Chpt 24 Functional and Dysfunctional Uterine Bleeding

What is the normal thickness of the myometrium?

1 to 2 cm.

What is the probability of endometrial cancer in postmenopausal woman with vaginal bleeding with endometrial thickness >10 mm?

10% to 20%.

What is the percentage of women with menorrhagia that consider their periods as light or moderate?

40%.

What percentage of women complaining of excessive or prolonged bleeding meet criteria for menorrhagia?

40%.

What is the incidence of dysmenorrhea?

50% to 75% of women report that they have experienced dysmenorrhea.

What is the volume of a normal endometrial cavity in a woman of reproductive age?

7 to 10 mL.

What is the size of the normal uterus?

7.5 to 9.5 cm in length (cervix to fundus), 4.5 to 6.5 cm in width (from cornua to cornua), and 2.5 to 3.5 cm in anteroposterior diameter. Uterine cavity averages 3.5 cm in length.

What are the components of the workup for abnormal uterine bleeding?

A complete history, physical examination, laboratory studies, imaging studies, and tissue sampling.

What is the next step in the evaluation of abnormal uterine bleeding following the history and physical examination in a woman of reproductive age?

A pregnancy test.

What is the most common reason for endometrial ablation to fail?

Adenomyosis.

What are the usual causes of abnormal genital bleeding in patients early after menarche?

Anovulation (hypothalamic immaturity), bleeding diathesis,stress (psychogenic, exercise induced), pregnancy, and infection.

What are the usual causes of abnormal genital bleeding in perimenopausal women?

Anovulation, polyps, fibroids, adenomyosis, and cancer.

What is the most common cause of postmenopausal bleeding?

Atrophic endometrium and/or atrophic vaginitis.

In what clinical situation is DUB best treated with a progestin containing IUD?

Bleeding associated with chronic illnesses (such as renal failure).

Define dysfunctional uterine bleeding (DUB).

Bleeding that is not attributable to an underlying organic pathologic condition. DUB usually refers to anovulatory bleeding (90%).

What additional laboratory studies are important in the workup of abnormal uterine bleeding?

CBC, PT/PTT, TSH, Prolactin levels, androgen levels, and testing for infection with Chlamydia and gonorrhea.

In women of reproductive age, what is the most common cause of estrogen excess bleeding?

Chronic anovulation associated with polycystic ovaries.

Failure of oral contraceptives to control bleeding when given twice daily for 5 and 7 days should prompt further evaluation. What are the most common diagnostic possibilities?

Complications of pregnancy (incomplete abortion, ectopic pregnancy), endometrial polyps, and endometrial neoplasia (including hyperplasia).

When should ultrasound be performed on premenopausal women for endometrium evaluation?

Days 4 and 6, when endometrium is expected to be the thinnest.

How does one measure the strength of a progestational agent?

Delay of menses.

What is the best medical treatment of severe acute menorrhagia secondary to atrophic bleeding?

Ethinyl estradiol (10-20 mg) for 2 to 3 weeks.

What are the most common bleeding patterns seen in a woman with cervical cancer?

Intermenstrual and postcoital bleeding.

What is the role of curettage in the treatment of DUB?

It is effective in controlling acute hemorrhage when hormonal therapy fails.

What is Halban syndrome?

It is the persistence of a corpus luteum. Patients commonly present with delayed menses, pelvic mass, and negative pregnancy test. Clinically, this is often confused with an ectopic pregnancy. Typically self-limited and usually does not recur.

Define oligomenorrhea.

Menses at intervals >35 days.

Define metrorrhagia.

Menses at irregular intervals.

Define hypomenorrhea.

Menses at regular intervals that is decreased in amount.

Define menorrhagia.

Menses at regular normal intervals with excessive flow and duration.

Define menometrorrhagia.

Menses with heavy and irregular bleeding.

What are the main treatments of dysmenorrhea?

NSAIDs, oral contraceptive pills (OCPs); alternatively GnRH agonist can be considered if first-line treatments fail.

Define dysmenorrhea.

Pain associated with menstruation.

What are the two direct (definitive) signs of ovulation?

Pregnancy and visualization of follicle rupture either during laparoscopy or ultrasound.

In what groups of patients other than postmenopausal women, can you find vaginal bleeding secondary to atrophic vaginitis?

Premenarchal girls, postpartum lactating women, and women on chronic progestins.

What are the earliest histologic changes in the endometrium following ovulation and when do they occur?

Progesterone causes mitotic arrest. The earliest histologic change that can be identified is the development of subnuclear vacuoles. Both mitotic arrest and subnuclear vacuoles are present by postovulatory day 3 (day 17, assuming a normal 28-day cycle).

What is the normal endometrial thickness in women of reproductive age?

Proliferative phase 4 and 8 mm and secretory phase 8 and 14 mm.

Define polymenorrhea.

Regular menses at intervals of 21 days or less

What vascular event triggers shedding of the endometrium?

Spasm of the spiral arteries resulting in ischemia of the tissue and sloughing.

A 14-year-old female presents with her first menses. Her bleeding is profuse and her hemoglobin is 4 g/dL. The pregnancy test is negative and to the best of your ability a bleeding disorder is excluded. What would be your pharmacologic approach to this patient?

Conjugated estrogens 25 mg intravenously (IV) every 4 hours until bleeding stops or for 4 doses (12 hours). Progestin treatment is started concurrently.

What are the medications that can cause vaginal bleeding?

Contraceptive medication [OCP, intrauterine device (IUD), Depo-Provera], hormone replacement therapy, anticoagulants, corticosteroids, chemotherapy, dilantin, antipsychotic medication, and antibiotics (eg, due to toxic epidermal necrolysis or Stevens-Johnson syndrome).

What are the three layers of the endometrium?

(1) The pars basalis, (2) the zona spongiosa, and (3) the superficial zona compacta. The zona spongiosa and zona compacta make up the stratum functionalis, which is shed during menses.

In what clinical situations should estrogen be the initial choice of treatment for abnormal uterine bleeding?

(1) When the bleeding has been heavy for many days, (2) when endometrial sampling yields minimal tissue, (3) when the patient has been on progestins and the endometrium is atrophic, and (4) when follow-up is uncertain, because estrogen will temporarily stop all categories of DUB.

What is the probability of endometrial cancer in postmenopausal woman with vaginal bleeding after a negative hysteroscopy?

0.4% to 0.5%.

What is the probability of endometrial cancer in a postmenopausal woman with vaginal bleeding with endometrial thickness <4 mm?

0.5%.

What is the best pharmacologic approach to treat a woman with ovulatory cycles but heavy menses?

A prostaglandin synthetase inhibitor (such as naproxen), beginning with the onset of symptoms.

A 37-year-old woman, G2 P2 presents with a history of lengthening menses and acquired dysmenorrhea. This problem had been subtly going on for 2 years and now is a quality-of-life issue. Examination reveals a top normal size globular shaped uterus. What is the most likely diagnosis?

Adenomyosis.

What are the usual causes of abnormal genital bleeding in reproductive years?

Anovulation, pregnancy, cancer, polyps, fibroids, adenomyosis, infection, endocrine dysfunction (PCOS, thyroid, pituitary adenoma), bleeding diathesis, medication related.

What percentage of patients present with chief complaint of abnormal vaginal bleeding?

Approximately 12% of gynecology referrals are because of menorrhagia. Among women between ages 30 and 49, 5% consult physician for evaluation of menorrhagia.

What is the life span of a normal corpus luteum in the absence of pregnancy?

Approximately 14 days.

How big is the dominant follicle at the time of ovulation?

Approximately 20 and 26 mm.

What percentage of adolescents that require hospitalization for abnormal bleeding have an underlying coagulation disorder?

Approximately 25%. The majority of these patients will have von Willebrand disease, problems with platelet count, or problems with platelet function.

Define normal menstrual flow quantitatively.

Approximately 30 cc.

What percentage decrease in blood loss can be expected with the use of a prostaglandin synthetase inhibitor?

Approximately 40% to 50%.

How much blood blow does the nonpregnant uterus receive?

Approximately 50 cc/min (as opposed to approximately 600 cc/min in the pregnant uterus).

What percentage of women develop amenorrhea following endometrial ablation?

Approximately 60%.

When does implantation of the fertilized ovum typically occur?

At approximately postovulatory day 9 (day 23, assuming a normal 28-day cycle).

When in the cycle should an endometrial biopsy be performed?

At or beyond day 18, because if it shows secretory endometrium, then it confirms that ovulation has occurred in that cycle.

What are the usual causes of abnormal genital bleeding in postmenopausal women?

Atrophy, cancer, and estrogen replacement therapy.

What are the risks of treatment with high dose estrogens?"

DVT and PE, particularly with IV estrogen. Nausea/vomiting, particularly with oral estrogen therapy.

Broadly characterize the major categories of DUB?

Estrogen breakthrough bleeding, estrogen withdrawal bleeding, and progesterone breakthrough bleeding.

Describe the effect of estrogen on the endometrium.

Estrogen causes proliferation of the endometrium. The endometrial glands lengthen and the glandular epithelium becomes pseudostratified. Mitotic activity is present in both the glands and the stroma.

A patient is taking a low-dose OCPs. She experiences repetitive spotting during the first week of therapy. How would you treat this?

Estrogen therapy for 7 days in addition to her OCP. This could be as conjugated estrogens 1.25 mg or estradiol 2.0 mg. This is preferable to changing pills. May reassure patient that this is normal and wait for 3 cycles, as most of such symptoms resolve by that time, if not then may change the pill.

What is the next step in the evaluation of a woman with abnormal uterine bleeding?

Evaluation of the endometrial cavity by hysterosalpingography (HSG), sonohysterography (SHG), or hysteroscopy.

What are the usual causes of abnormal genital bleeding in premenarchal patients?

Foreign body, trauma including sexual abuse, infection, urethral prolapse, sarcoma botryoides, ovarian tumor, and precocious puberty.

Name the hormones, and their source, that are involved in maintaining a normal menstrual cycle.

From the ovary: Estrogen, progesterone, and inhibin A. From the pituitary: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Prolactin and thyroid-stimulating hormone (TSH) are also vital in maintaining a normal menstrual cycle. From the hypothalamus: Gonadotropin-releasing hormone (GnRH).

What is the first step in the evaluation of abnormal uterine bleeding following the history and physical examination in a woman?

Hemodynamic status.

What is the best medical treatment of severe acute menorrhagia related to anovulation?

High-dose estrogens. IV conjugated equine estrogen (CEE) for up to 24 hours (25 mg IV/IM every 4 hours), followed with oral CEE (eg, 2.5 mg four times a day) for 21 to 25 days, with medroxyprogesterone acetate (10 mg per day) for the last 10 days to induce bleeding. A Foley catheter can be placed to tamponade bleeding temporarily. Antiemetics are required in 40% of patients.

What are the systemic illnesses that may cause anovulatory bleeding?

Hypo- and hyperthyroidism, chronic liver disease, chronic renal failure, Cushing disease, PCOS, prolactinoma, empty sella syndrome, Sheehan syndrome, adrenal and ovarian tumors, and tumors infiltrating the hypothalamus.

What percentage of patients after endometrial ablation require further procedures?

Hysterectomy or repeat endometrial ablation is required in 20% to 40% of patients within 4 years.

How can you determine ovulatory status based on menstrual history?

If there are predictable cyclic menses, with duration of cycle 24 and 35 days, then most likely they are ovulatory. If the cycles vary in length by >10 days from one cycle to the next, then they are most likely anovulatory.

What is the advantage of curettage?

In the woman with heavy bleeding, it may be therapeutic as well as diagnostic.

A woman normally has 32-day cycles. In this woman, when does ovulation occur?

In this clinical situation, ovulation should occur on day 18. The luteal phase of the cycle should remain constant at 14 days.

How does estrogen affect breakthrough vaginal bleeding?

Low doses of estrogen cause intermittent spotting that may be prolonged. High levels of estrogen lead to amenorrhea followed by acute, often profuse bleeding.

How can you determine ovulatory status?

Menstrual cycle charting, day 3 FSH, anti-Mullerian hormone levels, basal temperature monitoring, measurement of the serum progesterone concentration, monitoring of urinary LH excretion, and sonographic demonstration of periovulatory follicle.

Define primary amenorrhea.

No menarche by age 16 in a female with normal growth and secondary sex characteristics; or, no menarche by age 13 without development of secondary sex characteristics.

Decline in which hormone heralds the onset of menses?

Normal menses occurs because of progesterone withdrawal.

If a single value of serum progesterone is low for the luteal phase, does it mean that the patient is not in the luteal phase?

Not necessarily because it may be obtained between LH pulses, though a single level above 6 ng/mL is usually indicative of normal luteal phase.

What are the options for treatment of chronic or less severe acute menorrhagia?

OCPs, IUDs, NSAIDs, antifibrinolytics: tranexamic acid, danazol, D&C, and hysteroscopic endometrial ablation (if completed child bearing).

In a woman after age 30 with abnormal bleeding what should be obtained next?

Obtain a tissue biopsy. This may be in the form of endometrial biopsy or curettage.

In a normal menstrual cycle, when does ovulation typically occur?

Ovulation in a 28-day cycle occurs on day 14. The luteal (secretory) phase of the cycle is constant at 14 days. The estrogenic (follicular/proliferative) phase of the cycle can be variable.

On which postovulatory day does the endometrium demonstrate peak endometrial stromal edema?

Postovulatory day 8 (day 22, assuming a normal 28-day cycle).

On which postovulatory day does predecidual change first begin to appear and where does it first appear?

Postovulatory day 9 (day 23, assuming a normal 28 day cycle). Predecidual change (periarteriolar cuffing) first appears around the spiral arterioles. Predecidual cells contain glycogen.

How does progesterone work at the cellular level to control DUB when prescribed in pharmacologic doses?

Progestins are powerful antiestrogens. They stimulate 17β-hydroxysteroid dehydrogenase and sulfotransferase activity. This results in conversion of estradiol to estrone sulfate that is rapidly excreted in the urine. Progestins also inhibit augmentation of estrogen receptors. Additionally, progestins suppress estrogen-mediated transcription of oncogenes.

What are the causes of progesterone withdrawal bleeding?

Removal of the corpus luteum, medically or surgically. Pharmacologically a similar event can be achieved by administration and discontinuation of progesterone or a synthetic progestin, provided the endometrium is estrogen primed.

In what clinical situations is DUB best treated with a GnRH agonist?

Renal failure, blood dyscrasia, or organ transplantation (especially liver transplantation).

Broadly characterize the causes of abnormal uterine bleeding?

Reproductive tract disease, systemic disease, trauma, pharmacologic alterations, anovulation, and ovulation.

What are common clinical conditions present when medical therapy fails to control menorrhagia?

Submucous fibroids, endometrial polyps, hyperplasia, or cancer.

What are the lifestyle elements that may cause anovulatory bleeding?

Sudden weight loss, stress, and intense exercise.

Define secondary amenorrhea.

The absence of bleeding for at least three usual cycle lengths or 6 months in women who previously had menses.

What is the cause of midcycle spotting or light bleeding?

The decline in estrogen that occurs immediately prior to the LH surge.

Define the normal menstrual cycle.

The normal menstrual cycle is 28 days with a flow lasting 2 to 7 days. The variation in cycle length is set at 24 to 35 days.

What is the immediate objective of medical therapy in treating anovulatory bleeding?

To stabilize the endometrium and control acute hemorrhage.

True or False: A woman with acute DUB having failed medical options and does not want a hysterectomy may benefit from interventional radiology uterine artery embolization (UAE) procedures.

True, but only recommended if completed child bearing.

What percentage of women will develop improvement in their menstrual blood loss following endometrial ablation?

Up to 90%.

What are the diseases that may mimic vaginal bleeding?

Urethritis, bladder cancer, urinary tract infection, inflammatory bowel disease, and hemorrhoids.

Usual cause of abnormal genital bleeding in neonates?

Withdrawal from maternal estrogens.

Can severe acute menorrhagia related to anovulation be treated with progestins only?

Yes, but it is less effective. Treatment involves medroxyprogesterone acetate (20-40 mg per day in divided doses), or megestrol acetate (40-120 mg per day), or norethindrone (5-10 mg per day) for 5-10 days. A 2 to 3 weeks regimen may be prescribed to allow for an increase in the hemoglobin concentration of anemic patients.

What are the causes of estrogen withdrawal bleeding?

Bilateral oophorectomy, radiation of mature follicles, and administration of estrogen to a previously oophorectomized woman followed by its withdrawal

Define menorrhagia quantitatively.

Blood loss in excess of 80 mL.

How can you narrow the differential diagnosis of uterine bleeding in patients of reproductive age?

By establishing ovulatory status.

How can one increase sensitivity and specificity of transvaginal ultrasound in assessment of endometrial cavity?

By performing saline infusion sonography with instillation of sterile saline into the endometrial cavity. Sensitivity increases from 75% to 93%, specificity from 76% to 94%.

By which postovulatory day do the endometrial glands appear exhausted as it relates to the secretory phase?

By postovulatory 6 (day 20, assuming a normal 28-day cycle).

What is the most important diagnosis to rule out in the postmenopausal woman?

Cancer, primarily endometrial.