Surgical Indications for Dysfunctional Uterine Bleeding Case File

Surgical Indications for Dysfunctional Uterine Bleeding Case File

Eugene C. Toy, MD, Konrad P. Harms, MD, Keith O. Reeves, MD, Cristo Papasakelariou, MD, FACOG

Case 33

A 42-year-old G2P2 woman, with a recent last menstrual period (LMP), presents complaining of irregular periods for 4 years. She states that her periods are about three to four times a year and very long in duration, up to 21 days. She has gained 50 lb (22.68 kg) in the last 2 years. Four years ago, she was on oral contraceptive pills to regulate her periods. Her last doctor instructed her to take iron daily for her anemia. She is “tired of these heavy periods” and refuses further medical therapy. She wants surgical therapy. Her review of systems is negative for thyroid disease or galactorrhea. She denies any significant past medical, family, or social histories. She had a bilateral tubal ligation 3 years ago.

On examination, her weight is 262 lb (118.85 kg), BP 112/72 mmHg, and pulse 60 bpm. The head and neck examination, including the thyroid gland, is normal. The abdomen is nontender and there are no masses. On pelvic examination, the uterus is noted to be 8- to 10-week size and the adnexa are difficult to assess. A pelvic ultrasound is performed revealing a normal sized uterus, with an endometrial stripe of 10mm and no adenxal masses. A pregnancy test is negative.

➤ What is the most likely diagnosis?

➤ What is the next step?

ANSWERS TO CASE 33:

Surgical Indications for Dysfunctional Uterine Bleeding

Summary: 42-year-old G2 P2 woman has a 4 year history of irregular menses, oligomenorrhea, menorrhagia, obesity, and anemia. She desires surgical therapy.

➤ Diagnosis: Oligomenorrhea or dysfunctional uterine bleeding (DUB)

➤ Next step: Endometrial biopsy

ANALYSIS

Objectives

1. Recognize that DUB is a diagnosis of exclusion.
2. Know the common differential diagnoses that cause DUB.
3. Understand that surgical therapy is indicated only when medical therapy fails and future fertility is no longer desired.
4. Recognize the two surgical therapies for DUB, endometrial ablation, and hysterectomy.

Considerations

This patient has a long history of irregular periods. This is a classic case of anovulation, most likely secondary to her obesity. She weighs 100 lb (45.36 kg) over her ideal body weight. One has to consider an underactive thyroid being a contributor to her obesity. Her age warrants that the next step is to perform an endometrial biopsy. Women older than 35 years should receive an endometrial biopsy (EMB) for any abnormal uterine bleeding. Note that her endometrial stripe is 1 cm. Studies reveal that an EMB using the Pipelle type of device is highly effective in detecting pathology.1 Her differential diagnosis includes anovulation, hypothyroidism, endometrial polyp, and uterine fibroids. An endometrial polyp or endometrial hyperplasia/neoplasia can be the etiology for an enlarged endometrial stripe. A coagulation defect is unlikely, given the age of the patient. Since DUB is a diagnosis of exclusion, an organic etiology should be ruled out first. After obtaining a negative pregnancy test, check a thyroid-stimulating hormone (TSH), complete blood (cell) count (CBC), and prolactin, even though the patient has a negative past medical history. Premature ovarian failure can be ruled out if the folliclestimulating hormone (FSH) is less than 40 U/L. An EMB that reveals proliferative endometrium is consistent with anovulation. This patient should be offered medical treatment, first, with hormones. After medical therapy fails or in this case, is refused, surgical therapy is the next option. This patient is a candidate for an endometrial ablation because her uterine size is normal and without evidence of any organic etiology, such as fibroids. The fact that she received a tubal ligation confirms that she does not desire future fertility. Keeping in mind that endometrial ablation has shorter operative time, shorter recovery, and less hospital-associated cost, this procedure should be offered first. Even though hysterectomy is definitive, there is associated morbidity and mortality.2

APPROACH TO

Dysfunctional Uterine Bleeding

DEFINITIONS

DUB: Excessive uterine bleeding without any demonstrable organic cause.

MENORRHAGIA: Prolonged uterine bleeding longer than 7 days duration or greater than 80 cc.

ENDOMETRIAL ABLATION: Operative destruction, via a hysteroscope, of the endometrium with a variety of different instruments.

OLIGOMENORRHEA: Uterine bleeding that occurs at intervals of longer than 35 days.

MENOMETRORRHAGIA: Prolonged uterine bleeding that occurs at irregular intervals.

POLYMENORRHEA: Uterine bleeding that occurs at intervals every 21 days or fewer.

CLINICAL APPROACH

Heavy menstrual flow can become very disturbing to a woman and can result in disruption of her lifestyle. These changes include absenteeism from work, avoidance of social functions, and restriction to certain physical activities. Over a period of time, women will experience fatigue, anxiety, anemia, and a decrease in quality of life.3

Dysfunctional uterine bleeding is defined as noncyclic, menstrual flow, unrelated to organic pathology.3 It clinically manifests as abnormal volume, timing, and duration of flow. Traditional options for treatment include medical therapy with hormones and surgical therapy, such as endometrial ablation and hysterectomy. The choice of treatment depends on the woman’s age and her desire for future fertility.

During a normal menstrual cycle, the endometrium is exposed to the ovarian production of estrogen, in the first half of the cycle and after ovulation, progesterone, in the second half of the cycle. Menses occurs secondary to the estrogen and progesterone withdrawal, to begin another cycle. In DUB, or anovulatory bleeding, a corpus luteum does not form and progesterone is not produced from the ovary. In this clinical scenario, the endometrium continues to be primed with estrogen. As a result, the endometrial lining continues to proliferate. Once the lining is at its maximum thickness, inadvertent shedding of the endometrium will occur in a nonuniform, noncyclic manner. This occurs because the endometrium is very vascular, fragile, and not stable. The end result is prolonged, heavy, uterine bleeding.

A detailed history should be obtained from the patient. It is important to verify what “irregular” means to her. Is the uterine bleeding more than once a month or only monthly, with variable duration? Have the patient quantify her bleeding.

• Number of pads used in a 24-hour period
• Does the bleeding soil her clothes?
• Is her activity restricted?
• Does she stay home from work?
• Passage of clots? If so, what size . . . (ie, penny, nickel, dime, quarter, halfdollar size)

Obtain other relevant history. Certain medications can contribute to abnormal bleeding, such as hormones and psychotropic medications. On the physical examination, look closely for evidence of hirsutism and obesity. Perform a detailed pelvic examination. Examine the external genitalia for lacerations. Insert the speculum and evaluate for lacerations or trauma to the cervix or vagina. Foreign bodies, such as an IUD, can also cause abnormal bleeding. Obtain a Pap smear and cultures. Perform an endometrial biopsy in a woman older than 35 years. Studies show that the endometrial Pipelle is highly effective and accurate in sampling the endometrium.3 Malignancies can cause abnormal uterine bleeding. This test will usually rule out endometrial hyperplasia and endometrial carcinoma. A TSH and a prolactin should be obtained. If hypothyroidism is diagnosed, then levothyroxine should be prescribed. Once the thyroid hormonal status corrects, usually requiring 3 months, the menorrhagia should improve. Check the pregnancy test. A pelvic ultrasound will evaluate for any organic causes of the uterine bleeding, such as leiomyomas. DUB is a diagnosis of exclusion; other etiologies should be ruled out as a cause of bleeding. Developing a differential diagnosis is important and will differ based on the age of the patient (Table 33–1).

If the TSH, CBC, prolactin, and pelvic ultrasound are normal and the endometrial biopsy is negative for hyperplasia or neoplasia, DUB can be diagnosed. Remember, it is a diagnosis of exclusion.

For women younger than 20 years, a coagulation disorder should be eliminated. All adolescents with prolonged uterine bleeding since menarche need routine screening for coagulation defects. Disorders such as idiopathic thrombocytopenic purpura and von Willebrand disease should be considered. Other disorders that cause platelet dysfunction include leukemia or sepsis. However, the most common diagnosis for DUB in this age group is immaturity of the hypothalamic, pituitary, and gonadal axis. Look for petechiae or bruising on the

Table 33–1 DIFFERENTIAL DIAGNOSES OF DUB

Anovulation Systemic disease (thyroid) Pregnancy Coagulation defects Infection Endometrial hyperplasia Uterine fibroids Endometrial malignancy

skin during the physical examination. In addition to the earlier-mentioned laboratory tests, also check a prothrombin time and partial thromboplastin time (PTT). An endometrial biopsy (Pipelle) is not necessarily indicated in this age group, unless there is evidence of prolonged unopposed estrogen exposure.

For women, between 20 and 40 years of age, a common disorder is polycystic ovarian syndrome. A triad of symptoms includes obesity, hirsutism, and noncyclic menstrual bleeding (dysfunctional uterine bleeding [DUB]). Hypothyroidism, hyperprolactinemias, and premature ovarian failure should be ruled out. All contribute to irregular menses. On physical examination, note any evidence of acne, hirsutism, and body weight. Perform an endometrial biopsy on women older than 35 years. Check a TSH, FSH, and prolactin. If all are normal, DUB can be diagnosed.

For women between 40 and 51 years of age, anovulatory cycles are common secondary to declining ovarian function. Perform an EMB and ultrasound to rule out fibroids, hyperplasia, and neoplasia. Cancer and hyperplasia incidence is higher in this age group. Check TSH, FSH, and prolactin. If all are normal, DUB is the diagnosis.

Treatment

Treatment options are medical and surgical. The age of the patient will dictate therapy. Medical treatment consists of hormones, such as cyclic progestins, combination oral contraceptives, or nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs have been shown to decrease monthly menstrual blood loss and block prostaglandin production. This treatment may be continued up to 6 months. Once medical therapy has failed and the woman does not desire future fertility, surgery can be offered.

Surgical therapy for DUB is twofold: endometrial ablation and hysterectomy. Both are effective treatments for DUB, with hysterectomies being associated with more adverse events.3

Endometrial ablation is a minimally invasive technique that was introduced in 1937.4 It is used to treat heavy menstrual bleeding in women who do not desire future fertility. Its absolute contraindications include pregnancy, uterine size greater than 12 to 14 weeks, active pelvic infection, and evidence of a premalignant or malignant disorder. Older techniques involved the use

Table 33–2 METHODS OF ENDOMETRIAL ABLATION

RESECTOSCOPE

Loop electrode Rollerball

NONRESECTOSCOPE

Cryoabalation therapy (Her Option) Heated free fluid (Hydro Therm-Ablator) Microwave Radiofrequency electricity (NovaSure) Thermal balloon (ThermaChoice)

of the resectoscope and now there are newer nonresectoscopic techniques utilizing different energy sources. In the United States, there are several systems approved for use (Table 33–2).

Three instruments are needed to perform an ablation: (1) distention media, (2), operative hysteroscope, (3) ablation instrument. Counselling the patient prior to the procedure is very important. Women should be informed that hypomenorrhea is the usual outcome, even though more than 40% of women can become amenorrheic from the procedure.5 Priming agents are used before the ablation to thin the endometrium. Danazol and a gonadotropin-releasing hormone (GnRH) analogue (Lupron) are commonly used for 4 to 12 weeks prior to the procedure. Remember, the side effects of Danazol are clitorimegaly, deepening of the voice, acne, and alteration of low-density lipoprotein (LDL) cholesterol.6 Endometrial thinning can shorten the procedure time and ease the level of difficulty with surgery.

Most studies cite endometrial ablation as an alternative to hysterectomy. Dickersin et al. showed that both endometrial ablation and hysterectomy are effective at 24 months, in improving DUB. However, 32 out of 110 patients who received an endometrial ablation required another operation.3 Another randomized control trial revealed that 78% of women receiving endometrial ablation were satisfied at 12 months compared to 89% of those receiving a hysterectomy. However, morbidity was higher in the hysterectomy group. Gannon et al.7 who revealed that endometrial ablation is an alternative to hysterectomy with less operating time, shorter recovery time in the hospital, and cheaper cost compared to hysterectomy, found similar results. No one in this study required a hysterectomy during the follow-up of 12 to 16 months.8 Endometrial ablation is safe, and Garry et al. showed that out of 600 laser ablations performed, none of the participants experienced any operative morbidity.6

Table 33–3 TYPES OF DISTENTION MEDIA
CARBON DIOXIDE GAS
Electrolyte-rich Lactated Ringer solution Normal saline	Electrolyte-poor 3% Sorbitol 1.5% Glycine 5% Mannitol

Complications can occur with endometrial ablation and develop secondary to either the distention media or the operative technique. Table 33–3 shows the different distention media available. Complications with the distention media occur more commonly with the resectoscopic ablations.

Carbon dioxide (CO2) is a gas used for diagnostic hysteroscopies. If bleeding occurs, CO2 does not mix well with blood and can disrupt visualization of the endometrial cavity. Watch the flow rate, during the case, to reduce the risk of an air embolus. If the flow is greater than 100 mL/min, the patient is at risk. Sudden desaturation of oxygen, hypotension, or development of cardiac arrhythmias can occur suddenly. Immediately, place the patient in left lateral decubitus position at a 5-degree angle to move the air toward the right ventricle.9 When liquid media are used, fluid management is critical to avoid complications. Once a deficit of 1 L has been reached, the procedure should be discontinued immediately. The electrolyte-free solutions can get absorbed into the systemic circulation and cause hyponatremia, fluid overload, seizures, brain edema, and rarely death. Hyponatremia is corrected within 24 to 48 hours. Give the patient isotonic solution, normal saline, and infuse 1 to 2 mEq/L/h to correct the sodium level.9 A diuretic may be given to correct any pulmonary edema, as a result of the fluid overload. Use of the electrolyte-rich media is more likely to cause fluid overload, and not hyponatremia. Other complications described in the literature, during an ablation, include uterine perforation, lacerations of the cervix and vagina, hemorrhage, and thermal injury to the bowel and bladder. If uterine perforation occurs with dilation of the cervix, the perforation is usually in the midline. Lateral perforation can lead to severe bleeding. If this occurs, stop the procedure and perform a laparoscopy to visualize the extent of the damage. Admit the patient and follow serial hematocrits over 24 hours.9 If hemorrhage develops as a complication, a Foley balloon can be inserted to tamponade the bleeding or a vasopressin can be injected at the site of bleeding to help to decrease the blood loss.9 These adverse events occur because the ablation extends too deeply into the myometrium and breaches the integrity of surrounding structures.6

Hysterectomy, with or without a bilateral salpingo-oophorectomy, is the definitive therapy for DUB. Studies show that for long-term management of bleeding, hysterectomy will be required for DUB in 30% of women.10 Hysterectomy is the most frequently performed operation in the United States. It is associated with a higher satisfaction rate compared to endometrial ablation, but also its costs are higher.7 There are complications to consider. Febrile morbidity is the most frequent complication, with abdominal hysterectomies having higher rates compared to vaginal hysterectomies.2 Others adverse events include thromboembolism; vascular injury; hemorrhage; and damage to the bowel, bladder, and ureteral systems. Accurate knowledge of the anatomy is the key to reducing complication. Ureteral injures occur in 2 to 5 out of 1000 operations.2 The risk of death is low, keeping in mind that most cases occur as a complication of the surgery.

Comprehension Questions

33.1 A 37-year-old G4P4, with a history of hypothyroidism, stopped taking her medicine last year because she was “feeling fine.” Nine months ago, she started having two periods a month. Her laboratory work showed a TSH of 50 U/L and hemoglobin of 11.8 mg/dL. A pelvic ultrasound was normal. What is the most likely diagnosis?

A. Anovulation

B. Hypothyroidism

C. Leukemia

D. Uterine fibroids

33.2 A 17-year-old G0P0 woman presents complaining of heavy bleeding for 10 days every month with her periods, since menarche at the age of 12. Her hemoglobin is 7.5 mg/dL. What is the next step in her workup?

A. Check liver function tests.

B. Draw a TSH.

C. Draw coagulation tests.

D. Order a pelvic ultrasound.

33.3 A 41-year-old G3P3 woman has a resectoscopic endometrial ablation using 1.5% glycine. The ablation lasts for 2 hours and intraoperatively; the nurse states that the fluid deficit is 2500 cc. What is the most likely electrolyte abnormality?

A. Hyponatremia

B. Hypercalcemia

C. Hypoglycemia

D. Hyperkalemia

33.4 A 32-year-old G6P6 woman is having a NovaSure endometrial ablation. You dilate her uterus and insert the hysteroscope and visualize the bowel. What is the most appropriate next step?

A. Proceed with the ablation and repair the uterus after the case.

B. Stop the procedure, perform a laparoscopy, and check serial hematocrits.

C. Repair the uterus first before proceeding with the ablation.

D. Use a different ablation technique.

ANSWERS

33.1 B. Hypothyroidism is a systemic etiology for DUB. Once the thyroid gland is regulated with levothyroxine, the menorrhagia will abate in 3 to 6 months.

33.2 C. In teenagers, coagulation disorders are the most common etiology for the heavy uterine bleeding. Checking a PT/PTT and von Willebrand factor is the next step to establish a diagnosis.

33.3 A. This patient has fluid overload from intravascular absorption of glycine, the distention medium. Hyponatremia is the abnormality that needs to be corrected.

33.4 B. Uterine perforation is a complication of this ablation. After visualization of the bowel, the ablation is discontinued and a laparoscopy is performed to judge the extent of injury to the uterus and any other surrounding structures.

Clinical Pearls

See Table 1-2 for definition of level of evidence and strength of recommendation

➤ Once an organic etiology is ruled out, DUB is the diagnosis for heavy menstrual bleeding (Level B).

➤ An endometrial biopsy should be performed in all women older than 35 years with heavy uterine bleeding (Level B).

➤ Differential diagnoses may vary, based on the age of the patient (Level A).

➤ Surgical therapy for DUB is indicated after medical therapy has failed and future fertility is no longer desired (Level B).

➤ Endometrial ablation is an alternative to hysterectomy with less morbidity and mortality (Level A).

➤ Hysterectomy is the most definitive therapy for DUB (Level A).

REFERENCES

1. Goldchmit R, Katz Z, Blickstein I, Caspi B, and Dgani R. The accuracy of endometrial Pipelle sampling with and without sonographic measurement of endometrial thickness. Obstet Gynecol. 1993;82:727-730. 

2. Peipert JF, Weitzen S, Cruickshank C, Story E, Ethridge D, Lapane K. Risk factors for febrile morbidity after hysterectomy. Obstet Gynecol. 2004;103:86-91. 

3. Dickersin K, Munro, MG, Clark, M, et al. Hysterectomy compared with endometrial ablation for dysfunctional uterine bleeding. Obstet Gynecol. 2007;110:1279-1289. 

4. American College of Obstetricians and Gynecologists. Endometrial Ablation. ACOG Practice Bulletin. 2008:1356-1371. 

5. Garry R, Shelley-Jones D, Mooney P, et al. Six hundred endometrial laser ablations. Obstet Gynecol. 1995;85:24-29. 

6. Garry R. Good practice with endometrial ablation. Obstet Gynecol. 1995;86:144-151. 

7. Gannon MJ, Holt EM, Fairbank J, Fitzgerald M, Milne MA, Crystal AM, et al. A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia. BMJ. 1991;303:1362-1364. 

8. Goldenberg M, Sivan E, Bider D, et al. Endometrial resection vs. abdominal hysterectomy for menorrhagia. J Reprod Med. 1996;41:333-336. 

9. American College of Obstetricians and Gynecologists. Hysteroscopy. ACOG Practice Bulletin. 2008:350-353. 

10. Learman LA, Summitt RL Jr, Varner RE, Richter HE, Lin. F, Ireland CC, et al. Hysterectomy versus expanded medical treatment for abnormal uterine bleeding: clinical outcomes in the medicine or surgery trial. Obstet Gynecol. 2004; 103:824-833. 

11. American College of Obstetricians and Gynecologists. Anovulatory Bleeding. ACOG Practice Bulletin No. 2008:1049-1056. 

12. Pinion SB, Parkin DE, Abramovich DR, Naji A, Alexander. DA, Russell IT, et al. Randomised trial of hysterectomy, endometrial ablation, and transcervical endometrial resection for dysfunctional uterine bleeding. BMJ. 1994;309:979-983. 

13. Easterday CL, Grimes DA, Riggs JA. Hysterectomy in the United States. Obstet Gynecol. 1983;62:203-212. 

14. Unger JB, and Meeks GR. Hysterectomy after endometrial ablation. Am J Obstet Gynecol. 1996;175:1432-1437.

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