The impact of risk-reducing salpingo-oophorectomy

The idea of this thesis was formed on the basis of the expected disruption of quality of life in women choosing risk-reducing salpingo-oophorectomy (RRSO) as prevention strategy. In the search for the consequences of RRSO on menopausal symptoms, sexuality, depression and anxiety, osteoporosis, mental health and cardiovascular health, information was scattered. The lack of overview led to performing a systematic review, chapter 2. In over 3500 patients, described in more than 39 studies, we found that RRSO leads to more severe menopausal complaints and sexual dysfunction than natural menopause. In chapter 3 we specifically looked at the consequences of RRSO on bone health. Therefore we prospectively collected data on bone turnover markers (BTM). We found that the investigated BTMs, P1NP and CTX, increased in premenopausal women following RRSO, suggesting a higher bone turn-over. In postmenopausal women P1NP increased the first six weeks post-RRSO, but this effect was not permanent. Cardiovascular health following RRSO was assessed in chapter 4. In premenopausal women the levels of HDLcholesterol, the cholesterol ratio and HBA1c increased significantly over time, although still staying within reference range. In this group, hot flushes increased over time (p<0.001). In postmenopausal women, no significant changes were observed following RRSO. Our study, described in chapter 5, shows the effectiveness of HRT, even return of symptoms to pre-surgical levels. Women who underwent RRSO and used HRT had approximately the same levels of endocrine symptoms and sexual functioning as the women in the screening group. Although HRT is proven to be effective, the safety of HRT is still a point of discussion. Therefore, in chapter 6 we reviewed all available literature on the safety of HRT in this specific group of patients and also looked at the international guideline on this matter. The most important finding is that none of the published studies yielded evidence that shortterm use of HRT is unsafe in BRCA 1 and 2 mutation carriers with no personal history of BC. In chapter 7 we report the first study on the potential value of anti-Mullerian hormone (AMH) to predict menopausal symptoms following RRSO in premenopausal women. We hoped we could predict which women would suffer more than others following RRSO. Our findings indicate that AMH serum levels do not predict changes in endocrine and sexual symptoms or in psychological distress following RRSO in women at increased risk of OC. Though, having regular menses prior to RRSO was weakly associated with severe menopausal symptoms after surgery. In chapter 8 we describe a prospective observational cohort study of 57 pre- and 37 postmenopausal included opting for RRSO. We measured testosterone, androstenedione, estradiol and estrone levels in serum determined by liquid chromatography-tandem mass spectrometry were obtained one day before, six weeks and seven months after RRSO. At the same time points validated questionnaires on sexual functioning and menopausal complaints were obtained. In premenopausal women, all four steroids were decreased both six weeks (p<0.01) and seven months (p<0.01) after RRSO. Furthermore, in these women, decreases in estrogens were associated with a decrease in sexual functioning seven months after RRSO (p<0.05). In postmenopausal women, only testosterone was decreased six weeks and seven months (p<0.05) after RRSO, which was associated with an increase in menopausal complaints at seven months post-RRSO (p<0.05). Testosterone is decreased after RRSO, which indicates that postmenopausal ovaries maintain some testosterone production. Chapter 9 describes the pilot testing of a decision aid developed according to the IPDAS criteria regarding the choice for risk-reducing salpingo-oophorectomy in premenopausal BRCA 1/2 mutation carriers.