Why do Oral Contraceptives Prevent of Ovarian Cancer?
| Status: | Completed |
|---|---|
| Conditions: | Ovarian Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 30 - 45 |
| Updated: | 4/2/2016 |
| Start Date: | June 2014 |
| End Date: | June 2015 |
| Contact: | Leigh Pearce, PhD |
| Email: | cpearce@usc.edu |
| Phone: | 323-865-0437 |
Mechanisms of Prevention of Ovarian Cancer by Oral Contraceptives
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.
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.
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.
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.
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
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