opin Pediatr 1996;8:328-332.
9. Falcone T, et al. DUB in adolescents. J Reprod Med 1994;39(10):761-764.
10. Dawood MY, et al. Menstrual Disorders. Patient Care—Supplement Medical Economics Publishing. May 15, 1992:1-21.
11. Chuong CJ, Bronner PF. Management of Abnormal Uterine Bleeding. Am J Obstet Gynecol 1998;175(3 part 2):787-792.
12. Ash SJ, et al. Endometrial biopsy in DUB. J Reprod Med 1996;41(12):892-896.
13. Oriel KA, Schrager S. Abnormal uterine bleeding. Am Fam Physician 1999;60(5):1371-1380.
14. Pinkerton JV, et al. Individualized care for the perimenopausal woman. Patient Care 1999;3(4):47-73.
15. Hillard PA. Benign diseases of the female reproductive tract: Symptoms and signs. In Novak’s Gynecology. 12th ed. 331-354.
16. Notelovitz M. How to adjust estrogen therapy to patient response. Patient Care 2000;34(4):99-115.
17. Spencer CP, et al. Management of abnormal bleeding in women receiving hormone replacement therapy. BMJ 1997;315:37-42.
18. Patel SR, et al. Polycystic ovary syndrome: How best to establish the diagnosis. Womens Health Prim Care 2000;3(1):55-69.
19. Galle PC, McRae MA. Abnormal uterine bleeding. Finding and treating the cause. Postgrad Med 1993;93(2):73-81.
20. Smith-Bindman R, et al. Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities. JAMA 1998;280(17):1510-1517.
21. Weber AM, et al. Vaginal ultrasonography versus endometrial biopsy in women with postmenopausal bleeding. Am J Obstet Gynecol 1997;177(4):924-929.
22. Holbert TR. Transvaginal ultrasonographic measurement of endometrial thickness in postmenopausal women receiving estrogen replacement therapy. Am J Obstet Gynecol 1997; 176(6):1334-1339.
23. Goldstein SR, et al. Ultrasonography-based triage for perimenopausal patients with abnormal uterine bleeding. Am J Obstet Gynecol 1997;177(1):102-108.
24. Langer RD, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. N Engl J Med 1997;337(25):1792-1798.
25. Widrich T, et al. Comparison of saline infusion sonography with office hysteroscopy for the evaluation of the endometrium. Am J Obstet Gynecol 1996;174(4):1327-1334.
26. Baughan DM. Challenges in the management of the patient with dysfunctional uterine bleeding. Fam Pract Recertification 1993;15(5):68-78.
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Physician CME Questions
17. A common feature of polycystic ovary syndrome is:
a. weight loss.
b. more frequent menstrual periods.
c. elevated ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH).
d. pelvic pain secondary to ovarian enlargement.
18. The most common cause of anovulation in early adolescence is:
a. atresia of the ovaries.
b. congenital adrenal hyperplasia.
c. imperforate hymen.
d. immaturity of the hypothalamic-pituitary-ovarian axis.
19. Gonadotropin-releasing hormone agonists may be a useful treatment in all of the following disorders except:
a. polycystic ovary syndrome.
b. endometriosis.
c. prostate cancer.
d. uterine leiomyomas.
20. A factor that is associated with decreased menstrual bleeding is:
a. use of nonsteroidal anti-inflammatory drugs (NSAIDs) during menses.
b. smoking more than 16 cigarettes per day.
c. chlamydia infection of the cervix.
d. von Willebrand’s disease.
21. An appropriate treatment for anovulation in a young, reproductive age patient would be:
a. oral progesterone each day for one month.
b. oral contraceptives.
c. ibuprofen.
d. danazol.
22. Most cases of dysfunctional uterine bleeding are the result of:
a. thyroid disorders.
b. insufficient estradiol concentration.
c. excessive progesterone production.
d. anovulatory cycles.
23. Postmenopausal uterine bleeding:
a. should require an evaluation of the endometrium.
b. can be successfully treated with hormone replacement alone.
c. mandates a hysterectomy.
d. does not result from medications.
24. A medication that is not associated with abnormal uterine bleeding is:
a. coumadin.
b. phenytoin.
c. an oral contraceptive.
d. an antihistamine.
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