WHAM (What Happens After Menopause?) was a multicentre prospective study investigating the impact of risk reducing bilateral salpingo-oophorectomy on non-cancer outcomes in young high-risk women.

The ANZGOG supported study assessed the relationship between surgical menopause and mood, cardio-metabolic disease risk, sleep quality, sexual function, and menopause-related quality of life in the 12-month period after cancer risk-reducing oophorectomy.

Professor Martha Hickey BA (Hons); MSc (Clin Psych); MBChB, FRCOG, FRANZCOG, MDl.

Martha Hickey is Professor of Obstetrics and Gynaecology at the University of Melbourne, Director of the Gynaecology Research Centre, The Women’s Hospital, and an NHMRC Leadership (L2) Fellow. She designed, led and completed the WHAM study, which has generated new information to guide the clinical care of BRCA1/2 pathogenic variant carriers after RRSO.

Prof Martha Hickey, Principal Investigator of WHAM is excited to share the outcomes and impact of the study with ANZGOG.

What was the study’s purpose?

To determine the non-cancer consequences of premenopausal risk-reducing salpingo-oophorectomy (RRSO).

What were the study’s findings?

That RRSO in premenopausal women induced menopausal symptoms in around 80%, which affected quality of life but were considered mild in most cases. Sexual function was adversely affected by RRSO.

RRSO also disturbed sleep and adversely affected mood, with a doubling in depressive symptoms that persisted at 12 months. Women with previous depression or depressive symptoms at baseline were at particular risk. We also observed a reduction in bone density after RRSO and an apparent change in body fat distribution, with increased waist circumference. Overall, 60% chose to take menopausal hormone therapy after RRSO. Hormone therapy mitigated but did not resolve the new onset symptoms following RRSO. Specifically, new onset vasomotor symptoms, sexual dysfunction, mood and sleep disturbance persisted. Hormone therapy did not prevent loss of bone strength following RRSO.

Overall, our data shows that women considering RRSO should be aware that they may experience new adverse symptoms, which may not be fully resolved by menopausal hormone therapy.

Clinicians should be aware that women with a prior history of depression or symptoms at baseline may be at risk of recurrence. Ongoing follow-up of this cohort will indicate whether these symptoms persist beyond 12 months.

How will this benefit women?

By providing new evidence to inform decision making about RRSO and the potential benefits of menopausal hormone therapy.

What impact has the study had on the research space?

This is the largest prospective controlled study of RRSO. Our findings illustrate that women may experience significant negative consequences from premenopausal RRSO, which are reduced but not resolved by menopausal hormone therapy. These findings will directly translate into evidence-based clinical care for high-risk women.

What are the next steps?

We are compiling the 24-month data for analysis. This will inform the trajectory of these symptoms over 2 years. I am leading the development of international consensus guidelines on clinical care after RRSO – based on WHAM and existing published data.

We have the opportunity to participate in a new international study comparing salpingectomy with delayed oophorectomy with RRSO. This will provide critical new data about the safety and efficacy of salpingectomy for ovarian cancer prevention in BRCA1/2 pathogenic variant carriers.

If you would like to know about ANZGOG’s Fund For New Research grants, click here.