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      Menopausal symptoms and bone health in women undertaking risk reducing bilateral salpingo-oophorectomy: significant bone health issues in those not taking HRT

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          Abstract

          Background:

          Women at high ovarian cancer risk, especially those with mutations in BRCA1/BRCA2, are encouraged to undergo bilateral risk-reducing salpingo-oophorectomy (BRRSPO) prior to the natural menopause. The decision to use HRT to cover the period of oestrogen deprivation up to 50 years of age is difficult because of balancing the considerations of breast cancer risk, bone and cardiovascular health.

          Methods:

          We reviewed by questionnaire 289 women after BRRSPO aged ⩽48 years because of high ovarian cancer risk; 212 (73%) of women responded.

          Results:

          Previous HRT users ( n=67) had significantly worse endocrine symptom scores than 67 current users ( P=0.006). A total of 123 (58%) of women had ⩾24 months of oestrogen deprivation <50 years with 78 (37%) never taking HRT. Bone density (DXA) evaluations were available on 119 (56%) women: bone loss with a T score of ⩽−1.0 was present in 5 out of 31 (16%) women with no period of oestrogen deprivation <50 years compared with 37 out of 78 (47%) of those with ⩾24 months of oestrogen deprivation ( P=0.03).

          Interpretation:

          Women undergoing BRRSPO <50 years should be counselled concerning the risks/benefits of HRT, taking into consideration the benefits on symptoms, bone health and cardiovascular health, and that the risks of breast cancer from oestrogen-only HRT appear to be relatively small.

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          Most cited references22

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          Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group.

          of the World Health Organization World Health Organization Constitution (1994)
          Article 0 comments Cited 399 times – based on 0 reviews     Review now
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            Breast cancer and hormone-replacement therapy in the Million Women Study.

            Valerie Beral (2003)
            Current use of hormone-replacement therapy (HRT) increases the incidence of breast cancer. The Million Women Study was set up to investigate the effects of specific types of HRT on incident and fatal breast cancer. 1084110 UK women aged 50-64 years were recruited into the Million Women Study between 1996 and 2001, provided information about their use of HRT and other personal details, and were followed up for cancer incidence and death. Half the women had used HRT; 9364 incident invasive breast cancers and 637 breast cancer deaths were registered after an average of 2.6 and 4.1 years of follow-up, respectively. Current users of HRT at recruitment were more likely than never users to develop breast cancer (adjusted relative risk 1.66 [95% CI 1.58-1.75], p<0.0001) and die from it (1.22 [1.00-1.48], p=0.05). Past users of HRT were, however, not at an increased risk of incident or fatal disease (1.01 [0.94-1.09] and 1.05 [0.82-1.34], respectively). Incidence was significantly increased for current users of preparations containing oestrogen only (1.30 [1.21-1.40], p<0.0001), oestrogen-progestagen (2.00 [1.88-2.12], p<0.0001), and tibolone (1.45 [1.25-1.68], p<0.0001), but the magnitude of the associated risk was substantially greater for oestrogen-progestagen than for other types of HRT (p<0.0001). Results varied little between specific oestrogens and progestagens or their doses; or between continuous and sequential regimens. The relative risks were significantly increased separately for oral, transdermal, and implanted oestrogen-only formulations (1.32 [1.21-1.45]; 1.24 [1.11-1.39]; and 1.65 [1.26-2.16], respectively; all p<0.0001). In current users of each type of HRT the risk of breast cancer increased with increasing total duration of use. 10 years' use of HRT is estimated to result in five (95% CI 3-7) additional breast cancers per 1000 users of oestrogen-only preparations and 19 (15-23) additional cancers per 1000 users of oestrogen-progestagen combinations. Use of HRT by women aged 50-64 years in the UK over the past decade has resulted in an estimated 20000 extra breast cancers, 15000 associated with oestrogen-progestagen; the extra deaths cannot yet be reliably estimated. Current use of HRT is associated with an increased risk of incident and fatal breast cancer; the effect is substantially greater for oestrogen-progestagen combinations than for other types of HRT.
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              Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.

              Timothy R Rebbeck, Henry T Lynch, Susan L Neuhausen … (2002)
              Data concerning the efficacy of bilateral prophylactic oophorectomy for reducing the risk of gynecologic cancer in women with BRCA1 or BRCA2 mutations are limited. We investigated whether this procedure reduces the risk of cancers of the coelomic epithelium and breast in women who carry such mutations. A total of 551 women with disease-associated germ-line BRCA1 or BRCA2 mutations were identified from registries and studied for the occurrence of ovarian and breast cancer. We determined the incidence of ovarian cancer in 259 women who had undergone bilateral prophylactic oophorectomy and in 292 matched controls who had not undergone the procedure. In a subgroup of 241 women with no history of breast cancer or prophylactic mastectomy, the incidence of breast cancer was determined in 99 women who had undergone bilateral prophylactic oophorectomy and in 142 matched controls. The length of postoperative follow-up for both groups was at least eight years. Six women who underwent prophylactic oophorectomy (2.3 percent) received a diagnosis of stage I ovarian cancer at the time of the procedure; two women (0.8 percent) received a diagnosis of papillary serous peritoneal carcinoma 3.8 and 8.6 years after bilateral prophylactic oophorectomy. Among the controls, 58 women (19.9 percent) received a diagnosis of ovarian cancer, after a mean follow-up of 8.8 years. With the exclusion of the six women whose cancer was diagnosed at surgery, prophylactic oophorectomy significantly reduced the risk of coelomic epithelial cancer (hazard ratio, 0.04; 95 percent confidence interval, 0.01 to 0.16). Of 99 women who underwent bilateral prophylactic oophorectomy and who were studied to determine the risk of breast cancer, breast cancer developed in 21 (21.2 percent), as compared with 60 (42.3 percent) in the control group (hazard ratio, 0.47; 95 percent confidence interval, 0.29 to 0.77). Bilateral prophylactic oophorectomy reduces the risk of coelomic epithelial cancer and breast cancer in women with BRCA1 or BRCA2 mutations.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Cancer
                Title: British Journal of Cancer
                Publisher: Nature Publishing Group
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Print): 28 June 2011
                Publication date (Electronic): 07 June 2011
                Volume: 105
                Issue: 1
                Pages: 22-27
                Affiliations
                [1 ]simpleDepartment of Genetic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Central Manchester Foundation Trust, St Mary's Hospital , 6th Floor, Oxford Road, Manchester M13 9WL, UK
                [2 ]simpleManchester Breast Centre, University of Manchester, The Christie NHS Foundation Trust , Withington, Manchester M20 4BX, UK
                [3 ]simpleBreast Screening Service, Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust , Wythenshawe, Manchester M23 9LT, UK
                [4 ]simpleDepartment of Medicine, The University of Manchester, Manchester Academic Health Science Centre, Central Manchester Foundation Trust , Oxford Road, Manchester M13 9WL, UK
                [5 ]simpleDepartment of Psychonchology, Institute of Cancer Research , Downs Road, Sutton, Surrey, UK
                Author notes
                Article
                Publisher Item ID: bjc2011202
                DOI: 10.1038/bjc.2011.202
                PMC ID: 3137416
                PubMed ID: 21654687
                SO-VID: 44eb531d-2d6c-40ac-8e31-d2823415f120
                Copyright © Copyright © 2011 Cancer Research UK
                History
                Date received : 24 February 2011
                Date revision received : 12 May 2011
                Date accepted : 12 May 2011
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: hrt,oophorectomy,breast cancer,osteopenia,menopause,osteoporosis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: hrt, oophorectomy, breast cancer, osteopenia, menopause, osteoporosis

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