Ovarian Cysts: A Review

Cheryl Horlen, PharmD, BCPS Associate Professor of Pharmacy Practice University of the Incarnate Word Feik School of Pharmacy San Antonio, Texas

7/20/2010

US Pharm. 2010;35(7):HS-5-HS-8.

Ovarian cysts are a common cause of surgical procedures and hospitalizations among women worldwide. It has been reported that 5% to 10% of women will undergo surgery for an adnexal mass. Each year in the United States, more than 250,000 women are discharged from the hospital with a diagnosis of ovarian cyst. Because ovarian cysts are common, it is important for pharmacists to be knowledgeable about treatment options and the risk of malignancy.

Ovarian cysts may be classified as either functional ovarian cysts or ovarian cystic neoplasms. The most common functional ovarian cysts are follicular cysts and corpus luteum cysts, which develop as a result of ovulation. It is believed that follicular cysts occur when an ovarian follicle fails to rupture and continues to grow.3 Corpus luteum cysts may develop when the corpus luteum fails to regress normally after ovulation.3 Because these cysts occur as a result of normal physiologic processes, they are termed functional cysts. Functional cysts are the most common type of ovarian cyst in premenopausal women.

Ovarian cystic neoplasms are derived from neoplastic growth. They may be categorized into three types based on their cells of origin: surface epithelial cell tumors, germ cell tumors, and sex cordstromal tumors.5 The majority of these neoplasms are benign in women of reproductive age, but the risk of malignancy increases in postmenopausal women.4 As a group, epithelial tumors are the most common ovarian neoplasm; however, the single most common benign ovarian neoplasm is the

benign cystic teratoma (also known as dermoid cyst). severe lower-abdominal pain may indicate torsion or cyst rupture.3 Dermoid cysts are composed mainly of ectodermal tissue. Risk Factors for Malignancy The risk of ovarian malignancy increases dramatically with age.1. and physical features of the cyst. Acute. when the chance of survival is greatest. Symptoms Most ovarian cysts do not cause any noticeable symptoms and are found incidentally upon physical examination or ultrasound. as well as findings suggestive of malignancy. Measurement of CA-125 levels can be helpful for distinguishing between benign and malignant adnexal masses. other hereditary cancer syndromes.3 As an ovarian cyst enlarges. and ascites. Some women with functional ovarian cysts report a dull sensation or heaviness in the pelvis. uterine fibroids.6 Corpus luteum cysts are more likely than follicular cysts to cause pain.7 In addition to the low sensitivity. kidney disease. It is estimated that 13% of ovarian neoplasms in premenopausal women are malignant. Elevated concentrations have been found in approximately 90% of women with advanced-stage epithelial ovarian cancer.1.9 Serum cancer antigen 125 (CA-125) has been studied as a screening tool for ovarian cancer. thick septations. Although ovarian malignancy is less likely in . Diagnosis It is difficult to distinguish a functional ovarian cyst from an ovarian neoplasm based on signs and symptoms alone. and teeth. which gives them their characteristic features of sebaceous glands. which is a germ cell tumor. such as liver disease. especially in postmenopausal women. the patient may notice increased abdominal girth or pressure. and pregnancy.7 A thorough history may reveal other risk factors for ovarian cancer. and delayed menses. thick walls. CA-125 measurement is of most benefit in the postmenopausal population.7.1. endometriosis. papillary projections. increased vascularity within the cyst.8 Because these conditions occur more commonly in premenopausal women and ovarian cancer is more common in postmenopausal women.1 Carriers of the BRCA1 (breast cancer gene 1) mutation have a 60-fold increased risk of developing ovarian cancer by age 60 years. hair. size. bilaterality. and carriers of the BRCA2 gene mutation have a 30-fold increased risk. compared with 45% in postmenopausal women. sweat glands. specificity is low because CA-125 concentrations often are elevated in other benign conditions. but in only 50% of those with stage I ovarian cancer. and nulliparity. infertility.8 Findings on ultrasound that are suspicious for malignancy include the presence of solid components. Transvaginal and transabdominal ultrasonography are useful for determining the location. such as a family history of ovarian or breast cancer. peritoneal irritation. pelvic inflammatory disease.

this study found a modest 28% decrease in risk. This hypothesis led to the use of combined oral contraceptives to treat pre-existing functional ovarian cysts. however. since functional cysts occur as a result of ovulation. compared with expectant management. signs and symptoms.11 Holt and colleagues conducted a case-control study of women aged 18 to 39 years with functional ovarian cysts to assess the effect of low-dose oral contraceptives on cyst occurrence. Highdose oral combined hormonal contraceptives were shown in early epidemiologic studies to protect against cyst development.5 Management of Functional Ovarian Cysts Ovarian follicular cysts often resolve spontaneously within one to two menstrual cycles.10 Advances in the understanding of hormonal contraception have led to the development of oral contraceptives with lower steroid doses.8 In many cases. The result was the same regardless of whether the cyst was related to ovulation induction or occurred spontaneously. Two of the seven trials reported cysts associated with ovulation induction. controlled trials of oral contraceptives (any type) used for the treatment of functional ovarian cysts in a total of 500 women. low-dose oral contraceptives do not suppress all follicular activity.4 Cysts that persist or change most likely will require surgical management.6 The rupture of a follicular cyst may cause transient pelvic pain owing to the release of follicular fluid into the peritoneum.2 The primary outcome of the systematic review was cyst resolution. it was theorized that they may also accelerate spontaneous regression of functional ovarian cysts or decrease cyst size. any suspicion arising from patient history. Studies evaluating the effect of combined oral contraceptives on cyst occurrence have mixed results. however. The conclusion of the pooled analysis was that combined oral contraceptives did not hasten the resolution of functional ovarian cysts. Persistent cysts tended to not be physiologic.women of reproductive age. a definitive diagnosis of cyst type and status as malignant or benign cannot be made without surgical excision and histologic examination. imaging findings. Based on the available . or serologic testing should be further investigated. Transvaginal ultrasound may be repeated to check for disappearance of the cyst or a change in its size or characteristics. Since combined oral contraceptives reduced the risk of cyst occurrence. Resolution may occur following reabsorption of the cyst fluid or cyst rupture.12 Compared with the 40% to 90% reduced risk of cyst occurrence seen in studies from the 1970s. Combined Hormonal Contraception: Suppression of ovulation should result in decreased cyst development. Follicular growth and ovulation can be suppressed by inhibiting pituitary gonadotropins with combined oral contraceptives. However. A recent Cochrane review analyzed data from seven randomized. medical intervention usually is not necessary. available evidence does not support this practice. The risk of cyst occurrence was slightly lower in women using 35 mcg ethinyl estradiol monophasic oral contraceptives versus women using monophasic or multiphasic oral contraceptives with less than 35 mcg of ethinyl estradiol.

or if the CA-125 level increases. therefore. postmenopausal women with a small (<5 cm). headaches. their use is not appropriate for all patients.1 Based on these findings. uncontrolled hypertension. and bloating.13 In addition. they are more likely to result in ovarian torsion. Surgical Approach . Combined oral contraceptives should not be used in women with a history of thromboembolic disease. Large. simple (unilocular) ovarian cyst that is not suspicious for malignancy and who have a normal CA-125 level and no family history may choose expectant management with serial ultrasounds and CA-125 measurements.7 The risk of malignancy is low if the cyst is unilocular and less than 10 cm in diameter. so combined oral contraceptives are not recommended. the cyst should be surgically removed and examined for malignancy. Other benign ovarian neoplasms are often surgically removed as well.11 Although combined oral contraceptives may be used in the management of functional ovarian cysts to prevent the development of new cysts. the American College of Obstetricians and Gynecologists recommends that combined oral contraceptives not be used to treat existing functional ovarian cysts. complex cysts in postmenopausal women have an estimated frequency of malignancy of 6% to 39%. dermoid cysts are usually removed surgically owing to the increased risk of ovarian torsion and cyst rupture. owing to the potential for malignant transformation with increasing age. if the cyst is persistent. enlarges. Simple Cysts in Postmenopausal Women It is estimated that the incidence of adnexal masses in asymptomatic postmenopausal women is between 3% and 18%.evidence. or shows findings suggestive of malignancy on ultrasound.4 Although the rate of malignancy is low. dermoid cysts tend to be more buoyant in the pelvis than other types of neoplasms. nausea.7 However.13 Common adverse effects of combined oral contraceptives include breast tenderness. but some will persist or become complex. migraines with aura.4 For women desiring future fertility.14 Management of Benign Ovarian Neoplasms Owing to their typically high fat content. women who smoke--especially those over the age of 35 years--are at increased risk for myocardial infarction. hypercoagulable states or other risk factors for thromboembolism. conservative surgical treatment with cystectomy rather than oophorectomy may be possible in some cases.6. or cardiovascular or cerebrovascular disease. active liver disease.15 Many of these cysts resolve spontaneously.

The risk of an ovarian mass being malignant increases with age. Ovarian neoplasms often are benign in women of reproductive age.9. especially if the patient is using hormonal contraceptives or is undergoing ovulation induction. No difference was found in rates of fever. nodular or fixed pelvic mass.8 Laparotomy often is preferred in these patients owing to the risk of cyst rupture and tumor spillage with laparoscopy. studies have shown that survival is improved when the malignancy is properly staged and aggressively debulked by a gynecologic oncologist.8 Should a malignancy be found. While laparoscopy is commonly used to remove benign cysts. ascites. In women with certain findings suggestive of malignancy. For patients with a mass suspected of malignancy based on ultrasound findings. Postmenopausal women should be referred if they have a CA-125 level greater than 35 U/mL.18 Conclusion Ovarian cysts are a common occurrence in women of all ages. experienced less pain. CA-125 levels. Measurement of CA-125 may be helpful in distinguishing between benign and malignant ovarian masses. laparotomy is often preferred for removal of masses that may be malignant. postoperative infections. Functional ovarian cysts are physiologic and usually resolve spontaneously within a couple of menstrual cycles. or family history of breast or ovarian cancer in a first-degree relative. or family history of breast or ovarian cancer in a firstdegree relative be referred to a gynecologic oncologist for surgical evaluation.16 A recent Cochrane review evaluated the benefits and risks of laparoscopy versus laparotomy in 12 randomized trials involving 769 patients with benign ovarian tumors. however. survival is increased when prompt referral to a gynecologic oncologist is made. or tumor recurrence between the two procedures. and spent fewer days in the hospital than patients who underwent traditional laparotomy. Combined oral contraceptives may be used to prevent the occurrence of these cysts. The laparoscopic approach typically is used for benign ovarian cysts that are less than 10 cm in diameter. REFERENCES . Referral to Gynecologic Oncologist It is recommended that premenopausal women with a CA-125 level greater than 200 U/mL. evidence of abdominal or distant metastasis. especially in postmenopausal women. ascites.17. evidence of abdominal or distant metastasis. Pharmacists may be asked about the condition by their patients.16 Patients who underwent laparoscopy had a decreased risk of adverse events from surgery. they do not accelerate cyst resolution. laparotomy is generally recommended.The type of surgical approach used for ovarian cyst removal depends upon several factors. and clinical assessment.

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