Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Controlled Clinical Trial
. 2021 Aug 1;7(8):1203-1212.
doi: 10.1001/jamaoncol.2021.1590.

Association of Salpingectomy With Delayed Oophorectomy Versus Salpingo-oophorectomy With Quality of Life in BRCA1/2 Pathogenic Variant Carriers: A Nonrandomized Controlled Trial

Miranda P Steenbeek  1 , Marline G Harmsen  1 , Nicoline Hoogerbrugge  2 , Marieke Arts de Jong  1 , Angela H E M Maas  3 , Judith B Prins  4 , Johan Bulten  5 , Steven Teerenstra  6 , Majke H D van Bommel  1 , Helena C van Doorn  7 , Marian J E Mourits  8 , Marc van Beurden  9 , Ronald P Zweemer  10 , Katja N Gaarenstroom  11 , Brigitte F M Slangen  12 , Monique M A Brood-van Zanten  13   14 , M Caroline Vos  15 , Jurgen M J Piek  16 , Luc R C W van Lonkhuijzen  14 , Mirjam J A Apperloo  17 , Sjors F P J Coppus  18 , Leon F A G Massuger  19 , Joanna IntHout  20 , Rosella P M G Hermens  20 , Joanne A de Hullu  1
Affiliations
Controlled Clinical Trial

Association of Salpingectomy With Delayed Oophorectomy Versus Salpingo-oophorectomy With Quality of Life in BRCA1/2 Pathogenic Variant Carriers: A Nonrandomized Controlled Trial

Miranda P Steenbeek et al. JAMA Oncol. .

Abstract

Importance: Most women with a BRCA1/2 pathogenic variant undergo premature menopause with potential short- and long-term morbidity due to the current method of ovarian carcinoma prevention: risk-reducing salpingo-oophorectomy (RRSO). Because the fallopian tubes play a key role in ovarian cancer pathogenesis, salpingectomy with delayed oophorectomy may be a novel risk-reducing strategy with benefits of delaying menopause.

Objective: To compare menopause-related quality of life after risk-reducing salpingectomy (RRS) with delayed oophorectomy with RRSO in carriers of the BRCA1/2 pathogenic variant.

Design, setting, and participants: A multicenter nonrandomized controlled preference trial (TUBA study), with patient recruitment between January 16, 2015, and November 7, 2019, and follow-up at 3 and 12 months after surgery was conducted in all Dutch university hospitals and a few large general hospitals. In the Netherlands, RRSO is predominantly performed in these hospitals. Patients at the clinical genetics or gynecology department between the ages of 25 and 40 years (BRCA1) or 25 to 45 years (BRCA2) who were premenopausal, had completed childbearing, and were undergoing no current treatment for cancer were eligible.

Interventions: Risk-reducing salpingo-oophorectomy at currently recommended age or RRS after completed childbearing with delayed oophorectomy. After RRSO was performed, hormone replacement therapy was recommended for women without contraindications.

Main outcomes and measures: Menopause-related quality of life as assessed by the Greene Climacteric Scale, with a higher scale sum (range, 0-63) representing more climacteric symptoms. Secondary outcomes were health-related quality of life, sexual functioning and distress, cancer worry, decisional regret, and surgical outcomes.

Results: A total of 577 women (mean [SD] age, 37.2 [3.5] years) were enrolled: 297 (51.5%) were pathogenic BRCA1 variant carriers and 280 (48.5%) were BRCA2 pathogenic variant carriers. At the time of analysis, 394 patients had undergone RRS and 154 had undergone RRSO. Without hormone replacement therapy, the adjusted mean increase from the baseline score on the Greene Climacteric Scale was 6.7 (95% CI, 5.0-8.4; P < .001) points higher during 1 year after RRSO than after RRS. After RRSO with hormone replacement therapy, the difference was 3.6 points (95% CI, 2.3-4.8; P < .001) compared with RRS.

Conclusions and relevance: Results of this nonrandomized controlled trial suggest that patients have better menopause-related quality of life after RRS than after RRSO, regardless of hormone replacement therapy. An international follow-up study is currently evaluating the oncologic safety of this therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT02321228.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Consolidated Standards of Reporting Trials Flow Diagram of Participants
Women who underwent risk-reducing salpingectomy (RRS) used estrogen-based hormone replacement therapy (HRT) for menstrual cycle regulation after surgery. RRO indicates risk-reducing oophorectomy; RRSO, risk-reducing salpingo-oophorectomy.
Figure 2.
Figure 2.. Findings on the Female Sexual Functioning Index (FSFI) and Female Sexual Distress Scale (FSDS)
The blue lines indicate the validated cutoff scores of 26.55 points or less for the FSFI to identify women with impaired sexual functioning without hormone replacement therapy (HRT) (A) and with HRT after risk-reducing salpingo-oophorectomy (RRSO) (B), and 15 points or more for the FSDS to identify women with sexual distress without HRT (C) and with HRT after RRSO (D). Boxes indicate the 25th percentile, median, and 75th percentile. Dots represent outliers. Whiskers show the minimum and maximum ranges.Some bars do not have any whiskers as the used questionnaires had a minimum and maximum result. RRO indicates risk-reducing oophorectomy; RRS, risk-reducing salpingectomy.
Figure 3.
Figure 3.. The 10 Most Frequently Scored Items on the Greene Climacteric Scale 1 Year After Surgery
HRT indicates hormone replacement therapy; RRS, risk-reducing salpingectomy; and RRSO, risk-reducing salpingo-oophorectomy.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. ; BRCA1 and BRCA2 Cohort Consortium . Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402-2416. doi:10.1001/jama.2017.7112 - DOI - PubMed
    1. Oei AL, Massuger LF, Bulten J, Ligtenberg MJ, Hoogerbrugge N, de Hullu JA. Surveillance of women at high risk for hereditary ovarian cancer is inefficient. Br J Cancer. 2006;94(6):814-819. doi:10.1038/sj.bjc.6603015 - DOI - PMC - PubMed
    1. Integraal Kankercentrum Nederland. Richtlijn Erfelijk en Familiair Ovariumcarcinoom [Guideline Hereditary and Familial Ovarian Carcinoma]. Published June 1, 2015. Accessed October 6, 2017. https://www.nvog.nl/wp-content/uploads/2018/02/Erfelijk-en-familiair-ova...
    1. Domchek SM, Friebel TM, Singer CF, et al. . Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304(9):967-975. doi:10.1001/jama.2010.1237 - DOI - PMC - PubMed
    1. Vermeulen RFM, Beurden MV, Korse CM, Kenter GG. Impact of risk-reducing salpingo-oophorectomy in premenopausal women. Climacteric. 2017;20(3):212-221. doi:10.1080/13697137.2017.1285879 - DOI - PubMed

Publication types

Associated data