Ovarian cancer: modest overall increase with higher BMI; risk varies by histologic subtype (notably endometrioid
Ovarian cancer: modest overall increase with higher BMI; risk varies by histologic subtype (notably endometriosis)
Mechanisms include unopposed estrogen from adipose aromatization, hyperinsulinemia/IGF-1 signaling, chronic low-grade inflammation, adipokine imbalance (↑leptin/↓adiponectin), and overlap with anovulation/PCOS.
1) Endometrial cancer (uterine corpus)
Magnitude of risk
- Dose–response: Each 5 kg/m² increase in BMI is associated with a ~1.5–1.6× higher risk of endometrial cancer.
- High BMI classes: Class II–III obesity confers multi-fold higher risk compared with normal BMI, with earlier age at diagnosis and higher all-cause mortality observed in cohorts.
Mechanisms that matter clinically
- Estrogen excess without progesterone: Adipose aromatizes androgens → estrone; after menopause, this becomes the dominant estrogen source, promoting endometrial proliferation.
- Insulin/IGF axis & inflammation: Hyperinsulinemia reduces SHBG (↑free estrogen) and stimulates mitogenic pathways; cytokines (e.g., IL-6, TNF-α) and leptin further encourage tumorigenesis.
- PCOS/anovulation: Less luteal progesterone exposure amplifies the “unopposed estrogen” effect.
Precursors & progression
Endometrial intraepithelial neoplasia (EIN/atypical hyperplasia) is a recognized precursor; obesity raises the likelihood of both EIN and progression to carcinoma. Fertility-sparing progestin therapy is possible for selected EIN/grade 1 cancers but demands vigilant surveillance.
Risk modification
Weight loss & metabolic surgery:
- Intentional weight loss and bariatric surgery are associated with substantially lower subsequent endometrial cancer incidence and, in small series, histologic regression in selected early cases when combined with progestin therapy.
- Benefits likely mediated by reductions in estrogenic drive, insulin resistance, and inflammation.
Additional levers:
- Hormonal balance: Progestin-containing therapies (e.g., LNG-IUS) protect the endometrium in anovulatory or perimenopausal states.
- Lifestyle: Physical activity and avoidance of excess weight gain across adulthood reduce risk.
Clinical pearls
- There is no screening test for average-risk endometrial cancer; evaluate any postmenopausal bleeding or persistent abnormal bleeding at any age (especially with obesity, PCOS, or diabetes).
- Consider transvaginal ultrasound and, where indicated, endometrial sampling.
2) Ovarian cancer
Magnitude of risk
- Overall: Higher BMI is associated with a modest increase in ovarian cancer risk on average.
- By histology: Risks appear higher for endometrioid and some borderline tumors; the association is weaker or inconsistent for high-grade serous disease.
- Life course: Trajectories of adiposity from early–mid adulthood may shape risk; metabolic health likely modifies the effect.
Mechanisms (brief)
Shared pathways with endometrium (insulin/IGF, inflammation, adipokines) plus endocrine crosstalk with endometriosis for endometrioid subtypes. Obesity also increases perioperative risk and may slightly worsen survival after diagnosis.
Practical risk reduction
Helpful
Context-dependent
| Strategy | Notes |
|---|---|
| Healthy weight & activity Helpful | Improves metabolic & inflammatory milieu; likely lowers risk for select subtypes and improves surgical fitness. |
| Combined oral contraceptives Helpful | Reduces ovarian (and endometrial) cancer risk; balance against individual thromboembolic/cardiometabolic risk. |
| Risk-reducing salpingo-oophorectomy Context-dependent | For high-risk gene carriers (e.g., BRCA1/2),obesity management remains important for overall outcomes. |
3) How to counsel in clinic
- Use people-first language and shared decision-making; address weight stigma.
- Quantify risk simply: “Every 5 BMI points adds about half again as much risk for endometrial cancer.” Pair with visual aids and absolute numbers when possible.
- Offer concrete options: nutrition pattern (Mediterranean-style), progressive activity, treatment of anovulation/PCOS, and—when indicated,anti-obesity pharmacotherapy or metabolic surgery.
- Reinforce red-flags: intermenstrual or postmenopausal bleeding, persistent pelvic pain/bloating, early satiety, new urinary urgency,prompt evaluation is warranted.
Key takeaways
- Obesity is the dominant modifiable risk factor for endometrial cancer, with a strong dose-response.
- For ovarian cancer, the association is smaller overall but clearer for endometriosis and some borderline histologist.
- Weight reduction,especially after substantial, sustained loss (including post-bariatric surgery)appears to lower incidence and may even facilitate regression in carefully selected early endometrial disease under specialist care.
- No routine population screening exists; symptom-triggered evaluation is crucial.
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