IN-DEPTH REVIEW OF RESEARCH

Study background:

For very high-risk women, risk-reducing salpingo-oophorectomy (RRSO) is the most effective method to reduce ovarian cancer risk. In women with an inherited BRCA or other high-risk ovarian cancer mutation, RRSO significantly reduces ovarian cancer risk. However, RRSO has disadvantages.  In premenopausal women, it results in surgical menopause and infertility. Premature surgical menopause has known side effects, including increased risk of heart disease, osteoporosis, cognitive decline and sexual dysfunction. These side effects may be worse for women who are unable or chose not to use hormone replacement therapy. However, nonhormonal interventions may be available to mitigate some of these side effects

With increasing evidence that most ovarian cancer begins in the fallopian tubes, a number of clinical trials are currently evaluating risk-reducing early salpingectomy (removal of the fallopian tubes) followed by delayed oophorectomy (removal of the ovaries)—RRESDO—in high-risk women. This two-stage alternative offers some level of risk reduction (the extent is currently unknown) and avoids the consequences of premature menopause.

This study provides data from multiple centers in the United Kingdom on women at increased risk of ovarian cancer and the acceptability of RRESDO, the complications following RRSO and satisfaction/regret following RRSO.

Researchers of this study wanted to know:

How acceptable risk-reducing salpingectomy followed by delayed oophorectomy is among high-risk women. The researchers also looked at surgical menopause satisfaction and regret.
 

Populations looked at in this study:

Between October 2017 and June 2019 to total of 773 women at high risk for ovarian cancer were recruited from six clinics in the United Kingdom. Ninety people were excluded because they did not meet eligibility criteria.

Study design:

A total of 683 women completed a 39-item questionnaire.  They were asked about social and economic demographics, surgical procedures, menstrual data, family health information and consequences of premature menopause that influenced their decisions to undergo, delay or decline RRSO. Participants filled out different parts of the questionnaire depending on whether they had undergone RRSO.

Study findings:  

Between October 2017 and June 2019, 773 people completed the questionnaire. 

Of the remaining 683 participants:

• 49% (337/683) had not undergone RRSO.

• 51% (346/683) had undergone RRSO.

Among premenopausal women at high risk for ovarian cancer who did not previously have preventative surgery:

• 55% (145 of 262) found RRESDO acceptable.
• 20% (53/262) did not find RRESO acceptable.
• 24% (64/262) were unsure if RRESDO was acceptable.

When premenopausal women who had not undergone RRSO were asked if they would participate in a research study offering RRESDO:

• 70% (181/262) said they would consider taking part in a study that offered RRESDO.
• 31% (81/262) said they probably would not participate in an RRESDO study.
  • Premenopausal women concerned with sexual dysfunction were more likely to find RRESDO acceptable.

When premenopausal women who already had RRSO were asked whether they would have considered RRESDO instead:

• 38% (61/159) would have considered RRESDO.
• 62% (98/1590) would not have considered RRESDO.
  • Premenopausal women who experienced sexual dysfunction following RRSO were more likely to find RRESDO acceptable.

Among women who had undergone premenopausal RRSO:

• 89% (143/161) were satisfied with their decision.
• 9% (15/160) of premenopausal and 1% (1/81) of postmenopausal women regretted their decision.
  • These women experienced night sweats, sleep disturbances, sexual dysfunction and urinary incontinence, which led to them to regret their decision to undergo RRSO.
• Hormone replacement therapy (HRT) use among premenopausal women who did not have breast cancer and had RRSO was high (74%).
  • HRT use did not affect their satisfaction/regret with RRSO
  • HRT use did reduce vaginal dryness.

When women who had undergone premenopausal RRSO were asked whether they would have considered undergoing RRESDO instead of RRSO had it been offered:

• 38% (61/159) said ‘probably/maybe’.
• 62% (98/159) said ‘probably not/definitely’
  • These women were more likely to have experienced hot flashes, osteoporosis or fatigue compared to women who ‘probably/maybe’ would have considered RRESDO.

Strengths and limitations:

Strengths

This is the largest study to date reporting on RRESDO acceptability and menopausal satisfaction or regret following RRSO. A strength of this study is that all participants were counseled in detail about preventive surgery for ovarian cancer.

Limitations

Limitations include that most participants in this study were white, had at least a university degree and a relatively high household income, and may not be representative of all patients. These results may differ for minority women or women who are less educated or affluent. Participants in this study did not undergo RRESDO, and differences in outcome were not measured.
 

Context: 

RRSO has been shown to lower risk of ovarian cancer-related, breast cancer-related and overall mortality in high-risk women.

In this study, concerns about sexual dysfunction were identified as significant factors associated with both acceptance of RRESDO and regret after RRSO. The findings of this study are not surprising given concerns high-risk women have about sexual dysfunction. New data from a prospective study supports the validity of these concerns due to the significant decline in sexual function experienced by women who had undergone RRSO.

These findings should help direct additional research for high-risk women. While RRESDO and advances in reproductive technology and HRT benefit patients, they have resulted in an increasingly complex set of options for high-risk women.

Conclusions:

Most women find RRESDO acceptable, particularly if they are concerned about sexual dysfunction. However, it is important to note that the effect of RRESDO on ovarian cancer risk-reduction is unknown.

Although most women are satisfied with RRSO, regret is higher for premenopausal women than for postmenopausal women. Some research has shown that these women experience a decrease in sexual functioning. These symptoms are improved by HRT, but not to pre-surgical levels. In this study, HRT following RRSO did not increase satisfaction but did decrease vaginal dryness.

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