Menstrual cycle activity is the most important risk factor for sporadic serous ovarian carcinoma while a germline mutation in BRCA1 is the most important risk factor for the familial form. Given the rarity of BRCA1 mutations in sporadic ovarian cancers, we hypothesized that BRCA1 influences the menstrual cycle in a way that mimics the factors underlying sporadic ovarian cancer predisposition, making BRCA1 mutations redundant in such cancers. We compared the length of each phase of the estrus cycle (equivalent to the human menstrual cycle) and of circulating levels of estradiol in control mice and in mice carrying a Brca1 mutation in their ovarian granulosa cells, two thirds of which develop ovarian or uterine epithelial tumors. We also compared the length of the different phases of the cycle in mutants that subsequently developed tumors to those in mutants remained tumor free. Mutant mice as well as or oophorectomized wild type mice harboring mutant ovarian grafts showed a relative increase in the average length of the proestrus phase of the estrus cycle, which corresponds to the estrogen-dominated follicular phase of the human menstrual cycle. Total circulating levels of estradiol were also increased in mutant mice injected with pregnant mare serum gonadotropins. The relative increase in proestrus length was highest in mutant mice that subsequently developed reproductive epithelial tumors. We conclude that loss of a functional Brca1 increases murine ovarian epithelial tumor predisposition by increasing estrogen stimulation in the absence of progesterone, recapitulating conditions associated with sporadic ovarian cancer predisposition in humans.

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ObjectiveWomen make up a majority of the gynecologic oncology workforce. Increasing the numbers of women in leadership has been proposed as a path towards professional gender equity. This study examined whether leadership gender and departmental infrastructure impact the work environment for women gynecologic oncologists.MethodsMembers of a 472-member private Facebook group “Women of Gynecologic Oncology” (WGO) who self-identified as women gynecologic oncologists provided demographics, practice infrastructure, personal experience with workplace bullying, gender discrimination, microaggressions using a REDcap survey platform.ResultsOf 250 (53%) respondents to this survey, most were younger than age 50 years (93.6%); White (82.2%) and non-Hispanic (94.3%); married (84.7%); and parenting (75.2%). Practice environments included academic (n=152, 61.0%), hospital employed (n=57, 22.9%), and private practice (n=31, 12.4%), and 89.9% supervised trainees. A significant percent of respondents had experienced bullying (52.8%), gender discrimination (57%) and microaggressions (83%). Age, race, ethnicity, practice setting, or mentorship were not statistically significantly associated with these experiences. Reported perpetrators were varied and included colleagues (84%), patients (44%), staff (41%), administrators (18%), and trainees (16%). Prevalence of bullying (55.0 vs 47.7%, p=0.33), gender discrimination (59.1 vs 52.3%, p=0.33) and microaggressions (83.3 vs 83.0%, p=1.00) were similar irrespective of departmental leadership gender.ConclusionsWomen gynecologic oncologists report a high prevalence of workplace bullying, gender discrimination and microaggressions regardless of the gender of their immediate leadership. Proactive and deliberate structural interventions to improve the work environment for surgeons who are women are urgently needed.

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