# Changing Contraceptive Patterns and Ovarian Cancer Risk

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $528,213

## Abstract

ABSTRACT
Contraceptive patterns are changing and the implications for ovarian cancer risk are unknown. Oral
contraceptives (OCs), which are an established protective factor for ovarian cancer, are being used less
frequently and intrauterine device use (IUD) is on the rise. However, the impact of changing contraceptive
patterns on ovarian cancer incidence is unclear. While most studies of IUDs and ovarian cancer risk suggest
an inverse association, some studies report no association or even a slight increase in risk. Differences
between these studies could be attributable to IUD type, timing, or molecular features of tumors including
histotypes. Preliminary data from the New England Case Control (NEC) Study suggest the association
between IUDs and ovarian cancer risk vary by histotype, with a non-significant decrease in risk of low-grade
serous and clear cell tumors but not for other histotypes. Furthermore, we observed an increased risk of
ovarian cancer with low tumor stromal CD163 expression, reflecting heme scavenger receptor expression
decreased M2-type macrophage infiltration. These observations suggest the impact of IUD use on ovarian
cancer risk may differ by subtype and subgroup, but larger samples sizes are needed. Inflammation is known
to play a role in ovarian cancer pathogenesis, and IUDs exert their physiologic effect through local
inflammation. However, IUD-associated inflammation may be accompanied by an immune response that
could lead to clearance of premalignant cells or local infection. An appreciation of how ovarian cancer risk
varies by expression of immune markers within tumors may inform the biologic mechanisms possibly involved
(e.g. CD3, CD8, CD4, CD69, FOXP3, CD163). Here we propose to evaluate the association between IUD use
and ovarian cancer risk in 17 case control studies and 7 cohort studies with a total of more than 20,000 cases
that collected, with varying degrees of detail, data on IUD type and timing of use (e.g. age at use and
before/after first birth), as well as detailed histologic data critical for distinguishing ovarian cancer subtypes.
Importantly, our proposed research includes a case-control study of African American women enrolled
between 2010-2015, reflecting recent contraceptive trends and increasing diversity. The inclusion of cohort
studies with updated contraceptive use data and a case-control study which recently completed enrollment will
provide information on the contemporary contraceptive use. Furthermore, we will utilize unique resources and
innovative platforms to examine the potential mechanisms through which contraceptive choice influences
ovarian cancer risk. In more than 3,000 cases with detailed contraceptive data, we will simultaneously measure
a panel of immune markers by multiplex immunofluorescence which shows co-localization of marker
expression. Both the high prevalence and modifiable nature of contraceptive use make this an important
public health question with a significant impact...

## Key facts

- **NIH application ID:** 10184558
- **Project number:** 1R01CA258679-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Kathryn L. Terry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $528,213
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10184558

## Citation

> US National Institutes of Health, RePORTER application 10184558, Changing Contraceptive Patterns and Ovarian Cancer Risk (1R01CA258679-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10184558. Licensed CC0.

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