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American College of Obstetricians and GynecologistsFrom: Maria Helena (mhbastos@uol.com.br)Wed, 2 Oct 2002 22:06:11 -0300
Medical Library - American College of Obstetricians and Gynecologists Prophylactic Oophorectomy Prophylactic oophorectomy is the removal of the ovaries for the potential benefit of preventing long-term morbidity and mortality. The term prophylactic implies that the ovaries are normal at the time of removal. Oophorectomy can be performed either alone as a planned surgical procedure or in conjunction with other planned surgical procedures such as hysterectomy or colectomy. Incidental oophorectomy is a term commonly used when the ovaries are removed at the time of another indicated surgery, and this term should not be used interchangeably with prophylactic oophorectomy. The term incidental implies that the surgery occurs by chance or without consequence. There are obvious consequences associated with oophorectomy; therefore, when oophorectomy is performed for future benefit, the surgery should be termed prophylactic. Ovarian Physiology The ovary is a complex metabolic organ consisting of follicular and stromal compartments. Follicles produce both androgens and estrogen, and stromal tissue synthesizes androgens. With the loss of all follicles around menopause, both androgen and estrogen levels decrease, but the ovary remains a source of androgens that are peripherally converted to estrogen. The role of endogenous androgens and the consequences of their removal may be significant but have not yet been clarified. The positive effects of estrogen production on lipid metabolism and bone remodeling remain the primary argument for retention of the ovaries in premenopausal women. The benefits of estrogen are well documented (2-4), but any benefits of ovarian androgen production remain to be documented. Cancer Prevention In the United States, one in 70 women will develop ovarian cancer in her lifetime. Between 4% and 14% of these women will have had antecedent hysterectomies in which the ovaries were retained (5). Current screening techniques for ovarian cancer, including the use of ultrasonography and tumor markers, are neither sensitive nor specific enough to detect early cancer as part of a screening program for the general population. A high proportion of ovarian cancer is detected when it is in advanced stages. Prevention of ovarian cancer is the primary reason for prophylactic oophorectomy. Although oophorectomy does not eliminate the risk of cancer (patients still can develop peritoneal carcinoma, which acts like ovarian cancer), reported cases are rare (6). The literature has recorded elective oophorectomy rates of between 50% and 66% in women 40-64 years of age undergoing hysterectomy (7, 8). Data from the Centers for Disease Control and Prevention collected between 1988 and 1993 concur that ovarian retention occurs in approximately 40-50% of patients undergoing hysterectomy at 40 years of age or older (1). It has been suggested that, in the United States, approximately 1,000 cases of ovarian cancer can be prevented if prophylactic oophorectomy is practiced in all women older than 40 years of age who undergo hysterectomy. This assumes an annual incidence of 24,000 new ovarian cancer cases and does not take into account the incidence of peritoneal carcinoma. The dilemma for the patient and the clinician is whether the estimated number of cancer cases prevented (1,000) is worth the number of oophorectomies performed (approximately 300,000) (9). The benefit of prophylactic oophorectomy may be offset by the consequence of estrogen loss early in life. Factors to Consider for Prophylactic Oophorectomy The potential risks and benefits of this procedure need to be considered within the context of the potential risks and benefits of extended hormone production or prescribed hormone replacement. The potential for alleviation of symptoms related to ovarian function should be considered, especially in patients with documented premenstrual syndrome. New developments in genetic testing, early diagnosis, refinements in diagnostic imaging, knowledge of hormone interactions with the cardiovascular and central nervous systems, and refined surgical techniques must all be considered with the individual patient. Risk Factors for Ovarian Cancer There is no consensus regarding the benefits of oophorectomy performed at the time of hysterectomy. Patients at greater risk for developing ovarian cancer are those with low parity, decreased fertility, and delayed childbearing if they did not use oral contraceptives (6, 10-12). Women who have used oral contraceptives have a lower risk for invasive epithelial ovarian cancer than non-users do. Both hospital and population studies revealed that, among those who have used oral contraceptives, the risk continues to decrease as years of use increase, although there is little additional protection conferred by oral contraceptives beyond 6 years of use. The protective benefits of higher parity, as well as longer duration of breastfeeding, also have been reported. Use of fertility drugs may be associated with a higher risk of ovarian cancer, as is a history of longer premenopausal sexual activity without contraception. There are no consistent data linking age at menarche, age at menopause, or duration of estrogen replacement therapy with development of epithelial ovarian cancer (10). Operative Risk at the Time of Hysterectomy There are no studies evaluating increased operative risk or morbidity at the time of abdominal hysterectomy when prophylactic oophorectomy is included. Retrospective studies looking at prophylactic oophorectomy at the time of vaginal hysterectomy have shown that the ovaries can be removed successfully in 65-97% of patients (13, 14). One study found no significant increase in operating time, estimated blood loss, length of hospital stay, or postoperative morbidity between patients who had their ovaries removed and those who did not (13). Another study found that oophorectomy added 23.4 minutes to the total operating time compared with vaginal hysterectomy alone (14). Genetic Factors The emergence of data suggesting the close link of ovarian cancer with familial breast-ovarian cancer syndromes has contributed to arguments favoring oophorectomy in subsets of patients identified with genetic risk factors. The role of BRCA1 mutations in ovarian cancer indicates that these tumors have unique biologic clinical and pathologic features (15). Recent evidence identifies the significant contribution of BRCA1 mutations to the development of ovarian cancer, revealing that this mutation occurs in approximately 5% of women in whom cancer is diagnosed before 70 years of age (16). Although screening for BRCA1 mutations has been suggested, it is difficult to define those women at risk based only on the number of family members affected. Because of the relatively small number (5%) of all ovarian cancers related to inherited mutations in the BRCA1 gene, the optimal strategy for decreasing cancer mortality in these patients has yet to be determined. BRCA2 mutations increase the risk of ovarian cancer but to a lesser degree than BRCA1 mutations (17). The risk of ovarian cancer in families with Lynch syndrome II is reported to be 3.5 times higher than expected, with the estimated cumulative risk by 70 years of age still less than 10% (18). The mean age at diagnosis for ovarian cancer in women with Lynch syndrome II is approximately 45 years of age, roughly 20 years earlier than in the general population (19). References Lepine LA, Hillis SD, Marchbanks PA, Koonin LM, Morrow B, Kieke BA, et al. Hysterectomy surveillance--United States 1980-1993. MMWR Morb Mortal Wkly Rep 1997;46:1-15 Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, et al. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation 1987;75;1102-1109 Ettinger B, Genant HK, Cann CE. Postmenopausal bone loss is prevented by treatment with low-dosage estrogen with calcium. Ann Intern Med 1987;106:40-45 Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group of the PEPI Trial. JAMA 1995;273:199-208 Sightler SE, Boike GM, Estape RE, Averette HE. Ovarian cancer in women with prior hysterectomy: a 14-year experience at the University of Miami. Obstet Gynecol 1991;78:681-684 Piver MS, Jishi MF, Tsukada Y, Nava G. Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. Cancer 1993;71:2751-2755 Dicker RC, Scally MJ, Greenspan JR, Layde PM, Ory HW, Maze JM, et al. Hysterectomy among women of reproductive age. JAMA 1982;248:323-327 Pokras R, Hufnagel VG. Hysterectomy in the United States, 1965-84. Am J Public Health 1988;78:852-853 Averette HE, Nguyen HN. The role of prophylactic oophorectomy in cancer prevention. Gynecol Oncol 1994;55:S38-S41 Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992;136:1184-1203 NIH consensus conference. Ovarian cancer: screening, treatment, and follow-up. NIH Consensus Development Panel on Ovarian Cancer. JAMA 1995;273:491-497 Narod SA, Risch H, Moslehi R, Dorum A, Neuhausen S, Olsson H, et al. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med 1998;339:424-428 Ballard LA, Walters MD. Transvaginal mobilization and removal of ovaries and fallopian tubes after vaginal hysterectomy. Obstet Gynecol 1996;87:35-39 Davies A, O'Connor H, Magos AL. A prospective study to evaluate oophorectomy at the time of vaginal hysterectomy. Br J Obstet Gynaecol 1996;103:915-920 Rubin SC, Benjamin I, Behbakht K, Takahashi H, Morgan MA, LiVolsi VA, et al. Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1. N Engl J Med 1996;335:1413-1416 Stratton JF, Gayther SA, Russell P, Dearden J, Gore M, Blake P, et al. Contribution of BRCA1 mutations to ovarian cancer. N Engl J Med 1997;336:1125-1130 Ford D, Easton DF. The genetics of breast and ovarian cancer. Br J Cancer 1995;72:805-812 Burke W, Petersen G, Lynch P, Botkin J, Daly M, Garber J, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. JAMA 1997;277:915-919 Watson P, Lynch HT. Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 1993;71:677-685 Excerpted from: ACOG Practice Bulletin, No. 7, September 1999. Prophylactic Oophorectomy.
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