Why do Oral Contraceptives Prevent of Ovarian Cancer?
Ovarian Cancer Risk - Risk-reducing Surgery - Fallopian Tube Fimbriae - Ovarian Cortical Inclusion Cysts
Conditions: official terms
Ovarian Neoplasms
Conditions: Keywords
BRCA1, BRCA2, Risk-reducing surgery, Oral Contraceptives
Study Type
Study Phase
Phase 0
Study Design
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
Name: OrthoNovum 1/35
Type: Drug
Overall Status
Not yet recruiting
Use of oral contraceptives (OCs) reduces a woman's risk of ovarian cancer very significantly and the protective effect continues for at least 25 years after use of OCs is stopped; the mechanisms of how this occurs are not understood. We are proposing here to directly study the effect of OCs on the fallopian tube and inclusion cysts within the ovary - sites from which most ovarian cancers are thought to arise - in order to better understand the mechanistic basis for OC protection against ovarian cancer. We think the protection results from reduced cell proliferation. It will lay the foundation for further studies to ensure that the protection against ovarian cancer afforded by 'traditional' OCs is not lost with alterations in OC formulation, and, if possible, to guide development of OC formations to improve further on the protection afforded by OCs.
Detailed Description
Five-year survival for invasive epithelial ovarian cancer (ovarian cancer) is less than 50% because most women are diagnosed at an advanced stage. However, there is an effective chemoprevention strategy. Meta-analysis of epidemiological studies shows an approximately 40% reduction in risk of ovarian cancer with 5 years of oral contraceptive (OC) use. The protective effect increases significantly with duration of OC use and continues for at least 25 years after use of OCs is stopped. The mechanism(s) underlying this protective effect are not understood. One hypothesis is that protection is achieved by blocking ovulation, but growing evidence suggests that it may be related to promoting a favorable progestagenic environment. OC use would protect if the hormonal exposure while on OCs was less stimulatory to the possibly different types of cells of origin of ovarian cancer than the hormonal exposure in normal ovulatory cycles. Exposure to progestins is higher while on OCs than in normal cycling and this could explain the protective effect. We propose that a major source of the protection from OC use is due to their significantly reducing cell proliferation in the fallopian tube fimbriae (FTF) and in ovarian cortical inclusion cysts (CICs), two likely cells of origin for ovarian cancer. Proliferating cell populations are more susceptible to carcinogenic effects with the rise in cancer risk with cell proliferation being secondary to increased chances of mutation and progression. FTF proliferation has been reported to be almost confined to the follicular phase of the menstrual cycle with virtually no proliferation within a few days after ovulation and our preliminary data show the same pattern - OCs could thus protect against ovarian cancers arising in the FTF by mimicking the luteal phase of the cycle when progesterone exposure is high. Whether such changes occur in CICs is not known. Cell proliferation within different types of CICs during the menstrual cycle has not been studied. The effect of OCs on proliferation within the FTF and CICs has also not been studied. We are proposing to determine the effect of a 'traditional' high progestin dose OC on cell proliferation in the FTF and CICs in women undergoing a risk-reducing bilateral salpingo-oophorectomy (RR-BSO), and to compare these proliferation rates to the rates during the normal menstrual cycle of women also undergoing an RR-BSO. The results of this study will provide crucial information regarding the relationship between OC use and protection against ovarian cancer. It will lay the foundation for further studies examining the effects of lower progestin dose OCs and OCs with newer progestin formulations. Our long-term goal in studying the mechanism of OC protection is to determine whether it is likely that the protection against ovarian cancer afforded by OCs will be lost with alterations in OC formulation in terms of dose or type of progestin used, and, if possible, to guide development of OC formations to improve further on the protection afforded by OCs.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 45 Years
Minimum Age: 30 Years
Gender: Female
Criteria: Inclusion Criteria:

- Women seeking a risk-reducing bilateral salpingo-oophorectomy (RR-BSO), including BRCA1/2mut carriers, women with a strong family history of breast and/or ovarian cancer, and women with a personal history of breast cancer.

- Premenopausal

- 30 and 45 years of age

- Scheduled to undergo a laproscopically conducted RR-BSO

- Have at least one ovary

- Have had regular monthly menstrual cycles for at least three months, the last three of which do not differ in length by more than four days.

Exclusion Criteria:

- DVT or PE hx

- Known thrombophilia

- Known thrombogenic mutations

- Fam hx of DVT or PE (1st degree)

- Postpartum <4 month

- Current smoker

- Hx of bariatric surgery

- Hypertension, not pregnancy related (controlled or uncontrolled)

- Ischemic heart disease: hx

- Stroke: hx

- Known hyperlipidemias

- Valvular heart disease: complicated

- Peripartum cardiomyopathy

- Systemic lupus erythematosus (SLE)

- Migraine: hx

- Diabetes: nephropathy/retinopathy/neuropathy or >20 yrs duration

- Inflammatory bowel disease

- Gallbladder disease

- Cholestasis: OC related

- Viral hepatitis: acute or flare

- Cirrhosis: severe

- Liver tumors: adenoma or malignant

- Organ transplant

- Hysterectomy

- Prior ovarian cancer

- Currently taking anticonvulsants

- Currently taking Rifampicin

- Currently taking Rifabutin

- Currently taking Ritonavir - boosted protease inhibitor

- Taken Tamoxifen IN THE LAST 6 MONTHS

- Taken Raloxifene IN THE LAST 6 MONTHS

- Taken any chemotherapy IN THE LAST 6 MONTHS

- Taken hormonal contraceptives IN THE LAST 6 MONTHS

- Taken hormone replacement therapy IN THE LAST 6 MONTHS
USC Keck School of Medicine
Los Angeles, California, United States
Status: Not yet recruiting
UBC BC Cancer Agency
Vancouver, British Columbia, Canada
Status: Not yet recruiting
Contact: Karen Sill, RN - 604-875-6000 - ksill@bccancer.bc.ca
Start Date
June 2014
Completion Date
June 2015
University of Southern California
University of Southern California
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page