www.elsevier.com/locate/ygyno

Gynecologic Oncology 93 (2004) 280–286

Systematic review of management options for women with a hereditary

predisposition to ovarian cancer

Barry Rosen,a,* Janice Kwon,b Michael Fung Kee Fung,c

Anna Gagliardi,d and Alexandra Chamberse

Cancer Care Ontario’s Practice Guidelines Initiative Gynecology Cancer Disease Site GroupaPrincess Margaret Hospital, Toronto, Ontario, Canada

bUniversity of Ottawa, Ottawa, Ontario, CanadacUniversity of Western Ontario, London, Ontario, CanadadSurgical Oncology Network, Toronto, Ontario, Canada

eProgram in Evidence-Based Care, Cancer Care Ontario, Hamilton, Ontario, Canada

Received 11 November 2003

Abstract

Objective. To develop through consensus and literature review management options for women with a hereditary predisposition to ovarian

cancer, outcomes of interest were incidence of ovarian cancer, life expectancy, additional benefits of prophylactic oophorectomy,

complications of surgery, and alternatives to prophylactic oophorectomy.

Methods. MEDLINE, CANCERLIT, and the Cochrane Library databases were searched to September 2003 using the terms ovarian,

cancer, neoplasms, prophylactic oophorectomy, ovariectomy, clinical trial, metaanalysis, and systematic review.

Results. Four cohort studies (two retrospective, two prospective) examined whether prophylactic oophorectomy reduced the lifetime risk

of developing ovarian cancer. All the cohort studies found that prophylactic oophorectomy reduced the lifetime risk of developing ovarian

cancer; however, this risk reduction was statistically significant in only two cohort studies. The complication rate of laparoscopic surgery for

prophylactic oophorectomy is low (0.22–4.0%). However, there are long-term adverse effects of prophylactic oophorectomy, most notably

the onset of early menopause.

Conclusions. Based on the evidence from the four cohort studies, prophylactic oophorectomy does protect against the development of

ovarian cancer.

D 2004 Elsevier Inc. All rights reserved.

Keywords: Management; Predisposition; Ovarian cancer

Introduction carriers, the risk is lower ranging between 10% and 25% [4–

Kerlikowske et al. [1] and Ponder et al. [2] detected a high

lifetime risk of ovarian cancer in women with two first-

degree relatives with ovarian or breast cancer, a subgroup

later identified as being women with BRCA1 and 2 germ line

mutations. These mutations have been identified as the

genetic links to the increased lifetime risk of ovarian cancer

[3]. BRCA1 mutation carriers have an estimated 16–54%

lifetime risk of ovarian cancer, whereas in BRCA2 mutation

0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.ygyno.2004.02.013

* Corresponding author. Princess Margaret Hospital, 610 University

Avenue, Toronto, Ontario, Canada M5G 2M9. Fax: +1-416-946-2288.

E-mail address: barry.rosen@uhn.on.ca (B. Rosen).

6]. These risk estimates will vary depending on the popula-

tion being studied [6]. Approximately 10% of ovarian cancer

cases are attributed to the inheritance of a BRCA1 or 2

mutation [7,8]. Due to the high mortality rate and the absence

of effective screening for ovarian cancer, prophylactic oo-

phorectomy has been proposed as a preventive measure [9–

14]. In 1995, the National Institutes of Health (NIH) pub-

lished a consensus statement recommending prophylactic

oophorectomy after age 35 in women with a significant

family history of ovarian cancer [10]. This statement was

made before genetic testing became available outside of

clinical trial and therefore used family history as their criteria

for recommending surgery. The consensus did not specify

either the surgical approach (laparoscopy vs. laparotomy) or

B. Rosen et al. / Gynecologic Oncology 93 (2004) 280–286 281

whether the procedure should include a hysterectomy along

with the oophorectomy.

The aim of this systematic review is to present the current

literature surrounding the management options for women

with a hereditary predisposition to ovarian cancer.

Methods

Evidence was selected and reviewed by three members of

Cancer Care Ontario’s Practice Guidelines Initiative Gyne-

cology Cancer Disease Site Group and methodologists. This

systematic review has been reviewed and approved by the

Gynecology Cancer Disease Site Group, which comprises

gynecologic oncologists, medical oncologists, radiation

oncologists, an oncology nurse, a pathologist, and commu-

nity representatives.

MEDLINE (1966 to September 2003), CANCERLIT

(1985 to October 2002), and Cochrane Library (2003, Issue

2) databases were searched. ‘‘Ovariectomy’’ (medical sub-

ject heading [MeSH]) and ‘‘oophorectomy’’ (MeSH) were

combined with ‘‘ovarian neoplasms’’ (MeSH), ‘‘prophylac-

tic’’ (MeSH), and ‘‘elective’’ (MeSH). These terms were

then combined with the search terms for the following study

designs and publication types: practice guidelines, system-

atic reviews, metaanalyses, reviews, randomized controlled

trials, controlled clinical trials, case series, and cohort

studies. In addition, the Physician Data Query (PDQ)

clinical trials database on the Internet (www.cancer.gov/

search/clinicaltrials) was searched for reports of new or

ongoing trials.

Articles were selected for inclusion in this systematic

review of the evidence if they reported results on the

following:

� Randomized controlled trials or metaanalyses comparing

elective or prophylactic oophorectomy to another

strategy for the prevention of ovarian cancer in women

with confirmed BRCA1 or 2 mutations.� Phase II trials, cohort studies, or case series examining

the outcome of prophylactic oophorectomy in women

with confirmed BRCA1 or 2 mutations.

Results

There are no randomized controlled trials comparing

prophylactic oophorectomy to no surgery in women with

confirmed BRCA1 or 2 mutations. However, there were

four cohort studies that evaluated the outcome of prophy-

lactic surgery in women with a significant family history

[15] or confirmed BRCA1 or 2 mutations [16–18]. Two of

the cohort studies (one retrospective) compared prophylac-

tic oophorectomy to observation in women with germ line

BRCA mutations and subsequently compared rates of

developing ovarian and peritoneal cancers [19]. One pro-

spective study compared prophylactic oophorectomy to

observation in women with a strong family history of breast

or ovarian cancer [17]. The other cohort study reviewed

cases of familial ovarian cancer entered on a familial

ovarian cancer registry over a period of 10 years [18].

The results of the cohort studies could not be pooled

because of the variability in patient populations and study

methodology. Kauff et al. [16] put a restriction on the age of

participants (older than 35 years), while the other studies did

not restrict age [17–19]. Piver et al. [18] studied women with

a family history of ovarian or breast cancer; however, the

patients did not have confirmed BRCA1 or 2 mutations,

unlike the other three cohort studies. In Kauff et al.’s

prospective study patients were given the choice between

prophylactic oophorectomy and surveillance, an option not

possible in Rebbeck et al.’s retrospective study.

Evidence that prophylactic oophorectomy protects against

ovarian cancer

All four cohort studies found that prophylactic oophorec-

tomy had a protective effect against development of ovarian

cancer. [16–19]. Table 1 outlines the studies that are includ-

ed in the systematic review.

The retrospective cohort study by Rebbeck et al. [19]

matched 259 women with BRCA1 or 2 mutations who had

undergone prophylactic oophorectomy to 292 similar women

who had not undergone surgery. Among the women who had

undergone surgery, there were six cases of stage I ovarian

cancer identified during the procedure, and two cases of

peritoneal cancer identified 3.8 and 8.6 years after surgery.

There were 58 cases of ovarian cancer identified among the

women who had not undergone surgery (median follow-up

8.8 years). Only six of the fifty-eight ovarian cancers detected

in the no surgery group of women were stage I (11%), while

all six of the ovarian cancers detected in the women under-

going prophylactic oophorectomy were stage I. Rebbeck et

al. acknowledge that their study had limitations, due to the

retrospective nature of the data; however, they tried to reduce

the limitation by including the matched control group.

Kauff et al. [16] reported the results of a prospective study

that compared 98 women with BRCA1 or 2 mutations who

chose to undergo prophylactic oophorectomy to 72 women

with BRCA1 or 2 mutations who chose not to have surgery.

The two groups of women were similar in terms of mutation

type (BRCA1 or 2), age, history of breast cancer and oral

contraceptive use. Among the women undergoing surgery,

there was only one case of peritoneal cancer identified 16.3

months after her surgery. In the group of women who chose

not to undergo surgery, there were eight cases of breast

cancer, four cases of ovarian cancer, and one case of

peritoneal cancer identified. The median follow-up time

was 25.4 months with a range of 0.4–76.2. Kauff et al. do

not indicate the stage at which the cancers were identified

(i.e., whether or not they were potentially curable), nonethe-

less they were able to conclude that prophylactic oophorec-

Table 1

Outline of the studies included in the systematic review

Study Kauff, 2002 [16] Rebbeck, 2002 [19] Struewing, 1995 [17] Piver, 1993 [18]

Type of study prospective follow-up retrospective prospective follow-up retrospective

Age of patients > 35 years old no age restrictions NR no age restrictions

No. of patients with BRCA1

or 2 mutations

170 551 390 with family history of

breast/ovarian cancer

1568 with family history

of breast/ovarian cancer

No. of patients undergoing PO 98 259 44 324

No. of patients in control group 72 with mutations but chose

not to undergo PO

292 matched according to

age (within 5 years),

BRCA1 or 2 status, location

346 first-degree relatives

of oophorectomized

women

no control group

Outcomes

Incidence of cancer among 1 peritoneal 6 ovarian (diagnosed at time 2 peritoneal 6 peritoneal

PO group 3 breast of surgery)

2 peritoneal

Incidence of cancer among 4 ovarian 58 ovarian/peritoneal 8 ovarian N/A

control group 1 peritoneal

8 breast

Mean follow-up 24.2 months 8.2 years for PO NR ranged from 1 to 27 years

8.8 years for control

Outcomes measured disease-free survival: incidence of BRCA1 or 2 women who underwent compared incidence of

98% PO group related cancers in PO had a lifetime risk of cancer between mothers

83% control group

P = 0.04

follow-up:

0.8% for PO

19.9% for control group

developing ovarian cancer

13 times greater than the

general population,

and daughters and sisters.

Familial ovarian cancer

occurs most frequently in

P < 0.001 women who in control

group had 24 times the

lifetime risk

mothers and daughters

Note. N/A, not available; NR, not reported; PO, prophylactic oophorectomy.

B. Rosen et al. / Gynecologic Oncology 93 (2004) 280–286282

tomy can decrease the risk of breast and ovarian cancer

among women with BRCA1 and 2 mutations.

There was another prospective cohort study that reported

a reduction in the incidence of ovarian cancer; however,

these results are not statistically significant due to the small

and unbalanced sample: there were 44 women in the pro-

phylactic oophorectomy group versus 346 women in the

control group [17].

The fourth study reviewed the incidence of ovarian cancer

reported on a familial ovarian cancer registry over a 10-year

period [18]. Piver et al. [18] reviewed 324 cases of women

with a history of familial ovarian cancer (two or more first- or

second-degree relatives with ovarian cancer) who underwent

prophylactic oophorectomy. Six women developed primary

peritoneal carcinoma (1.9%); however, there was no com-

parison to women with similar family histories who did not

have prophylactic oophorectomy. The assumption is that the

risk reduction for ovarian cancer conferred by prophylactic

oophorectomy exceeds the risk of primary peritoneal carci-

noma. That is, it is supposed that there is less risk of

developing peritoneal carcinoma after oophorectomy than

there is of developing ovarian cancer without oophorectomy.

Based on the evidence from the four cohort studies,

prophylactic oophorectomy appears to be protective against

the development of ovarian cancer. In both Kauff et al.’s and

Rebbeck et al.’s studies, the risk of peritoneal cancer after

prophylactic oophorectomy was < 1% compared to 5–25%

risk of developing ovarian cancer in those women not

undergoing surgery. While follow-up in Rebbeck et al.’s

study is over 8 years, Kauff et al.’s mean follow-up is only

23.4 months for those undergoing surgery. It is important to

note that with longer follow-up data, the reported risk

reduction provided by prophylactic surgery may change. In

both studies, the risk reduction is high, and thus, this data

strongly support the use of prophylactic surgery in BRCA1

and 2 germline mutation carriers. This degree of risk reduc-

tion is particularly important for ovarian cancer, a disease

that has both a low detection rate for early stage, and a high

mortality rate for advanced stages.

Life expectancy following prophylactic oophorectomy

Three decision analyses have examined life expectancy

through the use of Markov modeling based on the probability

of ovarian cancer in women with a genetic predisposition

and in women without such a predisposition [9,15,20]. All

three analyses detected similar results. One decision analysis

determined that a 30-year-old BRCA1 or 2 carrier would

gain an additional 0.3–1.7 years in life expectancy following

prophylactic oophorectomy, and that prophylactic oophorec-

tomy could be delayed for 10 years with little loss in life

expectancy [9]. The second decision analysis detected that

prophylactic oophorectomy would contribute an additional

0.4–2.6 years of life expectancy to high-risk women and that

prophylactic oophorectomy plus prophylactic mastectomy

would improve survival by 3.3–6.0 years compared with

surveillance alone [15]. This decision analysis also reported

quality-adjusted life years (QALY), a value that takes into

B. Rosen et al. / Gynecologic Oncology 93 (2004) 280–286 283

account the negative features of prophylactic oophorectomy

as perceived by the women undergoing the procedure. The

QALYs saved were 0.5 for prophylactic oophorectomy and

1.9 for the combined procedure in high-risk women. The

third decision analysis found that there was prolongation in

quality-adjusted life expectancy for those undergoing pro-

phylactic oophorectomy with or without prophylactic mas-

tectomy, and this advantage was greatest before the age of

40 [20].

Complications of the prophylactic oophorectomy procedure

An Ontario hospital-based study [21] evaluated 41 insti-

tutions where prophylactic oophorectomies were performed

from 1992 to 1998. Surgery for 141 of the 274 patients

studied had coexistent gynecologic complaints. Only 18 had

BRCA testing. Surgical complications were reported in

15.7% of patients, including bleeding, injury to pelvic

organs, and infection. Most of these procedures had been

done by laparotomy. This study cohort is very different from

our current population of patients who undergo prophylactic

surgery from the point of view of both genetic test results and

availability of laparoscopic surgery. It is therefore difficult to

know if the complication rates from this study apply to our

current patient population. Kauff et al. [16], for example,

reported complications in 4 of 98 women undergoing surgery

from which only one patient required re-operation for a small

bowel obstruction. There is an increasing trend toward using

laparoscopy for various gynecologic procedures, including

prophylactic oophorectomy. The risk of complications with

laparoscopy are well recognized, with overall complication

rates in the range of 0.22–4.0% [22,23].

Long-term adverse effects of prophylactic oophorectomy

Prophylactic oophorectomy can lead to some long-term

adverse effects, mainly the early onset of menopause [7].

There are some known risks associated with menopause,

including adverse changes in lipid profile [24], a twofold

increase in coronary heart disease [25], and an increased

incidence of osteoporosis [26]. A cohort of 101 premeno-

pausal women undergoing hysterectomy and bilateral sal-

pingo-oophorectomy experienced a higher rate of decreased

libido and sexual satisfaction compared with women under-

going hysterectomy alone, as assessed by a questionnaire

[27].

The Society of Obstetricians and Gynaecologists of

Canada (SOGC) recently published revisions to the Canadi-

an Consensus on menopause and osteoporosis [28] in light of

the recent findings in the Women’s Health Initiative (WHI)

study [29] that evaluated the long-term benefits and risks of

hormone replacement therapy (HRT) among healthy post-

menopausal women. The SOGC concluded that HRT should

not be recommended for the sole purpose of preventing

future cardiovascular events; however, it remains the best

treatment for distressing menopausal symptoms, and there-

fore, a short-term trial of HRT to relieve these symptoms

may be indicated. According to the WHI study, the use of

estrogen-progestin treatment increases the lifetime risk of

breast cancer after 5 years of use, but this increase is not

statistically significant (an additional eight cases per 10000

women per year). The lifetime risk returns to baseline at 5

years after discontinuing HRT [29]. Since women who have

undergone hysterectomies require estrogen (without proges-

tin) treatment, it is important to note that the WHI’s study on

the use of estrogen-only treatment is still ongoing, and the

results of that study are not yet known [29].

Surgical options

The optimal type of prophylactic surgery has not been

determined. There is controversy in the medical community

regarding which medical procedures should be performed.

Colgan et al.’s [30] prospective cohort study and Paley et

al.’s [31] case series suggest that the minimal procedure is

bilateral salpingo-oophorectomy. Their argument for salpin-

gectomy in addition to oophorectomy is the identification

of occult ovarian or fallopian tube carcinoma in a signifi-

cant percentage of patients undergoing prophylactic oopho-

rectomy. The prospective study [30] detected two cases of

occult fallopian tube cancer and three cases of ovarian

cancer in 27 women with BRCA1 mutations undergoing

prophylactic bilateral salpingo-oophorectomy, an occult

malignancy rate of 18.5%. In the case series [31], two

BRCA1 positive patients who underwent prophylactic oo-

phorectomy were diagnosed with occult fallopian tube

carcinoma [31].

Another prospective cohort study by Colgan et al. [32]

examined the utility of peritoneal lavage for cytology

during prophylactic oophorectomy. Of the 35 women who

underwent peritoneal lavage at the time of prophylactic

surgery, three had malignant cells on cytology, one had

malignant cytology with no histopathologic evidence of

carcinoma in the ovaries or fallopian tubes, and another

had only adenocarcinoma in situ of the fallopian tube [32].

Paley et al. [31] also reported malignant cells in peritoneal

lavage specimens from a patient with adenocarcinoma in

situ of the fallopian tube. The presence of malignant cells in

peritoneal lavage, while not necessarily indicative of an

undetected invasive malignancy, may assist in the detection

of occult malignancy.

Several cohort studies have attempted to determine the

role of bilateral salpingo-oophorectomy at the time of

hysterectomy [33–35]. However, only one retrospective

study, by Piver et al. [18], commented on whether hysterec-

tomy should be performed at the time of bilateral salpingo-

oophorectomy and concluded that only an oophorectomy is

necessary. They recommended cytologic washings and com-

plete evaluation of the abdomen and pelvis laparoscopically

[18]. Brose et al. [36] reported the results of a retrospective

analysis investigating the risk of various cancers in 381

women with BRCA1 mutations. They reported that women

B. Rosen et al. / Gynecologic Oncology 93 (2004) 280–286284

with BRCA1 mutations had a 3% age-adjusted risk of

developing fallopian tube cancer compared to a 0.025% risk

in the general population (120-fold increase). There is

conflicting evidence regarding the possible increased risk

of endometrial cancer and uterine papillary serous carcinoma

in women with BRCA1 or 2 mutations [37–39]. More

studies are needed to establish if there is an increased risk

of endometrial cancer in this population of women. The

rationale for concurrent hysterectomy would be the assur-

ance of complete resection of the fallopian tube and simpli-

fication of HRT. However, the risks of hysterectomy are also

well recognized—there is a higher rate of infections, vault

hematomas, and blood loss [40,41].

Additional benefits

Women with BRCA1 and 2 germ line mutations are at an

increased lifetime risk of developing breast cancer in

addition to ovarian cancer. Both Rebbeck et al. [42] and

Kauff et al. [16] determined that prophylactic surgery was

protective against future development of breast cancer in

women with BRCA1 and 2 mutations, which is consistent

with earlier reports from Struewing et al. [17]. Rebbeck et

al. [42] reported the relative risk of breast cancer to be 0.47

(95% CI 0.29–0.77) for those undergoing prophylactic

oophorectomy. While not statistically significant, Kauff et

al. [16] determined that the projected proportion of women

who will be free of breast cancer 5 years from the time of

surgery or the beginning of surveillance is 94% in the

prophylactic oophorectomy group and 79% in the surveil-

lance group (P = 0.07). Rebbeck et al. concluded that the

use of HRT did not negate the reduction in breast cancer

risk after surgery.

Another benefit of prophylactic oophorectomy is the

detection of early disease. In Rebbeck et al.’s [19] review,

6 of 259 women with BRCA1 or 2 mutations had stage I

ovarian cancer detected at time of surgery. Identifying

malignancies at an early stage results in greater potential

for cure. There is evidence that BRCA1 mutation carriers

with ovarian cancer have a longer survival and potentially

respond better to chemotherapy than do noncarriers [43,44].

Therefore, prophylactic surgery has the potential to prevent

death from ovarian cancer through prevention or early

detection of cancer in women who are BRCA mutation

carriers.

Alternatives to prophylactic oophorectomy

Oral contraceptives

The lifetime risk reduction in ovarian cancer in women

with BRCA1 or 2 mutations who have used oral contra-

ceptives is addressed in two case-control studies. Narod et al.

[45] reported a significant risk reduction of 60% in women

with BRCA1 or 2 mutations who had used oral contra-

ceptives for over 6 years. In contrast, Modan et al.’s [46]

population-based case-control study did not find a risk

reduction among oral contraceptive users in their study in

Israel. However, a small number of women in their cohort

were long-term users, and the confidence limits Modan et al.

reported were wide.

Tubal ligation

Tubal ligation has been associated with a decreased risk of

ovarian cancer among women in the general population, with

no clear reason for this association [47,48]. One case-control

study addressed the risk of ovarian cancer after tubal ligation

in women with BRCA1 mutations. Narod et al. [49] reported

that among 232 BRCA1 mutation carriers, tubal ligation was

associated with an odds ratio of 0.39 (95% confidence

interval 0.22–0.70) for ovarian cancer. The combination of

tubal ligation and past use of an oral contraceptive was

associated with an odds ratio of 0.28 (95% confidence

interval 0.15–0.52). No protective effect of tubal ligation

was detected in carriers of BRCA2 mutations.

Perceptions of women with confirmed BRCA1 or

2 mutations

Tiller et al. [50] performed psychological testing on a

group of women with confirmed BRCA1 or 2 mutations

choosing prophylactic surgery and compared those results to

a group choosing observation. They reported that cancer

anxiety was significantly reduced in those undergoing sur-

gery. Eighty-six percent also reported a high degree of

satisfaction with the surgical procedure, suggesting that

prophylactic oophorectomy is well accepted by those women

with a hereditary lifetime risk.

Discussion

There are no randomized controlled studies comparing

prophylactic oophorectomy to no surgery in women with

germ line BRCA1 and 2 mutations. However, three cohort

studies (one retrospective) have identified a risk reduction

with prophylactic oophorectomy by comparing the incidence

of ovarian cancer in the control group to the incidence of

primary peritoneal carcinoma in the prophylactic oophorec-

tomy group. There is a significant lifetime risk reduction for

developing ovarian cancer and a low probability of perito-

neal cancer in those undergoing surgery.

Complications associated with prophylactic surgery are

estimated to be low now that most laparoscopic surgery is

done laparoscopically. Other complications resulting from

prophylactic surgery are related to menopause: a change in

lipid profile, decreased bone density and increased coronary

artery disease, as well as urogenital symptoms such as

decreased libido and sexual satisfaction.

The optimal surgical procedure for prophylaxis is not

well defined. The minimal procedure should be a bilateral

salpingo-oophorectomy. Occult ovarian or fallopian tube

malignancy has been detected in a small percentage of

B. Rosen et al. / Gynecologic Oncology 93 (2004) 280–286 285

patients undergoing prophylactic surgery, with the rate of

occult malignancy being as high as 18.5% in BRCA

mutation carriers undergoing this procedure. For this

reason, a detailed pathologic examination of prophylactic

specimens is necessary. The surgeon and pathologist are

strongly encouraged to communicate directly about these

cases to ensure appropriate pathologic examination. The

benefit of identifying these occult malignancies during

prophylactic surgery may be the greater potential for cure

because of an early stage diagnosis. In addition, BRCA

mutation carriers with ovarian cancer appear to have a

more favorable prognosis than do noncarriers. Possible

alternatives to surgery for reducing the risk of ovarian

cancer in women with BRCA1 or 2 mutations, oral contra-

ceptives and tubal ligation, have also been reported. While

these alternatives can reduce risk, it is our belief that

prophylactic surgery conveys the greatest risk reduction

and is a procedure that needs to be offered to all BRCA1

and 2 germline carriers at this time.

Conclusions

� Women with a personal or family history of ovarian

cancer should be assessed for genetic counseling and

testing to identify BRCA1 and 2 mutations. Other

women who are concerned about their risk of ovarian

cancer may also be assessed for appropriateness of

genetic counseling.� For women choosing prophylactic oophorectomy, the

role of routine cytology in this procedure has not been

fully studied.� When deciding on whether or not to include hysterec-

tomy as part of the surgical procedure, the surgeon needs

to inform the patient about the risk of developing

fallopian tube cancer in the remaining tissue if a

complete hysterectomy is not performed.� It is crucial that the entire ovary is removed during

prophylactic surgery. Any remnant of ovarian tissue is at

risk for developing carcinoma.� For BRCA1 mutation carriers who may be reluctant to

have definitive prophylactic surgery, oral contraceptives

and/or tubal ligation may reduce their risk of developing

ovarian cancer.� Hormone replacement therapy (HRT) remains the best

treatment for distressing menopausal symptoms after an

oophorectomy, and therefore a short-term trial of HRT

may be indicated to relieve these symptoms.

Acknowledgments

From the Program in Evidence-Based Care, Cancer Care

Ontario. Work on this systematic review was sponsored by

Cancer Care Ontario, and the Ontario Ministry of Health

and Long-Term Care.

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