Long-term morbidity and health after early menopause due to oophorectomy in women at increased risk of ovarian cancer: Protocol for a nationwide cross-sectional study with prospective follow-up (HARMOny Study)

L Terra, Maartje Hooning, Annette Heemskerk - Gerritsen, M van Beurden, Jeanine Roeters van Lennep, Lena van Doorn, JA de Hullu, C Mom, EB Van Dorst, MJE Mourits, BFM Slangen, KN Gaarenstroom, M.C. Zillikens, T Leiner, L van der Kolk, Margriet Collee, M Wevers, MG Ausems, K Engelen, LPV BergerCJ van Asperen, EB Gomez-Garcia, I van de Beek, MA Rookus, M Hauptmann, EMA Bleiker, SB Schagen, NK Aaronson, AHEM Maas, FE van Leeuwen

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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 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.

Original languageEnglish
Article numbere24414
JournalJMIR Research Protocols
Issue number1
Publication statusPublished - Jan 2021

Bibliographical note

Funding Information:
The Dutch Cancer Society (Koningin Wilhelmina Fonds [KWF]) has granted us the funding for this project (registered under grant 10164). The funding body had no role in the design of the study; collection, analysis, and interpretation of data; or writing of the manuscript. We would like to thank Y Rietdijk for designing the study logo and Figure 1.

Funding Information:
This study was funded by the Dutch Cancer Society in 2016. The Institutional Review Board of the Netherlands Cancer Institute approved this nationwide multicenter study in July 2018, and local approval from the participating sites followed in the months thereafter.

Publisher Copyright:
© Lara Terra, Maartje J Hooning, Bernadette A M Heemskerk-Gerritsen, Marc van Beurden, Jeanine E Roeters van Lennep, Helena C van Doorn, Joanne A de Hullu, Constantijne Mom, Eleonora B L van Dorst, Marian J E Mourits, Brigitte F M Slangen, Katja N Gaarenstroom, M Carola Zillikens, Tim Leiner, Lizet van der Kolk, Margriet Collee, Marijke Wevers, Margreet G E M Ausems, Klaartje van Engelen, Lieke PV Berger, Christi J van Asperen, Encarna B Gomez-Garcia, Irma van de Beek, Matti A Rookus, Michael Hauptmann, Eveline M Bleiker, Sanne B Schagen, Neil K Aaronson, Angela H E M Maas, Flora E van Leeuwen.

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