National Cancer Institute


Expert-reviewed information summary about factors that may influence the risk of developing ovarian, fallopian tube, and primary peritoneal cancers and about research aimed at the prevention of them.

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about ovarian, fallopian tube, and primary peritoneal cancer 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.

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).

Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention

Ovarian, Fallopian Tube, & Primary Peritoneal Cancer Prevention

Who Is at Risk?

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 histopathologic 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 histologic subtypes of low-grade ovarian carcinomas.

Risk factors for ovarian cancer include a personal history of breast cancer or a family history of breast and/or ovarian cancer, and inheritance of deleterious mutations in , , and selected other high-penetrance genes. (Refer to the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information.) Other risk factors for ovarian cancer include obesity, endometriosis, and the use of postmenopausal hormone therapy.

Associations with ovarian cancer of some risk factors vary by histopathologic subtype. Further, among carriers of deleterious mutations in or , increasing evidence suggests that many tumors previously classified as ovarian high-grade serous carcinoma may develop from malignant cells arising in tubal epithelium (serous tubal intraepithelial carcinoma [STIC]), although these tumors continue to be referred to as cancers in most writings. It is hypothesized that high-grade serous carcinomas among individuals who are not carriers of mutations in or 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 histologic 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.

Factors associated with a decreased risk of ovarian cancer include multiparity, use of oral contraceptives, multiple pregnancies, breast-feeding, tubal ligation, and salpingectomy. Compared with nulliparous women, the risk of ovarian cancer is reduced by 30% to 60% among parous women, with additive protection for each additional birth.

Overview

Note: Separate PDQ summaries on Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening and Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment are also available.

Factors With Adequate Evidence of an Increased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Family history and inherited susceptibility to ovarian, fallopian tube, and primary peritoneal cancer

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 or mutation, have an increased risk of developing ovarian cancer (refer to the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information).

Hormone replacement therapy

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 preparation type (estrogen only vs. combined estrogen/progestin).

Magnitude of Effect: Modest with observed relative risks (RRs) of 1.20 to 1.8.

  • Study Design: One randomized clinical trial, cohort and case-control studies.
  • Internal Validity: Good.
  • Consistency: Fair.
  • External Validity: Good.

Obesity and height

Based on fair evidence, obesity and height are associated with a modest increased risk of ovarian cancer.

Magnitude of Effect: 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 increase in body mass index 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.

  • Study Design: Cohort and case-control studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Factors With Adequate Evidence of a Decreased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Oral contraceptives

Benefits

Based on solid evidence, oral contraceptive use is associated with a decreased risk of developing ovarian cancer.

Magnitude of Effect: The degree of risk reduction varies by duration of oral contraceptive use and time since last use. For 1 to 4 years of oral contraceptive use, the RR reduction is 22%, and for 15 or more years of use, the RR reduction is 56%. The reduction in risk persisted for more than 30 years after use was discontinued, but the degree of reduction attenuated over time. The risk reduction per 5 years of oral contraceptive use was 29% for women who discontinued use less than 10 years ago and decreased to 15% for women who discontinued use 20 to 29 years ago. Ten years of use reduced cancer incidence before age 75 years from 1.2 to 0.8 per 100 users and reduced mortality from 0.7 to 0.5 per 100 users. The number needed-to-treat for 5 years was estimated to be about 185 women.

  • Study Design: Multiple case-control and cohort studies; meta-analyses.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Harms

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.

Magnitude of Effect: 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.

  • Study Design: Observational studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Tubal ligation

Benefits

Based on solid evidence, tubal ligation is associated with a decreased risk of ovarian cancer.

Magnitude of Effect: Adjusting for other forms of contraception, tubal ligation provides a relative reduction in the odds of developing ovarian cancer of about 30%.

  • Study Design: Multiple case-control studies and cohort studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Harms

Based on fair evidence, harms include surgical risks, including the following:

  • Major morbidity including blood transfusion, reoperation, or hospital readmission (rate of 1.0 per 100 procedures).
  • Minor morbidity including post-operative fever, urinary tract infections, or wound infections (rate of 6.0 per 100 procedures).

Multiparity

Based on good evidence, multiparity is associated with a decreased risk of ovarian cancer.

Magnitude of Effect: Based on good evidence from multiple observational epidemiological studies, parous women have appropriately 30% lower ovarian cancer risk than nulliparous women.

  • Study Design: Observational epidemiologic studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Salpingectomy

Based on limited data, salpingectomy is associated with a decrease in risk of ovarian cancer.

Magnitude of Effect: Approximately 50% decrease for bilateral salpingectomy, less protection for unilateral salpingectomy.

  • Study Design: Observational epidemiologic studies from several different countries.
  • Internal validity: Good.
  • Consistency: Good.
  • External validity: Good.

Breast-feeding

Based on solid evidence, breast-feeding is associated with a decreased risk of ovarian cancer.

Magnitude of Effect: 2% decrease with every month of breast-feeding.

  • Study Design: Multiple case-control and cohort studies; meta-analysis.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Risk-reducing bilateral salpingo-oophorectomy

Benefits

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.

Magnitude of Effect: 90% reduction in risk of ovarian cancer observed among women with a or mutation.

  • Study Design: Multiple case-control studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Harms

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.

Magnitude of Effect: 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).

  • Study Design: Cohort and case-control studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Areas of Uncertainty

Ovarian hyperstimulation for infertility treatment

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.

Magnitude of Effect: 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.

  • Study Design: Cohort and case-control studies; systematic review.
  • Internal Validity: Fair.
  • Consistency: Poor.
  • External Validity: Fair.

Description of the Evidence

Background

Incidence and mortality

In 2017, it is estimated that 22,440 new cases of ovarian cancer will be diagnosed and 14,080 deaths due to ovarian cancer will occur. Incidence and mortality rates are higher among whites than among blacks, but statistically significant decreases in incidence and mortality rates have been observed among both whites and blacks. Given that the Surveillance, Epidemiology, and End Results Program does not adjust for oophorectomy or salpingectomy, racial differences in the prevalence of women who had undergone these procedures could bias racial rate comparisons. A statistically significant decrease in delayed adjusted incidence of 0.9% among whites from 1987 to 2012 and 0.2% among blacks from 1992 to 2012 was observed. A statistically significant decrease in mortality rates of 2.0% per year among whites from 2002 to 2012 and 1.3% per year among blacks from 1992 to 2012 was observed. The population lifetime risk of ovarian cancer is 1.3%; the population lifetime risk of dying from ovarian cancer is 0.97%.

Histology and Pathogenesis of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

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:

Among type I tumors, endometrioid and clear cell carcinomas are numerically predominant and most important clinically. In general, type I ovarian carcinomas present at a lower stage than type II tumors and portend a better prognosis.

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 lesions in the epithelium of the fallopian tube fimbria, which 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 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 among women who are not carriers of 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.

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 etiologic data. Ovarian cancer is a rare cancer, thus sample size and power of studies to detect moderate associations by cancer subtype is limited. However, clearer subtyping of cancers may assist in improving our understanding of the etiology of ovarian malignancies in future studies.

Factors With Adequate Evidence of an Increased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Family history and inherited susceptibility to ovarian, fallopian tube, and primary peritoneal cancer

Some women are at an increased risk 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 accurate pedigrees and/or genetic markers of risk. Because of uncertainties about cancer risks associated with certain specific gene mutations, genetic information may be difficult to interpret outside of families with a high incidence of ovarian cancer.

This summary does not address multiple genetic syndromes or women who are at high risk because of inherited genetic factors. (Refer to the PDQ summaries on Genetics of Breast and Gynecologic Cancers and Genetics of Colorectal Cancer for specific information related to ovarian cancer risk associated with multiple genetic syndromes and ovarian cancer in mutation carriers.)

Hormone replacement therapy/hormone therapy

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 (relative risk [RR], 1.37; 95% confidence interval [CI], 1.29–1.46), with similar results for retrospective designs. Significant relationships were found for serous and endometrioid subtypes. Recent use was strongly related to risk even among women who had used hormone replacement 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.

Obesity and height

Obesity is associated with increased mortality from ovarian cancer. In cohort studies, height and body mass index (BMI), including high BMI during adolescence, were associated with an increased risk of ovarian cancer, suggesting a role for diet and nutrition interventions during adolescence to prevent excessive weight gain.

A meta-analysis found that a five-unit increase in BMI was associated with an RR of 1.07 (95% CI, 1.03–1.11), with a nonlinear increase indicating an association mainly for women with a BMI of 28 kg/m and greater. For every 10 cm increase in height, the RR was 1.16 (95% CI, 1.11–1.21). Other anthropometric measurements, such as weight gain, hip circumference, and waist-to-hip ratio were not associated with risk, on the basis of few studies.

Factors With Adequate Evidence of a Decreased Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Oral contraceptives

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. The studies included 13 prospective studies, 19 population-based case-control studies, and 12 hospital-based case-control studies. 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 meta-analysis that was restricted to 24 case-control and cohort studies published since 2000 for the primary analysis—in order to reflect more recent types of oral contraceptive preparations—also observed a dose-response by duration of use. The risk reduction among women using oral contraceptives for more than 1 year but less than 5 years was 0.77 (95% CI, 0.66–0.89), and for women using oral contraceptives for more than 10 years, the risk reduction was 0.43 (95% CI, 0.37–0.51). 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 reduction of ovarian cancer attributable to oral contraceptives of 0.54%.

(Refer to the PDQ summary on Genetics of Breast and Gynecologic Cancers for specific information related to ovarian cancer risk among mutation carriers.)

Depot-medroxyprogesterone acetate

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). However, only 22 of the cases had ever used DMPA and nine of these had used it for 6 months or less.

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 (odds ratio [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.

Tubal ligation

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). 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. 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.

Another pooling project with primary data from 13 population-based case-control studies examined the association between tubal ligation and ovarian cancer risk and included 7,942 epithelial ovarian cancers, and 13,904 controls. 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.

A pooled analysis from 21 prospective cohort studies examined 14 hormonal, reproductive, and lifestyle factors by histologic subtype among 5,584 invasive ovarian cancers within a total sample of 1.3 million women. 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.

Breast-feeding

A meta-analysis that included five prospective studies and 30 case-control studies examined the association between breast-feeding and the risk of ovarian cancer. Any breast-feeding 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 breast-feeding (95% CI, 0.90–0.95). Another meta-analysis that included five prospective studies and 35 case-control studies found that any breast-feeding 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 breast-feeding and greater levels of protection. 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 breast-feeding was greatest for the first 8 to 10 months.

Risk-reducing salpingo-oophorectomy

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. (Refer to the Oral contraceptives section in the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information on this as a risk-reducing intervention.) 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. Salpingectomy has also been discussed as a preferred means of sterilization.

Harms

Risks associated with benign oophorectomy (with or without salpingectomy or hysterectomy) have been analyzed in six published studies. Three cohorts have 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 obese women younger than 40 years 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.

Salpingectomy

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. 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 rates (HRs) for risk of ovarian cancer compared with women who had not undergone surgery:

  • For hysterectomy, HR was 0.79 (95% CI, 0.70–0.88).
  • For hysterectomy with bilateral salpingo-oophorectomy, HR was 0.06 (95% CI, 0.03–0.12).
  • For salpingectomy, HR was 0.65 (95% CI, 0.52–0.81).
  • For sterilization procedures, HR was 0.72 (95% CI, 0.64–0.81).

Protection for bilateral salpingectomy was approximately twice that for unilateral salpingectomy. This report included limited covariate data but results were similar to other smaller studies included in the meta-analysis.

Limited data based on circulating surrogate markers of ovarian reserve suggest that salpingectomy does not have an adverse effect on ovarian function.

Factors With Inadequate Evidence of an Association Risk of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Dietary factors

No consistent association has been observed between a variety of dietary factors and the risk of ovarian cancer.

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 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 systematic review of the role of diet in ovarian cancer included only prospective studies, with at least 200 reported cases in the publications. Twenty-four publications from ten cohort studies were reviewed and no dietary factors were consistently associated with the risk of ovarian cancer.

Aspirin and nonsteroidal anti-inflammatory drugs

A systematic review and meta-analysis of 21 observational studies found a decreased risk of invasive ovarian cancer associated with aspirin use (RR, 0.88; 95% CI, 0.79–0.98), but no statistically significant association with nonsteroidal anti-inflammatory drugs (NSAIDs). A study published subsequent to that review examined NSAIDs 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 NSAIDs use (RR, 0.93; 95% CI, 0.74–1.15). A population-based case-control study 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 cyclo-oxygenase-2 NSAIDs but not nonselective NSAIDs were associated with a decreased risk of ovarian cancer (OR, 0.60; 95% CI, 0.39–0.94).

Perineal talc exposure

The weight of evidence does not support an association between perineal talc exposure and an increased risk of ovarian cancer. Results from case-control and cohort studies are inconsistent. 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 pooled analysis from the Ovarian Cancer Association Consortium, composed of multiple case-control studies, included 8,525 cases and 9,859 controls 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 ( trend = .17). 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 increased risk with increasing frequency of use. 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 (hazard ratio) 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.

Areas of Uncertainty

Ovarian hyperstimulation due to infertility treatment

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., fertilization [IVF]), with 76 incident ovarian cancer cases observed, provided inconclusive evidence for an association. An increased risk of ovarian cancer was observed when the comparison group was the general population (RR, 1.50; 95% 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.

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 follow-up study of an infertility cohort was published subsequent to the aforementioned Cochrane review. 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.

Changes to This Summary (07/27/2017)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Overview

Added text to state that ovarian cancer risks associated with current or recent hormone therapy did not differ by preparation type (cited Mørch et al. as reference 1 and Beral et al. as reference 2).

This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about ovarian, fallopian tube, and primary peritoneal cancer 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.

Reviewers and Updates

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).

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Levels of Evidence

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 formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

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].”

The preferred citation for this PDQ summary is:

PDQ® Screening and Prevention Editorial Board. PDQ Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated . Available at: https://www.cancer.gov/types/ovarian/hp/ovarian-prevention-pdq. Accessed . [PMID: 26389359]

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 Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

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 Managing Cancer Care page.

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More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.

Blogs

September is Ovarian Cancer Awareness Month
by Christina Bach, MSW, LCSW, OSW-C
September 13, 2016


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