A 55-year-old postmenopausal woman comes to the office due to abdominal distension and decreased appetite. She also has lost 4.5 kg (9.9 lb) unintentionally over the past few months. The patient has no chronic medical conditions and takes no medications. She had 1 vaginal delivery in her 20s and has had no abdominal surgery. The patient had multiple abnormal Pap tests in the past and had a cervical conization at age 38; she did not receive the human papillomavirus vaccine. The patient does not use tobacco, alcohol, or illicit drugs. BMI is 24 kg/m2. Imaging studies reveal a right-sided ovarian mass and a large accumulation of free peritoneal fluid. A serum CA-125 level is elevated. Which of the following would most likely have reduced the risk of this patient's current condition?
Epithelial ovarian cancer | |
Risk factors |
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Protective factors |
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This postmenopausal patient's ovarian mass, abdominal distension, and elevated cancer antigen 125 (CA-125) level are consistent with epithelial ovarian cancer (EOC). Patients often have advanced disease at the initial presentation because symptoms (eg, decreased appetite, weight loss) can be subtle. The most likely pathogenesis of EOC is repeated injury and repair to the ovarian surface, which makes surface epithelial cells susceptible to malignant transformation (ie, acquiring oncogenic mutations).
The most common cause of injury is ovulation, which requires rupture of an ovarian follicle to release an oocyte. Therefore, patients with an increased lifetime number of ovulatory cycles (eg, increasing age, nulliparity, early menarche) are at increased risk for EOC (Choice D). In contrast, protective factors typically suppress ovulation. Combined oral contraceptive pills contain estrogen and progestin, which provide negative feedback to the hypothalamic-pituitary-ovarian axis. The estrogen component likely decreases FSH secretion (that normally stimulates follicular growth), and the progestin component may suppress the LH surge (that normally triggers ovulation).
Although combined oral contraceptive pills may not prevent ovulation during every menstrual cycle, the overall decrease in lifetime number of ovulatory cycles provides protection against EOC. Other risk-reducing factors include multiparity and breastfeeding.
(Choices A and B) Consistent condom use and human papillomavirus (HPV) vaccination can reduce transmission of high-risk HPV, which in turn can reduce the risk of oropharyngeal, cervical, vaginal, vulvar, and anogenital epithelial cancers. Neither protects against ovarian cancer because ovarian cancer is not linked to HPV infection.
(Choice C) Antioxidants neutralize reactive oxygen species and free radicals, thereby decreasing their damage to cells. However, long-term antioxidant supplementation (eg, vitamin C) does not appear to decrease the risk of any cancer type, including ovarian cancer.
Educational objective:
The risk of epithelial ovarian cancer increases with the lifetime number of ovulatory cycles. Combined oral contraceptive pills, multiparity, and breastfeeding are protective factors because they suppress ovulation and decrease the lifetime number of ovulatory cycles.