Menopausal Impact of Opportunistic Salpingectomy for Ovarian Cancer Prevention

Обзор

The goal of this clinical trial is to find out whether removing the fallopian tubes at the time of hysterectomy leads to an earlier menopause. The study includes women under 55 years of age who previously underwent hysterectomy as participants in the HOPPSA trial, where they were randomly assigned to either removal of the fallopian tubes or no removal. The main question is: • Does removing the fallopian tubes at the time of hysterectomy lead to an earlier menopause? Researchers will compare women who had their fallopian tubes removed during hysterectomy with women who had hysterectomy alone to see whether menopause occurs earlier after tube removal. Age at menopause will be estimated by measuring follicle-stimulating hormone (FSH) in small blood samples collected on a paper card. Participants will: * Collect 4-5 drops of blood using a finger prick * Place the drops on a paper card and mail it to the researchers * Complete an online questionnaire These steps will be done twice, one year apart.

Подробное описание

Opportunistic salpingectomy, defined as removal of the fallopian tubes during gynaecologic surgery performed for another indication, has been proposed as a strategy to reduce the risk of ovarian cancer. This approach is supported by accumulating evidence that many high-grade serous ovarian cancers originate in the distal fallopian tube. Although short-term surgical safety has been evaluated in randomized and observational studies, uncertainty remains regarding possible long-term effects on ovarian function.

The HOPPSA randomized trial was initiated to evaluate outcomes after hysterectomy with or without salpingectomy in women undergoing surgery for benign conditions. Previous analyses from this cohort have focused on perioperative safety and patient-reported outcomes. However, the effect of salpingectomy on the timing of menopause has not yet been determined. This question is clinically important because epidemiologic evidence shows that earlier menopause is associated with increased risks of cardiovascular mortality and all-cause mortality, with approximately a 2% relative increase in risk per year earlier menopause. Earlier menopause has also been associated with increased risks of osteoporosis, neurocognitive symptoms, sexual dysfunction, and reduced quality of life. Even modest shifts in menopausal timing could therefore have clinically meaningful long-term health implications.

The relevance of this knowledge gap is underscored by the relatively low lifetime risk of epithelial ovarian cancer in the general population, estimated at approximately 1.3-2%. Modelling studies suggest that between 96 and 148 opportunistic salpingectomy procedures may be required to prevent one ovarian cancer case. Consequently, even small changes in menopausal timing, if present, could influence the overall balance of benefits and risks associated with preventive salpingectomy.

Assessment of menopausal timing after hysterectomy presents methodological challenges because menstrual history cannot be used. Biochemical markers are therefore required. Follicle-stimulating hormone (FSH) is a well-established indicator of ovarian aging and menopausal transition, reflecting declining ovarian follicular activity. Measurement of FSH in blood samples enables estimation of menopausal timing independent of menstrual data.

Capillary blood sampling using self-collected dried blood spots enables biologic measurements in large populations without requiring clinic visits. This approach has been validated for hormone analyses and facilitates long-term follow-up with reduced logistical constraints, thereby supporting high participation and minimizing attrition in longitudinal studies, an important consideration for unbiased estimation of long-term outcomes.

The MISSION-O study uses extended follow-up of participants previously enrolled in the HOPPSA randomized trial to determine whether salpingectomy influences age at menopause. By leveraging a randomized surgical cohort with long-term biologic assessment, this study aims to generate robust evidence regarding the endocrine safety of opportunistic salpingectomy. The findings are expected to inform clinical counselling, individualized risk-benefit assessment, and future clinical guidelines regarding preventive salpingectomy at the time of gynaecologic surgery.

Вмешательства

• Процедура Opportunistic salpingectomy
  Removal of the fallopian tubes at the time of hysterectomy

Первичные конечные точки

• Age at menopause [Срок оценки: 1 year]

Вторичные конечные точки (2)

• Cardiovascular disease - CVD [Срок оценки: 10-30 years after enrolment.]
• Mortality [Срок оценки: 10-30 years after enrolment.]

Критерии участия

Критерии включения

• Having had hysterectomy for a benign indication
• Less than 55 years at surgery
• Was included in the ITT population of the HOPPSA register-based randomised controlled trial (R-RCT) of opportunistic salpingectomy
• Informed consent

Критерии исключения

• Ongoing systemic hormonal treatment using sex steroids
• Bilateral oophorectomy
• Cancer treatment affecting ovarian function
• Other treatments with major effects on ovarian function

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Швеция · 1 центр

• Umeå University — Umeå

Публикации

• Muka T, Oliver-Williams C, Kunutsor S, Laven JS, Fauser BC, Chowdhury R, Kavousi M, Franco OH. Association of Age at Onset of Menopause and Time Since Onset of Menopause With Cardiovascular Outcomes, Intermediate Vascular Traits, and All-Cause Mortality: A Systematic Review and Meta-analysis. JAMA Cardiol. 2016 Oct 1;1(7):767-776. doi: 10.1001/jamacardio.2016.2415. PMID 27627190
• Zhu D, Chung HF, Dobson AJ, Pandeya N, Giles GG, Bruinsma F, Brunner EJ, Kuh D, Hardy R, Avis NE, Gold EB, Derby CA, Matthews KA, Cade JE, Greenwood DC, Demakakos P, Brown DE, Sievert LL, Anderson D, Hayashi K, Lee JS, Mizunuma H, Tillin T, Simonsen MK, Adami HO, Weiderpass E, Mishra GD. Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient d PMID 31588031
• van der Schouw YT, van der Graaf Y, Steyerberg EW, Eijkemans JC, Banga JD. Age at menopause as a risk factor for cardiovascular mortality. Lancet. 1996 Mar 16;347(9003):714-8. doi: 10.1016/s0140-6736(96)90075-6. PMID 8602000
• Piek JM, Schauwaert J, Ellis LB, Zapardiel I, Planchamp F, Koblos K, Kacperczyk-Bartnik J, Bowden SJ, El Hajj H, Grigore M, Steenbeek MP, Bizzarri N, Kyrgiou M, Gultekin M. Opportunistic Salpingectomy for Prevention of Tubo-Ovarian Carcinoma: The European Society of Gynaecological Oncology Consensus Statements. JAMA. 2026 Mar 10;335(10):894-902. doi: 10.1001/jama.2025.24510. PMID 41627806
• Idahl A, Darelius A, Sundfeldt K, Palsson M, Strandell A. Hysterectomy and opportunistic salpingectomy (HOPPSA): study protocol for a register-based randomized controlled trial. Trials. 2019 Jan 5;20(1):10. doi: 10.1186/s13063-018-3083-8. PMID 30611296
• Idahl A, Liv P, Darelius A, Collins E, Sundfeldt K, Palsson M, Strandell A. HOPPSA update: changes in the study protocol of Hysterectomy and OPPortunistic SAlpingectomy, a registry-based randomized controlled trial. Trials. 2023 Mar 24;24(1):222. doi: 10.1186/s13063-023-07244-w. PMID 36959664
• Magarakis L, Idahl A, Sundfeldt K, Liv P, Palsson M, Strandell A. SALpingectomy for STERilisation (SALSTER): study protocol for a Swedish multicentre register-based randomised controlled trial. BMJ Open. 2023 Sep 4;13(9):e071246. doi: 10.1136/bmjopen-2022-071246. PMID 37666548
• Collins E, Strandell A, Granasen G, Idahl A. Menopausal symptoms and surgical complications after opportunistic bilateral salpingectomy, a register-based cohort study. Am J Obstet Gynecol. 2019 Jan;220(1):85.e1-85.e10. doi: 10.1016/j.ajog.2018.10.016. Epub 2018 Oct 12. PMID 30321526

Идентификаторы

NCT: NCT07423143 · MISSION-O-26 · 2024-06333 · RV-1004811 · Dnr. 2025-08086-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗