۱- Introduction

۲- Materials and methods

۳- Results

۴- Discussion

References

Abstract

Introduction
Prophylactic bilateral salpingo-oophorectomy (BSO) is recommended at an early age to BRCA mutation carriers to prevent ovarian cancer. It is critical to evaluate the impact of BSO on non-cancer outcomes, including quality of life (QOL), menopausal symptoms and sexual functioning.
Methods BRCA mutation carriers who elected to undergo a BSO completed three questionnaires prior to surgery and then again approximately one and three years following surgery which included: 1) medical history questionnaire, 2) Menopause-Specific Quality of Life Intervention questionnaire and 3) Sexual Activity Questionnaire. The change in quality of life, menopausal symptoms and sexual functioning before and after oophorectomy was determined using a paired t-test and stratified by menopausal status at surgery.
Results We included 140 BRCA mutation carriers with an average follow-up of 3.5 years following BSO. Among 93 women who were premenopausal, oophorectomy was associated with an increase in menopausal symptoms (vasomotor, physical) (P < ۰٫۰۰۱) and a decline in sexual functioning (discomfort, pleasure) (P ≤ ۰٫۰۰۰۱), but had no impact on overall QOL (P = ۰٫۳۱). HRT mitigated, but did not eliminate the adverse effects. Women who were postmenopausal at surgery (n = ۴۷) experienced an increase in physical symptoms (P = ۰٫۰۳) and a decline in sexual functioning (discomfort) (P = ۰٫۰۰۴) and in overall QOL (P = ۰٫۰۴).
Conclusions This study demonstrates that 3.5 years after oophorectomy, BRCA mutation carriers experience a significant worsening of menopausal symptoms and a decline in sexual functioning, particularly among those who underwent surgery prior to natural menopause. The use of HRT mitigated some but not all the effects. Overall, women who were premenopausal at surgery did not experience a decline in their QOL.

Introduction

Women with a BRCA1 or BRCA2 mutation face a high lifetime risk of developing ovarian cancer and preventive bilateral salpingooophorectomy (BSO) (referred to as oophorectomy hereafter) is recommended prior to menopause [1]. Screening for ovarian cancer in highrisk women has not been shown to be reliable and currently surgical risk reduction is the most effective option [2]. Oophorectomy is currently recommended between the ages of 35 and 40 for BRCA1 mutation carriers and between 40 and 45 for BRCA2 mutation carriers [1,3]. Oophorectomy reduces the risk of developing ovarian cancer as well as all-cause mortality [4]. Despite the well-established reduction in cancer risk, oophorectomy induces surgical menopause and its associated risks and sequelae. The abrupt decline in circulating sex hormones (e.g., estrogen, testosterone, and progesterone) causes menopausal symptoms, including vasomotor symptoms and loss of libido, and is associated with a decline in cardiac and bone health, and perhaps in memory and attention [5–۷]. This may be most apparent among those women who undergo surgery prior to natural menopause. Many of the side effects can be ameliorated by hormonal replacement therapy (HRT), but for women with a personal history of breast cancer, exogenous hormones are contraindicated due to fear of recurrence [8]. To date, there have been few prospective studies among women with a BRCA mutation who represent a unique population given their high rate of surgical menopause [reviewed in [9,10]]. Women undergoing preventive surgery experience reduced cancerspecific distress and a sustained level of overall quality of life [10].