A controlled study of mental distress and somatic complaints after risk-reducing salpingo-oophorectomy in women at risk for hereditary breast ovarian cancer
Introduction
Ovarian cancer is the fifth most common cancer among women, and hereditary forms represent about 10% of cases [1]. The lifetime risk of ovarian cancer is about 40% for BRCA1 and 18% for BRCA2 mutation carriers, while the risk of sporadic ovarian cancer in the general female population is 1.7% [2]. Risk-reducing salpingo-oophorectomy (RRSO) reduces the risk of ovarian cancer by 80% and the risk of breast cancer considerably, but leads to an estimated 4% cumulative incidence of peritoneal cancer in 20 years after the procedure [3], [4], [5]. BRCA mutation carriers are counseled to perform RRSO before natural menopause, and in most cases, RRSO leads to surgical menopause [6].
Hot flashes and vasomotor symptoms are well known symptoms associated with estrogen deficiency in menopausal women [7]. Studies in post-RRSO samples have demonstrated more vasomotor symptoms and poorer sexual functioning compared to controls who chose ovarian cancer surveillance programs instead of RRSO [8]. The effect of the sudden onset of menopause on bowel function is not well-known, although at least one large study has assessed bowel habits in relation to age and gender [9]. Non-oncologic morbidity and especially somatic complaints are hardly studied in post-RRSO samples. However, a small study by Fry et al. [10] reported more aches and pains in women who had RRSO compared to women who remained in an ovarian cancer screening program. A recent longitudinal study of peri-menopausal Australian women with annual measurements showed a significant association between peri-menopause and aches and joint pain [11].
RRSO has been reported to be associated with a reduced fear of developing cancer, but also with a less favorable body image [12]. In a longitudinal study of 2500 middle-aged American women with an average risk of ovarian cancer, those with surgical menopause had significantly higher depression scores than women with natural menopause [13]. Madalinska et al. [8] examined a Dutch sample of women at high risk for ovarian cancer and compared those who had RRSO to those who had gynecological surveillance. They found that the RRSO group had less cancer worries than the surveillance group [8]. A prospective study by van Oostrom et al. [12] demonstrated that RRSO was associated with decreasing levels of anxiety in the short term. However, at 5 years follow-up, there was a trend towards increasing levels of anxiety, approaching the levels measured pre-surgery.
To the best of our knowledge, no studies have examined anxiety and depression levels after RRSO and compared the findings to that of age-matched controls from the general population using internationally validated instruments. In addition, few studies have addressed non-oncologic long-term morbidity in post-RRSO samples.
This study of a sample of Norwegian women who had RRSO due to BRCA mutation testing or pedigree evidence of hereditary breast ovarian cancer, had three aims: 1) to examine levels of mental distress and prevalence of somatic complaints compared to age-matched female controls from the general population. 2) To make internal comparisons of mental distress and somatic complaints in RRSO subgroups according to age at surgery and history of cancer. 3) To study the strength of associations between RRSO, BRCA mutation status, anxiety and total mental distress in the total sample (RRSO and control groups).
Section snippets
Cases
The sample consisted of 503 Norwegian women who had RRSO after genetic counseling at the Department of Medical Genetics, the Norwegian Radium Hospital. All women were either carriers of BRCA1 or BRCA2 mutation or at risk for hereditary breast/ovarian cancer due to pedigree evidence and they were identified through surgical records. The RRSO procedure was performed at three university hospitals (Stavanger University Hospital, Ullevål University Hospital and the Norwegian Radium Hospital) between
Questionnaire items
Paired relations were defined as being married or cohabiting. Educational level was dichotomized into low (≤ 12 years) and high (> 12 years) based on the number of completed school years. Paid work consisted of those having income from employment or independent business. Daily smoker was defined as those who reported any daily cigarette smoking. Smoking was assessed because of documented associations with mental distress [15], [16]. Hormonal replacement therapy (HRT) was self-reported and defined
Attrition analysis
Mean age in the RRSO group in this study was 54.6 (SD 9.3) years, while mean age among invited non-participants was 54.4 (SD 9.5) years (p = 0.83). Mean age at surgery was 48.5 (SD 8.2) years and 48.0 (SD 8.8) years in the RRSO group and among non-participants, respectively (p = 0.53). No other clinical data were available for more extensive attrition analyses, and in 14 non-participants we did not have data on age at surgery.
Demographic findings
Mean age at survey was 54.6 (SD 9.3) years in the RRSO group and 54.6 (SD
Discussion
The RRSO group had more somatic symptoms than controls. The RRSO subgroup with surgery before the age of 50 years had significantly more palpitations, and the subgroup with cancer had significantly more nausea than the rest of the RRSO group. The RRSO group had significantly less depression (HADS-D) and total mental distress (HADS-T) compared to controls. In multivariate analyses, RRSO versus controls was significantly associated with lower levels of depression and total mental distress.
As
Conclusion
We have shown that RRSO in women at risk for hereditary breast ovarian cancer was significantly associated with lower levels of depression and total mental distress compared to controls from the general population. The RRSO group had more somatic morbidity including osteoporosis and musculoskeletal diseases as well as symptoms like palpitations, constipation and pain and stiffness. These findings need to be reproduced in future studies.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
HUNT is a collaboration between HUNT Research Centre, Faculty of Medicine, Norwegian University of Science and Technology (NTNU, Verdal), Norwegian Institute of Public Health, and Nord-Trøndelag County Council.
Funding sources: Trond Melbye Michelsen, MD holds a research career grant from Sørlandet Hospital and the National Resource Centre for Women's Health, Rikshospitalet.
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