The results of the HARMOny study published in JACC: CardioOncology by Beekman et al did not reveal a long-term adverse effect of prophylactic surgical menopause on the development of coronary artery calcium—a marker of cardiovascular disease risk—in women with a high familial risk of ovarian cancer.
“These results provide important and reassuring information for patients and health professionals involved in elective bilateral oophorectomy,” the investigators commented. “[They] may also have broader relevance for women who experience iatrogenic menopause after cancer treatment.”
Study Details
This cross-sectional study was conducted to investigate the long-term effects of risk-reducing salpingo-oophorectomy on cardiovascular disease, bone health, cognition, and quality of life. Participants were recruited from the nationwide HEBON cohort, which included women with a high familial risk of breast and/or ovarian cancer from all eight Dutch University Medical Centers and the Netherlands Cancer Institute.
An extensive online questionnaire collected information on traditional and female-specific cardiovascular disease risk factors, medical history, and medication use. During the study visit, the participants underwent CT screening for coronary artery classification (CAC) score measurement, blood sampling, and anthropometric assessments (ie, height, weight, heart rate, blood pressure, waist and hip circumference).
Within the group aged 60 to 70 years at the time of the study visit (n = 328; median age = 64.5 years), using multivariable Poisson analyses, the investigators compared the CAC scores between those who underwent a premenopausal (age ≤ 45 years; n = 207) vs postmenopausal (age ≥ 54 years; n = 121) risk-reducing salpingo-oophorectomy. The effect of age at surgery (early [age < 41 years; n = 159] vs late [age 41–45 years; n = 339]) was examined within the entire population with surgical menopause (n = 498). Additionally, an eligible subset of these women (n = 270) was compared with an external Dutch population–based reference cohort from the ROBINSCA study (n = 5,226).
Key Findings
Among the group aged 60 to 70 years at the time of the study visit, the median time since risk-reducing salpingo-oophorectomy was 21.0 years for those who underwent the procedure before menopause and 10.7 years for their postmenopausal counterparts. A median of 20.9 and 16.6 years elapsed since early and late surgical menopause, respectively, in the entire premenopausal risk-reducing salpingo-oophorectomy group.
Based on multivariable analyses, the prevalence rates of any (score > 0; relative risk [RR] = 0.93), at least moderate (score > 100; RR = 0.71), and severe (score > 400; RR = 0.81) coronary artery calcium were comparable between the premenopausal and postmenopausal surgical groups. No difference in CAC scores was observed between the entire surgical menopause and ROBINSCA reference groups. The investigators reported that the timing of premenopausal risk-reducing salpingo-oophorectomy (early vs late) did not affect the outcomes.
The investigators concluded: “Twenty-one years after surgical menopause, we did not observe increased CAC scores in women who underwent a premenopausal risk-reducing salpingo-oophorectomy, neither when compared with women who underwent postmenopausal risk-reducing salpingo-oophorectomy nor with an external reference population. Furthermore, an early premenopausal risk-reducing salpingo-oophorectomy, compared with a late premenopausal risk-reducing salpingo-oophorectomy, was not associated with increased CAC scores.”
Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute, Amsterdam, is the corresponding author of the JACC: CardioOncology article.
Disclosure: The study was funded by grants from the Dutch Cancer Society (KWF) and the Maarten van der Weijden foundation. For full disclosures of the study authors, visit jacc.org.
