US Pharm. 2008;33(9):HS-5-HS-10.
In 2003, most hysterectomies (90%) performed in the United States were done for benign conditions, which make up the majority of indications for this procedure. A total of 600,000 hysterectomies were performed that year, with 66% done abdominally, 22% vaginally, and 12% with laparoscopic assistance.1,2 In all, nearly one-third of all women will have a hysterectomy by the age of 65.1,2 Although hysterectomy is a relatively common procedure, complications may occur during or after the surgery that require the attention of a woman's health care provider. Pharmacists can help this population of women in many ways, one of which is the recognition of symptoms that necessitate immediate attention by the patient's physician.
Hysterectomies are performed for a number of reasons. These conditions fall into one of the following diagnostic categories:
Uterine Leiomyoma: Leiomyomas, or uterine fibroids, are noncancerous growths of uterine muscle that develop in one-third of all women. These fibroids can lead to pain and excessive, irregular vaginal bleeding. Leiomyoma is the most common indication for hysterectomy; once performed, the procedure alleviates both current and recurrent symptoms.3 Medical management of symptomatic fibroids is available, but numerous studies report a lack of long-term effectiveness with most medicinal agents.4,5
Pelvic Organ Prolapse: Pelvic organ prolapse is when the stretching and weakening of the pelvic muscles and ligaments causes the uterus to fall into the vagina. Women with a prolapsed uterus often report pelvic heaviness, low back pain, stress urinary incontinence, difficulty voiding, and sexual dysfunction. Risk factors for prolapse include genetic predisposition, increased age, estrogen deficiencies, pregnancy, vaginal birth, and chronic increased pressure on the abdomen due to chronic constipation or coughing.6,7 In mild cases, exercises and physical therapy to strengthen the pelvic floor, in combination with behavioral modification, should be attempted before surgery is considered.8 For severe prolapse, however, hysterectomy is the preferred treatment for symptom relief.7
Abnormal Uterine Bleeding: A woman may undergo hysterectomy to eliminate abnormal or irregular uterine bleeding. Menorrhagia is excessive uterine bleeding that lasts longer than seven days; metrorrhagia, which is irregular uterine bleeding or spotting occurring at unexpected times, often occurs in conjunction with menorrhagia. Abnormal uterine bleeding can be caused by a hormonal imbalance or by structural problems such as fibroids or polyps.9 Once the cause is identified, medications or surgical methods other than hysterectomy should be attempted to treat the bleeding. If these treatments fail, hysterectomy is an acceptable next step.10,11
Endometriosis: Endometriosis, the excessive growth of endometrial tissue outside of the uterus, occurs in one of every five women worldwide.12 While infertility and endometrial cancer can result from endometriosis, pain is the most commonly reported symptom.13 Pain control is the primary goal of treatment, and pharmacologic options should be initiated prior to surgical intervention.14 Hysterectomy should be considered when the pain becomes severe or fails to improve with conservative surgery or medicinal treatments.14,15
Malignant and Premalignant Disease: Women with premalignant or malignant disease that cannot be cured by cone biopsy, laser surgery, or cryosurgery are candidates for hysterectomy. Some examples of premalignant or malignant disease are stage IB and IIA cervical cancer; stage II endometrial adenocarcinoma; upper-vaginal carcinoma; uterine and cervical sarcomas; and other rare malignancies of the cervix, uterus, and upper vagina.16,17
Types of Hysterectomy
Once an indication is determined, the type of hysterectomy to be performed is selected. There are four types of hysterectomy. Total hysterectomy, in which the entire uterus (including the fundus and the cervix) is removed, is the type most commonly performed. Hysterectomy with bilateral salpingo-oophorectomy refers to the removal of both ovaries and the fallopian tubes. In supracervical hysterectomy, the body of the uterus is removed and the cervix is left intact.18,19 Finally, radical hysterectomy is the removal of the uterus, the cervix, the top portion of the vagina, and most of the tissue surrounding the cervix in the pelvic cavity. Pelvic lymph nodes also may be removed during this surgery. Although radical hysterectomy is done relatively rarely, it is usually performed in women with cervical cancer or endometrial cancer that has spread to the cervix.19
Methods of Hysterectomy
There are multiple routes by which a hysterectomy can be performed, including abdominal, vaginal, and laparoscopically-assisted approaches. Determination of which method is most appropriate is based on several factors, such as the pathology of the problem, the individual patient's anatomy, patient preference, and physician expertise.18
Although hysterectomy is generally considered safe, several possible complications are associated with the procedure. These complications can result in mild-to-severe morbidity and even (although rare) mortality.18,20,21 Although their incidence is low, it is important to be aware of the immediate and long-term complications that can result from hysterectomy.
Immediate Complications: Ureteral injuries are common, owing to the size and location of the ureter, and generally are the result of excessive electrocautery and lasering adjacent to the ureter during surgery.20 The incidence is reported to be 0.5% for hysterectomy performed for benign disease and up to 1.6% for laparoscopically-assisted hysterectomy.21 If injury occurs during surgery, repair is more likely to be successful if performed intraoperatively at the time of injury.20,22
The risk of bowel injury varies depending on the type and method of the hysterectomy. While uncommon, injury to the rectum or to the ascending or descending colon can occur.23 The incidence of bowel injuries is 0.4%, with laparoscopically-assisted abdominal hysterectomy carrying the largest risk.24
Bladder injuries occur in up to 2% of hysterectomy cases.25 In vaginal hysterectomy, the bladder can be perforated during entry into the anterior cul-de-sac; in abdominal hysterectomy, injury can occur when the peritoneum is opened or during dissection of the bladder off the lower uterine segment, cervix, and upper vagina.18 Although most of these complications are corrected during the procedure, postoperative incontinence due to bladder injury during surgery is commonly reported.26,27
The most serious postoperative complication of hysterectomy is hemorrhage, which occurs in 1% to 3% of patients.25 Although all patients are at risk, those having a peripartum hysterectomy, hysterectomy for gynecologic cancer, elective hysterectomy for pelvic inflammatory disease, or pelvic abscesses are at greater risk for developing postoperative bleeding complications.18,22 If postoperative vaginal bleeding develops and is determined to occur below the vaginal cuff, outpatient suturing of the site will generally stop the bleeding. If the hemorrhage is above the vaginal cuff, further examination in the operating room is warranted. The patient is then stabilized with IV fluids and transfused with two to four units of packed red blood cells. Next, the bleeding will generally tamponade, stop, and form a hematoma that will eventually be reabsorbed into the body.18,23,28
Infection is a common postoperative complication associated with hysterectomy. Four percent to 10% of patients undergoing vaginal hysterectomy and 6% to 25% of those having abdominal hysterectomy develop an infection postsurgery.18,19 In all, regardless of the careful precautions taken, approximately one-third of patients develop postoperative febrile infection.19 Because of this, the use of preoperative and postoperative interventions, such as prophylactic treatment with broad-spectrum antibiotics, can contribute greatly to the reduction of infections occurring with hysterectomies.
While the aforementioned complications are more common, the following complications, although rare, also can occur: atelectasis, fallopian tube prolapse, thromboembolic disease, myocardial infarction, stroke, and renal failure.23,25,28
Long-Term Complications: Early menopause is the result of hormonal changes secondary to hysterectomy. Early onset of menopause can be associated with hysterectomy even when the ovaries are retained. One study found that menopause occurred four years earlier in premenopausal women who underwent hysterectomy (both ovaries retained) compared with similar women without hysterectomy.29 Another study examining women who underwent hysterectomy (retaining one or both ovaries) showed that onset of menopause occurred up to 5.5 years earlier than in women who did not have a hysterectomy.18 One theory for this is that reduced blood flow to the ovaries disrupts their functioning, resulting in improper production of sex hormones.30,31
Psychological effects that may manifest following hysterectomy vary from individual to individual. While some studies have found that women experience new feelings of depression, anxiety, decreased libido, or social disruption due to the lengthy postprocedural recovery, other studies have concluded that women undergoing hysterectomy have improved quality of life because their previous unpleasant symptoms have been relieved.32,33 It is important for patients and their physicians to communicate regularly after the hysterectomy. Patients who experience ongoing depression after surgery should speak with a health care provider to determine the need for counseling or the use of antidepressant medications.
Although multiple complications may result from this procedure, it is important to keep in mind that most women are quite satisfied with the results of surgery and with the significant symptom relief they experience (TABLE 1).34
Preoperative and Intraoperative Medications: To prevent the onset of infection, it is recommended that patients undergoing hysterectomy be treated prophylactically with a broad-spectrum antibiotic 30 minutes prior to surgery.35 In addition, patients at risk for developing deep venous thrombosis or pulmonary embolism may be given heparin or enoxaparin before the procedure to prevent the occurrence of these events.22,23,28 Various medications used preoperatively and intraoperatively, and their doses, are detailed in TABLE 2.18,23,28,36
Postoperative Medications: With up to 85% of patients experiencing moderate-to-severe pain after hysterectomy, postoperative pain management is essential.37 Successful pain control leads to increased patient satisfaction, shorter recovery time, and decreased overall health care costs for the procedure.37,38 In the most severe cases, IV or intramuscular injections of an opiate such as morphine, fentanyl, or hydromorphone should be utilized; however, oral analgesic agents are likely to be adequate on the first postoperative day.23 Acetaminophen and nonsteroidal anti-inflammatory drugs are two nonopioid treatment options to be considered. Because they are well tolerated, are nonaddictive, and carry a more desirable side-effect profile than opiates, these agents should be used when appropriate for the management of postoperative inpatient and outpatient pain.39
Hysterectomy patients may experience the early onset of menopausal symptoms, including hot flashes, night sweats, vaginal dryness, anxiety, irritability, depression, and loss of libido.40 For relief, the North American Menopause Society first recommends lifestyle and behavioral changes, such as lowering the body's core temperature (e.g., meditation, caloric restriction), regular exercise, practicing relaxation techniques, and avoiding hot-flash triggers (i.e., spicy food, caffeine, alcohol). If these lifestyle changes do not control the symptoms, hormonal (estrogen replacement therapy) or nonhormonal drug therapy may be used.40
Estrogen replacement is the most effective therapy for the treatment of moderate-to-severe vasomotor symptoms associated with menopause, reducing hot flashes from 50% to 100% within the first four weeks of medication initiation.41 While there are no current guidelines as to the duration of estrogen therapy, the FDA recommends the lowest dose for the least amount of time, with continual physician follow-up to evaluate effectiveness. Estrogen-containing products available for use in the treatment of menopausal symptoms are listed in TABLE 3.36
Although no nonhormonal treatments for menopausal symptoms are approved by the FDA, several agents are often used off-label to treat the vasomotor symptoms associated with menopause. They include the following: selective serotonin reuptake inhibitors, venlafaxine, clonidine, gabapentin, vitamin E, isoflavones, and black cohosh.42
Role of the Pharmacist
While pharmacists may not play a direct role in provision for hysterectomies, they are nevertheless in a unique position to educate women about the risks and benefits associated with the procedure. It is imperative for pharmacists to be aware of the postoperative complications of hysterectomy, as they are likely to encounter patients who are seeking relief from these symptoms. A knowledgeable pharmacist will be able to provide assistance with OTC agents when appropriate, as well as recognize serious symptoms that warrant referral of the patient to a physician.
1. Centers for Disease Control and Prevention. Women's reproductive health: hysterectomy fact sheet. www.cdc.gov/
2. Lewis CE, Groff JY, Herman CJ, et al. Overview of women's decision making regarding elective hysterectomy, oophorectomy, and hormone replacement therapy. J Womens Health Gend Based Med. 2000;9(suppl):S5-S14.
3. US Agency for Healthcare Research and Quality. Management of uterine fibroids. www.ahrq.gov/clinic/epcsums/
4. Carlson KJ, Miller BA, Fowler FJ. The Maine Women's Health Study: II. Outcomes of nonsurgical management of leiomyomas, abnormal bleeding, and chronic pelvic pain. Obstet Gynecol. 1994;83:556-565.
5. Department of Health and Human Services. Agency for Healthcare Research and Quality. 34. Management of uterine fibroids volume 1. Evidence report. www.ncbi.nlm.nih.gov/books/bv.
6. Novi JM, Jeronis S, Morgan MA, Arya LA. Sexual function in women with pelvic organ prolapse compared to women without pelvic organ prolapse. J Urol. 2005;173:1669-1672.
7. Kohli N, Goldstein DP. An overview of the clinical manifestations, diagnosis, and classification of pelvic organ prolapse. UpToDate Online 16.2. http://utdol.com/online/
8. ACOG Committee on Practice Bulletins--Gynecology. ACOG practice bulletin no. 85: pelvic organ prolapse. Obstet Gynecol. 2007;110:717-729.
9. Jurema M, Zacur HA. Management of menorrhagia. UpToDate Online 16.2. http://utdol.com/online/
10. Reich H, Ribeiro SC, Vidali A. Hysterectomy as treatment for dysfunctional uterine bleeding. Baillieres Best Pract Res Clin Obstet Gynaecol. 1999;13:251-269.
11. Lethaby A, Shepperd S, Cooke I, Farquhar C. Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding. Cochrane Database Syst Rev. 2000;CD000329.
12. Memarzadeh S, Muse KN Jr, Fox MD. Endometriosis. In: DeCherney AH, Nathan L, eds. Current Obstetric and Gynecologic Diagnosis and Treatment. 9th ed. New York, NY: McGraw-Hill Medical; 2003:767-775.
13. Schenken RS. Overview of the treatment of endometriosis. UpToDate Online 16.2. http://utdol.com/online/
14. ACOG Committee on Practice Bulletins--Obstetrics. ACOG practice bulletin. Medical management of endometriosis. No. 11. Clinical management guidelines for obstetrician-gynecologists. Int J Gynaecol Obstet. 2000;71:183-196.
15. Crosignani PG, Vercellini P, Biffignandi F, et al. Laparoscopy versus laparotomy in conservative surgical treatment for severe endometriosis. Fertil Steril. 1996;66:706-711.
16. Mann WJ. Radical hysterectomy. UpToDate Online 16.2. http://utdol.com/online/
17. Nijhuis ER, van der Zee AG, In 't Hout BA, et al. Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery. Int J Radiat Oncol Biol Phys. 2006;66:699-705.
18. Rice CN, Howard CH. Complications of hysterectomy. US Pharm. 2006;31(9):HS-16-HS-24.
19. National Women's Health Network. Hysterectomy. www.nwhn.org/healthinfo/
20. Stovall TG, Mann WJ. Overview of gynecologic laparoscopic surgery. UpToDate Online 16.2. http://utdol.com/online/
21. Chelmow D, Aronson MP, Wosu U. Intraoperative and postoperative complications of gynecologic surgery. In: DeCherney AH, Nathan L, Goodwin TM, Laufer N, eds. Current Diagnosis & Treatment: Obstetrics & Gynecology. 10th ed. New York, NY: McGraw-Hill Medical; 2007.
22. Dandade D, Malinak LR, Wheeler JM. Therapeutic gynecologic procedures. In: DeCherney AH, Nathan L, Goodwin TM, Laufer N, eds. Current Diagnosis & Treatment: Obstetrics & Gynecology. 10th ed. New York, NY: McGraw-Hill Medical; 2007.
23. Stovall TG, Mann WJ. Vaginal hysterectomy. UpToDate Online 16.2. http://utdol.com/online/
24. Dicker RC, Greenspan JR, Strauss LT, et al. Complications of abdominal and vaginal hysterectomy among women of reproductive age in the United States. The Collaborative Review of Sterilization. Am J Obstet Gynecol. 1982;144:841-848.
25. Maresh MJ, Metcalfe MA, McPherson K, et al. The VALUE national hysterectomy study: description of the patients and their surgery. BJOG. 2002;109:302-312.
26. van der Vaart CH, van der Bom JG, de Leeuw JR, et al. The contribution of hysterectomy to the occurrence of urge and stress urinary incontinence symptoms. BJOG. 2002;109:149-154.
27. Brown JS, Sawaya G, Thom DH, Grady D. Hysterectomy and urinary incontinence: a systematic review. Lancet. 2000;356:535-539.
28. Stovall TG, Mann WJ. Abdominal hysterectomy. UpToDate Online 16.2. http://utdol.com/online/
29. Farquhar CM, Sadler L, Harvey SA, Stewart AW. The association of hysterectomy and menopause: a prospective cohort study. BJOG. 2005;112:956-962.
30. Ahn EH, Bai SW, Song CH, et al. Effect of hysterectomy on conserved ovarian function. Yonsei Med J. 2002;43:53-58.
31. Rhodes JC, Kjerulff KH, Langenberg PW, Guzinski GM. Hysterectomy and sexual functioning. JAMA. 1999;282:1934-1941.
32. Falcone T, Cogan-Levy SL. Overview of hysterectomy. UpToDate Online 16.2. http://utdol.com/online/
33. Wright JB, Gannon MJ, Greenberg M. Psychological aspects of heavy periods: does endometrial ablation provide the answer? Br J Hosp Med. 1996;55:289-294.
34. Kjerulff KH, Langenberg PW, Rhodes JC, et al. Effectiveness of hysterectomy. Obstet Gynecol. 2000;95:319-326.
35. Meeks GR, Harris RL. Surgical approach to hysterectomy: abdominal, laparoscopy-assisted, or vaginal. Clin Obstet Gynecol. 1997;40:886-894.
36. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook. 15th ed. Hudson, OH: Lexi-Comp Inc; 2007.
37. Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003;97:534-540.
38. Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin North Am. 2005;23:21-36.
39. Akarsu T, Karaman S, Akercan F, et al. Preemptive meloxicam for postoperative pain relief after abdominal hysterectomy. Clin Exp Obstet Gynecol. 2004;31:133-136.
40. North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society. Menopause. 2004;11:11-33.
41. Maclennan A, Broadbent JL, Lester S, Moore JV. Oral oestrogen and combined oestrogen/progesterone therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004;4:CD002978.
42. Treatment of menopausal vasomotor symptoms. Med Lett Drugs Ther. 2004;46:98-99.