BRCA mutations and ovarian Ageing in normo-oVulAtory women

Rationale:
In the current study, by comparing serum anti-müllerian hormone (AMH) levels between cohorts of normo-ovulatory BRCA (BReast CAncer) mutation-positive women and normo-ovulatory controls, we will be able to study the effect of BRCA mutations on ovarian ageing. The primary hypothesis is that normo-ovulatory women with a BRCA mutation have lower levels of AMH compared to normo-ovulatory BRCA mutation-negative women, with at least a difference of 0.40 ng/ml, suggesting an effect size of three years in menopausal age.



Objective:

To confirm whether a BRCA mutation is a determinant of advanced ovarian ageing.



Study design:

A cross sectional multi-centre study will be performed, recruiting normo-ovulatory BRCA mutation-positive women as the case group and normo-ovulatory BRCA mutation-negative women as controls.



Study population:

The study population will be recruited by using to different approaches, a prospective and retrospective recruitment. For the prospective approach, women with an age ranging between 18 and 45 years, who present at the department of Medical Genetics for predictive BRCA mutation screening, will be asked to participate. For the retrospective, women with a current age ranging between 18 and 45 years, and with a known BRCA mutation carrier status, who have had a predictive DNA-test at the department of Medical Genetics up to 5 years earlier, are asked to participate.



Participating hospitals:

University Medical Centre (UMC) Utrecht, UMC Groningen and The Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital, Amsterdam.



Intervention: Not applicable.



Main study endpoint:

The main study endpoint will be advanced ovarian ageing, which is primary measured by age specific AMH levels.



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Burden associated with participation in the study consists of taken a blood sample, and filling out a questionnaire. Participating may be of benefit to the included women as they will receive a VVV-voucher to the value of 15 euros after providing blood and sending a completed questionnaire. Thereby, retrospective recruited participants will receive a travel allowance as stated by the UMC Utrecht.

The primary hypothesis is that normo-ovulatory women with a BRCA mutation have lower levels of AMH compared to normo-ovulatory BRCA mutation-negative women, with at least a difference of 0.40 ng/ml, suggesting an effect size of three years in menopausal age.

The aim is to screen and investigate a total of 120 BRCA mutation-positive and 120 BRCA mutation-negative women in a period of approximately 2.5 years. A half year is calculated for data analysis and publishing results, resulting in a total study duration of three years.

26-jul-2014: The intervention has been a blood sample from the start of the trial. Due to misinterpretation, this was first interpreted as a therapeutical item.