Osteoporosis risk and management in BRCA1 and BRCA2 carriers who undergo risk-reducing salpingo-oophorectomy

Garcia, Christine; Lyon, Liisa; Conell, Carol; Littell, Ramey D.; Powell, C. Bethan

doi:10.1016/j.ygyno.2015.06.020

Cited by 28 publications

(35 citation statements)

References 16 publications

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“…3 Garcia et al also recently reported that among 225 BRCA1 /2 carriers, followed for a median of 41 months post oophorectomy, nearly a third had normal DEXA scan results, while 55.6% showed osteopenia and 12.1% osteoporosis. 5 Additional recent studies among BRCA carriers identified similar trends of lower BMD following oophorectomy. 7,6 In contrast, a recent study by Fakkert et al found that BMD was not significantly lower among premenopausal women (n=212) 5 years post-oophorectomy compared to general population data, though BRCA status was not considered.…”

Section: Discussionmentioning

confidence: 79%

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Bone loss after oophorectomy among high-risk women: an NRG oncology/gynecologic oncology group study

et al. 2016

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OBJECTIVE Women undergo premenopausal oophorectomy for a variety of reasons, including to reduce ovarian or breast cancer risk. However, surgically-induced menopause is associated with adverse sequelae, including accelerated bone loss, that have not been well characterized. METHODS The Gynecologic Oncology Group (GOG)-0215 randomized phase II trial of zoledronic acid was initiated to determine if post-oophorectomy bisphosphonate therapy could prevent this bone loss. The study was closed after slow accrual prevented evaluation of the primary study endpoint. We analyzed changes in bone mineral density (BMD) among the 80 women randomized to the observation arm of this study, as measured 3, 9 and 18 months post-enrollment. RESULTS The mean change in BMD from baseline to 18 months was −0.09 (95% Confidence Interval (CI) −0.12- −0.07), −0.05 (95% CI −0.07- −0.03), and −0.06 (95% CI −0.07- −0.05) g/cm2 across the lumbar spine, right hip, and left hip, respectively. This represents a BMD decrease of −8.5% for the lumbar spine and −5.7% for both the right and left hips from baseline to 18 months’ observation. CONCLUSIONS These results demonstrate that premenopausal women undergoing oophorectomy clearly experience bone loss, an adverse effect of oophorectomy, which requires attention and active management. BMD should be monitored post-oophorectomy, and treated per standard practice guidelines. Future studies will be required to determine if early treatment can mitigate fracture risk, and to test promising therapeutic interventions and novel prevention strategies, such as increased physical activity or alternative medications, in randomized trials.

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Section: Discussionmentioning

confidence: 79%

“…1–4 Those women who are premenopausal at the time of oophorectomy experience immediate, surgically-induced, menopause and are at increased risk of bone loss associated with premature loss of estrogen, and thus increased risk of osteoporosis. 1,5–7 …”

Section: Introductionmentioning

confidence: 99%

Bone loss after oophorectomy among high-risk women: an NRG oncology/gynecologic oncology group study

et al. 2016

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“…Three studies evaluated the effect of HT on bone loss [30, 33, 37]. Two studies included the time frame of DXA screening post-RRSO (6.3 years [33] and 1.25 years [30]).…”

Section: Resultsmentioning

confidence: 99%

“…Two studies included the time frame of DXA screening post-RRSO (6.3 years [33] and 1.25 years [30]). HT users had less bone loss compared to non-users in 2 studies [33, 37].…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, the use of ET alone in the WHI in younger women who have had a hysterectomy showed no increase in breast cancer risk [19, 50, 51]. Unfortunately we were unable to further explore the relative impact of ET versus EPT on breast cancer or other outcomes, as few studies reported the outcomes by specific treatment [20, 21] and not all specified the type of HT [29, 30, 35, 37]. …”

Section: Discussionmentioning

confidence: 99%

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The effect of hormone therapy on quality of life and breast cancer risk after risk-reducing salpingo-oophorectomy: a systematic review

et al. 2017

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BackgroundIt is unclear if the use of hormone therapy (HT) in carriers of BRCA mutations improves the quality of life (QOL) without increasing the risk of breast cancer following a risk-reducing salpingo-oophorectomy (RRSO). Our objective was to assess the effect of HT on QOL and breast cancer risk, after RRSO.MethodsWe searched MEDLINE, EMBASE, CINHAL, and others, from inception to July 22, 2016, to identify relevant studies. Two reviewers independently screened identified records for controlled trials and observational studies that addressed the effect of HT on QOL and breast cancer risk in women with BRCA mutations, post RRSO. Two reviewers independently extracted data on populations, interventions, comparators, outcomes, and methodological quality. Studies addressing the same outcome were synthesized using written evidence summaries or tables.ResultsOf the 1,059 records identified, 13 met our inclusion criteria. All studies were observational. Six studies assessed the effect on QOL. Of these, 3 showed improvement in QOL with HT use. The risk of breast cancer was evaluated in 4 studies. The mean duration of follow-up was 2.6 years (range 0.1-19.1). The risk of breast cancer did not change with HT use in all 4 studies.ConclusionsCumulative evidence from our review suggests that short-term HT use following RRSO improves QOL. The effect on breast cancer risk is still unclear. There are too few long-term studies to draw any strong conclusions. The need for future well-designed RCTs for more established evidence is imperative.Electronic supplementary materialThe online version of this article (doi:10.1186/s12905-017-0370-6) contains supplementary material, which is available to authorized users.

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Changes in Bone Mineral Density After Prophylactic Bilateral Salpingo-Oophorectomy in Carriers of a BRCA Mutation

et al. 2019

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IMPORTANCE Preventive surgery is strongly recommended for individuals with a BRCA mutation at a young age to prevent ovarian cancer and improve overall survival. The overall effect of early surgical menopause on various health outcomes, including bone health, has not been clearly elucidated. OBJECTIVE To evaluate the association of prophylactic bilateral salpingo-oophorectomy with bone mineral density (BMD) loss among individuals with a BRCA mutation. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study of participants with a BRCA mutation who underwent oophorectomy through the University Health Network, Toronto, Ontario, Canada, recruited participants from January 2000 to May 2013. Eligibility criteria included having a BRCA mutation, at least 1 ovary intact prior to surgery, and no history of any cancer other than breast cancer. Bone mineral density was measured using dual-energy x-ray absorptiometry before and after surgery. Data analysis began in December 2018 and finished in January 2019. MAIN OUTCOMES AND MEASURES The annual change in BMD from baseline to follow-up was calculated for the following 3 anatomical locations: (1) lumbar spine, (2) femoral neck, and (3) total hip. RESULTS A total of 95 women had both a baseline and postsurgery BMD measurement with a mean (SD) follow-up period of 22.0 (12.7) months. The mean (SD) age at oophorectomy was 48.0 (7.4) years. Among women who were premenopausal at time of surgery (50 [53%]), there was a decrease in BMD from baseline to follow-up across the lumbar spine (annual change, −3.45%; 95% CI, −4.61% to −2.29%), femoral neck (annual change, −2.85%; 95% CI, −3.79% to −1.91%), and total hip (annual change, −2.24%; 95% CI, −3.11% to −1.38%). Self-reported hormone therapy use was associated with significantly less bone loss at the lumbar spine (−2.00% vs −4.69%; P = .02) and total hip (−1.38% vs −3.21; P = .04) compared with no hormone therapy use. Among postmenopausal women at time of surgery (45 [47%]), there was also a significant decrease in BMD across the lumbar spine (annual change, −0.82%; 95% CI, −1.42% to −0.23%) and femoral neck (annual change, −0.68%; 95% CI, −1.33% to −0.04%) but not total hip (annual change, −0.18%; 95% CI, −0.82% to 0.46%). CONCLUSIONS AND RELEVANCE This study found that oophorectomy was associated with postoperative bone loss, especially among women who were premenopausal at the time of surgery. Targeted management strategies should include routine BMD assessment and hormone therapy use to improve management of bone health in this population.

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Osteoporosis risk and management in BRCA1 and BRCA2 carriers who undergo risk-reducing salpingo-oophorectomy

Cited by 28 publications

References 16 publications

Bone loss after oophorectomy among high-risk women: an NRG oncology/gynecologic oncology group study

Bone loss after oophorectomy among high-risk women: an NRG oncology/gynecologic oncology group study

The effect of hormone therapy on quality of life and breast cancer risk after risk-reducing salpingo-oophorectomy: a systematic review

Changes in Bone Mineral Density After Prophylactic Bilateral Salpingo-Oophorectomy in Carriers of a BRCA Mutation

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