Longer lifetime ovulation increases risk for epithelial ovarian cancer
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Longer duration of ovulation across the life span was associated with a greater risk for epithelial ovarian cancer, according to data published in the Journal of the National Cancer Institute.
“For this study, my colleagues and I aimed to understand the link among factors associated with reduced risk of ovarian cancers — oral contraceptive use, pregnancies and breastfeeding,” Francesmary Modugno, PhD, a professor of obstetrics, gynecology and reproductive sciences at Magee-Womens Research Institute and the University of Pittsburgh Medical Center Hillman Cancer Center, told Healio. “There are several hypotheses in the literature to explain these associations. The most frequently cited is the ‘incessant ovulation’ hypothesis, which links the different factors through reducing ovulation and posits that these factors protect against ovarian cancer by reducing the trauma to the ovary associated with ovulation (when a woman ovulates, the egg breaks through the surface of the ovary creating a type of wound). With this study, we wanted to delve deeper and try to determine whether the mechanism of action of these factors is through ovulation suppression alone or whether there were other effects these factors were having that impact ovarian cancer risk.”
Modugno and colleagues analyzed data from 25 case-control studies from the Ovarian Cancer Association Consortium to evaluate the association between lifetime ovulatory years — which was calculated by subtracting the number of years of anovulation from the number of years between menarche and last menstrual period — and epithelial ovarian cancer diagnosis. The researchers used 12 separate algorithms to calculate lifetime ovulatory years with this formula.
In total, there were 26,204 controls and 21,267 cases included for analyses. The median lifetime ovulatory years ranged from 31.67 to 35.75 years among the 12 algorithms implemented.
Link between diagnosis, lifetime ovulation
Across the algorithms, the risk for endothelial ovarian cancer was greater with each additional lifetime ovulatory year, ranging from an OR of 1.014 (95% CI, 1.009-1.02) to 1.044 (95% CI, 1.041-1.048).
Further analyses of the effect of lifetime ovulatory years revealed that older age at last menstrual cycle was associated with a greater risk for epithelial ovarian cancer (OR = 1.011; 95% CI, 1.004-1.019), and a lower risk for epithelial ovarian cancer with longer oral contraceptive use (OR = 0.95; 95% CI, 0.945-0.956), more incomplete pregnancies (OR = 0.968; 95% CI, 0.944-0.992), more full-term births (OR = 0.877; 95% CI, 0.857-0.897) and more years of breastfeeding (OR = 0.858; 95% CI, 0.816-0.901). The association between age at menarche and epithelial ovarian cancer was not significant.
Subtype associations
In analyses of epithelial ovarian cancer subtypes, the researchers found that more lifetime ovulatory years were associated with greater risks for high-grade serous (OR = 1.054; 95% CI, 1.048-1.061), low-grade serous (OR = 1.04; 95% CI, 1.019-1.061), endometrioid (OR = 1.065; 95% CI, 1.053-1.076) and clear cell (OR = 1.098; 95% CI, 1.079-1.117) disease. There were no significant associations with mucinous disease.
“We were surprised to see that for the most common and deadly type of ovarian cancer — high-grade serous ovarian cancer (HGSOC) — the mechanism of action for these factors appears to be through ovulation suppression alone,” Modugno said. “This is surprising because most HGSOCs likely arise in the fallopian tube and not the ovary. Thus, it must be something about ovulation beyond ovarian trauma that impacts risk of HGSOC.”
Future studies should focus on evaluating the mechanisms behind these associations, Modugno said.