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A Pooled Analysis of the World Health Organization and New Zealand Studies

David C. G. Skegg, MB, DPhil; Elizabeth A. Noonan, MS; Charlotte Paul, MB, PhD; George F. S. Spears, MSc; Olav Meirik, MD, PhD; David B. Thomas, MD, DrPH

JAMA. 1995;273(10):799-804.

Abstract
Background.
—Although depot medroxyprogesterone acetate (DMPA) (Depo-Provera) has now been approved for marketing as a contraceptive in the United States, there are still unresolved issues about the relation between DMPA and risk of breast cancer. The two substantial case-control studies of this association yielded similar but inconclusive results. Because their designs were compatible, these studies were pooled to obtain more adequate data for analysis.

Design.
—Pooled results from two case-control studies.

Setting.
—New Zealand (entire country), Thailand (three centers), Mexico (one center), and Kenya (one center).

Participants.
—A total of 1768 women with breast cancer and 13905 controls, most of whom were younger than 55 years.

Main Outcome Measure.
—Relative risk (RR) of breast cancer in women who had used DMPA.

Results.
—The RR of breast cancer for women who had ever used DMPA was 1.1 (95% confidence interval [CI], 0.97 to 1.4). There was no increase in risk with increasing duration of use of DMPA, but RR estimates were higher in certain subgroups of women. Further analyses suggested that recent (or current) use was the key factor, with women who had started using DMPA within the previous 5 years estimated to have an RR of 2.0 (95% CI, 1.5 to 2.8).

Conclusions.
—The increased risk of breast cancer observed in recent (or current) users could be due to enhanced detection of breast tumors in women using DMPA or to acceleration of the growth of preexisting tumors. Women who had used DMPA more than 5 years previously had no increase in risk of breast cancer, regardless of their duration of use.

(JAMA. 1995;273:799-804)

Author Affiliations
From the Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand (Drs Skegg and Paul and Mr Spears); Fred Hutchinson Cancer Research Center, Seattle, Wash (Ms Noonan and Dr Thomas); Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland (Dr Meirik).

Footnotes
Corresponding author: David C. G. Skegg, MB, DPhil, Department of Preventive and Social Medicine, University of Otago Medical School, PO Box 913, Dunedin, New Zealand.

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