Research eyes DMPA, cancer risks/benefits

Family planning clinicians are familiar with the injectable contraceptive depot medroxyprogesterone acetate (DMPA) as an effective form of reversible birth control, following only the contraceptive implant and intrauterine device (IUD) in contraceptive efficacy.1 New data has emerged regarding risk of cancer with DMPA (Depo-Provera, Pfizer, New York City; Medroxyprogesterone Acetate Injectable Suspension USP, Teva Pharmaceuticals USA, North Wales, PA).

In the first study, researchers note that recent DMPA use (within five years) for 12 months or longer in women ages 20-44 was associated with a 2.2-fold increased risk of invasive breast cancer. This risk appeared to dissipate within months after contraceptive use was discontinued.2 Researchers also found that women who used the contraceptive for less than a year or who had stopped using it more than a year earlier did not have an increased risk of breast cancer.

In the second study, results suggest that use of the injectable contraceptive might have a protective effect against epithelial ovarian cancer.3

DMPA is a popular contraceptive choice in the United States: 3.2% of women ages 15-44 in 2006-2008 who were using a method chose the shot, compared to 28% selecting the Pill, 16.1% for condoms, and 5.5% preferring the IUD.4 Many teens look to DMPA for pregnancy prevention. About 20% of teens ages 15-19 in 2002 and 2006–2010 reported using hormonal contraceptive injectables, primarily DMPA.5

The first study, conducted by researchers at of Fred Hutchinson Cancer Research Center in Seattle, looked at 1,028 area women ages 20 to 44 who had been diagnosed with breast cancer and 919 age-matched controls who did not have a history of the disease. Of these, about 10% reported using DMPA.

Prior studies showed link to risk

Why examine DMPA as a possible breast cancer link?

According to Christopher Li, MD, PhD, a breast cancer epidemiologist at the Hutchinson Center, results of prior studies, conducted primarily in developing countries, have indicated such a link to risk.6-8 Also, data from the Women's Health Initiative clinical trials of menopausal hormone therapy strongly implicated use of medroxyprogesterone acetate with risk of breast cancer in postmenopausal women, says Li.

"DMPA is the only form of hormonal contraception widely used in the U.S. that contains this same form of progestin, and so we were interested in investigating if it was associated with breast cancer risk among premenopausal women," Li states.

The findings of the current study stand in contrast to those of the Women's CARE Study, conducted by the Centers for Disease Control and Prevention,9 says Andrew Kaunitz, MD, professor and associate chair in the Obstetrics and Gynecology Department at the University of Florida College of Medicine — Jacksonville.

Based on 4,575 cases, the Women's CARE study found that use of DMPA was not associated with an elevated risk of breast cancer in current/recent users or in women who had initiated DMPA five years prior, observes Kaunitz. "It was interesting and surprising to note that the authors of the Washington state study did not cite the Women's Care Study in their References," notes Kaunitz.

Breast cancer is rare among premenopausal women. A woman's chance of being diagnosed with breast cancer is 0.43% from age 30 through age 39, according to the National Cancer Institute.10 Existing clinical trial data is therefore limited, so analyses will come from observational data such as evidenced in the current study, researchers note. Clinicians and women will need to weigh such factors in choosing an appropriate contraceptive, they state.

"There are numerous contraceptive options, and so further clarifying the benefits and risks associated with each option is important as women consider what choices might be best for them," the researchers comment.1

Add benefit to list

While use of oral contraceptives is associated with a reduced future risk of epithelial ovarian cancer, such an association between use of DMPA and epithelial ovarian cancer has not been well studied. Current research indicates a strong protective link.3

DMPA has been widely used in Thailand since 1965, and it remains a popular contraceptive choice there. In the current multicenter case-control study, investigators enrolled women between ages 20-70 with epithelial ovarian cancer who were treated between 2006 and 2008 at one of 12 institutions. They age-matched them to women admitted for surgical, ear-nose-throat, and ophthalmologic care to the same institutions.

Ever use of DMPA (18% and 26% of cases and controls, respectively) was associated with a 39% reduced risk of epithelial ovarian cancer (P=.002). Greater duration of DMPA use was associated with more robust protection against the disease, with two, three, and over three years of use associated with risk reductions of 14%, 63%, and 83%, respectively. Of the 330 cases and 982 controls, the mean age was 50 and 49, respectively. The proportion of women who were parous was 75% in cases and 90% in controls (P<.05>

According to the researchers, the protection against epithelial ovarian cancer associated with DMPA use is of a magnitude similar to that seen with oral contraceptives, notes Kaunitz.

"The authors' observation that reproductive parameters known to be associated with a lower epithelial ovarian cancer risk — use of oral contraceptives, breastfeeding, and parity — indeed were found to be protective in this study and that a family history of epithelial ovarian cancer was indeed associated with an elevated risk of this disease strengthens the findings of the current study," notes Kaunitz.

References

  1. Trussell J, Guthrie KA. Choosing a contraceptive: efficacy, safety, and personal considerations. In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20th revised edition. New York: Ardent Media; 2011.
  2. Li CI, Beaber EF, Chen Tang MT, et al. Effect of depo-medroxyprogesterone acetate on breast cancer risk among women 20 to 44 years of age. Cancer Res 2012; 72(8):2,028-2,035.
  3. Wilailak S, Vipupinyo C, Suraseranivong V, et al. Depot medroxyprogesterone acetate and epithelial ovarian cancer: a multicentre case-control study. BJOG 2012; 119(6):672-677.
  4. Guttmacher Institute. Facts on contraceptive use in the United States. Fact sheet. June 2010. Accessed at http://bit.ly/2Bzdq6.
  5. Martinez G, Copen CE, Abma JC. Teenagers in the United States: Sexual Activity, Contraceptive Use, and Childbearing, 2006–2010 National Survey of Family Growth. Accessed at http://1.usa.gov/o1lF0S.
  6. Breast cancer and depot-medroxyprogesterone acetate: a multinational study. WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Lancet 1991; 338:833-838.
  7. Paul C, Skegg DC, Spears GF. Depot medroxyprogesterone (Depo-Provera) and risk of breast cancer. BMJ 1989; 299:759-762.
  8. Shapiro S, Rosenberg L, Hoffman M, et al. Risk of breast cancer in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen contraceptives. Am J Epidemiol 2000; 151:396-403.
  9. Strom BL, Berlin JA, Weber AL, et al. Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer. Contraception 2004; 69(5):353-360.
  10. National Cancer Institute. Probability of breast cancer in American women. Fact sheet. Sept. 17, 2010. Accessed at http://1.usa.gov/gy2JSo.