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... Show moreObjective: 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. Show less
Winden, L.J. van; Vermeulen, R.F.M.; Noort, V. van den; Gaarenstroom, K.N.; Kenter, G.G.; Brood-van Zanten, M.M.A.; ... ; Rossum, H.H. van 2022
Context: Risk-reducing salpingo-oophorectomy (RRSO) is performed in BRCA1 or 2 mutant carriers to minimize ovarian cancer risk. Although studies have been performed investigating sex steroid levels... Show moreContext: Risk-reducing salpingo-oophorectomy (RRSO) is performed in BRCA1 or 2 mutant carriers to minimize ovarian cancer risk. Although studies have been performed investigating sex steroid levels, menopausal complaints, and sexual functioning in relation to RRSO, their exact relationship remains unknown. Objectives: To investigate the impact of RRSO on serum sex steroid levels and their association with menopausal complaints and sexual functioning. Methods: This prospective observational cohort study included 57 premenopausal and 37 postmenopausal women at risk of ovarian cancer and opting for RRSO. Data collection involved validated questionnaires on sexual functioning and menopausal complaints.Testosterone, androstenedione, estradiol, and estrone levels in serum determined by liquid chromatography-tandem mass spectrometry were obtained 1 day before, 6 weeks, and 7 months after RRSO. Results: In premenopausal women, all 4 steroids were decreased both 6 weeks (P < 0.01) and 7 months (P < 0.01) after RRSO. Furthermore, in these women, decreases in estrogens were associated with a decrease in sexual functioning 7 months after RRSO (P < 0.05). In postmenopausal women, only testosterone was decreased 6 weeks and 7 months (P < 0.05) after RRSO, which was associated with an increase in menopausal complaints at 7 months post-RRSO (P < 0.05). Conclusion: Our results suggest that in premenopausal women, decreases in estrogens are related to a decrease in sexual functioning and that in postmenopausal women, testosterone is decreased after RRSO, which indicates that postmenopausal ovaries maintain some testosterone production. Furthermore, in postmenopausal women, a large decrease of testosterone was associated with more menopausal complaints, indicating that future studies investigating testosterone supplementation are warranted. Show less
Background: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the... Show moreBackground: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited.Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer.Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery.Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study.Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO. Show less
