Quality of life after risk-reducing salpingo-oophorectomy in women with a pathogenic BRCA variant.

BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) is recommended to women with a pathogenic BRCA variant, but as a main side effect, RRSO could lead to an early onset of menopause. AIM: To evaluate the impact of RRSO and preoperative menopausal status on menopausal symptoms, sexual functioning, and quality of life (QOL). METHODS: The study was conducted between November 2019 and April 2020. Women were included who tested positive for a pathogenic BRCA1/2 variant between 2015 and 2018. Depression levels, QOL, and global health status were measured and compared with those of women who opted against RRSO. Furthermore, women who underwent RRSO treatment were asked to report menopausal complaints that they experienced at 1 month postsurgery and any current complaints. OUTCOMES: RRSO had no significant impact on QOL, but women who were premenopausal at the time of surgery reported more sexual complaints than postmenopausal women. RESULTS: In total, 134 carriers of a BRCA mutation were included: 90 (67%) underwent RRSO and 44 (33%) did not. At the time of the survey, neither the control nor experimental group experienced significant changes in QOL (b = -0.18, P = .59). Women who underwent RRSO reported a significantly lower global health status (b = -0.66, P = .05). Women who were premenopausal at the time of surgery were bothered more by sexual symptoms (b = 0.91, P = .19) but experienced fewer vasomotor complaints (b = -1.09, P = .13) than women who were postmenopausal at the time of RRSO. CLINICAL IMPLICATIONS: The decrease of sexual functioning after RRSO should be an integral part of preoperative counseling because it is important for BRCA carriers, especially for premenopausal women. STRENGTHS AND LIMITATIONS: Some strengths of the present study were the long follow-up, a high response rate, and the existence of a control group, whereas defining menopausal status by last menstrual bleeding and self-report of data (eg, breast cancer history) increased the risk of errors. CONCLUSION: Our study indicated that women who underwent RRSO experienced no difference in QOL when compared with women without RRSO and that patients with premenopausal status seemed to be at higher risk to experience sexual complaints after surgery.

Impact of risk-reducing salpingo-oophorectomy on lipid determinants, HbA1c and CRP.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) is advised before 40-45 years of age for BRCA1/2 mutation carriers. This study describes the effect of RRSO on lipid determinants, hemoglobin A1c (HbA1c) and C-reactive protein (CRP). METHODS: A total of 142 women with increased risk of ovarian cancer were included, 92 premenopausal and 50 postmenopausal. Serum levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and total cholesterol, triglycerides, HbA1c and CRP were determined at three points in time: before (T0) and 6 weeks (T1) and 7 months (T2) following RRSO. The Hot Flush Rating Scale was administered at the same time points. RESULTS: In premenopausal women, levels of HDL-cholesterol, the cholesterol ratio and HBA1c increased significantly over time, although still staying within the reference range. In this group, hot flushes increased over time (p < 0.001). In postmenopausal women, no significant changes were observed following RRSO. At T2, serum LDL-cholesterol, triglycerides, HbA1c and CRP were significantly lower in premenopausal women compared to postmenopausal women, whereas HDL was increased. CONCLUSIONS: Seven months after RRSO, the lipid profile in premenopausal women had changed, although still staying within the reference range. For postmenopausal women, we did not observe any significant changes. Our results do not suggest a worsening of cardiovascular risk within 7 months of RRSO.

Postoperative Outcomes After Staged Versus Coordinated Breast Surgery and Bilateral Salpingo-Oophorectomy.

BACKGROUND: The objective of this study was to compare postoperative complication rates and healthcare charges between patients who underwent coordinated versus staged breast surgery and bilateral salpingo-oophorectomy (BSO). PATIENTS AND METHODS: The MarketScan administrative database was used to identify adult female patients with invasive breast cancer or BRCA1/BRCA2 mutations who underwent BSO and breast surgery (lumpectomy or mastectomy with or without reconstruction) between 2010 and 2015. Patients were assigned to the coordinated group if a breast operation and BSO were performed simultaneously or assigned to the staged group if BSO was performed separately. Primary outcomes were (1) incidence of 90-day postoperative complications and (2) 2-year aggregate perioperative healthcare charges. Fisher's exact tests, Wilcoxon rank-sum tests, and multivariable regression analyses were performed. RESULTS: Of the 4228 patients who underwent breast surgery and BSO, 412 (9.7%) were in the coordinated group and 3816 (90.3%) were in the staged group. The coordinated group had a higher incidence of postoperative complications (24.0% vs. 17.7%, p < 0.01), higher risk-adjusted odds of postoperative complications [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.06-1.76, p = 0.02], and similar aggregate healthcare charges before (median charges: $106,500 vs. $101,555, p = 0.96) and after risk-adjustment [incidence rate ratio (IRR) 1.00, 95% CI 0.93-1.07; p = 0.95]. In a subgroup analysis, incidence of postoperative complications (12.9% for coordinated operations vs. 11.7% for staged operation, p = 0.73) was similar in patients whose breast operation was a lumpectomy. CONCLUSIONS: While costs were similar, coordinating breast surgery with BSO was associated with more complications in patients who underwent mastectomy, but not in patients who underwent lumpectomy. These data should inform shared decision-making in high-risk patients.

Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on cognition in women with high familial risk of ovarian cancer: A cross-sectional study.

OBJECTIVE: To examine the effect of a premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of ovarian cancer on objective and subjective cognition at least 10 years after RRSO. DESIGN: A cross-sectional study with prospective follow-up, nested in a nationwide cohort. SETTING: Multicentre in the Netherlands. POPULATION OR SAMPLE: 641 women (66% BRCA1/2 pathogenic variant carriers) who underwent either a premenopausal RRSO ≤ age 45 (n = 436) or a postmenopausal RRSO ≥ age 54 (n = 205). All participants were older than 55 years at recruitment. METHODS: Participants completed an online cognitive test battery and a questionnaire on subjective cognition. We used multivariable regression analyses, adjusting for age, education, breast cancer, hormone replacement therapy, cardiovascular risk factors and depression. MAIN OUTCOME MEASURES: The influence of RRSO on objective and subjective cognition of women with a premenopausal RRSO compared with women with a postmenopausal RRSO. RESULTS: After adjustment, women with a premenopausal RRSO (mean time since RRSO 18.2 years) performed similarly on objective cognitive tests compared with women with a postmenopausal RRSO (mean time since RRSO 11.9 years). However, they more frequently reported problems with reasoning (odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.1-3.1) and multitasking (OR 1.9, 95% CI 1.1-3.4) than women with a postmenopausal RRSO. This difference between groups disappeared in an analysis restricted to women of comparable ages (60-70 years). CONCLUSIONS: Reassuringly, approximately 18 years after RRSO, we found no association between premenopausal RRSO and objective cognition.

Bone health after RRBSO among BRCA1/2 mutation carriers: a population-based study.

OBJECTIVE: Examine the risks of fractures and osteoporosis after risk-reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA1/2 mutations. METHODS: In this retrospective population-based study in British Columbia, Canada, between 1996 to 2017, we compared risks of osteoporosis and fractures among women with BRCA1/2 mutations who underwent RRBSO before the age of 50 (n=329) with two age-matched groups without known mutations: 1) women who underwent bilateral oophorectomy (BO) (n=3,290); 2) women with intact ovaries who had hysterectomy or salpingectomy (n=3,290). Secondary outcomes were: having dual-energy X-ray absorptiometry (DEXA) scan, and bisphosphonates use. RESULTS: The mean age at RRBSO was 42.4 years (range, 26-49) and the median follow-up for women with BRCA1/2 mutations was 6.9 years (range, 1.1-19.9). There was no increased hazard of fractures for women with BRCA1/2 mutations (adjusted hazard ratio [aHR]=0.80; 95% confidence interval [CI]=0.56-1.14 compared to women who had BO; aHR=1.02; 95% CI=0.65-1.61 compared to women with intact ovaries). Among women who had DEXA-scan, those with BRCA1/2 mutations had higher risk of osteoporosis (aHR=1.60; 95% CI=1.00-2.54 compared to women who had BO; aHR=2.49; 95% CI=1.44-4.28 compared to women with intact ovaries). Women with BRCA1/2 mutations were more likely to get DEXA-scan than either control groups, but only 46% of them were screened. Of the women with BRCA1/2 mutations diagnosed with osteoporosis, 36% received bisphosphonates. CONCLUSION: Women with BRCA1/2 mutations had higher risk of osteoporosis after RRBSO, but were not at increased risk of fractures during our follow-up. Low rates of DEXA-scan and bisphosphonates use indicate we can improve prevention of bone loss.

Laparoscopic resection surgery for malignant transformation of extragonadal endometriosis by the "pincer" approach.

Up to 1% of women with endometriosis develop endometriosis-associated neoplasms [1]. Most endometriosis-associated malignant tumors develop from the ovarian endometriomas, whereas those developing from extragonadal lesions are extremely rare, estimated at 0.2% [2]. Because they are uncommon, a treatment protocol for the malignant transformation of extragonadal endometriosis lesions has not been clearly defined. When the lesion is confined to the site of origin and R0 resection is achieved, the 5-year survival rate is between 82% and 100%; therefore, complete resection should be performed [3]. The patient in this video had previously undergone hysterectomy, bilateral salpingo-oophorectomy, left nephrectomy, and low-anterior resection of the rectum due to severe endometriosis. Ten years after the surgery, the patient had a 6 cm endometrioid adenocarcinoma developing from the residual endometriosis lesion at the left uterosacral ligament that involved the bladder, left ureter, and rectum. In this case, the tumor was attached to the pelvis due to infiltration of the left sacrospinous ligament. To completely remove the tumor, we used laterally extended endopelvic resection with abdominoperineal resection of the rectum. We used the laparoscopic-perineal-laparoscopic approach (pincer approach) because improved visualization of the left sacrospinous ligament increases the probability of achieving complete resection [4]. Pathological R0 resection was achieved without intraoperative or postoperative complications. Thus, for tumors that are firmly attached to the pelvic floor, the pincer approach can be useful for achieving R0 resection. The informed consent for use of this video was taken from the patient.

Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis.

PURPOSE: After risk-reducing salpingo-oophorectomy (RRSO), BRCA1/2 pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO. METHODS: Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a BRCA-PV with and without STIC at RRSO until September 2020. Primary outcome was the hazard ratio for the risk of PC between BRCA-PV carriers with and without STIC at RRSO, and the corresponding 5- and 10-year risks. Primary analysis was based on a one-stage Cox proportional-hazards regression with a frailty term for study. RESULTS: From 17 studies, individual patient data were available for 3,121 women, of whom 115 had a STIC at RRSO. The estimated hazard ratio to develop PC during follow-up in women with STIC was 33.9 (95% CI, 15.6 to 73.9), P < .001) compared with women without STIC. For women with STIC, the five- and ten-year risks to develop PC were 10.5% (95% CI, 6.2 to 17.2) and 27.5% (95% CI, 15.6 to 43.9), respectively, whereas the corresponding risks were 0.3% (95% CI, 0.2 to 0.6) and 0.9% (95% CI, 0.6 to 1.4) for women without STIC at RRSO. CONCLUSION: BRCA-PV carriers with STIC at RRSO have a strongly increased risk to develop PC which increases over time, although current data are limited by small numbers of events.

Combined Mastectomy and Laparoscopic Hysterectomy with Salpingo-Oophorectomy in Transgender Men: a Cohort Study.

There are few data on complications with gender affirming surgery. The aim of this study was to assess peri- and postoperative complications of laparoscopic hysterectomy and mastectomy performed in a single sitting in transgender men. Assessment of intra- and postoperative complications in a series of 65 transgender men (mean age 27, range 18-47) undergoing concomitant mastectomy and laparoscopic hysterectomy with salpingo-oophorectomy. Mean operating time was 292 ± 47 min. Thirty-four (52%) patients experienced complications: 28 (41%) DINDO grade I, 0 DINDO grade 2, 6 (11%) DINDO grade III. The six grade 3 complications consisted of 5 hematomas requiring evacuation after mastectomy and 2 vaginal tears requiring transvaginal repair. Three patients were readmitted within 30 days, all for postoperative bleeding/hematoma. In transgender men, performing laparoscopic hysterectomy and mastectomy at a single sitting has a modest rate of perioperative complications, and may improve resource utilization.

Risk of cardiovascular disease among women carrying BRCA mutations after risk-reducing bilateral salpingo-oophorectomy: A population-based study.

OBJECTIVE: Examine the risk of cardiovascular disease (CVD) following risk reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA mutations. METHODS: In this retrospective population-based study in British Columbia, Canada, between 1996 and 2017, we compared the risk of CVD among women with known BRCA mutations who underwent RRBSO before the age of 50 (n = 360) with two groups of age-matched women without known BRCA mutations: 1) women who underwent bilateral oophorectomy (BO) for benign conditions (n = 3600); and, 2) women with intact ovaries who had hysterectomy or salpingectomy (n = 3600). Our primary outcome was CVD (a composite (any of) myocardial infarction, heart failure, and/or cerebrovascular disease). Secondary outcomes included a diagnostic code for predisposing conditions (hypertension, dyslipidemia, and/or diabetes mellitus), and use of cardioprotective medications (statins and/or beta-blockers). RESULTS: We report no significant increased risk for CVD between women with BRCA mutations and women who underwent BO (aHR = 1.08, 95%CI: 0.72-1.62), but women with BRCA mutations were less likely to be diagnosed with predisposing conditions (aHR = 0.69, 95%CI: 0.55-0.85). Compared to women without BRCA mutations with intact ovaries who underwent hysterectomy or salpingectomy, women with BRCA mutations had significantly increased risk for CVD (aHR = 1.82, 95%CI: 1.18-2.79) and were less likely to be diagnosed with predisposing conditions (aHR = 0.78, 95%CI: 0.62-0.97) and to fill cardioprotective medications (aHR = 0.88, 95%CI: 0.64-1.22). CONCLUSION: Our results suggest an opportunity for improved prevention of CVD in women with BRCA mutations after prophylactic oophorectomy. Despite the observed lower prevalence of predisposing conditions for CVD and lesser use of cardioprotective medications, this population did not have a lower rate of CVD.

What happens after menopause? (WHAM): A prospective controlled study of sleep quality up to 12 months after premenopausal risk-reducing salpingo-oophorectomy.

OBJECTIVE: Sleep difficulties impair function and increase the risk of depression at menopause and premenopausal oophorectomy may further worsen sleep. However, prospective data are limited, and it remains uncertain whether Hormone Therapy (HT) improves sleep. This prospective observational study measured sleep quality before and up to 12 months after risk-reducing salpingo-oophorectomy (RRSO) compared to a similar age comparison group who retained their ovaries. METHODS: Ninety-five premenopausal women undergoing RRSO and 99 comparisons were evaluated over a 12-month period using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Almost half reported poor sleep quality at baseline. Overall sleep quality was not affected by RRSO until 12 months (p = 0.007). However, sleep disturbance increased by 3 months and remained significantly elevated at 12 months (p < 0.001). Trajectory analysis demonstrated that 41% had increased sleep disturbance after RRSO which persisted in 17.9%. Risk factors for sleep disturbance included severe vasomotor symptoms, obesity and smoking. Around 60% initiated HT after RRSO. Sleep quality was significantly better in HT users vs non users (p = 0.020) but HT did not restore sleep quality to baseline levels. CONCLUSIONS: Overall sleep quality is not affected by RRSO, but new onset sleep disturbance is common, particularly in those with severe vasomotor symptoms. Clinicians should be alert to new-onset sleep disturbance and the potential for HT to improve sleep quality.

What Happens After Menopause? (WHAM): A prospective controlled study of cardiovascular and metabolic risk 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: To prospectively measure cardiometabolic risk 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared to a similar age comparison group, and the effects of Hormone Therapy (HT) on cardiometabolic risk. METHODS: Prospective observational study of 95 premenopausal women planning RRBSO and 99 comparisons who retained their ovaries. At baseline and 12 months, blood pressure (BP), Body Mass Index (BMI), waist and hip circumference, fasting total, HDL and LDL cholesterol, triglycerides, high-sensitivity C-reactive protein, glucose and insulin were measured and HOMA-IR was calculated. Chi-square tests, t-tests and adjusted logistic regression models were used to compare groups. RESULTS: Baseline cardiometabolic phenotypes were similar between groups but more RRBSO participants were overweight/obese with higher waist/hip ratios. By 12 months, BP and cardiometabolic phenotypes were largely unchanged. Paired t-tests showed statistically significant increases in BMI (p = 0.037) and weight (p = 0.042) and larger increases in waist circumference (p < 0.001) and waist-hip ratio (p = 0.009) after RRBSO vs comparisons. However, these were not significant when adjusted for baseline values. After RRBSO 60% initiated Hormone Therapy (HT). Paired t-tests demonstrated that non-HT users had a significantly greater mean increase in waist circumference of 4.3 cm (95% CI 2.0-6.5) compared to 1.3 cm in HT users (95% CI -0.2-2.7, p < 0.001), which remained significant when adjusted for baseline values (p = 0.02). At 12 months, mean waist circumference was 2.94 cm greater in non-HT users compared to HT users. CONCLUSIONS: Cardiometabolic risk markers are largely unchanged 12 months after RRBSO. Hormone Therapy after RRBSO may prevent against an increase in waist circumference.

Salpingo-oophorectomy versus cystectomy in patients with borderline ovarian tumors: a systemic review and meta-analysis on postoperative recurrence and fertility.

BACKGROUND: To compare the postoperative recurrence and fertility in patients with borderline ovarian tumors (BOTs) who underwent different surgical procedures: salpingo-oophorectomy versus cystectomy. METHODS: Potentially relevant literature from inception to Nov. 06, 2020, were retrieved in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (Pubmed). We applied the keywords "fertility-sparing surgery," or "conservative surgery," or "cystectomy," or "salpingo-oophorectomy," or "oophorectomy," or "adnexectomy," or "borderline ovarian tumor" for literate searching. Systemic reviews and meta-analyses were performed on the postoperative recurrence rates and pregnancy rates between patients receiving the two different surgical methods. Begger's methods, Egger's methods, and funnel plot were used to evaluate the publication bias. RESULT: Among the sixteen eligible studies, the risk of recurrence was evaluated in all studies, and eight studies assessed the postoperative pregnancy rates in the BOT patients. A total of 1839 cases with borderline ovarian tumors were included, in which 697 patients (37.9%) received unilateral salpingo-oophorectomy and 1142 patients (62.1%) underwent unilateral/bilateral cystectomy. Meta-analyses showed that BOT patients with unilateral/bilateral cystectomy had significantly higher recurrence risk (OR=2.02, 95% CI: 1.59-2.57) compared with those receiving unilateral salpingo-oophorectomy. Pooled analysis of four studies further confirmed the higher risk of recurrence in patients with cystectomy (HR=2.00, 95% CI: 1.11-3.58). In addition, no significant difference in postoperative pregnancy rate was found between patients with the two different surgical procedures (OR=0.92, 95% CI: 0.60-1.42). CONCLUSION: Compared with the unilateral/bilateral cystectomy, the unilateral salpingo-oophorectomy significantly reduces the risk of postoperative recurrence in patients with BOT, and it does not reduce the pregnancy of patients after surgery. TRIAL REGISTRATION: PROSPERO CRD42021238177.

What happens after menopause? (WHAM): A prospective controlled study of depression and anxiety up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: Risk-reducing bilateral salpingo-oophorectomy (RRBSO) substantially reduces ovarian cancer risk in women with pathogenic gene variants and is generally recommended by age 34-45 years. Natural menopause is a vulnerable period for mood disturbance, but the risk of depression and anxiety in the first 12 months after RRBSO and potential modifying effect of hormone therapy are uncertain. METHODS: Prospective controlled observational study of 95 premenopausal women planning RRBSO and a Comparison group of 99 premenopausal women who retained their ovaries,- 95% of whom were at population level risk of ovarian cancer. Clinically significant symptoms of depression and anxiety were measured using standardised instruments at baseline, 3, 6 and 12 months. Chi-square tests and adjusted logistic regression models compared differences between groups. RESULTS: Baseline symptoms and previous depression or anxiety did not differ between groups. At 3 months after RRBSO clinically significant depressive symptoms were doubled (14.5% vs 27.1%, p = 0.010), which persisted at 12 months. Depressive symptoms were stable in comparisons. At 3 months after RRBSO, clinically significant anxiety symptoms almost trebled (6.1% vs 17.7%, p = 0.014) before plateauing at 6 months and returning to baseline at 12 months. Compared to comparisons, RRBSO participants were at 3.0-fold increased risk of chronic depressive symptoms (Wald 95% CI 1.27-7.26), 2.3-fold increased risk of incident depression (95% Wald CI 1.08-5.13) and 2.0-fold increase of incident anxiety (Wald 95% CI 0.78-5.00). Depression and anxiety were slightly more common in Hormone Therapy users after RRBSO vs non-users. CONCLUSIONS: RRBSO leads to a rapid increase in clinically significant depressive and anxiety symptoms despite Hormone Therapy use.

Satisfaction with prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers is very high and little dependent on the participants' characteristics at surgery: a prospective study.

OBJECTIVE: BRCA carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO). Possible adverse health impacts of RRSO, particularly when done before natural menopause, can reduce the long-term satisfaction with this risk-reducing strategy. The aim of this study was to prospectively evaluate the level of satisfaction of women undergoing RRSO, also in relation to some specific characteristics at RRSO. METHODS: A prospective cohort study was performed in the Modena Family Cancer Clinic of the University Hospital of Modena (Italy). All BRCA1/2 confirmed mutation carriers who decided to undergo RRSO were recruited between 2016 and 2019. RESULTS: Fifty-five women (29 BRCA1 and 26 BRCA2) (mean age: 50.4 ±â€Š7.7 years [range 35-79]) were included with a mean follow-up after RRSO of 660.9 days (1.8 years) (range 35-1,688 days) (median: 549 days). No intraepithelial (Serous Tubal Intraepithelial Carcinoma)/invasive cancers were found (0%) at RRSO. No vasomotor symptoms at 1 month after surgery were reported by 11/22 (50%) premenopausal women at RRSO. All women (100%) with new "RRSO-caused" vasomotor symptoms with no previous breast cancer initiated postmenopausal hormone therapy. At the final follow-up the satisfaction rate (0-100 visual analog scale points) of the participants was 96.4 ±â€Š8.6 points (range 62-100). To the question "Would you undergo RRSO again if it was proposed today? (0-100 visual analog scale points)" the answer was 99.4 ±â€Š3.2 points (range 79-100). These scores were in general very high and did not change in the different groups according to pre/postmenopausal status at RRSO, cancer survivors versus healthy women at RRSO, BRCA status, hormone therapy users/nonusers after RRSO, "RRSO-caused" symptoms versus not RRSO-caused (P > 0.05). CONCLUSIONS: Findings from this prospective study suggest that satisfaction with RRSO is very high and little dependent on the participants' characteristics at surgery. Women at high risk for ovarian cancer are very satisfied with their choice of risk-reduction strategy.

Video Summary:http://links.lww.com/MENO/A712.

Loss of bone density and bone strength following premenopausal risk-reducing bilateral salpingo-oophorectomy: a prospective controlled study (WHAM Study).

Prophylactic oophorectomy is recommended for women at high risk for ovarian cancer, but the associated impact on bone health is of clinical concern. This prospective, controlled study demonstrated substantial loss of bone density and bone strength following surgical menopause. Postoperative hormone therapy alleviated, but not fully prevented, spinal bone loss. INTRODUCTION: This prospective study investigated bone health in women following premenopausal oophorectomy. METHODS: Dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and pQCT-based finite element analysis (pQCT-FEA) were used to assess bone health between systemic hormone therapy (HT) users and non-users after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared with premenopausal controls over 24-month follow-up. RESULTS: Mean age was 42.4 ± 2.6 years (n = 30) for the surgery group and 40.2 ± 6.3 years for controls (n = 42), and baseline bone measures were similar between groups. Compromised bone variables were observed at 24 months after RRBSO, among which areal bone mineral density (aBMD) at the lumbar spine, tibial volumetric cortical density (Crt vBMD), and tibial bending stiffness (kbend) had decreased by 4.7%, 1.0%, and 12.1%, respectively (all p < 0.01). In non-HT users, significant losses in lumbar spine (5.8%), total hip (5.2%), femoral neck (6.0%) aBMD, tibial Crt vBMD (2.3%), and kbend (14.8%) were observed at 24 months (all p < 0.01). HT prevented losses in kbend, tibial Crt vBMD, and aBMD, except for modest 2.3% loss at the lumbar spine (p = 0.01). CONCLUSION: This prospective, controlled study of bone health following RRBSO or premenopausal oophorectomy demonstrated substantial loss of bone density and bone strength following RRBSO. HT prevented loss of bone density and bone stiffness, although there was still a modest decrease in lumbar spine aBMD in HT users. These findings may inform decision-making about RRBSO and clinical management following premenopausal oophorectomy.

Management of menopausal symptoms and ovarian function preservation in women with gynecological cancer.

Gynecological cancers affect a growing number of women globally, with approximately 1.3 million women diagnosed in 2018. Menopausal symptoms are a significant health concern after treatment for gynecological cancers and may result from oncologic treatments such as premenopausal bilateral oophorectomy, ovarian failure associated with chemotherapy or radiotherapy, and anti-estrogenic effects of maintenance endocrine therapy. Additionally, with the growing availability of testing for pathogenic gene variants such as BRCA1/2 and Lynch syndrome, there is an increasing number of women undergoing risk-reducing oophorectomy, which in most cases will be before age 45 years and will induce surgical menopause. Not all menopausal symptoms require treatment, but patients with cancer may experience more severe symptoms compared with women undergoing natural menopause. Moreover, there is increasing evidence of the long-term implications of early menopause, including bone loss, cognitive decline and increased cardiovascular risk. Systemic hormone therapy is well established as the most effective treatment for vasomotor symptoms and vaginal (topical) estrogen therapy is effective for genitourinary symptoms. However, the role of hormone receptors in many gynecological cancers and their treatment pose a challenge to the management of menopausal symptoms after cancer. Consequently, the use of menopausal hormone therapy in this setting can be difficult for clinicians to navigate and this article aims to provide current, comprehensive guidance for the use of menopausal hormone replacement therapy in women who have had, or are at risk of developing, gynecological cancer to assist with these treatment decisions.

Short- and long-term outcomes for single-port risk-reducing salpingo-oophorectomy with and without hysterectomy for women at risk for gynecologic cancer.

INTRODUCTION: Risk-reducing salpingo-oophorectomy has been established as one of the most effective strategies in risk reduction for ovarian and breast cancers among women at increased genetic risk. However, there are limited data regarding the single-port laparoscopic platform in the field of risk-reducing surgery. Our objective was to describe outcomes after single-port risk-reducing salpingo-oophorectomy with or without hysterectomy for reduction of ovarian, breast, or endometrial cancer risk. METHODS: A retrospective, single institution (Canadian Task Force Classification II.2) analysis was performed in women at high genetic or familial risk for ovarian/tubal/primary peritoneal cancer or with personal history of breast cancer who underwent single-port laparoscopic risk-reducing salpingo-oophorectomy with or without hysterectomy between October 2009 and December 2015. Data were collected on patient demographics, surgical procedure and characteristics, intra-operative findings, and post-operative outcomes. RESULTS: In total, 187 single-port laparoscopic surgeries were performed with a median follow-up of 204 (IQR 25-749) days. BRCA1/2, Lynch syndrome, or Cowden syndrome was diagnosed in 64.0% of patients. Additionally, 32.1% had a personal history of breast cancer, and 3.2% reported strong family history of ovarian and/or breast cancer. Single-port risk-reducing salpingo-oophorectomy with hysterectomy was performed in 53.5% of patients. The rate of adverse outcomes, including conversion to multiport laparoscopy or laparotomy (1.6%), intra-operative injury (1.6%), deep vein thrombosis (0.5%), urinary tract infection (2.7%), and/or incisional cellulitis (4.3%) were low. Three patients (1.6%) were diagnosed with malignancy on final pathology. All three patients were BRCA1-positive and their CA125 values were significantly lower than those without malignancy (p=<0.0001). CONCLUSIONS: Single-port laparoscopy is a safe option for patients undergoing risk-reducing salpingo-oophorectomy with or without hysterectomy. Standardized pre-operative evaluation criteria are needed to determine absolute risk of incidental malignancy, and the risk of identifying a malignancy should be reiterated to patients during pre-operative counseling.

Patient reported experiences following laparoscopic prophylactic bilateral salpingo-oophorectomy or salpingectomy in an ambulatory care hospital.

Women at risk of developing ovarian cancer because of a BRCA1 or BRCA2 pathogenic variant are candidates for prophylactic bilateral salpingo-oophorectomy (BSO). While BSO surgeries are routinely performed, to our knowledge there are no studies that have examined patient-reported experiences following laparoscopic BSO performed in an ambulatory care setting. The objective of this study was to examine whether women undergoing prophylactic laparoscopic BSO felt they were adequately informed about post-operative outcomes. A telephone interview was conducted among 46 women undergoing laparoscopic BSO to collect detailed information regarding surgical outcomes, complications, symptoms, and time to return to daily activities. The average age at surgery was 45.0 years (range 34-66) and 67% of women underwent BSO prior to age 50. The mean reported hospital stay was 7.2 h (range 4-12 h) and at time of discharge, 78% of the women felt well enough to go home. None of the women required a readmission to hospital. Forty-three percent (n = 20) of the women did not feel well informed about what to expect post-operatively. Most of the patient-reported outcomes (including pain, vaginal bleeding, and nausea/vomiting) were expected and patient-reported menopausal symptoms were more common among women who were premenopausal at surgery. In terms of returning to regular activities, premenopausal women (n = 36) resumed sexual activity on average at 43 days (range 2-365), which is later than postmenopausal women (n = 15) at 19 days (range 7-30). On average, women returned to full-time work in 16 days (range 1-56 days). Despite patients receiving pre-surgery counselling, our findings suggest that there is a need to provide supplemental, reinforcing patient materials in preparing patients for what to expect after surgery.

Surgical ovarian suppression for adjuvant treatment in hormone receptor positive breast cancer in premenopausal patients.

OBJECTIVE: Ovarian suppression is recommended to complement endocrine therapy in premenopausal women with breast cancer and high-risk features. It can be achieved by either medical ovarian suppression or therapeutic bilateral salpingo-oophorectomy. Our objective was to evaluate characteristics of patients with stage I-III hormone receptor positive primary breast cancer who underwent bilateral salpingo-oophorectomy at our institution. MATERIALS AND METHODS: Premenopausal women with stage I-III hormone receptor positive primary breast cancer diagnosed between January 2010 and December 2014 were identified from a database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of characteristics between treatment groups was assessed using χ2 test and univariate logistic regression. A multivariate model was based on factors significant on univariate analysis. RESULTS: Of 2740 women identified, 2018 (74%) received endocrine treatment without ovarian ablation, 516 (19%) received endocrine treatment plus ovarian ablation, and 206 (7.5%) did not receive endocrine treatment. Among patients undergoing ovarian ablation 282/516 (55%) received medical ovarian suppression, while 234 (45%) underwent bilateral salpingo-oophorectomy. By univariate logistic analyses, predictors for ovarian ablation were younger age (OR 0.97), histology (other vs ductal: OR 0.23), lymph node involvement (OR 1.89), higher International Federation of Gynecology and Obstetrics (FIGO) stage (stage II vs I: OR 1.48; stage III vs I: OR 2.86), higher grade (grade 3 vs 1: OR 3.41; grade 2 vs 1: OR 2.99), chemotherapy (OR 1.52), and more recent year of diagnosis (2014 vs 2010; OR 1.713). Only year of diagnosis, stage, and human epidermal growth factor receptor 2 (HER-2) treatment remained significant in the multivariate model. Within the cohort undergoing ovarian ablation, older age (OR 1.05) was associated with therapeutic bilateral salpingo-oophorectomy. Of 234 undergoing bilateral salpingo-oophorectomy, 12 (5%) mild to moderate adverse surgical events were recorded. CONCLUSIONS: Bilateral salpingo-oophorectomy is used frequently as an endocrine ablation strategy. Older age was associated with bilateral salpingo-oophorectomy. Perioperative morbidity was acceptable. Evaluation of long-term effects and quality of life associated with endocrine ablation will help guide patient/provider decision-making.

The psychosexual effects of risk-reducing bilateral salpingo-oophorectomy in female BRCA1/2 mutation carriers: A systematic review of qualitative studies.

INTRODUCTION: It is estimated that up to 20% of ovarian cancers have an inherited genetic etiology with the most common being BRCA1/2 mutations. For women with these mutations risk-reducing bilateral salpingo-oophorectomy (RRBSO) to reduce the risk of primary ovarian cancer is often performed, however the surgery results in immediate onset of surgical menopause. AIM: The aim of this systematic review was to explore the psychosexual impacts of risk reducing bilateral salpingo oophorectomy in the published qualitative literature. METHODS: PubMed, Medline, Web of Science and PsycInfo were searched for qualitative papers that looked at the psychosexual impact of RRBSO on individuals who were pre-menopausal at the time of surgery. Studies were quality assessed using Mixed Method Appraisal Tool (MMAT) and Standard for Reporting Qualitative Research (SRQR) checklists and data were extracted. Thematic synthesis of the results was performed. RESULTS: Of 143 papers identified in searching, 5 qualitative papers were identified relating to interviews with 115 women after RRBSO published between 2000 and 2020. The quality of the papers was moderate. Five different themes were identified related to individual experiences with RRBSO: (1) information needs, (2) psychological impact, (3) psychosexual impact, (4) partner support and (5) hormone replacement therapy (HRT). CONCLUSION: Individual experiences of RRBSO were varied and influenced by multiple factors but psychosexual problems were common, often caused significant distress to the women and their partners and were often poorly explained before surgery. Women do not feel adequately prepared for the psychological and sexual side effects of RRBSO. The qualitative data provides invaluable insight into the individual experiences of women and can be used to better help women mitigate the effects of the surgery.