US Pharm. 2006;31(9):HS-16-HS-24.

According to the most recent surveillance data from the CDC, hysterectomy is the second most frequently performed surgical procedure for women of reproductive age, topped only by cesarean delivery.1 The United States has the highest rate of hysterectomy in the industrialized world, with 5.5 per 1,000 women undergoing the procedure each year.1,2 Many indications for hysterectomy are poorly defined and based more on expert opinion than on evidence from well-designed clinical trials.2,3

Regardless of the surgical technique used, hysterectomy is associated with short- and long-term complications. All women considering hysterectomy should be aware of these risks prior to surgery, in order to make an informed decision as to whether the procedure is the best treatment option. This article reviews the short- and long-term complications associated with hysterectomy and thereby aids pharmacists in providing care for this large population of women.

Indications for Hysterectomy
Health care providers have limited data from well-designed clinical trials to guide determination of when hysterectomy is the most appropriate treatment option. Some well-established indications for hysterectomy include life-threatening conditions such as serious complications during childbirth, unmanageable uterine hemorrhage, and invasive cancer of the uterus, cervix, va­ gina, fallopian tubes, or ovaries.2,4 Outside of these situations, however, guidance is scarce regarding the appropriate indications for hysterectomy.

According to the CDC, from 1994 to 1999, uterine leiomyoma, endometriosis, and uterine prolapse were the most common indications for hysterectomy and accounted for 73% of all hysterectomies performed.1 This figure is quite staggering, considering that much of the current literature recommends conservative management of most benign gynecologic conditions, with hysterectomy considered as a last resort in refractory cases.5

In 2002, the Society of Obstetricians and Gynecologists of Canada (SOGC) published clinical practice guidelines that provide common indications for hysterectomy.4 According to these guidelines, endometriosis with severe symptoms that are refractory to other medical treatment options, symptomatic leiomyomas (uterine fibroids), and pelvic relaxation are benign conditions in which hysterectomy may be considered. In the case of abnormal uterine bleeding, endometrial lesions must be excluded and medical alternatives should be considered first-line therapy prior to consideration of surgical intervention.4 The SOGC guidelines recommend that in all cases pertaining to benign conditions, risks and benefits of surgery as well as loss of fertility should be discussed prior to surgery, and a woman's preference should be highly respected.

Types of Hysterectomy
There are several types of hysterectomy, all of which include the removal of the uterus. In a subtotal hysterectomy (also referred to as a supracervical or partial hysterectomy), the upper two thirds of the uterus is removed, while the cervix is left in place.2 Although this procedure is common, the majority of women decide to have a total hysterectomy. A total hysterectomy (or complete hysterectomy) involves the removal of the entire uterus as well as the cervix. If both the ovaries and the fallopian tubes are removed during a total hysterectomy, the procedure is called a bilateral salpingo-oophorectomy. Finally, the most extreme type of hysterectomy, a radical hysterectomy, involves removal of the uterus, cervix, ovaries, fallopian tubes and, possibly, upper portions of the vagina and affected lymph glands. This procedure is strongly recommended for serious complications and diseases such as cancer.2

A hysterectomy may be performed via abdominal, vaginal, or laparoscopic-assisted abdominal or vaginal approaches.2 The appropriate route of surgery is determined by the type of pathology expected, anatomic considerations, patient preference, and physician experience and training. According to the SOGC clinical practice guidelines, vaginal hysterectomy should be considered the first choice for all benign indications, while laparoscopic-assisted approaches should be considered when using such an approach reduces the need for a laparotomy.4 Although there is limited information concerning direct comparisons of hysterectomy procedures, preliminary data suggest that LAVH may be associated with shorter hospital stays, less pain, more rapid recovery, and fewer complications; however, this approach is associated with higher surgical costs.1

 

Surgical and Postsurgical Complications
Hysterectomy is generally a safe procedure, but with any major surgery comes the risk of surgical and postsurgical complications. Such complications commonly include infection, hemorrhage, vaginal vault prolapse, and injury to the ureter, bowel, or bladder.6,7 Although hysterectomy is associated with fewer complications than many other major operations, risks and complications depend upon the type of hysterectomy performed, the individual woman's health status, and the surgeon's expertise and experience.4,6,7

Infection: Postoperative fever and infection are responsible for the majority of minor complications following hysterectomy. Infection occurs in approximately 6% to 25% of patients who undergo abdominal hysterectomy versus 4% to 10% of those who undergo vaginal hysterectomy. Despite impeccably sterile surgical technique and careful patient selection, women undergoing a hysterectomy procedure have a 30% chance of postoperative febrile infection.2

In both abdominal and vaginal hysterectomy, pelvic infection occurs in approximately 4% of cases.8,9 Pelvic cellulitis is an infection of the soft tissues and usually occurs around the third day following surgery. Although some degree of cuff cellulitis probably occurs following the majority of hysterectomies, antibiotics are not required unless fever persists. Additionally, the rate of postoperative symptomatic urinary tract infection is approximately 1% to 5% in patients who undergo hysterectomy. Immediate catheter removal postoperatively is strongly recommended to reduce the risk of this complication.8-10

Risk of postoperative infection can be lowered substantially with the use of prophylactic antibiotics.8,9 Studies reveal that women who receive prophylactic antibiotics prior to an abdominal or vaginal hysterectomy have a reduced rate of wound infection, pelvic cellulitis, vaginal cuff abscess, and pelvic abscess.9 The proper dosage should be administered 30 minutes prior to surgery to ensure that therapeutic levels are achieved in tissue at the surgical site. Agents such as cefazolin, cefotetan, cefoxitin, metronidazole, and clindamycin have all proved effective.8-10 If postoperative fever persists and infection is suspected or identified, a broad-spectrum intravenous antibiotic covering anticipated pathogens should be initiated. Antibiotics should be continued for 24 to 48 hours after the resolution of fever and symptoms.8,9

Ureteral Injury: Ureteral injury is becoming a more frequent posthysterectomy complication as the number of laparoscopic-assisted procedures increases. The incidence rate of this complication in laparoscopic-aided procedures is 0.7% to 1.7% with abdominal hysterectomy and 0% to 0.1% with vaginal hysterectomy.10 Injuries generally occur with excessive electrocautery and lasering adjacent to the ureter. These injuries are best managed with resection of the damaged portion and reimplantation of the ureter.11 Surgeons should recognize urologic injuries and correct them intraoperatively to avoid serious postoperative complications that occur from urinary extravasation.10,11

 

Bladder Injury: Injury to the bladder occurs in approximately 0.5% to 2% of all hysterectomies. 8,12 Bladder injury most likely occurs during entry to the peritoneum or during dissection of the bladder off the lower uterine segment, cervix, and upper vagina. Several studies have concluded that partial disruption of the innervation of the bladder during hysterectomy may result in postoperative incontinence.13,14 A systematic review reported that hysterectomy was considered a risk factor for urinary incontinence in women older than 60. 14 In another study, urge incontinence was found to be more common than stress incontinence in women posthysterectomy.13 In 2002, a large cohort study revealed that women older than 50 were less likely to have improvement with urinary incontinence after hysterectomy compared to younger women.15

 

Bowel Injury: Although bowel injury is uncommon, particularly with vaginal hysterectomy, it is a serious complication associated primarily with laparoscopic-assisted abdominal hysterectomy. During both abdominal and vaginal surgery, the rectum and ascending and descending colon can be injured.8 Bowel injuries occur during the lysis of adhesions involving the bowel and dissection of the posterior cul-de-sac. Preoperative bowel preparations will allow for incidental colon surgery without the necessity of colostomy. If a large bowel injury should occur and no preoperative bowel preparation was given, a temporary diverting colostomy may be indicated to protect the suture line and lower the risk of peritonitis and sepsis.10

Hemorrhage: One of the most serious postoperative complications associated with hysterectomy is hemorrhage. Excessive bleeding complicates approximately 1% to 3% of all hysterectomies.12 In most cases, bleeding originates at the lateral vaginal angles and is amenable to vaginal resuturing. Average intraoperative blood loss can range anywhere from 300 to 400 mL.16 Early postoperative signs of hemorrhage after vaginal hysterectomy include bleeding from the vagina, deterioration in vital signs, decreased hematocrit level, and flank abdominal pain.

It is routine to cross-match blood in patients undergoing hysterectomy. Two to four units of packed red blood cells should be available at all times. Women who are more likely to need blood transfusion include those undergoing peripartum hysterectomy or hysterectomy for gynecologic cancer, as well as those undergoing elective hysterectomy with pelvic inflammatory disease, or pelvic abscesses or adhesions.10





Thromboembolic Disease: The risk of venous thromboembolism following abdominal hysterectomy in low- and high-risk patients is 0.2% and 2.4%, respectively.9,10 The risk of deep venous thrombosis and pulmonary embolism can be minimized with the use of graduated compression stockings perioperatively and early ambulation postoperatively. The type of prophylaxis recommended depends upon each patient's risk factors. Risk factors include obesity, malignancy, previous radiation therapy, immobilization, estrogen use, prolonged anesthesia, radical surgery, and personal or family history of thromboembolic disease. Patients at high risk for thromboembolism may be given a low-molecular-weight heparin or 5,000 units of subcutaneous heparin preoperatively and then every eight to 12 hours postoperatively to reduce the risk of thromboembolic events.8-10

Fallopian Tube Prolapse: Fallopian tube prolapse is an uncommon postoperative complication of hysterectomy. A predisposing factor for prolapse is the presence of a hematoma or abscess at the vaginal apex.8,9,11 If the tissue does not respond to conservative treatment, such as cryotherapy or silver nitrate application, a biopsy of the area may be warranted.9 Surgical interventions are recommended for the management of fallopian tube prolapse. 8,9

Vaginal Vault Prolapse: Vaginal vault prolapse is a type of pelvic organ prolapse that can happen following surgical removal of the uterus. It often occurs when the top of the vagina loses the support of the uterus and then sags or drops into the vaginal canal. Most women with vaginal vault prolapse will also have bulging of the small bowel into the vagina, as well as other bladder and bowel problems such as urinary incontinence and constipation.6,7,15,16 It is important to note that vaginal vault prolapse may be treated with a vaginal pessary, a special device that holds the vagina in place; in some cases, surgery may be warranted.16

Vaginal Cuff Evisceration: A rare complication that can occur following a hysterectomy is evisceration of the small intestine into the vagina.7,9,17 It is associated with the Valsalva's maneuver, severe vomiting, or coughing. Symptoms usually include vaginal bleeding or discharge, abdominal-pelvic pain, pressure in the vagina, and protrusion of bowel. Although eviscerations usually occur early in the postoperative period, one study of 12 patients reported occurrence 27 months after various pelvic procedures.17 Medical treatment usually includes administration of intravenous fluids and broad-spectrum antibiotics and immediate laparotomy with replacement of the mesentery and small bowel. 6,7,9

Possible Long-Term Complications
Many of the clinical findings concerning the long-term side effects of hysterectomy are conflicting. Data show some women develop the complication, while others experience relief from the same complication. For example, some studies have shown increases in psychosexual dysfunction after hysterectomy, while others have shown improvements in this area.3,18 Discrepancies in the data make it difficult for clinicians to clearly identify the long-term risks of hysterectomy and for women to determine if the possible benefits of hysterectomy outweigh the risks.

 

Early Menopause: Many of the long-term complications associated with hysterectomy arise secondary to changes in hormonal balance. Bilateral oophorectomy is performed in more than 50% of hysterectomies in the U.S. and is controversial.1 Some practitioners believe the ovaries should be removed to prevent future development of malignancy, while others prefer to conserve "normal ovaries" to preserve sex hormone secretion and avoid long-term hormone therapy (HT), especially in women with contraindications to estrogen therapy (Table 1 ).19 When the ovaries are removed, levels of ovarian sex hormones, namely estrogen, progesterone, and testosterone, rapidly decline, resulting in sudden menopause.

Studies have found that even those women who keep one or both ovaries experience menopause at an earlier age. A retrospective trial found that women who had had a hysterectomy with preservation of one or both ovaries experienced menopause an average of 5.5 years earlier than women who had not undergone hysterectomy. In this study, no difference was found between women with one versus both ovaries, though some studies have reported differences.19 It has been theorized that early ovarian failure may occur due to disruptions in ovarian blood flow, which is necessary for proper sex hormone production.19,20

Studies have consistently shown HT to be effective for the reduction of menopausal symptoms.21-24 Common symptoms of menopause include hot flashes, night sweats, vulvar and vaginal atrophy, vaginal dryness, insomnia, and sleep disturbances. Initiating estrogen therapy immediately after hysterectomy with bilateral oophorectomy is important in order to prevent onset of menopausal symptoms, although some practitioners may be hesitant to prescribe long-term HT due to the findings that led to the early termination of the Women's Health Initiative (WHI) trial. 25

In February 2004, the NIH decided to terminate the WHI estrogen-only trial before its proposed March 2005 end. Because this trial failed to show that estrogen protects women from coronary heart disease and demonstrated statistically significant increases in the incidence of stroke and deep venous thrombosis, the NIH deemed it unacceptable to subject healthy women to these risks and therefore stopped the trial early. It is important to note that the WHI estrogen-only trial did find a significant reduction in hip and other fractures, as well as an unexpected decrease in breast cancer incidence (P = .06). The WHI trial also demonstrated that when estrogen replacement therapy (ERT) is used for the treatment of menopausal symptoms after hysterectomy, an overall balance of risks and benefits exists, and most importantly, no effect on total mortality was seen throughout the 6.8-year follow-up period.25

Women whose ovaries are preserved should be counseled concerning common menopausal symptoms, and estrogen therapy may be considered when these symptoms are present.19 The duration of ERT after hysterectomy has been debated, and no current guidelines are available to aid practitioners with this treatment decision. Many clinicians are now using ERT through the average age of natural menopause (approximately age 50) and then tapering women off therapy slowly to help prevent reappearance of symptoms.25 If symptoms recur during dose tapering, ERT may need to be restarted or nonhormonal agents may be tried. Nonpharmacologic techniques for treating menopausal symptoms are outlined in Table 2. If a woman simply undergoes oophorectomy and her uterus is preserved, progesterone should be added to the treatment regimen to prevent endometrial hyperplasia.24,26




Impaired Sexual Function: Studies have found that concern about posthysterectomy sexual dysfunction is the most common cause of anxiety for women undergoing the procedure.20 There are many plausible mechanisms by which sexual dysfunction may occur, including shortening of the vagina, disruption of innervation of the vagina, and vaginal dryness due to estrogen deficiency.3,20,28,29

Conversely, sexual function may improve posthysterectomy. It has been postulated that sexual function is improved through relief of pain during intercourse due to removal of pelvic pathology, relief of dysmenorrhea, and increased libido due to decreased fear of conception.20

Clinical data are split concerning the true effects of hysterectomy on a woman's sexual function. Early retrospective data found that hysterectomy causes a significant decline in sexual function.3 To the contrary, more current data derived from prospective clinical trials show improvements in sexual function, including increases in frequency of intercourse, sexual desire, and strength and occurrence of orgasms, as well as reductions in dyspareunia.20,28

It was once thought that retaining the cervix would result in less sexual dysfunction due to a decrease in neurologic and anatomic disruption, although clinical trials have not supported this theory.28,29 A 2003 prospective observational study examined the differences between the effects of vaginal, subtotal abdominal, and total abdominal hysterectomy on sexual function and found significant improvements in sexual function with all three types of hysterectomy, with no significant differences among the three types.28

Psychological Effects

Data are also mixed concerning the effects of hysterectomy on psychological functioning. As seen with other complications of hysterectomy, retrospective studies have reported adverse psychological outcomes, whereas prospective studies have not supported these claims.3 In fact, prospective studies have shown that hysterectomy improves mood and quality of life in many women by relieving preexisting distressing gynecologic symptoms.3,26

It has been well established that one of the most important influences on postoperative psychiatric morbidity is preoperative psychiatric state.26 Women with psychiatric illness prior to surgery are much less likely to show improvement in this regard after hysterectomy.3,26 Other factors that have been associated with increased risk of emotional distress posthysterectomy include loss of childbearing capacity, adverse effects on a woman's self-image, social disruption due to a long recovery time, and history of inadequately dealing with loss.3,30 The results of a meta-analysis showed that early detection of ovarian failure, immediate initiation of HT in perimenopausal women and in those undergoing oophorectomy, and regular follow-up may improve psychological outcomes of hysterectomy.31

Conclusions
Although hysterectomy is generally a safe procedure, it is pertinent for pharmacists to be aware of the surgical, postsurgical, and long-term complications involved. Educating women concerning the possible complications involved with hysterectomy may ease patients' preoperative anxiety and ultimately improve outcomes. Pharmacists have an important role in the care of this population of women and can aid in the prevention and treatment of complications associated with hysterectomy by providing proper education, identifying high-risk patients, and assisting with the management of medications.

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