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</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"></div><div class="body"><div class="t">Ovarian, Fallopian Tube, and Primary Peritoneal Cancers Prevention (PDQ®): Health Professional Version</div><div class="j">PDQ Cancer Information Summaries [Internet]</div></div><div class="tail"></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 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id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK65921_"><span class="title" itemprop="name">Ovarian, Fallopian Tube, and Primary Peritoneal Cancers Prevention (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contribs">PDQ Screening and Prevention Editorial Board.</p><p class="fm-aai"><a href="#_NBK65921_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062771__225">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about ovarian, fallopian tube, and primary peritoneal cancers prevention. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062771__226">This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062771__99"><h2 id="_CDR0000062771__99_">Who Is at Risk?</h2><p id="CDR0000062771__244">Ovarian cancer is a rare disease, with carcinomas comprising approximately 90% of tumors and germ cell and stromal tumors accounting for the remainder. Ovarian carcinoma is a disease that predominantly affects postmenopausal women. Ovarian carcinomas consist of several histopathological types, with high-grade serous being both the most common and most lethal. The category of ovarian borderline tumor or tumor of low-malignant potential, which historically had been considered in the context of ovarian cancer, is now generally considered a nonmalignant entity, although it has a postulated relationship with the development of some histological subtypes of low-grade ovarian carcinomas.[<a class="bibr" href="#CDR0000062771_rl_99_1" rid="CDR0000062771_rl_99_1">1</a>]</p><p id="CDR0000062771__245">Risk factors for ovarian cancer include a family history of breast and/or ovarian cancer and inheritance of deleterious mutations in <i>BRCA1</i>, <i>BRCA2</i>, and selected other high-penetrance genes.[<a class="bibr" href="#CDR0000062771_rl_99_2" rid="CDR0000062771_rl_99_2">2</a>-<a class="bibr" href="#CDR0000062771_rl_99_6" rid="CDR0000062771_rl_99_6">6</a>] For more information, see <a href="/books/n/pdqcis/CDR0000062855/?report=reader">Genetics of Breast and Gynecologic Cancers</a>. Other risk factors for ovarian cancer include obesity, tall height, endometriosis, and the use of postmenopausal hormone therapy.[<a class="bibr" href="#CDR0000062771_rl_99_7" rid="CDR0000062771_rl_99_7">7</a>-<a class="bibr" href="#CDR0000062771_rl_99_9" rid="CDR0000062771_rl_99_9">9</a>]</p><p id="CDR0000062771__246">Associations of some risk factors with ovarian cancer vary by histopathological subtype. The association of endometriosis with ovarian cancer is stronger for nonserous subtypes, especially clear cell carcinoma and endometrioid subtypes.[<a class="bibr" href="#CDR0000062771_rl_99_10" rid="CDR0000062771_rl_99_10">10</a>] Further, among carriers of deleterious mutations in <i>BRCA1</i> or <i>BRCA2</i>, increasing evidence suggests that many tumors previously classified as ovarian high-grade serous carcinoma may develop from malignant cells arising in the tubal epithelium (serous tubal intraepithelial carcinoma [STIC]), although these tumors continue to be referred to as <i>ovarian</i> cancers in most writings. It is hypothesized that high-grade serous carcinomas among individuals who are not carriers of mutations in <i>BRCA1</i> or <i>BRCA2</i> may also develop in the fallopian tube, but few STICs have been identified among these women in the absence of concurrent high-stage disease. Further, data suggest that the distinction of high-grade serous carcinomas from other histological types of high-grade carcinomas, particularly endometrioid carcinomas, is not reliable. Reported rates of mucinous carcinoma diagnoses have declined dramatically, but expert pathology reviews suggest that this reflects increased recognition of metastases from occult gastrointestinal primary tumors to the ovary, rather than a true decline in rates of ovarian primary tumors.[<a class="bibr" href="#CDR0000062771_rl_99_11" rid="CDR0000062771_rl_99_11">11</a>]</p><div id="CDR0000062771_rl_99"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062771_rl_99_1">Kurman RJ, Carcangiu ML, Young RH, eds.: WHO Classification of Tumours of Female Reproductive Organs. 4th ed. International Agency for Research on Cancer, 2014.</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_2">Bolton KL, Ganda C, Berchuck A, et al.: Role of common genetic variants in ovarian cancer susceptibility and outcome: progress to date from the Ovarian Cancer Association Consortium (OCAC). J Intern Med 271 (4): 366-78, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22443200" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22443200</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_3">Weissman SM, Weiss SM, Newlin AC: Genetic testing by cancer site: ovary. Cancer J 18 (4): 320-7, 2012 Jul-Aug. [<a href="https://pubmed.ncbi.nlm.nih.gov/22846732" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22846732</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_4">Hunn J, Rodriguez GC: Ovarian cancer: etiology, risk factors, and epidemiology. Clin Obstet Gynecol 55 (1): 3-23, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22343225" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22343225</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_5">Pal T, Akbari MR, Sun P, et al.: Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer. Br J Cancer 107 (10): 1783-90, 2012. [<a href="/pmc/articles/PMC3493867/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3493867</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23047549" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23047549</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_6">Gayther SA, Pharoah PD: The inherited genetics of ovarian and endometrial cancer. Curr Opin Genet Dev 20 (3): 231-8, 2010. [<a href="/pmc/articles/PMC3073171/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3073171</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20456938" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20456938</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_7">Lacey JV, Brinton LA, Leitzmann MF, et al.: Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst 98 (19): 1397-405, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/17018786" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17018786</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_8">Trabert B, Wentzensen N, Yang HP, et al.: Ovarian cancer and menopausal hormone therapy in the NIH-AARP diet and health study. Br J Cancer 107 (7): 1181-7, 2012. [<a href="/pmc/articles/PMC3461172/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3461172</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22929888" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22929888</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_9">Lahmann PH, Cust AE, Friedenreich CM, et al.: Anthropometric measures and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 126 (10): 2404-15, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/19821492" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19821492</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_10">Poole EM, Lin WT, Kvaskoff M, et al.: Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses. Cancer Causes Control 28 (5): 437-445, 2017. [<a href="/pmc/articles/PMC5410866/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5410866</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28299512" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28299512</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_99_11">Seidman JD, Kurman RJ, Ronnett BM: Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 27 (7): 985-93, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12826891" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12826891</span></a>]</div></li></ol></div></div><div id="CDR0000062771__1"><h2 id="_CDR0000062771__1_">Overview</h2><p id="CDR0000062771__2">Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.</p><p id="CDR0000062771__342">Other PDQ summaries on <a href="/books/n/pdqcis/CDR0000062760/?report=reader">Ovarian, Fallopian Tube, and Primary Peritoneal Cancers Screening</a> and <a href="/books/n/pdqcis/CDR0000062829/?report=reader">Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment</a> are also available.</p><div id="CDR0000062771__101"><h3>Factors With Adequate Evidence of an Increased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancers</h3><div id="CDR0000062771__234"><h4>Family history and inherited susceptibility to ovarian, fallopian tube, and primary peritoneal cancers</h4><p id="CDR0000062771__235">Based on solid evidence, women with a family history of ovarian cancer, especially in a first-degree relative, and those with an inherited predisposition to ovarian cancer, such as a <i>BRCA1</i> or <i>BRCA2</i> mutation, have an increased risk of developing ovarian cancer. For more information, see <a href="/books/n/pdqcis/CDR0000062855/?report=reader">Genetics of Breast and Gynecologic Cancers</a>.</p></div><div id="CDR0000062771__299"><h4>Endometriosis</h4><p id="CDR0000062771__300">Based on fair evidence, self-reported and laparoscopically confirmed endometriosis is associated with an increased risk of ovarian cancer.[<a class="bibr" href="#CDR0000062771_rl_1_1" rid="CDR0000062771_rl_1_1">1</a>,<a class="bibr" href="#CDR0000062771_rl_1_2" rid="CDR0000062771_rl_1_2">2</a>] The association is stronger with nonserous histological subtypes, specifically endometrioid and clear cell carcinomas.[<a class="bibr" href="#CDR0000062771_rl_1_2" rid="CDR0000062771_rl_1_2">2</a>,<a class="bibr" href="#CDR0000062771_rl_1_3" rid="CDR0000062771_rl_1_3">3</a>]</p><p id="CDR0000062771__301"><b>Magnitude of Effect</b>: Modest with observed relative risks (RRs) of 1.8 to 2.4.</p><ul id="CDR0000062771__302" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Cohort and case-control studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Fair.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__102"><h4>Hormone replacement therapy</h4><p id="CDR0000062771__103">Based on fair evidence, current or recent hormone therapy is associated with a small increased risk of ovarian cancer. Risks attenuate after hormone therapy is discontinued. Risks did not differ by oral preparation type (estrogen only vs. combined estrogen/progestin).[<a class="bibr" href="#CDR0000062771_rl_1_4" rid="CDR0000062771_rl_1_4">4</a>,<a class="bibr" href="#CDR0000062771_rl_1_5" rid="CDR0000062771_rl_1_5">5</a>] Cutaneous hormone therapy may have a lower risk than oral hormone therapy.[<a class="bibr" href="#CDR0000062771_rl_1_6" rid="CDR0000062771_rl_1_6">6</a>]</p><p id="CDR0000062771__104"><b>Magnitude of Effect</b>: Modest with observed RRs of 1.20 to 1.8.</p><ul id="CDR0000062771__105" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: One randomized clinical trial, cohort and case-control studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Fair.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__113"><h4>Obesity and height </h4><p id="CDR0000062771__114">Based on fair evidence, increases in height and body mass index (BMI) are associated with a modest increased risk of ovarian cancer.</p><p id="CDR0000062771__265"><b>Magnitude of Effect</b>: Based on an overview analysis of 25,157 women with ovarian cancer and 81,211 women without ovarian cancer from 47 epidemiological studies, the RR of ovarian cancer per 5 cm increase in height is 1.07 (95% confidence interval [CI], 1.05–1.09). The RR of ovarian cancer per 5 kg/m<sup>2</sup> increase in BMI is 1.10 (95% CI, 1.07–1.13) among never-users of hormone therapy and 0.95 (95% CI, 0.92–0.99) among ever-users of hormone therapy.[<a class="bibr" href="#CDR0000062771_rl_1_7" rid="CDR0000062771_rl_1_7">7</a>]</p><ul id="CDR0000062771__136" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Cohort and case-control studies. </div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good. </div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div></div><div id="CDR0000062771__115"><h3>Factors With Adequate Evidence of a Decreased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancers</h3><div id="CDR0000062771__116"><h4>Oral contraceptives: benefits</h4><p id="CDR0000062771__276">Based on solid evidence, oral contraceptive use is associated with a decreased risk of developing ovarian cancer. </p><p id="CDR0000062771__277"><b>Magnitude of Effect</b>: The degree of risk reduction varies by duration of oral contraceptive use and time since last use. A prospective, contemporary, nationwide cohort study of women aged 15 to 49 years in Denmark found that any use of hormonal contraception was associated with an absolute reduction in the rate of ovarian cancer of 3.2 cases per 100,000 person-years. The reduction in risk persists for more than 30 years after use is discontinued, but the degree of reduction attenuates over time.[<a class="bibr" href="#CDR0000062771_rl_1_8" rid="CDR0000062771_rl_1_8">8</a>]</p><ul id="CDR0000062771__278" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Multiple case-control and cohort studies; meta-analyses.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__313"><h4>Oral contraceptives: harms</h4><p id="CDR0000062771__267">Based on solid evidence, combined current use of estrogen-progestin oral contraceptive use is associated with an increased risk of venous thromboembolism, particularly among smokers, for whom use is contraindicated. Oral contraceptives are not associated with a long-term increased risk of breast cancer but may be associated with a short-term increased risk while a woman is taking oral contraceptives. The risk of breast cancer declines with time since last use.</p><p id="CDR0000062771__268"><b>Magnitude of Effect</b>: The risks may vary by preparation. Overall, the absolute risk of venous thromboembolism is about three events per 10,000 women per year while taking oral contraceptives. The risk is modified by smoking. Breast cancer risk among long-term (>10 years) current users is estimated at one extra case per year per 100,000 women. The risk dissipates with time since last use.</p><ul id="CDR0000062771__269" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Observational studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__191"><h4>Tubal ligation: benefits</h4><p id="CDR0000062771__280">Based on solid evidence, tubal ligation is associated with a decreased risk of ovarian cancer.</p><p id="CDR0000062771__281"><b>Magnitude of Effect</b>: Adjusting for other forms of contraception, tubal ligation provides a relative reduction in the odds of developing ovarian cancer of about 30%.</p><ul id="CDR0000062771__282" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Multiple case-control studies and cohort studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__311"><h4>Tubal ligation: harms</h4><p id="CDR0000062771__271">Based on fair evidence, harms include surgical risks, including the following:[<a class="bibr" href="#CDR0000062771_rl_1_9" rid="CDR0000062771_rl_1_9">9</a>]</p><ul id="CDR0000062771__272"><li class="half_rhythm"><div>Major morbidity including blood transfusion, reoperation, or hospital readmission (rate of 1.0 per 100 procedures).</div></li><li class="half_rhythm"><div>Minor morbidity including postoperative fever, urinary tract infections, or wound infections (rate of 6.0 per 100 procedures).</div></li></ul></div><div id="CDR0000062771__248"><h4>Multiparity</h4><p id="CDR0000062771__249">Based on good evidence, multiparity is associated with a decreased risk of ovarian cancer.</p><p id="CDR0000062771__250"><b>Magnitude of Effect</b>: Based on good evidence from multiple observational epidemiological studies, parous women have an approximately 30% lower ovarian cancer risk than nulliparous women.[<a class="bibr" href="#CDR0000062771_rl_1_7" rid="CDR0000062771_rl_1_7">7</a>,<a class="bibr" href="#CDR0000062771_rl_1_10" rid="CDR0000062771_rl_1_10">10</a>-<a class="bibr" href="#CDR0000062771_rl_1_12" rid="CDR0000062771_rl_1_12">12</a>]</p><ul id="CDR0000062771__251" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Observational epidemiological studies.</div></li><li class="half_rhythm"><div>
|
|
<b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div>
|
|
<b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__252"><h4>Salpingectomy</h4><p id="CDR0000062771__253">Based on limited data, salpingectomy is associated with a decrease in risk of ovarian cancer.</p><p id="CDR0000062771__254"><b>Magnitude of Effect</b>: Approximately 50% decrease for bilateral salpingectomy, less protection for unilateral salpingectomy.</p><ul id="CDR0000062771__255" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Observational epidemiological studies from several different countries.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__200"><h4>Breastfeeding</h4><p id="CDR0000062771__201">Based on solid evidence, breastfeeding is associated with a decreased risk of ovarian cancer. </p><p id="CDR0000062771__202"><b>Magnitude of Effect</b>: 2% decrease with every month of breastfeeding.[<a class="bibr" href="#CDR0000062771_rl_1_13" rid="CDR0000062771_rl_1_13">13</a>]</p><ul id="CDR0000062771__203" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Multiple case-control and cohort studies; meta-analysis.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__122"><h4>Risk-reducing bilateral salpingo-oophorectomy: benefits</h4><p id="CDR0000062771__294">Based on solid evidence, risk-reducing bilateral salpingo-oophorectomy is associated with a decreased risk of ovarian cancer. Peritoneal carcinomatosis has been reported rarely following surgery. Risk-reducing surgery is generally reserved for women at high risk of developing ovarian cancer, such as women who have an inherited susceptibility to ovarian cancer. </p><p id="CDR0000062771__295"><b>Magnitude of Effect</b>: 90% reduction in risk of ovarian cancer observed among women with a <i>BRCA1</i> or <i>BRCA2</i> mutation.</p><ul id="CDR0000062771__134" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Multiple case-control studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062771__312"><h4>Risk-reducing bilateral salpingo-oophorectomy: harms</h4><p id="CDR0000062771__284">Based on solid evidence, prophylactic oophorectomy among women who are still menstruating at the time of surgery is associated with infertility, vasomotor symptoms, decreased sexual interest, vaginal dryness, urinary frequency, decreased bone-mineral density, and increased cardiovascular disease.</p><p id="CDR0000062771__285"><b>Magnitude of Effect</b>: Reported prevalence of vasomotor symptoms varies from 41% to 61.4% among women who underwent oophorectomy before natural menopause. Women with bilateral oophorectomy who did not take hormone therapy were twice as likely to have moderate or severe hot flashes, compared with women who underwent natural menopause. The RR of cardiovascular disease among women with bilateral oophorectomy and early menopause was 4.55 (95% CI, 2.56–9.01). </p><ul id="CDR0000062771__286" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Cohort and case-control studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div></div><div id="CDR0000062771__212"><h3>Areas of Uncertainty</h3><div id="CDR0000062771__106"><h4>Ovarian hyperstimulation for infertility treatment</h4><p id="CDR0000062771__107">Evidence is poor to determine the association between ovarian hyperstimulation and the risk of ovarian cancer. Risk of ovarian cancer may be increased among women who remain nulligravid after being treated with ovarian stimulating medications.</p><p id="CDR0000062771__108"><b>Magnitude of Effect</b>: Uncertain—risk of invasive ovarian cancer may be increased among women who remain nulligravid after treatment; risk of borderline ovarian tumors may be increased among women treated with infertility drugs.</p><ul id="CDR0000062771__131" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Cohort and case-control studies; systematic review. </div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Poor.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Fair.</div></li></ul></div></div><div id="CDR0000062771_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062771_rl_1_1">Poole EM, Lin WT, Kvaskoff M, et al.: Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses. Cancer Causes Control 28 (5): 437-445, 2017. [<a href="/pmc/articles/PMC5410866/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5410866</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28299512" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28299512</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_2">Pearce CL, Templeman C, Rossing MA, et al.: Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13 (4): 385-94, 2012. [<a href="/pmc/articles/PMC3664011/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3664011</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22361336" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22361336</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_3">Mogensen JB, Kjær SK, Mellemkjær L, et al.: Endometriosis and risks for ovarian, endometrial and breast cancers: A nationwide cohort study. Gynecol Oncol 143 (1): 87-92, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/27430396" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27430396</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_4">Mørch LS, Løkkegaard E, Andreasen AH, et al.: Hormone therapy and ovarian cancer. JAMA 302 (3): 298-305, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19602689" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19602689</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_5">Beral V, Gaitskell K, Hermon C, et al.: Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet 385 (9980): 1835-42, 2015. [<a href="/pmc/articles/PMC4427760/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4427760</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25684585" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25684585</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_6">Simin J, Tamimi RM, Callens S, et al.: Menopausal hormone therapy treatment options and ovarian cancer risk: A Swedish prospective population-based matched-cohort study. Int J Cancer 147 (1): 33-44, 2020. [<a href="https://pubmed.ncbi.nlm.nih.gov/31584190" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31584190</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_7">Braem MG, Onland-Moret NC, van den Brandt PA, et al.: Reproductive and hormonal factors in association with ovarian cancer in the Netherlands cohort study. Am J Epidemiol 172 (10): 1181-9, 2010. [<a href="/pmc/articles/PMC2970782/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2970782</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20861144" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20861144</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_8">Iversen L, Fielding S, Lidegaard Ø, et al.: Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study. BMJ 362: k3609, 2018. [<a href="/pmc/articles/PMC6283376/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6283376</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30257920" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30257920</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_9">Lawrie TA, Kulier R, Nardin JM: Techniques for the interruption of tubal patency for female sterilisation. Cochrane Database Syst Rev (9): CD003034, 2015. [<a href="https://pubmed.ncbi.nlm.nih.gov/26343930" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26343930</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_10">Fortner RT, Ose J, Merritt MA, et al.: Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort. Int J Cancer 137 (5): 1196-208, 2015. [<a href="/pmc/articles/PMC6284794/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6284794</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25656413" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25656413</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_11">Yang HP, Trabert B, Murphy MA, et al.: Ovarian cancer risk factors by histologic subtypes in the NIH-AARP Diet and Health Study. Int J Cancer 131 (4): 938-48, 2012. [<a href="/pmc/articles/PMC3505848/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3505848</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21960414" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21960414</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_12">Lee AW, Rosenzweig S, Wiensch A, et al.: Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies. J Natl Cancer Inst 113 (3): 301-308, 2021. [<a href="/pmc/articles/PMC7936053/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7936053</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32766851" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32766851</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_1_13">Feng LP, Chen HL, Shen MY: Breastfeeding and the risk of ovarian cancer: a meta-analysis. J Midwifery Womens Health 59 (4): 428-37, 2014 Jul-Aug. [<a href="https://pubmed.ncbi.nlm.nih.gov/25066743" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25066743</span></a>]</div></li></ol></div></div><div id="CDR0000062771__227"><h2 id="_CDR0000062771__227_">Incidence and Mortality</h2><p id="CDR0000062771__228">In
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2024 in the United States, ovarian cancer will cause an estimated 19,680 new cases
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and 12,740 deaths.[<a class="bibr" href="#CDR0000062771_rl_227_1" rid="CDR0000062771_rl_227_1">1</a>] Based on statistical models for analysis, rates for new ovarian cancer cases fell, on average, by 2.7% each year from 2012 to 2021. Death rates fell, on average, by 2.4% each year from 2013 to 2022.[<a class="bibr" href="#CDR0000062771_rl_227_2" rid="CDR0000062771_rl_227_2">2</a>] In 2021, the overall incidence rate for ovarian cancer among women aged 65 years and older was 33.5 cases per 100,000 women-years.[<a class="bibr" href="#CDR0000062771_rl_227_3" rid="CDR0000062771_rl_227_3">3</a>] Given that the Surveillance, Epidemiology, and End Results (SEER) Program does not adjust for oophorectomy or salpingectomy, racial differences in the prevalence of women who have undergone these procedures could bias racial rate comparisons. A statistically significant decrease in delayed-adjusted incidence rates of 1.7% per year among White women from 2000 to 2015 and 0.7% per year among Black women from 2000 to 2021 was observed. A statistically significant decrease in mortality rates of 2.5% per year among White women from 2005 to 2022 and 1.9% per year among Black women from 2003 to 2022 was observed. The population lifetime risk of ovarian cancer is 1.12%; the population lifetime risk of dying from ovarian cancer is 0.71%.[<a class="bibr" href="#CDR0000062771_rl_227_3" rid="CDR0000062771_rl_227_3">3</a>]</p><div id="CDR0000062771_rl_227"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062771_rl_227_1">American Cancer Society: Cancer Facts and Figures 2024. American Cancer Society, 2024. <a href="https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed December 30, 2024.</div></li><li><div class="bk_ref" id="CDR0000062771_rl_227_2">National Cancer Institute: SEER Stat Fact Sheets: Ovarian Cancer. Bethesda, Md: National Institutes of Health. <a href="https://seer.cancer.gov/statfacts/html/ovary.html" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed October 7, 2024.</div></li><li><div class="bk_ref" id="CDR0000062771_rl_227_3">Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. <a href="https://seer.cancer.gov/statistics-network/explorer/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed December 30, 2024.</div></li></ol></div></div><div id="CDR0000062771__138"><h2 id="_CDR0000062771__138_">Histology and Pathogenesis of Ovarian, Fallopian Tube, and Primary Peritoneal Cancers</h2><p id="CDR0000062771__139">Ovarian carcinoma is a biologically and clinically heterogeneous class of tumors that includes several major subtypes: serous, mucinous, endometrioid, and clear cell. Classification of ovarian carcinomas into type I and type II tumors has been proposed. In this system, type I tumors include the following:[<a class="bibr" href="#CDR0000062771_rl_138_1" rid="CDR0000062771_rl_138_1">1</a>] </p><ol id="CDR0000062771__290"><li class="half_rhythm"><div>Endometriosis-related subtypes, such as endometrioid, clear cell, and seromucinous.</div></li><li class="half_rhythm"><div>Low-grade serous.</div></li><li class="half_rhythm"><div> Mucinous and malignant Brenner tumors.</div></li></ol><p id="CDR0000062771__292">Among type I tumors, endometrioid and clear cell carcinomas are most common and most important clinically. In general, type I ovarian carcinomas present at a lower stage than type II tumors and portend a better prognosis.</p><p id="CDR0000062771__291">Type II tumors are comprised mainly of high-grade serous carcinomas, the most common and lethal of all ovarian carcinoma subtypes. These cancers usually present with symptomatic bulky stage III or IV disease and ascites. Many, but possibly not all, high-grade serous carcinomas appear to arise from malignant <i>in situ</i> lesions in the epithelium of the fallopian tube fimbria. These lesions spread to the ovaries secondarily but continue to be referred to as ovarian carcinomas. Evidence for a tubal origin is based mainly on examination of risk-reducing salpingo-oophorectomy specimens, performed among <i>BRCA1/BRCA2</i> mutation carriers, in which incidental low-volume disease enables recognition of serous tubal intraepithelial carcinoma (STIC). However, not all women with high-grade serous carcinomas have identifiable STIC, and few studies of the fallopian tubes of women who are not carriers of <i>BRCA1/BRCA2</i> mutations have been performed, suggesting that pathogenesis of these tumors is not fully known. Serous carcinomas can be further divided on the basis of molecular characteristics.[<a class="bibr" href="#CDR0000062771_rl_138_2" rid="CDR0000062771_rl_138_2">2</a>]</p><p id="CDR0000062771__140">The heterogeneity in the etiology and pathogenesis of different ovarian cancer subtypes and variability in the classification of tumors over time and between studies pose challenges for interpretation of etiological data. Ovarian cancer is rare, thus sample size and power of studies to detect moderate associations by cancer subtype is limited. However, clearer subtyping of cancers may help improve our understanding of the etiology of ovarian malignancies in future studies.</p><div id="CDR0000062771_rl_138"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062771_rl_138_1">Kurman RJ, Shih IeM: The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded. Am J Pathol 186 (4): 733-47, 2016. [<a href="/pmc/articles/PMC5808151/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5808151</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27012190" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27012190</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_138_2">Cancer Genome Atlas Research Network: Integrated genomic analyses of ovarian carcinoma. Nature 474 (7353): 609-15, 2011. [<a href="/pmc/articles/PMC3163504/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3163504</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21720365" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21720365</span></a>]</div></li></ol></div></div><div id="CDR0000062771__15"><h2 id="_CDR0000062771__15_">Factors With Adequate Evidence of an Increased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancers</h2><div id="CDR0000062771__240"><h3>Family History and Inherited Susceptibility to Ovarian, Fallopian Tube, and Primary Peritoneal Cancers</h3><p id="CDR0000062771__241">Some women are at an increased risk of these cancers because of an inherited mutation, with the magnitude of that risk dependent on the affected gene and specific mutation. Underlying ovarian cancer risk can be assessed through
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accurate pedigrees and/or genetic markers of risk. Because of uncertainties
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about cancer risks associated with certain specific gene mutations, genetic information
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may be difficult to interpret outside of families with a high incidence of
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ovarian cancer.</p><p id="CDR0000062771__242">This summary does not address multiple genetic syndromes or women who are at high risk because of inherited genetic factors. For specific information related to ovarian cancer risk associated with multiple genetic syndromes and ovarian cancer in <i>BRCA1/BRCA2</i> mutation carriers, see <a href="/books/n/pdqcis/CDR0000062855/?report=reader">Genetics of Breast and Gynecologic Cancers</a> and <a href="/books/n/pdqcis/CDR0000062863/?report=reader">Genetics of Colorectal Cancer</a>.</p></div><div id="CDR0000062771__328"><h3>Endometriosis</h3><p id="CDR0000062771__329">Endometriosis has been associated with a modestly increased risk of ovarian cancer. The association is stronger with nonserous histological subtypes, specifically endometrioid and clear cell carcinomas. In one analysis, data were pooled from 13 ovarian cancer case-control studies, including 13,226 controls and 7,911 women with invasive ovarian cancer who were part of the Ovarian Cancer Association Consortium. Logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Self-reported endometriosis was associated with a significantly increased risk of clear cell (odds ratio [OR], 3.05; 95% confidence interval [CI], 2.43–3.84; <i>P</i> < .0001), low-grade serous (OR, 2.11; 95% CI, 1.39–3.20; <i>P</i> < .0001), and endometrioid invasive ovarian cancers (OR, 2.04; 95% CI, 1.67–2.48; <i>P</i> < .0001). No association was noted between endometriosis and risk of mucinous (OR, 1.02; 95% CI, 0.69–1.50; <i>P</i> = .93) or high-grade serous invasive ovarian cancer (OR, 1.13; 95% CI, 0.97–1.32; <i>P</i> = .13), or borderline tumors of either subtype (OR, 1.20; 95% CI, 0.95–1.52; <i>P</i> = .12 for serous and OR, 1.12; 95% CI, 0.84–1.48; <i>P</i> = .45 for mucinous).[<a class="bibr" href="#CDR0000062771_rl_15_1" rid="CDR0000062771_rl_15_1">1</a>] Considering that the clear cell and endometrioid ovarian cancers represented approximately 15% of all ovarian cancers, the lifetime risk of these histological subtypes is approximately 0.2%, which, on the basis of these data, would increase to approximately 0.4% to 0.6% in the presence of self-reported endometriosis.</p><p id="CDR0000062771__330">A cohort study from the Danish National Patient Register identified 45,790 women with a clinical diagnosis of endometriosis between 1977 and 2012. Data were linked to the Danish Cancer Register, which identified 186 women with a diagnosis of ovarian cancer. Endometriosis was associated with modestly increased risks of ovarian cancer overall (standardized incidence ratio [SIR], 1.34; 95% CI, 1.16–1.55). This was primarily caused by increases in endometrioid (SIR, 1.64; 95% CI, 1.09–2.37) and clear cell subtypes (SIR, 3.64; 95% CI, 2.36–5.38). No increased risk of serous or mucinous histological subtypes was reported.[<a class="bibr" href="#CDR0000062771_rl_15_2" rid="CDR0000062771_rl_15_2">2</a>]</p><p id="CDR0000062771__331">Using data from the Nurses’ Health Study II, 228 ovarian cancers were identified from among 102,025 eligible women. Cox proportional hazards regression models were used to assess associations between endometriosis and cancer risk, evaluating the impacts of self-reported versus laparoscopically confirmed endometriosis, delayed diagnosis, and postendometriosis diagnosis changes in risk-factor exposures. Self-reported endometriosis was associated with ovarian cancer (relative risk [RR], 1.81; 95% CI, 1.26–2.58), which was stronger for laparoscopically confirmed endometriosis diagnoses (RR, 2.14; 95% CI, 1.45–3.15). Diagnosis delays or postendometriosis diagnosis changes in risk factors had little impact on risk. Although this study had limited power to detect differences in risk on the basis of histological subtype, nonserous cases were shown to have an increased risk (RR, 2.44; 95% CI, 1.48–4.01), and serous cases were not (RR, 1.69; 95% CI, 0.92–3.11).[<a class="bibr" href="#CDR0000062771_rl_15_3" rid="CDR0000062771_rl_15_3">3</a>] A large case-control study in African American women found similar associations with a history of endometriosis and ovarian cancer (OR, 1.78; 95% CI, 1.09–2.90), suggesting that findings from populations of predominantly White women are also observed in Black women.[<a class="bibr" href="#CDR0000062771_rl_15_4" rid="CDR0000062771_rl_15_4">4</a>]</p></div><div id="CDR0000062771__143"><h3>Hormone Replacement Therapy/Hormone Therapy</h3><p id="CDR0000062771__256">A meta-analysis of 52 studies (17 prospective and 35 retrospective) including 21,488 ovarian cancers found increased risks with current or recent hormone replacement use in prospective studies (RR, 1.37; 95% CI, 1.29–1.46), with similar results for retrospective designs. Significant relationships were found for serous and endometrioid subtypes.[<a class="bibr" href="#CDR0000062771_rl_15_5" rid="CDR0000062771_rl_15_5">5</a>] Recent use was strongly related to risk even among women who had used hormone replacement therapy for less than 5 years (RR, 1.41; 95% CI, 1.32–1.50). Risk declined among women who had discontinued use, with greater effects for longer periods of cessation. Risks did not differ by preparation types (estrogen only vs. combined estrogen/progestin). Risks also did not differ by age at use.[<a class="bibr" href="#CDR0000062771_rl_15_6" rid="CDR0000062771_rl_15_6">6</a>,<a class="bibr" href="#CDR0000062771_rl_15_7" rid="CDR0000062771_rl_15_7">7</a>] Cutaneous hormone therapy may have a lower risk than oral hormone therapy.[<a class="bibr" href="#CDR0000062771_rl_15_8" rid="CDR0000062771_rl_15_8">8</a>]</p><p id="CDR0000062771__326">Tibolone, a synthetic steroid with estrogenic, progestogenic, and androgenic properties, has been associated with an increased incidence rate ratio of 3.56 (95% CI, 3.08–4.69) for endometrial cancer for current users compared with never-users. Tibolone is approved for use to manage menopausal symptoms or to prevent osteoporosis in many countries. However, it is not approved for use in Canada or the United States. Other combined therapy with estrogen and progestin may also increase the risk of breast cancer, so the risks and benefits must be considered.[<a class="bibr" href="#CDR0000062771_rl_15_9" rid="CDR0000062771_rl_15_9">9</a>]</p></div><div id="CDR0000062771__153"><h3>Obesity and Height</h3><p id="CDR0000062771__155">Ovarian cancer risk increases with increasing height and weight (body mass index [BMI]).[<a class="bibr" href="#CDR0000062771_rl_15_10" rid="CDR0000062771_rl_15_10">10</a>] The Collaborative Group on Epidemiological Studies of Ovarian Cancer compiled individual data, both published and unpublished, from 47 epidemiological studies including 12,157 women with ovarian cancer and 81,311 controls. RR increased significantly with increasing height (1.07 per 5 cm of height) and with increasing BMI (1.10 per 5 kg/m<sup>2</sup>). These findings were unaffected by other factors known to be associated with ovarian cancer risk, with the exception that ever-users of hormone therapy had no increased risk with increasing BMI. Given that height, weight, and BMI are thought to be strongly correlated, separating out the individual effects can be difficult.[<a class="bibr" href="#CDR0000062771_rl_15_11" rid="CDR0000062771_rl_15_11">11</a>,<a class="bibr" href="#CDR0000062771_rl_15_12" rid="CDR0000062771_rl_15_12">12</a>] Ovarian cancer mortality has also been shown to be increased in women with obesity.[<a class="bibr" href="#CDR0000062771_rl_15_13" rid="CDR0000062771_rl_15_13">13</a>,<a class="bibr" href="#CDR0000062771_rl_15_14" rid="CDR0000062771_rl_15_14">14</a>]</p></div><div id="CDR0000062771_rl_15"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062771_rl_15_1">Pearce CL, Templeman C, Rossing MA, et al.: Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13 (4): 385-94, 2012. [<a href="/pmc/articles/PMC3664011/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3664011</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22361336" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22361336</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_2">Mogensen JB, Kjær SK, Mellemkjær L, et al.: Endometriosis and risks for ovarian, endometrial and breast cancers: A nationwide cohort study. Gynecol Oncol 143 (1): 87-92, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/27430396" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27430396</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_3">Poole EM, Lin WT, Kvaskoff M, et al.: Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses. Cancer Causes Control 28 (5): 437-445, 2017. [<a href="/pmc/articles/PMC5410866/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5410866</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28299512" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28299512</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_4">Park HK, Schildkraut JM, Alberg AJ, et al.: Benign gynecologic conditions are associated with ovarian cancer risk in African-American women: a case-control study. Cancer Causes Control 29 (11): 1081-1091, 2018. [<a href="/pmc/articles/PMC6230481/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6230481</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30269307" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30269307</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_5">Beral V, Gaitskell K, Hermon C, et al.: Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet 385 (9980): 1835-42, 2015. [<a href="/pmc/articles/PMC4427760/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4427760</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25684585" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25684585</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_6">Lacey JV, Brinton LA, Leitzmann MF, et al.: Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst 98 (19): 1397-405, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/17018786" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17018786</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_7">Trabert B, Wentzensen N, Yang HP, et al.: Ovarian cancer and menopausal hormone therapy in the NIH-AARP diet and health study. Br J Cancer 107 (7): 1181-7, 2012. [<a href="/pmc/articles/PMC3461172/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3461172</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22929888" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22929888</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_8">Simin J, Tamimi RM, Callens S, et al.: Menopausal hormone therapy treatment options and ovarian cancer risk: A Swedish prospective population-based matched-cohort study. Int J Cancer 147 (1): 33-44, 2020. [<a href="https://pubmed.ncbi.nlm.nih.gov/31584190" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31584190</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_9">Løkkegaard ECL, Mørch LS: Tibolone and risk of gynecological hormone sensitive cancer. Int J Cancer 142 (12): 2435-2440, 2018. [<a href="https://pubmed.ncbi.nlm.nih.gov/29349823" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29349823</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_10">Collaborative Group on Epidemiological Studies of Ovarian Cancer: Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies. PLoS Med 9 (4): e1001200, 2012. [<a href="/pmc/articles/PMC3317899/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3317899</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22606070" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22606070</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_11">Dixon-Suen SC, Nagle CM, Thrift AP, et al.: Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study. Br J Cancer 118 (8): 1123-1129, 2018. [<a href="/pmc/articles/PMC5931085/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5931085</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29555990" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29555990</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_15_12">Qian F, Rookus MA, Leslie G, et al.: Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers. Br J Cancer 121 (2): 180-192, 2019. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/25250505" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25250505</span></a>]</div></li></ol></div></div><div id="CDR0000062771__156"><h2 id="_CDR0000062771__156_">Factors With Adequate Evidence of a Decreased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancers</h2><p id="CDR0000062771__361">Factors associated with a decreased risk of ovarian cancer include multiparity, use of oral contraceptives, breastfeeding, and risk-reducing surgical procedures like tubal ligation, salpingectomy, and salpingo-oophorectomy.[<a class="bibr" href="#CDR0000062771_rl_156_1" rid="CDR0000062771_rl_156_1">1</a>-<a class="bibr" href="#CDR0000062771_rl_156_5" rid="CDR0000062771_rl_156_5">5</a>] Each of these contributes to a decrease in ovulatory years. Pooled data from 25 case-control studies conducted by the Ovarian Cancer Association Consortium was used to quantify the association between lifetime ovulatory years and epithelial ovarian cancer risk. Lifetime ovulatory years was calculated by subtracting the years of anovulation from an individual’s menstrual span (i.e., age at last menstrual period subtracted from age at menarche).[<a class="bibr" href="#CDR0000062771_rl_156_6" rid="CDR0000062771_rl_156_6">6</a>] The odds ratio (OR) for ovarian cancer per lifetime ovulatory year with anovulation caused by pregnancy, oral contraceptive use, and breastfeeding was 1.041 (95% confidence interval [CI], 1.036–1.045).</p><div id="CDR0000062771__362"><h3>Multiparity</h3><p id="CDR0000062771__363">Compared with nulliparous women, the risk of ovarian cancer was reduced by 30% to 60% among parous women, with additive protection for each additional birth.[<a class="bibr" href="#CDR0000062771_rl_156_1" rid="CDR0000062771_rl_156_1">1</a>] The risk of developing ovarian cancer was lower for parous women (relative risk [RR], 0.69; 95% CI, 0.64–0.74) than for women who never had children, with increased risk reduction with increasing number of children for one child (RR, 0.82; 95% CI, 0.43–0.91) to four or more children (RR, 0.58; 95% CI, 0.53–0.64).[<a class="bibr" href="#CDR0000062771_rl_156_7" rid="CDR0000062771_rl_156_7">7</a>]</p></div><div id="CDR0000062771__157"><h3>Oral Contraceptives</h3><p id="CDR0000062771__158">A collaborative analysis was performed of individual data from 23,257 women with ovarian cancer and 87,303 women without ovarian cancer from 45 studies in 21 countries.[<a class="bibr" href="#CDR0000062771_rl_156_8" rid="CDR0000062771_rl_156_8">8</a>] Oral contraceptive use was associated with a dose-response effect by duration of use, without observed changes in risk reduction by decade of use from the 1960s to 1980s, over which time the amount of estrogen in oral contraceptives was approximately halved. No risk reduction was observed for women who used oral contraceptives for less than 1 year. The risk reduction associated with use from 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 years or more was 0.78 (99% CI, 0.73–0.893), 0.64 (99% CI, 0.59–0.69), 0.56 (99% CI, 0.50–0.62), and 0.42 (99% CI, 0.36–0.49), respectively. The observed risk reduction persisted after cessation of oral contraceptive therapy but attenuated over time since last use. The proportional reduction in risk per 5 years of use was 29% (95% CI, 23%–34%) for women who had discontinued use within the last 10 years. The reduction in risk was 15% (95% CI, 9%–21%) for women who discontinued use 20 to 29 years ago.[<a class="bibr" href="#CDR0000062771_rl_156_9" rid="CDR0000062771_rl_156_9">9</a>]</p><p id="CDR0000062771__159">A meta-analysis, in which the primary analysis was restricted to 24 case-control and cohort studies published since 2000 to reflect more recent types of oral contraceptive preparations, also observed a dose-response by duration of use.[<a class="bibr" href="#CDR0000062771_rl_156_2" rid="CDR0000062771_rl_156_2">2</a>] The authors estimated that 185 women needed to be treated for 5 years to prevent one case of ovarian cancer. Based on an estimated lifetime risk of 1.38% and prevalence of ever-use of oral contraceptives of 83%, the authors estimated a lifetime relative reduction of ovarian cancer attributable to oral contraceptives of 0.54%. A prospective cohort study from Denmark, which represented nearly 1.9 million women, also examined contemporary oral contraceptive formulations and found that current oral contraceptive formulation users had an RR reduction of 0.58 (95% CI, 0.49–0.68), and former oral contraceptive formulation users had a RR reduction of 0.77 (95% CI, 0.66–0.91). The benefits were strengthened by longer duration of use and weakened by more time since last use. No benefit was found for progesterone-only birth control products. This study was limited by only including incident ovarian cancers that occurred in women younger than 50 years.[<a class="bibr" href="#CDR0000062771_rl_156_10" rid="CDR0000062771_rl_156_10">10</a>]</p><p id="CDR0000062771__355">For specific information related to ovarian cancer risk among <i>BRCA1/BRCA2</i> mutation carriers, see <a href="/books/n/pdqcis/CDR0000062855/?report=reader">Genetics of Breast and Gynecologic Cancers</a>.</p></div><div id="CDR0000062771__161"><h3>Depot-Medroxyprogesterone Acetate</h3><p id="CDR0000062771__162">Limited information is available on the use of injectable progestational contraceptives (depot-medroxyprogesterone acetate [DMPA]) and the risk of ovarian cancer. Studies are confounded by the use of other contraceptive methods, particularly oral contraceptives. A hospital-based study conducted in Mexico and Thailand, with 224 cases and 1,781 controls (the World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives), did not observe an association between DMPA and ovarian cancer (RR, 1.07; 95% CI, 0.6–1.8).[<a class="bibr" href="#CDR0000062771_rl_156_11" rid="CDR0000062771_rl_156_11">11</a>] However, only 22 of the participants had ever used DMPA, and nine of them had used it for 6 months or less.</p><p id="CDR0000062771__163">A subsequent multicenter study conducted in 12 hospitals in Thailand, including 330 cases and 982 matched controls, observed a statistically significant decreased risk of ovarian cancer associated with DMPA use, controlling for oral contraceptive use and other associated factors (OR, 0.52; 95% CI, 0.33–0.88). A dose-response association was observed, but the sample size was limited in longer-term use categories.[<a class="bibr" href="#CDR0000062771_rl_156_12" rid="CDR0000062771_rl_156_12">12</a>]</p></div><div id="CDR0000062771__164"><h3>Tubal Ligation</h3><p id="CDR0000062771__165">A meta-analysis of 16 case-control studies, three retrospective studies, and two prospective cohort studies observed a decreased risk of ovarian cancer associated with tubal ligation (RR, 0.66; 95% CI, 0.60–0.73).[<a class="bibr" href="#CDR0000062771_rl_156_4" rid="CDR0000062771_rl_156_4">4</a>] The reduced risk was observed up to 14 years after tubal ligation. A population-based case-control study of 902 cases and 1,802 controls published subsequent to the meta-analysis observed an adjusted OR of 0.62 (95% CI, 0.51–0.75) associated with a history of a tubal ligation.[<a class="bibr" href="#CDR0000062771_rl_156_13" rid="CDR0000062771_rl_156_13">13</a>] The association was adjusted for oral contraceptive use, which was also associated with a lower risk of ovarian cancer (OR, 0.62; 95% CI, 0.47–0.85) and other risk factors.[<a class="bibr" href="#CDR0000062771_rl_156_13" rid="CDR0000062771_rl_156_13">13</a>] Salpingectomy has also been discussed as a preferred means of sterilization.[<a class="bibr" href="#CDR0000062771_rl_156_14" rid="CDR0000062771_rl_156_14">14</a>,<a class="bibr" href="#CDR0000062771_rl_156_15" rid="CDR0000062771_rl_156_15">15</a>] For more information, see the <a href="#CDR0000062771__260">Salpingectomy</a> section.</p><p id="CDR0000062771__166">Another pooling project with primary data from 13 population-based case-control studies examined the association between tubal ligation and ovarian cancer risk. It included 7,942 individuals with epithelial ovarian cancers and 13,904 controls.[<a class="bibr" href="#CDR0000062771_rl_156_16" rid="CDR0000062771_rl_156_16">16</a>] Overall, tubal ligation was associated with a 29% reduction in risk (OR, 0.71; 95% CI, 0.66–0.77). The observed risk reduction varied by subtype of invasive cancers and was 52% (OR, 0.48; 95% CI, 0.40–49) for endometrioid cancer; 48% (OR, 0.52; 95% CI, 0.40–0.67) for clear cell cancer; 32% (OR, 0.68; 95% CI, 0.52–89) for mucinous cancer; and 19% (OR, 0.81; 95% CI, 0.74–0,89) for serous cancer. </p><p id="CDR0000062771__287">A pooled analysis from 21 prospective cohort studies examined 14 hormonal, reproductive, and lifestyle factors by histological subtype among 5,584 women with invasive ovarian cancer within a total sample of 1.3 million participants. Overall, tubal ligation was associated with an 18% reduction in risk (OR, 0.82; 95% CI, 0.73–0.93). The observed risk reduction varied by subtype of invasive cancer and was 40% (OR, 0.60; 95% CI, 0.41–88) for endometrioid cancer; 65% (OR, 0.35; 95% CI, 0.18–0.69) for clear cell cancer; and 9% (OR, 0.91; 95% CI, 0.79–1.06) for serous cancer. There was a nonsignificant increase in risk of 1% (OR, 1.01; 95% CI, 0.60–1.71) for mucinous cancer.[<a class="bibr" href="#CDR0000062771_rl_156_7" rid="CDR0000062771_rl_156_7">7</a>]</p></div><div id="CDR0000062771__168"><h3>Breastfeeding</h3><p id="CDR0000062771__169">A meta-analysis [<a class="bibr" href="#CDR0000062771_rl_156_3" rid="CDR0000062771_rl_156_3">3</a>] that included five prospective studies and 30 case-control studies examined the association between breastfeeding and the risk of ovarian cancer. Any breastfeeding was associated with a decreased risk of ovarian cancer (RR, 0.76; 95% CI, 0.69–0.83). The risk of ovarian cancer decreased 8% for every 5-month increase in duration of breastfeeding (95% CI, 0.90–0.95). Another meta-analysis that included five prospective studies and 35 case-control studies found that any breastfeeding was associated with a decreased risk of ovarian cancer (RR, 0.70; 95% CI, 0.64–0.76). These results are consistent with a previous meta-analysis and further support the prior finding of a suggested association between increased duration of breastfeeding and greater levels of protection.[<a class="bibr" href="#CDR0000062771_rl_156_17" rid="CDR0000062771_rl_156_17">17</a>] Another meta-analysis of 19 studies, including four cohort and 15 case-control studies, found an overall decreased risk of ovarian cancer with an OR of 0.66 (95% CI, 0.57–0.76) and an association with duration (2% decrease per month). The benefit of breastfeeding was greatest for the first 8 to 10 months.[<a class="bibr" href="#CDR0000062771_rl_156_18" rid="CDR0000062771_rl_156_18">18</a>]</p></div><div id="CDR0000062771__170"><h3>Risk-Reducing Salpingo-Oophorectomy</h3><p id="CDR0000062771__171">Risk-reducing surgery is an option considered by women who are at high risk of ovarian cancer, such as those with an inherited susceptibility to cancer. For more information on this as a risk-reducing intervention, see the <a href="/books/n/pdqcis/CDR0000062855/?report=reader#CDR0000062855__348">Surgical history</a> section in Genetics of Breast and Gynecologic Cancers. Among women in the general population, opportunistic salpingectomy, oophorectomy, or salpingo-oophorectomy have been considered as possible interventions at the time of surgery for other benign indications.</p><div id="CDR0000062771__263"><h4>Harms</h4><p id="CDR0000062771__259">Risks associated with benign oophorectomy (with or without salpingectomy or hysterectomy) have been analyzed in six published studies. Studies of three cohorts found that oophorectomy performed before menopause (age 45 or 50 years) was associated with increased overall mortality, likely related to cardiovascular disease. This finding was noted particularly among individuals not using hormone replacement. In the Women’s Health Initiative, bilateral salpingo-oophorectomy was not associated with increased mortality. In the National Health and Nutrition Examination Survey (NHANES III), oophorectomy overall was not related to mortality, but mortality was increased among women younger than 40 years with obesity who did not use hormone replacement. The California Teachers Study did not find a mortality risk with oophorectomy, but only 3% of women did not use hormone replacement. Overall, data suggest that oophorectomy among younger women likely increases overall mortality and that this risk may be attenuated with hormone replacement.[<a class="bibr" href="#CDR0000062771_rl_156_19" rid="CDR0000062771_rl_156_19">19</a>-<a class="bibr" href="#CDR0000062771_rl_156_24" rid="CDR0000062771_rl_156_24">24</a>] Risk-reducing salpingo-oophorectomy has been associated with worsened menopausal symptoms, decreased sexual activity, and decreased sexual functioning.[<a class="bibr" href="#CDR0000062771_rl_156_25" rid="CDR0000062771_rl_156_25">25</a>]</p></div><div id="CDR0000062771__260"><h4>Salpingectomy</h4><p id="CDR0000062771__261">Data relating salpingectomy to risk of ovarian/tubal cancer are limited but consistent. A meta-analysis of three studies found an OR of 0.51 (95% CI, 0.35–0.71) for risk of these cancers among women who had undergone salpingectomy, compared with women who had intact fallopian tubes.[<a class="bibr" href="#CDR0000062771_rl_156_5" rid="CDR0000062771_rl_156_5">5</a>] These studies included a Swedish record linkage study conducted from 1973 to 2009 with a mean follow-up of 23 years, which found the following hazard ratios (HRs) for risk of ovarian cancer, compared with women who had not undergone surgery:[<a class="bibr" href="#CDR0000062771_rl_156_26" rid="CDR0000062771_rl_156_26">26</a>]</p><ul id="CDR0000062771__288"><li class="half_rhythm"><div>For hysterectomy, the HR was 0.79 (95% CI, 0.70–0.88).</div></li><li class="half_rhythm"><div>For hysterectomy with bilateral salpingo-oophorectomy, the HR was 0.06 (95% CI, 0.03–0.12).</div></li><li class="half_rhythm"><div>For salpingectomy, the HR was 0.65 (95% CI, 0.52–0.81).</div></li><li class="half_rhythm"><div>For sterilization procedures, the HR was 0.72 (95% CI, 0.64–0.81).</div></li></ul><p id="CDR0000062771__289"> Another population-based cohort study of all individuals in British Columbia, Canada, between 2008 and 2017, examined observed versus expected rates of ovarian cancer among individuals who had undergone opportunistic salpingectomy. The study included 25,889 individuals who underwent opportunistic salpingectomy, compared with 32,080 individuals who underwent hysterectomy or tubal ligation alone. There were no serous ovarian cancers in the opportunistic-salpingectomy group, while the age-adjusted expected rate was 5.27 (95% CI, 1.78–19.29) serous cancers based on the age-adjusted incidence rate in the control group.[<a class="bibr" href="#CDR0000062771_rl_156_27" rid="CDR0000062771_rl_156_27">27</a>] The risk reduction for ovarian cancer of unspecified histology associated with bilateral salpingectomy was approximately twice that of unilateral salpingectomy (HR, 0.35; 95% CI, 0.17–0.73 vs. HR, 0.71; 95% CI, 0.56–0.91, respectively).[<a class="bibr" href="#CDR0000062771_rl_156_26" rid="CDR0000062771_rl_156_26">26</a>] This report included limited covariate data, but results were similar to other smaller studies included in the meta-analysis.[<a class="bibr" href="#CDR0000062771_rl_156_5" rid="CDR0000062771_rl_156_5">5</a>]</p><p id="CDR0000062771__372">A nested case-control study from Denmark compared 16,822 epithelial ovarian cancer cases, each matched to 40 controls.[<a class="bibr" href="#CDR0000062771_rl_156_28" rid="CDR0000062771_rl_156_28">28</a>] This analysis observed an overall risk reduction for epithelial ovarian cancer incidence after both unilateral salpingectomy (OR, 0.73; 95% CI, 0.60–0.87) and bilateral salpingectomy (OR, 0.46; 95% CI, 0.31–0.67). Outcomes by histological type were also evaluated, and a similar risk reduction was observed for serous histology of any grade after bilateral salpingectomy (OR, 0.44; 95% CI, 0.27–0.73). The risk reduction for ovarian cancer incidence increased with time since salpingectomy (OR, 0.72; 95% CI, 0.55–0.95) for individuals 10 to 19 years postsalpingectomy and (OR, 0.55; 95% CI, 0.42–0.73) for individuals 20 years or more postsalpingectomy. Age-stratified analysis suggested that salpingectomy protected against ovarian cancer when salpingectomy was performed in individuals younger than 50 years (OR, 0.61; 95% CI, 0.51–0.73), but not when performed in individuals aged 50 years or older (OR, 1.21; 95% CI, 0.78–1.88). However, the small number of ovarian cancer cases among individuals who had a salpingectomy at age 50 years or older (n = 21) may have limited this finding. Other study limitations included small numbers of ovarian cancer cases of other histological subtypes. The study also did not provide information about tumor grade and hereditary disposition (i.e., <i>BRCA</i> mutation).</p><p id="CDR0000062771__373">Data based on circulating surrogate markers of ovarian reserve suggest that salpingectomy does not have an adverse effect on ovarian function.[<a class="bibr" href="#CDR0000062771_rl_156_29" rid="CDR0000062771_rl_156_29">29</a>,<a class="bibr" href="#CDR0000062771_rl_156_30" rid="CDR0000062771_rl_156_30">30</a>]</p></div></div><div id="CDR0000062771_rl_156"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062771_rl_156_1">Permuth-Wey J, Sellers TA: Epidemiology of ovarian cancer. Methods Mol Biol 472: 413-37, 2009. 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[<a href="/pmc/articles/PMC3619957/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3619957</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23569193" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23569193</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_17">Li DP, Du C, Zhang ZM, et al.: Breastfeeding and ovarian cancer risk: a systematic review and meta-analysis of 40 epidemiological studies. Asian Pac J Cancer Prev 15 (12): 4829-37, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24998548" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24998548</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_18">Feng LP, Chen HL, Shen MY: Breastfeeding and the risk of ovarian cancer: a meta-analysis. J Midwifery Womens Health 59 (4): 428-37, 2014 Jul-Aug. [<a href="https://pubmed.ncbi.nlm.nih.gov/25066743" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25066743</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_19">Duan L, Xu X, Koebnick C, et al.: Bilateral oophorectomy is not associated with increased mortality: the California Teachers Study. Fertil Steril 97 (1): 111-7, 2012. [<a href="/pmc/articles/PMC3245786/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3245786</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22088205" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22088205</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_20">Rocca WA, Grossardt BR, de Andrade M, et al.: Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. Lancet Oncol 7 (10): 821-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/17012044" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17012044</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_21">McCarthy AM, Menke A, Ouyang P, et al.: Bilateral oophorectomy, body mass index, and mortality in U.S. women aged 40 years and older. Cancer Prev Res (Phila) 5 (6): 847-54, 2012. [<a href="/pmc/articles/PMC3401905/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3401905</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22556202" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22556202</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_22">Rivera CM, Grossardt BR, Rhodes DJ, et al.: Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 16 (1): 15-23, 2009 Jan-Feb. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/21518944" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21518944</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_25">Mai PL, Huang HQ, Wenzel LB, et al.: Prospective follow-up of quality of life for participants undergoing risk-reducing salpingo-oophorectomy or ovarian cancer screening in GOG-0199: An NRG Oncology/GOG study. Gynecol Oncol 156 (1): 131-139, 2020. [<a href="/pmc/articles/PMC6980744/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6980744</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31759774" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31759774</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_26">Falconer H, Yin L, Grönberg H, et al.: Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst 107 (2): , 2015. [<a href="https://pubmed.ncbi.nlm.nih.gov/25628372" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25628372</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_27">Hanley GE, Pearce CL, Talhouk A, et al.: Outcomes From Opportunistic Salpingectomy for Ovarian Cancer Prevention. JAMA Netw Open 5 (2): e2147343, 2022. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/37683548" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37683548</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_29">Findley AD, Siedhoff MT, Hobbs KA, et al.: Short-term effects of salpingectomy during laparoscopic hysterectomy on ovarian reserve: a pilot randomized controlled trial. Fertil Steril 100 (6): 1704-8, 2013. [<a href="/pmc/articles/PMC3844119/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3844119</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23993887" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23993887</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_156_30">Venturella R, Lico D, Borelli M, et al.: 3 to 5 Years Later: Long-term Effects of Prophylactic Bilateral Salpingectomy on Ovarian Function. J Minim Invasive Gynecol 24 (1): 145-150, 2017. [<a href="https://pubmed.ncbi.nlm.nih.gov/27621194" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27621194</span></a>]</div></li></ol></div></div><div id="CDR0000062771__183"><h2 id="_CDR0000062771__183_">Factors With Inadequate Evidence of an Association Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancers</h2><div id="CDR0000062771__184"><h3>Dietary Factors</h3><p id="CDR0000062771__185">No consistent association has been observed between a variety of dietary factors and the risk of ovarian cancer.</p><p id="CDR0000062771__210">A systematic review and meta-analysis that included 23 case-control studies and three cohort studies found no evidence of an association between alcohol use and epithelial ovarian cancer.[<a class="bibr" href="#CDR0000062771_rl_183_1" rid="CDR0000062771_rl_183_1">1</a>]</p><p id="CDR0000062771__186">A case-control study of the Healthy Eating Index (HEI), based on current U.S. Department of Agriculture dietary guidelines, found no association between the highest HEI score and ovarian cancer risk for any specific food group.[<a class="bibr" href="#CDR0000062771_rl_183_2" rid="CDR0000062771_rl_183_2">2</a>] A systematic review of the role of diet in ovarian cancer included only prospective studies, with at least 200 reported cases in the publications.[<a class="bibr" href="#CDR0000062771_rl_183_3" rid="CDR0000062771_rl_183_3">3</a>] Twenty-four publications from ten cohort studies were reviewed, and no dietary factors were consistently associated with the risk of ovarian cancer.</p></div><div id="CDR0000062771__179"><h3>Aspirin and Nonsteroidal Anti-Inflammatory Drugs</h3><p id="CDR0000062771__180">A systematic review and meta-analysis of 21 observational studies found a decreased risk of invasive ovarian cancer associated with aspirin use (relative risk [RR], 0.88; 95% confidence interval [CI], 0.79–0.98), but no statistically significant association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs).[<a class="bibr" href="#CDR0000062771_rl_183_4" rid="CDR0000062771_rl_183_4">4</a>] A study published after that review examined NSAID use and ovarian cancer risk in the National Institutes of Health–AARP Diet and Health Study. No association was observed between the development of ovarian cancer and regular aspirin use (RR, 1.06; 95% CI, 0.87–1.29) or NSAID use (RR, 0.93; 95% CI, 0.74–1.15).[<a class="bibr" href="#CDR0000062771_rl_183_5" rid="CDR0000062771_rl_183_5">5</a>] A population-based case-control study [<a class="bibr" href="#CDR0000062771_rl_183_6" rid="CDR0000062771_rl_183_6">6</a>] of 902 incident cases and 1,802 population controls observed a decreased risk of ovarian cancer associated with continual use (0.71; 95% CI, 0.53–0.97) or low-dose daily use (0.72; 95% CI, 0.53–0.97). In that study, selective cyclooxygenase-2 NSAIDs, but not nonselective NSAIDs, were associated with a decreased risk of ovarian cancer (odds ratio [OR], 0.60; 95% CI, 0.39–0.94). A cohort analysis of about 200,000 women in the Nurses' Health Studies, which used detailed data about the intensity and duration of aspirin use over time, showed a reduced hazard ratio (HR) for ovarian cancer of 0.77 (95% CI, 0.61–0.96) for low-dose aspirin use (≤100 mg/d) but no reduction for standard-dose aspirin use (HR, 1.17; 95% CI, 0.92–1.49).[<a class="bibr" href="#CDR0000062771_rl_183_7" rid="CDR0000062771_rl_183_7">7</a>]</p></div><div id="CDR0000062771__220"><h3>Perineal Talc Exposure</h3><p id="CDR0000062771__221">Results from case-control and cohort studies are inconsistent, so the data are inadequate to support an association between perineal talc exposure and an increased risk of ovarian cancer. </p><p id="CDR0000062771__349"> A meta-analysis of 16 studies observed an increased risk with the use of talc (RR, 1.33; 95% CI, 1.16–1.45); however, a dose-response relationship was not found.[<a class="bibr" href="#CDR0000062771_rl_183_8" rid="CDR0000062771_rl_183_8">8</a>] A pooled analysis from the Ovarian Cancer Association Consortium, composed of multiple case-control studies, included 8,525 cases and 9,859 controls. The analysis found a modest increased risk of epithelial ovarian cancer associated with genital powder use (OR, 1.24; 95% CI, 1.15–1.33), but the trend across increasing lifetime number of applications was not statistically significant (<i>P</i> trend = .17).[<a class="bibr" href="#CDR0000062771_rl_183_9" rid="CDR0000062771_rl_183_9">9</a>] A meta-analysis of ten case-control studies and a highly selected subset analysis of one prospective cohort study found an association (OR, 1.47; 95% CI, 1.31–1.65) among women who used perineal talc at least twice a week.[<a class="bibr" href="#CDR0000062771_rl_183_10" rid="CDR0000062771_rl_183_10">10</a>] The subset analysis of the prospective study was inconsistent with the main findings of the original report.[<a class="bibr" href="#CDR0000062771_rl_183_11" rid="CDR0000062771_rl_183_11">11</a>] However, because of the structure of this analysis, the results should be interpreted with care.[<a class="bibr" href="#CDR0000062771_rl_183_10" rid="CDR0000062771_rl_183_10">10</a>] A population-based case-control study of African American women in the United States found an association between genital powder use and risk of epithelial ovarian cancer (OR, 1.44; 95% CI, 1.11–1.86).[<a class="bibr" href="#CDR0000062771_rl_183_12" rid="CDR0000062771_rl_183_12">12</a>] In this study of 584 cases and 745 controls, a dose-response relationship for <i>any</i> genital powder use was reported. Specifically, among <i>any</i> genital powder use, daily powder use was associated with increased adjusted OR of developing ovarian cancer (OR, 1.71; 95% CI, 1.26–2.33) compared with less than daily use (OR, 1.12; 95% CI, 0.80–1.58).</p><p id="CDR0000062771__334"> A cohort study among nurses did not observe a risk of ovarian cancer associated with perineal talc use (RR, 1.09; 95% CI, 0.86–1.37), and there was no evidence of increasing risk with increasing frequency of use.[<a class="bibr" href="#CDR0000062771_rl_183_13" rid="CDR0000062771_rl_183_13">13</a>] Another prospective study, the Women’s Health Initiative, examined the association between perineal powder use and the development of ovarian cancer among 61,576 women without a history of cancer at enrollment and who provided exposure information. Among this group, 429 cases of ovarian cancer occurred. Powder use on genitals, sanitary napkins, and diaphragms was examined individually and as a combined exposure. Women were followed for a mean of 12.4 years. An association of ovarian cancer with ever-use was not found when analyzed either by individual method of exposure or by overall combined exposure. The observed risk (HR) for combined exposure to perineal powder was 1.06 (95% CI, 0.87–1.28), and there was no increased risk observed for increasing duration of use.[<a class="bibr" href="#CDR0000062771_rl_183_14" rid="CDR0000062771_rl_183_14">14</a>] The cohort study cited above,[<a class="bibr" href="#CDR0000062771_rl_183_11" rid="CDR0000062771_rl_183_11">11</a>] which included 250,000 women enrolled in four long-term studies of women’s health, was consistent with other cited cohort studies, as the risk of ovarian cancer in perineal talc exposure never-users was similar to that in ever-users, with an HR of 1.08 (95 % CI, 0.99–1.17).[<a class="bibr" href="#CDR0000062771_rl_183_11" rid="CDR0000062771_rl_183_11">11</a>]</p></div><div id="CDR0000062771_rl_183"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062771_rl_183_1">Rota M, Pasquali E, Scotti L, et al.: Alcohol drinking and epithelial ovarian cancer risk. a systematic review and meta-analysis. Gynecol Oncol 125 (3): 758-63, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22449732" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22449732</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_2">Chandran U, Bandera EV, Williams-King MG, et al.: Healthy eating index and ovarian cancer risk. Cancer Causes Control 22 (4): 563-71, 2011. [<a href="/pmc/articles/PMC3131161/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3131161</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21286802" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21286802</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_3">Crane TE, Khulpateea BR, Alberts DS, et al.: Dietary intake and ovarian cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev 23 (2): 255-73, 2014. [<a href="/pmc/articles/PMC4077283/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4077283</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24142805" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24142805</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_4">Baandrup L, Faber MT, Christensen J, et al.: Nonsteroidal anti-inflammatory drugs and risk of ovarian cancer: systematic review and meta-analysis of observational studies. Acta Obstet Gynecol Scand 92 (3): 245-55, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23240575" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23240575</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_5">Murphy MA, Trabert B, Yang HP, et al.: Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control 23 (11): 1839-52, 2012. [<a href="/pmc/articles/PMC3469773/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3469773</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22972000" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22972000</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_6">Lo-Ciganic WH, Zgibor JC, Bunker CH, et al.: Aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, or acetaminophen and risk of ovarian cancer. Epidemiology 23 (2): 311-9, 2012. [<a href="/pmc/articles/PMC3454462/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3454462</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22252409" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22252409</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_7">Barnard ME, Poole EM, Curhan GC, et al.: Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses' Health Studies. JAMA Oncol 4 (12): 1675-1682, 2018. [<a href="/pmc/articles/PMC6400245/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6400245</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30286239" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30286239</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_8">Huncharek M, Geschwind JF, Kupelnick B: Perineal application of cosmetic talc and risk of invasive epithelial ovarian cancer: a meta-analysis of 11,933 subjects from sixteen observational studies. Anticancer Res 23 (2C): 1955-60, 2003 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/12820486" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12820486</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_9">Terry KL, Karageorgi S, Shvetsov YB, et al.: Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls. Cancer Prev Res (Phila) 6 (8): 811-21, 2013. [<a href="/pmc/articles/PMC3766843/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3766843</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23761272" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23761272</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_10">Woolen SA, Lazar AA, Smith-Bindman R: Association Between the Frequent Use of Perineal Talcum Powder Products and Ovarian Cancer: a Systematic Review and Meta-analysis. J Gen Intern Med 37 (10): 2526-2532, 2022. [<a href="/pmc/articles/PMC9360263/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9360263</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35112281" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35112281</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_11">O'Brien KM, Tworoger SS, Harris HR, et al.: Association of Powder Use in the Genital Area With Risk of Ovarian Cancer. JAMA 323 (1): 49-59, 2020. [<a href="/pmc/articles/PMC6990816/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6990816</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31910280" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31910280</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_12">Schildkraut JM, Abbott SE, Alberg AJ, et al.: Association between Body Powder Use and Ovarian Cancer: The African American Cancer Epidemiology Study (AACES). Cancer Epidemiol Biomarkers Prev 25 (10): 1411-1417, 2016. [<a href="/pmc/articles/PMC5050086/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5050086</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27197282" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27197282</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_13">Gertig DM, Hunter DJ, Cramer DW, et al.: Prospective study of talc use and ovarian cancer. J Natl Cancer Inst 92 (3): 249-52, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10655442" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10655442</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_183_14">Houghton SC, Reeves KW, Hankinson SE, et al.: Perineal powder use and risk of ovarian cancer. J Natl Cancer Inst 106 (9): , 2014. [<a href="/pmc/articles/PMC4200058/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4200058</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25214560" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25214560</span></a>]</div></li></ol></div></div><div id="CDR0000062771__214"><h2 id="_CDR0000062771__214_">Areas of Uncertainty</h2><div id="CDR0000062771__147"><h3>Ovarian Hyperstimulation Due to Infertility Treatment</h3><p id="CDR0000062771__148">Controversy persists concerning the association between ovarian hyperstimulation and ovarian cancer. Results of a systematic review and meta-analysis of nine cohort studies comprised 109,969 women who were exposed to ovarian hyperstimulation for infertility treatment (i.e., <i>in vitro</i> fertilization [IVF]), with 76 incident ovarian cancer cases observed, provided inconclusive evidence for an association.[<a class="bibr" href="#CDR0000062771_rl_214_1" rid="CDR0000062771_rl_214_1">1</a>] An increased risk of ovarian cancer was observed when the comparison group was the general population (relative risk [RR], 1.50; 95% confidence interval [CI], 1.17–1.92), but no statistically significant increased risk was observed when the reference group was unexposed infertile women (RR, 1.26; 95% CI, 0.62–2.55). A major limitation was that only one of the cohort studies included in the meta-analysis had a follow-up period longer than 10 years for those exposed to IVF.</p><p id="CDR0000062771__149">A Cochrane systematic review that included 11 case-control studies and 14 cohort studies, for a total of 186,972 women, was also indeterminate for an association. Summary statistics were not calculated because of methodological and clinical heterogeneity. Among seven cohort studies that compared treated women with untreated subfertile women, no excess risk was noted in association with hyperstimulation medications. Two cohorts noted an increased risk of twofold to fivefold when treated women were compared with the general population. An increased risk of borderline ovarian tumors was noted in three case-control studies and two cohort studies. Overall, the authors concluded there was no convincing evidence that an increased risk of invasive ovarian tumors was associated with fertility drug treatments.[<a class="bibr" href="#CDR0000062771_rl_214_2" rid="CDR0000062771_rl_214_2">2</a>]</p><p id="CDR0000062771__150">After the Cochrane review, a follow-up study of an infertility cohort [<a class="bibr" href="#CDR0000062771_rl_214_3" rid="CDR0000062771_rl_214_3">3</a>] was published. A retrospective cohort of 9,825 women enrolled between 1965 and 1988 was followed through 2010. Ovarian cancer occurred in 85 women. Overall, there was no association between ovarian cancer and clomiphene citrate (RR, 1.34; 95% CI, 0.86–2.07) or gonadotropins (RR, 1.00; 95% CI, 0.48–2.08). Among the subgroup of women who remained nulligravid after treatment, an increased risk of ovarian cancer was associated with clomiphene citrate (RR, 3.63; 95% CI, 1.36–9.72). No increased risk was observed among women who successfully conceived after being treated, compared with women who were not treated.</p></div><div id="CDR0000062771_rl_214"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062771_rl_214_1">Siristatidis C, Sergentanis TN, Kanavidis P, et al.: Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer--a systematic review and meta-analysis. Hum Reprod Update 19 (2): 105-23, 2013 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/23255514" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23255514</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_214_2">Rizzuto I, Behrens RF, Smith LA: Risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility. Cochrane Database Syst Rev 8: CD008215, 2013. [<a href="/pmc/articles/PMC6457641/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6457641</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23943232" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23943232</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062771_rl_214_3">Trabert B, Lamb EJ, Scoccia B, et al.: Ovulation-inducing drugs and ovarian cancer risk: results from an extended follow-up of a large United States infertility cohort. Fertil Steril 100 (6): 1660-6, 2013. [<a href="/pmc/articles/PMC3873340/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3873340</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24011610" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24011610</span></a>]</div></li></ol></div></div><div id="CDR0000062771__37"><h2 id="_CDR0000062771__37_">Latest Updates to This Summary (12/09/2024)</h2><p id="CDR0000062771__39">The PDQ cancer information summaries are reviewed regularly and updated as
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new information becomes available. This section describes the latest
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changes made to this summary as of the date above.</p><p id="CDR0000062771__375">Editorial changes were made to this summary.</p><p id="CDR0000062771__disclaimerHP_3">This summary is written and maintained by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/screening-prevention" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Screening and Prevention Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062771__AboutThis_1">About This PDQ Summary</a> and <a href="https://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® Cancer Information for Health Professionals</a> pages.
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</p></div><div id="CDR0000062771__AboutThis_1"><h2 id="_CDR0000062771__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062771__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062771__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about ovarian, fallopian tube, and primary peritoneal cancers prevention. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062771__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062771__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/screening-prevention" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Screening and Prevention Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062771__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062771__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062771__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p id="CDR0000062771__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062771__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062771__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a <a href="/books/n/pdqcis/CDR0000304747/?report=reader">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062771__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062771__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062771__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062771__AboutThis_15">PDQ® Screening and Prevention Editorial Board. PDQ Ovarian, Fallopian Tube, and Primary Peritoneal Cancers Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/types/ovarian/hp/ovarian-prevention-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/types/ovarian/hp/ovarian-prevention-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389359]</p><p id="CDR0000062771__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062771__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062771__AboutThis_19">The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062771__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062771__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div><div class="fm-sec"><h2 id="_NBK65921_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">PDQ Screening and Prevention Editorial Board</span>.</p><h3>Publication History</h3><p class="small">Published online: December 9, 2024.</p><h3>Version History</h3><ul class="simple-list" style="padding:0"><li><span class="bk_col_itm">NBK65921.35</span> December 9, 2024 (Displayed Version)</li><li><span class="bk_col_itm"><a href="/books/NBK65921.34/?report=reader">NBK65921.34</a></span> October 8, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK65921.33/?report=reader">NBK65921.33</a></span> March 6, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK65921.32/?report=reader">NBK65921.32</a></span> October 16, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65921.31/?report=reader">NBK65921.31</a></span> June 29, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65921.30/?report=reader">NBK65921.30</a></span> March 23, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65921.29/?report=reader">NBK65921.29</a></span> February 9, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65921.28/?report=reader">NBK65921.28</a></span> November 3, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK65921.27/?report=reader">NBK65921.27</a></span> June 16, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK65921.26/?report=reader">NBK65921.26</a></span> May 6, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK65921.25/?report=reader">NBK65921.25</a></span> July 8, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65921.24/?report=reader">NBK65921.24</a></span> March 26, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65921.23/?report=reader">NBK65921.23</a></span> December 17, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65921.22/?report=reader">NBK65921.22</a></span> October 8, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65921.21/?report=reader">NBK65921.21</a></span> April 22, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65921.20/?report=reader">NBK65921.20</a></span> March 31, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65921.19/?report=reader">NBK65921.19</a></span> February 21, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65921.18/?report=reader">NBK65921.18</a></span> December 13, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65921.17/?report=reader">NBK65921.17</a></span> October 4, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65921.16/?report=reader">NBK65921.16</a></span> May 30, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65921.15/?report=reader">NBK65921.15</a></span> March 1, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65921.14/?report=reader">NBK65921.14</a></span> January 4, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65921.13/?report=reader">NBK65921.13</a></span> December 21, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65921.12/?report=reader">NBK65921.12</a></span> June 22, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65921.11/?report=reader">NBK65921.11</a></span> March 16, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65921.10/?report=reader">NBK65921.10</a></span> February 7, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65921.9/?report=reader">NBK65921.9</a></span> November 30, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK65921.8/?report=reader">NBK65921.8</a></span> July 27, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK65921.7/?report=reader">NBK65921.7</a></span> June 16, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK65921.6/?report=reader">NBK65921.6</a></span> April 7, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK65921.5/?report=reader">NBK65921.5</a></span> February 4, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65921.4/?report=reader">NBK65921.4</a></span> January 8, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65921.3/?report=reader">NBK65921.3</a></span> December 11, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK65921.2/?report=reader">NBK65921.2</a></span> October 16, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK65921.1/?report=reader">NBK65921.1</a></span> May 15, 2015</li></ul><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>PDQ Screening and Prevention Editorial Board. Ovarian, Fallopian Tube, and Primary Peritoneal Cancers Prevention (PDQ®): Health Professional Version. 2024 Dec 9. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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