Progestin in oral contraceptives associated with lower risk of ovarian cancer

About the study

The Duke researchers analyzed 390 women with a diagnosis of ovarian cancer (case subjects) and 2865 women without ovarian cancer (control subjects) from eight different U.S. states. The case subjects were between the ages of 20 and 54 and were identified from the Cancer and Steroid Hormone (CASH) study, conducted between 1980 and 1982. The CASH study had collected data on ovarian cancer and OCs. The control subjects were also between 20 and 54, had lived in the same geographic region as the case subjects, and were recruited through random phone calling. Women who had any history or signs of prior ovarian cancer were excluded from the control group.

Data on oral contraceptive use was reported via a questionnaire administered in the participants' homes. Participants were asked for detailed information about their OC use, the formulations taken, length of time taken, age at menarche and/or menopause, infertility, family history of cancer, and history of breast-feeding. Women were asked to recall their contraceptive use up to the time of their diagnosis of ovarian cancer (for case subjects) or the date of the interview (for controls).

The original CASH study found that all the various formulations of OC pills appeared to be associated with reduced risk of ovarian risk. However, the data were not categorized according to the dosages of estrogen and progestin, and there were too few numbers of each type of pill to detect significant differences. Therefore, the Duke researchers reanalyzed the original data to include associations between the potency of estrogen and progestin in each formula and reduction in ovarian cancer risk. Each oral contraceptive used by the participants was classified according to estrogen and progestin potency. The four classifications included:

• High progestin/high estrogen
• High progestin/low estrogen
• Low progestin/high estrogen
• Low progestin/low estrogen

The findings

Compared with women who took high progestin/high estrogen OCs, women taking low progestin/high estrogen OCs were more than twice as likely to develop ovarian cancer. Women taking low progestin/low estrogen OCs were 60% more likely to develop ovarian cancer, and women taking no OCs were nearly three times as likely to develop ovarian cancer. The authors report that the reduction in ovarian cancer risk appeared to be related to the progestin levels in the OCs, not the estrogen levels. These findings were significant regardless of how long the women took OCs.

There are some limitations to the study, however. The researchers say that some of the oral contraceptives may have been misclassified as to their specific formulations. And because case subjects were asked to recall their oral contraceptive use from some time in the past, accuracy of the self-reporting may have been compromised. The women who participated in the CASH study were relatively young, and the results may not be applicable to menopausal women who develop ovarian cancer.

How does this affect you?

It is important to note that the oral contraceptives reanalyzed for this study were marketed more than 20 years ago. More recent OCs have much lower levels of both estrogen and progestin, and according to the researchers, are less likely to have an effect on the risk of ovarian cancer. The authors also caution that while pills higher in progestin appear to be protective against ovarian cancer, they might increase the risk of certain types of breast cancer.

While your current oral contraceptive most likely will not offer enough progestin to provide protection against ovarian cancer, the reanalysis of the data does provide hope for the future.

According to the researchers, their findings about high levels of progestin in OCs tie in nicely with animal research showing that high doses of progestin might activate cancer-protective pathways in ovarian tissue. According to Joellen Schildkraut, the lead author of this study, "these two studies show that there are biological effects related to progestin that play a role in reducing the risk of ovarian cancer...and that future ovarian cancer research will capitalize on this information to achieve maximum protection against ovarian cancer while minimizing side effects."