Psychological Impact of Prophylactic Oophorectomy in Women at Increased Risk of Developing Ovarian Cancer: A Prospective Study

Gynecologic Oncology 86, 212–219 (2002) doi:10.1006/gyno.2002.6737

Psychological Impact of Prophylactic Oophorectomy in Women at Increased Risk of Developing Ovarian Cancer: A Prospective Study K. Tiller,* ,1 B. Meiser,† P. Butow,‡ M. Clifton,* B. Thewes,* M. Friedlander,* and K. Tucker* *Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia; †Department of Psychological Medicine, Royal North Shore Hospital, Sydney, Australia; and ‡Medical Psychology Unit, University of Sydney, Sydney, Australia Received December 12, 2001

Objectives. The objectives of this study were twofold: to prospectively assess whether expressed intention to undergo prophylactic oophorectomy translated into uptake and to evaluate the psychological impact of the procedure in a sample of unaffected women with a strong family history of breast/ovarian cancer. Methods. Ninety-five women, initially assessed at the time of their first attendance at a familial cancer clinic, were followed-up 3 years later. A total of 22 women (23.2%) in this study had undergone a prophylactic oophorectomy. Ten women (10.5%) who had undergone a prophylactic oophorectomy during the 3-year follow-up period were compared to 73 women (76.9%) who did not have a prophylactic oophorectomy. Twelve women (12.6%) who had the procedure prior to study entry were also assessed for psychological adjustment and associated information needs. Results. Age emerged as a significant predictor of uptake of prophylactic oophorectomy (␹ 2 ⴝ 7.13, P ⴝ 0.009). Among those who had the procedure after study entry, a significant reduction in ovarian cancer anxiety was observed (Z ⴝ ⴚ2.19, P ⴝ 0.029). Of the 22 women who had undergone a prophylactic oophorectomy in total (both before and after study entry), 86.4% reported a high degree of satisfaction with their decision to have the procedure. A low level of screening uptake was also reported by women who did not have a prophylactic oophorectomy but for whom screening was recommended. Conclusion. Findings demonstrate that prophylactic oophorectomy is successful in reducing anxiety about ovarian cancer. The results also suggest that women perceive that the benefit of anxiety reduction may outweigh the potentially adverse effects of the procedure, given that women expressed a high level of satisfaction with their decision. © 2002 Elsevier Science (USA) Key Words: prophylactic oophorectomy; prospective study.

INTRODUCTION The strongest risk factor for ovarian cancer identified to date is an inherited predisposition to the disease [1]. Women with a family history consistent with a hereditary ovarian cancer 1 To whom correspondence and reprint requests should be addressed at Department of Medical Oncology, Prince of Wales Hospital, Randwick, NSW 2031, Australia. Fax: 0061-2-9382 2588. E-mail: [email protected].

0090-8258/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.

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syndrome, which includes the occurrence of ovarian or related cancers (such as breast cancer) in multiple members in two or more generations, are at significantly increased risk for ovarian cancer. The exact ovarian cancer risk associated with germline mutations in the breast cancer genes BRCA1 and BRCA2 and hereditary nonpolyposis colorectal cancer (HNPCC) genes remain uncertain. Female carriers of germline BRCA1 mutations are thought to have an estimated lifetime risk of ovarian cancer as high as 60% [2, 3]. Mutations in the BRCA2 gene and genes associated with HNPCC lead to a lifetime risk of 10% or higher [4]. Several expert panels have developed risk management guidelines for women with identified pathogenic germline mutations or with a family history indicative of a breast/ovarian cancer syndrome [2, 5–7]. In women from families with suspected or proven HNPCC, the recommendations are similar [8]. Recommendations include annual transvaginal ovarian ultrasound and annual CA-125 serum testing as an additional screening test after menopause [9]. Prophylactic surgery is also recommended as an option for some high-risk women after age 35 or once childbearing is complete [2, 9]. Because of the uncertain efficacy of ovarian cancer screening and the high mortality associated with ovarian cancer, prophylactic oophorectomy is emerging as the most effective option for women at high risk. Findings from a retrospective, case-control study of 248 carriers of BRCA1 and BRCA2 mutations who had undergone a prophylactic oophorectomy with a mean follow-up of 9 years from surgery have recently been presented in a conference paper [10]. Of the 248 women who had undergone prophylactic oophorectomy, only 1 woman (0.4%) developed ovarian cancer after the procedure, and 5 women (2%) were diagnosed with ovarian cancer at the time of oophorectomy. Excluding women diagnosed at the time of surgery, the number of predicted cancers and deaths far exceeded the number of those observed, and bilateral oophorectomy led to a statistically significant 90 to 95% reduction in expected ovarian cancer incidence. These findings confirm results from previous, less rigorously designed retrospective studies [11, 12].

IMPACT OF PROPHYLACTIC OOPHORECTOMY

In our previous cross-sectional study of 95 women with a strong family history of breast/ovarian cancer, assessed around the time of their first attendance at a familial cancer clinic, consideration of prophylactic oophorectomy was positively associated with increased levels of breast/ovarian cancer anxiety, but not with objective risk [13]. These results have been replicated in a recent study that found for women with a family history of ovarian cancer, interest in prophylactic oophorectomy was motivated by a desire to reduce anxiety/uncertainty and that this interest was independent of objective risk [14]. Fry et al. similarly reports the desire to reduce cancer worry as being the most important factor in a woman’s decision to undergo prophylactic oophorectomy [15]. To date, it is unknown whether women’s intention to undergo prophylactic oophorectomy would translate into actual uptake, due to the cross-sectional design of these published studies. Findings from a qualitative study on the psychosexual impact of prophylactic oophorectomy among high-risk women indicate that for most women, the procedure had decreased their concern and anxiety about developing ovarian cancer [16]. Hallowell’s study reported similar findings [17]. However, a recent retrospective study that compared 29 women who had undergone prophylactic oophorectomy with 28 women who continued screening to manage their ovarian cancer risk found no significant difference in cancer worry between the groups [18], implying that this procedure may not be effective in reducing fears about developing cancer. This is of concern when one of the main reasons women choose to have a prophylactic oophorectomy appears to be to reduce anxiety about developing ovarian cancer. To our knowledge, no prospective studies are currently available on predictors of uptake of prophylactic oophorectomy and the impact of the procedure in high-risk women. Our study fills this gap in the literature. Therefore, in this study of a sample of unaffected women with a strong family history of breast/ovarian cancer, our objectives were twofold: 1. To prospectively assess intention to undergo prophylactic oophorectomy and 2. To ascertain the psychological impact of the procedure. Using validated measures of psychological outcome, this study tests the following hypotheses: (i) women’s intention to undergo prophylactic oophorectomy will translate into actual uptake; (ii) breast/ovarian cancer anxiety at baseline will be associated with subsequent uptake of prophylactic oophorectomy; and (iii) prophylactic oophorectomy will lead to a reduction in breast/ovarian cancer anxiety. METHODS Participants We have previously reported on the attitudes toward prophylactic oophorectomy of 95 women from breast/ovarian

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cancer families who had attended one of 14 familial cancer clinics in five Australian states (New South Wales, Victoria, South Australia, Queensland. and Western Australia) between November 1996 and January 1999 [13]. All women were assessed at baseline around the time of their first attendance at a familial cancer clinic and intention to undergo prophylactic oophorectomy was assessed [13]. We are now reporting prospective data involving the same cohort, followed up 3 years later with regard to actual uptake of prophylactic oophorectomy, psychological adjustment, and associated information needs. As this study reports on the same cohort of women, eligibility criteria, ethics approval, and recruitment protocols had already been established for the previous study. Women were considered ineligible for study participation if they had a prior diagnosis of ovarian or breast cancer, were unable to give informed consent, or had limited literacy in English, since data were collected using self-report questionnaires. The study was approved by 16 institutional ethics committees. Familial cancer clinic staff had invited women to participate in the study during the preclinic telephone call, before initial face-to-face counseling, where possible. Questionnaires, consent forms, and replypaid envelopes were then mailed out centrally. Women were subsequently telephoned by the central research staff and given further information about the study and issues of informed consent. Women were asked to return the completed questionnaire and consent form before attending the familial cancer clinic, where possible. Once the completed questionnaires were returned, follow-up questionnaires were prepared and dated for mailing 3 years postcounseling. Reminder calls were made as required. The findings from the 3-year follow-up questionnaires are the basis of this current study. Measures During the initial study the following data were collected at baseline: Sociodemographic data. Age, education level, and marital status were assessed. Ovarian cancer burden. The number of first- and seconddegree relatives who had developed ovarian cancer was assessed, because it may act as a psychological risk factor in addition to reflecting objective risk. Objective ovarian cancer risk. To provide an estimate of objective risk, clinic staff were asked to make a judgment on whether a participant’s family history was either consistent or not consistent with a dominantly inherited predisposition to breast/ovarian cancer, and participants were thus classified as being at “high risk” or “moderately increased risk” respectively. Clinic staff made this judgment following the risk assessment interview at the familial cancer clinic and once pedigree information [19, 20] and relatives’ diagnoses confirmed by medical records were available.

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Attitude toward prophylactic oophorectomy. This item asked women whether they would consider having a prophylactic oophorectomy should genetic testing show that they are carriers. Response options included “No,” “Yes,” “Don’t know,” and “Done/in progress.” Women who reported as having had an oophorectomy for reasons unrelated to their risk status were not included in the analyses on attitude toward oophorectomy. Impact of Event Scale. This measure was administered at each time point. The 15-item scale measures anxiety responses in relation to a specific stressor and has well-documented psychometric characteristics [21]. In a previous validation study of women with a family history of breast and/or ovarian cancer, the intrusion and avoidance subscales have been found to be highly consistent with Cronbach’s coefficient ␣ of 0.84 and 0.91, and a test–retest reliability of r ⫽ 0.75 and r ⫽ 0.78, respectively [22]. In the current study the particular stressor was concern about being at risk of developing breast/ovarian cancer. Participants were asked to rate symptoms of anxiety (for example, “I had strong waves of feelings about being at risk of breast/ovarian cancer”) on a scale ranging from “Not at all” to “Often.” Scores range from 0 to 75. For the prospective data on which this current study reports, the following variables were assessed 3 years postcounseling: Uptake of prophylactic oophorectomy. Women were asked whether they had undergone a prophylactic oophorectomy. They were also asked about their menopausal status at the time of the procedure and their subsequent HRT use. Satisfaction with prophylactic oophorectomy. Major themes identified by our previous qualitative study on the psychological impact of prophylactic oophorectomy [16] were used to design 14 items to quantitatively measure these aspects of the procedure. These items assessed factors influencing decisions regarding HRT use, whether or not prophylactic oophorectomy had impacted negatively on a woman’s sense of femininity or libido, satisfaction with physicians’ sensitivity during the decision-making process, and overall satisfaction with the decision to have a prophylactic oophorectomy. Response options for overall satisfaction ranged from “Not at all” to “Very much.” Ovarian cancer screening uptake. Utilization of ovarian ultrasound and CA-125 test were assessed. For each screening test, participants were asked whether they had had the screening test during the past year. Statistical Analysis For operational reasons a significant proportion of participants (42.1%) completed baseline questionnaires shortly after initial counseling. A “before/after counseling” variable was created to categorize women as having completed the questionnaire before versus after initial face-to-face counseling. The statistical analyses were carried out in four stages. The overall uptake of prophylactic oophorectomy in the whole

sample was calculated first. Next we assessed the uptake of screening tests among women for whom screening was recommended and who had not had a prophylactic oophorectomy. For the analyses of the predictors of uptake of prophylactic oophorectomy and its psychological impact, women who had already undergone a prophylactic oophorectomy prior to study entry were excluded. ␹ 2 analysis (with Fisher’s exact test correction due to the small sample size) was used to describe the relationship between sociodemographic, family history, and psychological variables at baseline and uptake of prophylactic oophorectomy at the 3-year follow up. The following independent variables were included: age group (⬍35 years versus ⱖ35 years, using the age at which oophorectomy should be performed as recommended by U.S. and Australian consensus guidelines as a cutoff point [2, 5]); the before/after counseling variable; number of first- and second-degree relatives with ovarian cancer as a measure of cancer burden (⬍2 versus 2 or more); attitude to prophylactic oophorectomy; parity; and breast/ovarian cancer anxiety. Participants were divided into low and high breast/ovarian cancer anxiety groups, using the median as a cutoff point, because breast/ovarian cancer anxiety scores were not normally distributed and transformations were not successful in normalizing the data. For the analyses on the psychological impact of prophylactic oophorectomy, contingency tables were used to compare mutation status across the surgery and nonsurgery groups to ascertain whether having received a genetic testing result since attending the clinic could have acted as a potential confounder. Then a Mann–Whitney U test was performed to assess differences in breast/ovarian cancer anxiety change scores between women who had and those who had not undergone a prophylactic oophorectomy. RESULTS Response Rate and Characteristics of Study Participants A total of 110 women met the eligibility criteria and were invited to participate in the study. Three women declined participation when invited by clinic staff, and 12 women who were mailed baseline questionnaires never returned them (response rate of 86%). Of the 95 women who had returned baseline questionnaires, 68 women also returned the 3-year follow-up questionnaire (retention rate 71.6%), resulting in a response rate to both questionnaires of 61.8%. The analysis of possible participation bias showed that there were no statistically significant differences between women who were retained and those lost to follow-up (n ⫽ 27). Specifically, there were no statistically significant differences in age, education level, or the number of first- or second-degree relatives affected by ovarian cancer, the variables hypothesized to influence a woman’s decision regarding prophylactic oophorectomy. We have previously reported in detail on the sociodemographic and family history variables of the cohort of 95 women

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TABLE 1 Factors Associated with Prophylactic Oophorectomy Decision (N ⴝ 83) Independent variable Before/after counseling c Age (years) Parity Attitude toward P.O. d

Ovarian cancer burden Objective ovarian cancer risk Impact of Events Scale

Level

Na

Percentage who had prophylactic oophorectomy b

Before counseling After counseling ⬍35 35⫹ No children Children Would consider P.O. Would NOT consider P.O. Uncertain ⬍2 FDR & SDR 2⫹ FDR & SDR e Moderately increased risk High increased risk Low breast/ovca anxiety High breast/ovca anxiety

48 35 32 41 22 61 20 24 39 30 35 8 72 39 42

8.3 17.1 0 19.6 4.5 14.8 25 0 13 3.3 17.1 0 13.9 7.7 16.7

␹2

p

1.48

0.22

7.13

0.009

1.59

0.207

6.47

0.039

3.20

0.073

1.27

0.26

1.60

0.22

a

Sample sizes vary due to missing data. Excludes women who had a prophylactic oophorectomy prior to baseline assessment. c The “before/after counseling” variable refers to whether the baseline questionnaire was completed before or after initial counseling. d The attitude toward P.O. variable refers to whether women who would consider, would not consider, or are unsure prior to study entry about having a prophylactic oophorcctomy should genetic testing show they were carriers. e FDR & SDR, First- and second-degree relatives with ovarian cancer. b

assessed at baseline [13]. Briefly, the median age of the sample was 40 years, ranging from 19 to 75 years. Geneticists and counselors judged 91% of participants to have a family history consistent with a dominantly inherited susceptibility to breast/ ovarian cancer, and the remaining 9% were reported as being at moderately increased risk only. The number of self-reported first-degree and second-degree relatives with a diagnosis of ovarian cancer ranged from 0 to 7. (One woman from a family with an identified BRCA1 mutation reported not having any first- or second-degree relatives with ovarian cancer, but had more distant relatives with ovarian cancer.) All baseline assessments took place prior to receiving a genetic testing result.

inantly inherited susceptibility to ovarian cancer). Of the 30 women for whom ultrasound was recommended, 6 (33.3%) reported having had an ultrasound in the past year and 12 (66.6%) had not. Among women aged 50 years or older (using the age when menopause most typically occurs as a cutoff point) who had not had a prophylactic oophorectomy, were carriers or of unknown mutation status, and had a family history consistent with a dominantly inherited susceptibility to ovarian cancer, we also assessed uptake of the CA-125 test during the past year. Of the 14 women for whom the CA-125 test was recommended, only 1 (12.5%) had a CA-125 test during the past year.

Overall Uptake of Prophylactic Oophorectomy

Study Objective 1: Predictors of Uptake of Prophylactic Oophorectomy

A total of 22 women (23.2%) included in our study had undergone a prophylactic oophorectomy. This is a deceptively small number, as ovarian cancer risk management guidelines recommend that high-risk women consider prophylactic oophorectomy after the age of 35 [2, 5, 6]. When we leave aside those women for whom prophylactic oophorectomy is not recommended (aged ⬍35 years, proven noncarriers, moderately increased risk only), the proportion of high-risk women who chose to have a prophylactic oophorectomy increases to 40%. At the 3-year follow-up assessment, we also assessed transvaginal ultrasound uptake of women who have not undergone a prophylactic oophorectomy and for whom annual ultrasound screening is recommended (35 years or older, carriers or unknown mutation status, family history consistent with a dom-

Twelve women (12.6%) had already undergone a prophylactic oophorectomy prior to study entry and were therefore not included in this analysis. Ten women (10.5%) reported having undergone a prophylactic oophorectomy between 3 and 32 months since their attendance at the clinic. Table 1 shows bivariate associations between age, parity, expressed intention to undergo prophylactic oophorectomy, number of first- and second-degree relatives with ovarian or breast cancer, objective risk, the before/after counseling variable, and breast/ovarian cancer anxiety level on the one hand and uptake of prophylactic oophorectomy on the other. There were no observed differences between those who completed the baseline questionnaire before their initial coun-

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seling session or after it, with regard to uptake of a prophylactic oophorectomy (␹ 2 ⫽ 1.48, P ⫽ 0.22). Intention to undergo prophylactic oophorectomy was significantly associated with actual uptake (␹ 2 ⫽ 6.47, P ⫽ 0.039). Of the 20 women who reported at baseline considering prophylactic oophorectomy should genetic testing show that they were carriers, 5 (25%) subsequently opted for prophylactic oophorectomy. None of the 24 women who reported that they would not consider a prophylactic oophorectomy at baseline had had the surgery in the 3-year follow-up period, and of the 39 women who reported at baseline that they did not know whether or not to have a prophylactic oophorectomy, 5 (13%) subsequently underwent a prophylactic oophorectomy. Age was also significantly associated with uptake of oophorectomy (␹ 2 ⫽ 7.13, P ⫽ 0.009). All women who reported having had the procedure were 35 years and older. There was a trend for women with more than one first- or second-degree relative with ovarian cancer to choose having a prophylactic oophorectomy (␹ 2 ⫽ 3.20, P ⫽ 0.073). There was no significant association between uptake of prophylactic oophorectomy and breast/ovarian cancer anxiety (␹ 2 ⫽ 1.60, P ⫽ 0.22), objective risk (␹ 2 ⫽ 1.27, P ⫽ 0.26), or parity (␹ 2 ⫽ 1.59, P ⫽ 0.207). Study Objective 2: Psychological Impact of Prophylactic Oophorectomy Among the women who had surgery after baseline assessment, 2 women were known to be positive for a predisposing mutation and 8 had an unknown mutation status at the time of surgery. Among women who did not have prophylactic surgery, 18 were negative for the known mutation in their families, 5 were positive, and 50 were of unknown mutation status. A ␹ 2 analysis showed that mutation status did not differ significantly between women who had and those who had not undergone a prophylactic oophorectomy (␹ 2 ⫽ 1.11, P ⫽ 0.57). Thus it is unlikely that having received a genetic testing result since attending the clinic acted as a confounder. There was no statistically significant association between age and 3-year postcounseling breast/ovarian cancer anxiety change scores (r ⫽ 0.18, P ⫽ 0.15), indicating that statistical adjustment for age was unnecessary. Mean baseline breast/ovarian cancer anxiety scores were somewhat higher in the surgery group (mean 23.4, SD 17.4) compared to the nonsurgery group (mean 15.9, SD 15.5). However, a Mann–Whitney U test showed that this difference was not significant with Z ⫽ ⫺1.47, P ⫽ 0.14. The mean 3-year postcounseling breast/ ovarian cancer anxiety scores were similar for both groups, with mean scores of 4.5 (SD 9.5) and 9.0 (SD 13.7) for the surgery and nonsurgery groups, respectively. However, the mean 3-year postcounseling breast/ovarian cancer anxiety change scores were ⫺18.9 (SD 14.1) for the surgery and ⫺9.4 (SD 15.9) for the nonsurgery groups, indicating a higher decrease in women who had undergone pro-

phylactic oophorectomy. This difference in mean breast/ovarian cancer anxiety change scores was statistically significant (Z ⫽ ⫺2.19, P ⫽ 0.029). Satisfaction with Decision to Undergo Prophylactic Surgery This and the following analyses include all women in the study who had undergone prophylactic oophorectomy (n ⫽ 22), those who had the procedure before (n ⫽ 12), and those who had the procedure after baseline assessment (n ⫽ 10). There was no difference between these groups with regard to satisfaction, with the majority of women expressing a “high degree of satisfaction” with their decision to have the procedure (86.4%). Of these, 7 women reported they were “quite happy,” and 12 that they were “very happy,” with their decision. Of the remaining three women, there were 2 reports of “not at all” satisfied and 1 “somewhat satisfied” with their decision (13.6%). Fifteen women who had a prophylactic oophorectomy were premenopausal at the time of the procedure (68.2%). The remaining 7 (31.8%) were either peri- or postmenopausal. Eighteen women commenced HRT (81.8%) following surgery. Of the 4 women who chose not to have HRT, 3 were premenopausal at the time of the procedure. The deciding factors against taking HRT that were consistently cited by these women were the advice given to them by their doctor or oncologist and the unclear connection between HRT and breast cancer. These women also consistently reported that their sex life had been negatively affected by the procedure. Of the 18 women who were on HRT, only 1 reported that oophorectomy had a negative impact on her libido. These women also cited advice from their doctor or oncologist as the main factor that influenced their decision to commence HRT but the second most important factor was information that they found out themselves (Table 2). DISCUSSION Study Objective 1: Predictors of Uptake of Prophylactic Oophorectomy In our previous study, we found that breast/ovarian cancer anxiety, rather than objective risk, was the major factor that determined women’s intention to undergo prophylactic oophorectomy around the time of their attending a familial cancer clinic [13]. Therefore, we hypothesized that breast/ovarian cancer anxiety at baseline would be associated with subsequent uptake of prophylactic oophorectomy. Although we found high baseline anxiety levels among women in the surgery group, compared to those in the nonsurgery group, there was no statistically significant association between breast/ovarian cancer anxiety and uptake of prophylactic oophorectomy. This finding raises the possibility that other factors, including physician recommendation and women’s plans for childbearing,

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TABLE 2 Factors Endorsed as “Quite Important” or “Very Important” in Decision to Commence Hormone Replacement Therapy (HRT) (n ⴝ 22)

a

Factors endorsed as quite/very important a

Percentage of those deciding to have HRT (n ⫽ 18)

Percentage of those deciding against having HRT (n ⫽ 4)

Advice from physician Information women found out themselves Level of menopausal symptoms Unclear connection between HRT and breast cancer Advice from other women with similar experiences

78 61 55 50 33

100 75 25 100 0

Response choices ranged from “not at all,” “somewhat,” “quite,” to “very important.”

are more powerful determinants for uptake of prophylactic oophorectomy. Our findings on the significant association between age and uptake of prophylactic oophorectomy support this explanation. Specifically we found that all women who reported having had a prophylactic oophorectomy since attending the familial cancer clinic were aged 35 years and over. Most consensus guidelines for the management of women at increased risk for ovarian cancer recommend prophylactic oophorectomy when childbearing is completed or at least by 35 years of age [2, 5, 6]. It should be noted, however, that evidence is accumulating which shows that the risk of ovarian cancer in high-risk individuals is not increasing over and above population risk until after age 40 [23, 24], and it has been suggested that the recommended age of prophylactic oophorectomy be increased to 40 years [25]. Therefore, given that risk management guidelines for high-risk women do not tend to advocate prophylactic oophorectomy before the age of 40 or 35 at the very earliest [2, 5– 8], the resulting association with age is not surprising. The significant association with between attitude toward prophylactic oophorectomy and actual uptake illustrates that asking women about their attitude that is a useful indicator for actual uptake. All the women who proceeded with prophylactic oophorectomy reported being disposed to, or uncertain about, the procedure, whereas none of the women who said they would not consider the procedure changed their mind within the 3-year follow-up period. Among high-risk women who had not had a prophylactic oophorectomy, 33% of those aged 30 years and over had an ovarian ultrasound, and 12.5% of women aged 50 years and over had a serum CA-125 in the past year. It is unlikely that women at increased risk reject all forms of risk management options including screening because we have found a very high uptake of breast cancer screening in the same cohort [26]. However, this finding may be due in part to the high profile of breast cancer screening in the media. In Australia, all women in the general population aged 40 years and over are recommended, and regularly reminded, to have mammograms. Some women at increased risk of ovarian cancer may also regard screening modalities for ovarian cancer (transvaginal ultra-

sounds/CA-125) as having limited positive predictive power and may want to avoid the anxiety associated with yearly screening [27]. Similar findings of low uptake of screening in women at increased risk of ovarian cancer have also been found by Lerman and colleagues [28]. In this study only 15% of BRCA1/2 carriers reported having a transvaginal ultrasound 1 year following genetic testing and only 21% as having a CA-125 test [28]. Study Objective 2: Psychological Impact of Prophylactic Oophorectomy Our third hypothesis, that prophylactic oophorectomy will lead to a reduction in breast/ovarian cancer anxiety, was supported. We observed decreases in anxiety in both the surgery and nonsurgery groups, a finding that most likely reflects the anxiety-reducing effects of specialist counseling for high-risk women [29 –31]. However, despite the small number of women who had undergone prophylactic oophorectomy and were followed up prospectively, we found a significantly larger decrease in breast/ovarian cancer anxiety in the surgery group compared to women who did not have the procedure. Significant findings despite sample size limitations indicate a substantial decrease in breast/ovarian cancer anxiety in the surgery group (approx. 0.6 of an effect size). This finding is particularly relevant given that previous studies cite the desire to reduce breast/ovarian cancer anxiety as one of the most important factors in a woman’s decision to have the procedure [14, 15, 32]. Our results do not appear to differ from findings of the retrospective study by Fry et al. [18], who found no significant differences in cancer worry among women who underwent surgery and those who continued screening. We also found similar breast/ovarian cancer anxiety in the surgery and nonsurgery groups in our 3-year follow-up assessment. However, a prospective design enabled us to take both before and after measures of breast/ovarian cancer anxiety and also to ascertain whether the surgical and nonsurgical groups were psychologically similar before the procedure. Our findings have demonstrated that women in the surgery group experienced a sub-

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stantial decrease in anxiety levels postprocedure. By contrast, anxiety levels of those who chose not to have a prophylactic oophorectomy were relatively low at baseline and remained so. Attitudes to Hormone Replacement Therapy A small group who did not go on HRT reported the surgery as having a detrimental impact on their libido. Nevertheless, despite these reported adverse sexual effects, almost all women in this study maintained that they were very happy with their decision to have a prophylactic oophorectomy. This may be explained by the aforementioned significant decrease in anxiety reported by women followed-up prospectively. HRT may be seen as a possible solution to the potentially adverse sexual impact of prophylactic oophorectomy [16]; attitude toward HRT was therefore a focus of this study. The factor cited as most important both in deciding to take and in deciding not to take HRT was advice from the physician. For those who decided against HRT, the unclear connection between HRT and a possible increase in breast cancer risk was of equal importance. For women who chose to take HRT, information that they found out themselves was the second most important deciding factor cited. Perhaps these women found information that allayed their concerns about the potential risk of breast cancer. Alternatively women may selectively process information to support their decision. Those deciding to take HRT also reported that the level of menopausal symptoms they were experiencing as a deciding factor, which is not surprising given that the majority of participants were premenopausal at the time of surgery. What is more surprising is that three of the four women who decided against HRT were premenopausal. It is of concern that some women choose not to take HRT despite being premenopausal, given the implications of long-term estrogen deprivation. Therefore, it may be advisable for clinicians to ascertain a woman’s intentions regarding HRT use prior to the procedure [16]. The emerging evidence that calls into question the protective effect of the oral contraceptive pill (OCP) against ovarian cancer is also relevant here [33]. If one takes into consideration these recent findings together with its potential for increasing the risk of breast cancer, the OCP may be losing its place as a risk reduction option for those at increased risk of ovarian cancer. Given the lack of sensitivity of current screening modalities, prophylactic oophorectomy is becoming the frontrunner in risk management options. Therefore, further research on the physical and psychosocial consequences of this procedure is imperative if women are to make informed decisions. SUMMARY OF FINDINGS The limitations of this study should be noted. Given the study’s sample size, it was not possible to use multivariate analysis and nonsignificant results were sometimes hard to

interpret. Moreover, the sample as a whole had high educational levels, as previously reported [13], suggesting that generalizations to the broader population of women at increased risk of developing hereditary breast/ovarian cancer need to be made cautiously. Nonetheless, our findings are highly relevant to women who seek information about prophylactic and surveillance options from familial cancer clinics. Despite these limitations, the findings from this prospective study have highlighted several important issues. First, we observed that actual uptake of prophylactic oophorectomy was associated with age, but not anxiety about developing ovarian cancer. This finding is perhaps reassuring as it suggests that women’s decision-making is not dominated by cancer worry. Second, we demonstrated a significant reduction in breast/ ovarian cancer anxiety following surgery. By reducing the risk of ovarian cancer, anxiety regarding possibly developing ovarian cancer is also reduced for these women. As mentioned previously, research indicates that reducing anxiety is a motivating factor for women considering prophylactic oophorectomy [14, 15, 32]. These findings indicate that, for the women in this study, this was a successful strategy. As over 86% of our participants expressed a high degree of satisfaction with their decision to have a prophylactic oophorectomy, it appears that women perceive the advantages associated with the procedure as outweighing the disadvantages. ACKNOWLEDGMENTS The authors thank the following individuals for their contributions to this study: Dr. Alex Barratt and Dr. Vivienne Schnieden for their involvement in this study and Dr. Maggie Watson, for generously discussing similar work undertaken in the United Kingdom. We also thank Meryl Smith, Margaret Gleeson, Karen Harrop, Helen Hopkins, Annette Hattam, Lucille Stace, Julie White, Anne Baxendale, Susan White, Step Daly, Mary-Anne Young, Bronwyn Burgess, and Monica Tucker; Drs. Clara Gaff, Agnes Bankier, Ian Walpole, Kristiina Aittoma¨ ki, Mac Gardner, Alison Colley, Tracy Dudding, Jack Goldblatt, and Elizabeth Thompson; and Professor Gillian Turner for assistance with patient recruitment, data collection, and the ethics application process. Finally, we are most grateful for the valuable contribution of all the women who participated in this study. This research was supported by the National Health and Medical Research Council of Australia Project Grant 113877.

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