Ovarian Cyst Clinical Trials, Diagnosis, and Treatment

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Ovarian Cyst

An Ovarian Cyst is any collection of fluid, surrounded by a very thin wall, within an ovary. Any ovarian follicle that is larger than about two centimeters is termed an ovarian cyst. An ovarian cyst can be as small as a pea, or as large as a cantaloupe.

Most ovarian cysts are functional in nature, and harmless (benign). In the US ovarian cysts are found in nearly all premenopausal women, and in up to 14.8% of postmenopausal women. The incidence of ovarian carcinoma is approximately 15 cases per 100,000 women per year.

Ovarian cysts affect women of all ages. They occur most often, however, during a woman's childbearing years.

Some ovarian cysts cause problems, such as bleeding and pain. Surgery may be required to remove those cysts.

Current Research

For current research articles click - here

Types

Functional Cysts

Some, called functional cysts, or simple cysts, are part of the normal process of menstruation. They have nothing to do with disease, and can be treated.

Graafian Follicle Cyst

One type of simple cyst, which is the most common type of ovarian cyst, is the graafian follicle cyst, follicular cyst, or dentigerous cyst. This type can form when ovulation doesn't occur, and a follicle doesn't rupture or release its egg but instead grows until it becomes a cyst, or when a mature follicle involutes (collapses on itself). It usually forms during ovulation, and can grow to about 2.3 inches in diameter. It is thin-walled, lined by one or more layers of granulosa cell, and filled with clear fluid. Its rupture can create sharp, severe pain on the side of the ovary on which the cyst appears. This sharp pain (sometimes called mittelschmerz) occurs in the middle of the menstrual cycle, during ovulation. About a fourth of women with this type of cyst experience pain. Usually, these cysts produce no symptoms and disappear by themselves within a few months. Ultrasound is the primary tool used to document the follicular cyst. A pelvic exam will also aid in the diagnosis if the cyst is large enough to be seen. A doctor monitors these to make sure they disappear, and looks at treatment options if they do not.

Corpus Luteum Cyst

Another is a corpus luteum cyst (which may rupture about the time of menstruation, and take up to three months to disappear entirely). This type of functional cyst occurs after an egg has been released from a follicle. The follicle then becomes a new, temporarily little secretory gland that is known as a corpus luteum. The ruptured follicle begins producing large quantities of estrogen and progesterone in preparation for conception. If a pregnancy doesn't occur, the corpus luteum usually breaks down and disappears. It may, however, fill with fluid or blood, causing the corpus luteum to expand into a cyst, and stay on the ovary. Usually, this cyst is on only one side, and does not produce any symptoms. It can however grow to almost 4 inches in diameter and has the potential to bleed into itself or twist the ovary, causing pelvic or abdominal pain. If it fills with blood, the cyst may rupture, causing internal bleeding and sudden, sharp pain. The fertility drug clomiphene citrate (Clomid, Serophene), used to induce ovulation, increases the risk of a corpus luteum cyst developing after ovulation. These cysts don't prevent or threaten a resulting pregnancy. Women on birth control pills usually do not form these cysts; in fact, preventing these cysts is one way the pill works.

Hemorrhagic Cyst

A third type of functional cyst, which is common, is a Hemorrhagic cyst, which is also called a blood cyst, hematocele, and hematocyst. It occurs when a very small blood vessel in the wall of the cyst breaks, and the blood enters the cyst. Abdominal pain on one side of the body, often the right side, may be present. The bleeding may occur quickly, and rapidly stretch the covering of the ovary, causing pain. As the blood collects within the ovary, clots form which can be seen on a sonogram. Occasionally hemorrhagic cysts can rupture, with blood entering the abdominal cavity. No blood is seen out of the vagina. If a cyst ruptures, it is usually very painful. Hemorrhagic cysts that rupture are less common. Most hemorrhagic cysts are self-limiting; some need surgical intervention. Even if a hemorrhagic cyst ruptures, in many cases it resolves without surgery. Patients who don't require surgery will experience pain for 4 - 10 days after, and may require several days rest. Studies have found that women on tetracycline antibiotics recover 25% earlier than the majority of patients, a surprising correlation found in 2004. Sometimes surgery is necessary, such as a laparoscopy ("belly-button surgery" that uses small tools inserted through one or more tiny slits in the abdomen).

Endometrioid Cyst<.H3> An endometrioma, endometrioid cyst, endometrial cyst, or chocolate cyst is caused by endometriosis, and formed when a tiny patch of endometrial tissue (the mucous membrane that makes up the inner layer of the uterine wall) bleeds, sloughs off, becomes transplanted, and grows and enlarges inside the ovaries. As the blood builds up over months and years, it turns brown. When it ruptures, the material spills over into the pelvis and onto the surface of the uterus, bladder, bowel, and the corresponding spaces between. Treatment for endometriosis can be medical or surgical. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used first in patients with pelvic pain, particularly if the diagnosis of endometriosis has not been definitively established. The goal of directed medical treatment is to achieve an anovulatory state. Typically, this is achieved initially using hormonal contraception. This can also be accomplished with progestational agents (i.e., medroxyprogesterone), danazol, gestrinone, or gonadotropin-releasing hormone agonists (GnRH), as well as other less well-known agents. These agents are generally used if oral contraceptives and NSAIDs are ineffective. GnRH can be combined with estrogen and progestogen (add-back therapy) without loss of efficacy but with fewer hypoestrogenic symptoms. Laparoscopic surgical approaches include ablation of implants, lysis of adhesions, removal of endometriomas, uterosacral nerve ablation, and presacral neurectomy. They frequently require surgical removal. Conservative surgery can be performed to preserve fertility in young patients. Laparoscopic surgery provides pain relief and improved fertility over diagnostic laparoscopy without surgery. Definitive surgery is a hysterectomy and bilateral oophorectomy.

Pathological Cysts

Other cysts are pathological, such as those found in polycystic ovary syndrome, or those associated with tumors.

A polycystic-appearing ovary is diagnosed based on its enlarged size — usually twice normal —with small cysts present around the outside of the ovary. It can be found in "normal" women, and in women with endocrine disorders. An ultrasound is used to view the ovary in diagnosing the condition. Polycystic-appearing ovary is different from the polycystic ovarian syndrome, which includes other symptoms in addition to the presence of ovarian cysts, and involves metabolic and cardiovascular risks linked to insulin resistance. These risks include increased glucose tolerance, type 2 diabetes, and high blood pressure. Polycystic ovarian syndrome is associated with infertility, abnormal bleeding, increased incidences of pregnancy loss, and pregnancy-related complications. Polycystic ovarian syndrome is extremely common, is thought to occur in 4-7% of women of reproductive age, and is associated with an increased risk for endometrial cancer. More tests than an ultrasound alone are required to diagnose polycystic ovarian syndrome.

Symptoms

Some or all of the following symptoms may be present, though it is possible not to experience any symptoms:

Dull aching, or severe, sudden, and sharp pain or discomfort in the lower abdomen (one or both sides), pelvis, vagina, lower back, or thighs; pain may be constant or intermittent -- this is the most common symptom
Fullness, heaviness, pressure, swelling, or bloating in the abdomen
Breast tenderness
Pain during or shortly after beginning or end of menstrual period
Irregular periods, or abnormal uterine bleeding or spotting
Change in frequency or ease of urination (such as inability to fully empty the bladder), or difficulty with bowel movements due to pressure on adjacent pelvic anatomy
Weight gain
Nausea or vomiting
Fatigue
Infertility
Increased level of hair growth
Increased facial hair or body hair

Treatment

About 95% of ovarian cysts are benign, meaning they are not cancerous.

Treatment for cysts depends on the size of the cyst and symptoms. For small, asymptomatic cysts, the wait and see approach with regular check-ups will most likely be recommended.

Pain caused by ovarian cysts may be treated with:

pain relievers, including nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin, Advil), acetaminophen (Tylenol), or narcotic pain medicine (by prescription) may help reduce pelvic pain. NSAIDs usually work best when taken at the first signs of the pain.
a warm bath, or heating pad, or hot water bottle applied to the lower abdomen near the ovaries can relax tense muscles and relieve cramping, lessen discomfort, and stimulate circulation and healing in the ovaries. Bags of ice covered with towels can be used alternately as cold treatments to increase local circulation.
chamomile herbal tea (Matricaria recutita) can reduce ovarian cyst pain and soothe tense muscles.
urinating as soon as the urge presents itself.
avoiding constipation, which does not cause ovarian cysts but may further increase pelvic discomfort.
in diet, eliminating caffeine and alcohol, reducing sugars, increasing foods rich in vitamin A and carotenoids (e.g., carrots, tomatoes, and salad greens) and B vitamins (e.g., whole grains).
combined methods of hormonal contraception such as the combined oral contraceptive pill -- the hormones in the pills may regulate the menstrual cycle, prevent the formation of follicles that can turn into cysts, and possibly shrink an existing cyst. (American College of Obstetricians and Gynecologists, 1999c; Mayo Clinic, 2002e)

Also, limiting strenuous activity may reduce the risk of cyst rupture or torsion.

Cysts that persist beyond two or three menstrual cycles, or occur in post-menopausal women, may indicate more serious disease and should be investigated through ultrasonography and laparoscopy, especially in cases where family members have had ovarian cancer. Such cysts may require surgical biopsy. Additionally, a blood test may be taken before surgery to check for elevated CA-125, a tumor marker, which is often found in increased levels in ovarian cancer, although it can also be elevated by other conditions resulting in a large number of false positives.

For more serious cases where cysts are large and persisting, doctors may suggest surgery. Some surgeries can be performed to successfully remove the cyst(s) without hurting the ovaries, while others may require removal of one or both ovaries.

(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Ovarian_Cysts)

Findings From Current Research

Leptin Secretory Burst Mass Correlates with Body Mass Index and Insulin in Normal Women but Not in Women with Polycystic Ovary Syndrome

Authors: Iuorno MJ, Islam LZ, Veldhuis PP, Boyd DG, Farhy LS, Johnson ML, Nestler JE, Evans WS.

Division of Endocrinology, Department of Internal Medicine, Virginia Commonwealth University Health System, Virginia Commonwealth University, Richmond, VA 22908, USA.

Leptin secretion exhibits a pulsatile, circadian pattern and may play a role in reproduction. No previous studies have compared leptin secretory burst characteristics in normal eumenorrheic women and women with polycystic ovary syndrome (PCOS) who are appropriately matched for body mass index (BMI). To determine if leptin secretory burst characteristics and/or the relationships of BMI, insulin, or testosterone to these characteristics differ between PCOS and normal women, we studied 9 normal eumenorrheic women and 9 women with PCOS. Each woman underwent blood sampling every 10 minutes for 24 hours to measure leptin and insulin under controlled conditions. Leptin secretory bursts were identified and characterized using multiparameter deconvolution procedures (Deconv), and the 24-hour periodicity of leptin was characterized with cosinor analysis. Relationships between BMI, area under the curve (AUC) insulin, and testosterone and leptin secretory burst characteristics in PCOS and normal women were sought using linear regression. There were no significant differences in mean serum leptin concentrations or in secretory burst characteristics between PCOS and normal women. Although the 24-hour serum leptin concentration correlated with BMI in both normal and PCOS women, leptin secretory burst mass correlated with BMI only in normal women. Similarly, the 24-hour serum leptin concentration correlated with serum insulin AUC in both normal and PCOS women; but insulin AUC correlated with leptin burst mass only in normal women. Although there was a strong trend toward a correlation between both mean 24-hour serum leptin concentration and leptin secretory burst mass with the serum testosterone concentration in normal women, such trends were not seen in PCOS women. Both normal and PCOS women exhibited a diurnal rhythm of leptin secretion with the peak occurring at night. However, neither the peak amplitude nor the timing of the peak amplitude differed between normal and PCOS women. The presence of strong relationships between BMI and insulin with both mean serum leptin and leptin secretory burst mass in normal women as opposed to PCOS women suggests that the mechanisms subserving leptin secretion differ in these 2 groups.

Journal: Metabolism. 2007 Nov;56(11):1561-5.
Adapted from PubMed; click here to access full journal article.

Laparoscopic Surgery for Large Benign Ovarian Cysts

Authors: Eltabbakh GH, Charboneau AM, Eltabbakh NG.

Lake Champlain Gynecologic Oncology, P.C., South Burlington, VT 05403, USA. geltabbakh@lcgo.com

OBJECTIVE: To assess the feasibility and surgical outcome of laparoscopic surgery among women with large benign ovarian cysts. METHODS: We conducted a prospective study applying laparoscopic surgery among women with ovarian cysts whose maximum diameter was > or = 10 cm and radiologic and laboratory features suggestive of benign disease. Patients' demographics, clinical and ultrasound features, CA-125 values, surgical procedures, operative and post-operative complications, estimated amount of blood loss (EBL), operative time, conversion to laparotomy and the pathologic findings were recorded. RESULTS: Thirty-three consecutive patients underwent laparoscopic surgery over 7 years. The mean (range) age and body mass index were 45.2 (17-73 years) and 30 (21-42), respectively. Laparoscopic surgery was successful in 31 (93.9%) patients. The procedure was converted to laparotomy in 2 patients secondary to adhesions. There were no operative or post-operative complications. The mean (range) operative time, EBL and hospital stay were 82 (45-125 min), 89 (20-250 mL) and 0.94 (0-4 days), respectively. Twenty-three (70%) patients were discharged home the day of the surgery. The surgical procedures performed were: unilateral salpingo-oophorectomy (SO) (n=16), bilateral SO (n=4), ovarian cystectomy (n=2) and laparoscopically assisted vaginal hysterectomy and bilateral SO (n=9). The cysts were extracted after aspiration through the vagina (n=11), lower quadrant incision (n=5) or the umbilical incision (n=15). Pathologic findings included serous cystadenoma (n=11), mucinous cystadenoma (n=6), dermoid (n=6), endometriosis (n=5), benign epithelial-lined cyst (n=3) and borderline ovarian tumors (n=2). CONCLUSION: Laparoscopy is feasible and safe for women with large ovarian cysts with benign features and results in a short hospital stay.

Journal: Gynecol Oncol. 2008 Jan;108(1):72-6. Epub 2007 Oct 18.
Adapted from PubMed; click here to access full journal article.

The Reproductive Phenotype in Polycystic Ovary Syndrome

Authors: Chang RJ.

Division of Reproductive Endocrinology, Department of Reproductive Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093-0633, USA. rjchang@ucsd.edu

The symptoms of women with polycystic ovary syndrome (PCOS) include hirsutism and irregular menstrual bleeding due to ovarian androgen excess and chronic anovulation. Typically, these features emerge late in puberty or shortly thereafter. The proposed mechanism(s) responsible for increased ovarian androgen production include heightened theca cell responsiveness to gonadotropin stimulation, increased pituitary secretion of luteinizing hormone, and hyperinsulinemia. The cause of ovulatory dysfunction is not well understood, but is linked to abnormal follicle growth and development within the ovary. As a result, infertility is common among women with PCOS and, in many instances, is the initial presenting complaint. Insulin resistance and obesity are frequently associated with PCOS and probably contribute to the severity of symptoms. The polycystic ovary that accompanies the syndrome has recently been defined as having 12 or more follicles per ovary or an ovarian volume greater than 10 ml as determined by ultrasonography. In addition, there is an increased number of growing follicles in the polycystic ovary. Despite this distinctive appearance, the cause and development of the polycystic ovary are completely unknown.

Journal: Nat Clin Pract Endocrinol Metab. 2007 Oct;3(10):688-95.
Adapted from PubMed; click here to access full journal article.

Obligatory Roles for Follicle-Stimulating Hormone (FSH), Estradiol and Androgens in the Induction of Small Polyfollicular Ovarian Cysts in Hypophysectomized Immature Rats

Authors: Bogovich K.

Department of Obstetrics & Gynecology, University of South Carolina School of Medicine, Building 28, First Floor, Columbia, SC 29209, USA. bogovich@gw.med.sc.edu

Immature hypophysectomized (HYPOXD) rats develop large, polyfollicular ovarian cysts in response to unabated, combined stimulation by subovulatory doses of human chorionic gonadotropin (hCG) and highly purified ovine follicle-stimulating hormone (FSH). Further, circulating amounts of androstenedione (A4) and estradiol (E2), but not testosterone or dihydrotestosterone (DHT), change in parallel with the development of these cysts. To determine the potential roles of either A4 or E2 at the level of the ovary in the induction of ovarian cysts, pellets containing either (1) cholesterol (placebo; controls); (2) A4; or (3) E2 were administered subcutaneously (sc) to immature HYPOXD rats. Some of these animals also received either twice-daily sc injections of 1 IU hCG, or daily s.c. injections of 2 microg FSH, for 13 days. Ovaries and sera were harvested from all treatment groups on the morning of day 14 of the combined-hormone treatment schedule. As expected, ovaries from HYPOXD rats treated with placebo, A4, or E2 pellets (with or without hCG) failed to display antral follicles. Ovaries from HYPOXD rats treated with FSH and a placebo pellet displayed polyfollicular, atretic, small antral follicles with unstimulated thecal shells. In addition, the ovarian stromal-interstitial tissue had an unstimulated appearance. In contrast, ovaries from HYPOXD rats treated with FSH plus either A4 or E2 implants displayed stimulated stromal-interstitial tissue as well as small follicular cysts and precysts with stimulated thecal shells. The number of cysts and precysts observed in the largest ovarian cross-sections for animals treated with FSH + A4 (17.0 +/- 3.0) was less than that observed in the largest ovarian cross-sections for HYPOXD rats treated with FSH + E2 (40.2 +/- 10.1; p < 0.05). To determine if the development of ovarian cysts in response to FSH + A4 was due, at least in part, to the metabolism of A4 to E2, HYPOXD rats were treated with either (1) placebo pellets; (2) pellets containing dihydrotestosterone (DHT) which cannot be metabolized to estrogen; (3) E2 pellets plus DHT pellets (E2 + DHT); (4) FSH + DHT; or (5) FSH + E2 + DHT. The largest ovarian cross-sections from FSH + DHT-treated HYPOXD rats displayed 18.3 +/- 4.1 small follicles with a mean diameter of approximately 0.437 mm which possessed few granulosa cells. The thecal and stromal-interstitial tissues in these ovaries were unstimulated, which indicates that these small degenerating follicles were atretic rather than cystic. In contrast, the largest ovarian cross-sections from FSH + E2 + DHT-treated HYPOXD rats displayed 51.6 +/- 2.4 cysts with stimulated thecal shells and a mean diameter of approximately 0.634 mm. Further, these cysts were arranged in a "string of pearls" pattern and the ovarian stromal-interstitial tissue possessed a stimulated appearance. These data demonstrate a direct, unambiguous role at the level of the ovary for unabated tonic stimulation by FSH plus estrogen in the development of small polyfollicular cysts in HYPOXD rats. Further, the data also indicate that, at least in HYPOXD rats, combined, tonic stimulation by FSH plus estrogen and androgen is sufficient for the development of small, polyfollicular ovarian cysts in a "string of pearls" pattern. These observations are in distinct contrast to our previous observations that tonic stimulation by FSH + hCG results in the induction of large ovarian cysts in HYPOXD rats and provide tantalizing new insights regarding the potential importance of specific hormones at the level of the ovary in the induction of specific types of cystic follicles.

Journal: Endocrine. 2007 Apr;31(2):179-92.
Adapted from PubMed; click here to access full journal article.

Neuroendocrine Effects of Androgens in Adult Polycystic Ovary Syndrome and Female Puberty

Authors: Blank SK, McCartney CR, Helm KD, Marshall JC.

The Center for Research in Reproduction, University of Virginia Health System, Charlottesville, VA 22908, USA. sek2h@virginia.edu

In addition to hyperandrogenism and ovulatory dysfunction, polycystic ovary syndrome (PCOS) is characterized by neuroendocrine abnormalities including a persistently rapid gonadotropin-releasing hormone (GnRH) pulse frequency. Rapid GnRH pulsatility favors pituitary secretion of luteinizing hormone (LH) over that of follicle-stimulating hormone (FSH). Excess LH stimulates ovarian androgen production, whereas relative deficits in FSH impair follicular development. The rapid GnRH pulse frequency is a result of reduced progesterone-mediated feedback inhibition of the GnRH pulse generator secondary to infrequent luteal phase increases in progesterone, as well as reduced hypothalamic sensitivity to progesterone feedback. Progesterone sensitivity is restored by treatment with the androgen receptor blocker flutamide. As such, hyperandrogenemia appears to play an important pathophysiologic role in PCOS. Adolescent hyperandrogenemia is believed to be a precursor to adult PCOS. In addition to increased LH concentrations and pulse frequency, some girls with elevated androgen levels also demonstrate reduced hypothalamic sensitivity to progesterone feedback. We hypothesize that excess peripubertal androgens may reduce the sensitivity of the GnRH pulse generator to sex steroid inhibition in susceptible individuals, resulting in increased GnRH pulse frequency and subsequent abnormalities in gonadotropin secretion, ovarian androgen production, and ovulatory function. Over time, these abnormalities may progress to the clinical hyperandrogenism and chronic oligo-ovulation typical of adult PCOS.

Journal: Semin Reprod Med. 2007 Sep;25(5):352-9.
Adapted from PubMed; click here to access full journal article.

Polycystic Ovarian Syndrome

Authors: Khan KA, Stas S, Kurukulasuriya LR.

Cosmopolitan-International Diabetes and Endocrinology Center, Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65212, USA.

Polycystic ovarian syndrome (PCOS) is the most common reproductive endocrinopathy of women during their childbearing years. A significant degree of controversy exists regarding the etiology of this syndrome, but there is a growing consensus that the key features include insulin resistance, androgen excess, and abnormal gonadotropin dynamics. Familial and genetic factors cause predisposition to PCOS. Insulin resistance and adiposity put women with PCOS at a higher risk for diabetes, hypertension, dyslipidemia, and cardiovascular disease. Even though the adverse health consequences associated with PCOS are substantial, most women are not aware of these risks. Early recognition and treatment of metabolic sequelae should be the main focus of clinicians. Lifestyle modifications, mainly a balanced diet, weight loss, and regular exercise, are of utmost importance. On the pharmacologic front, various therapies including metformin, thiazolidinediones, and others appear to be very promising in the management of cardiometabolic aspects of PCOS.

Journal: J Cardiometab Syndr. 2006 Spring;1(2):125-30; quiz 131-2.
Adapted from PubMed; click here to access full journal article.

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