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JOURNAL OF REPRODUCTIVE MEDICINE. 1996 May; 41(5 Suppl):419-25.This article reviews recent epidemiological data assessing the risk of breast, endometrial, ovarian, and cervical cancer in women using the injectable contraceptive depot medroxyprogesterone acetate (DMPA). A review is also provided of epidemiological and biostatistical concepts which relate to the literature on the relationship between the use of hormonal contraception and cancer. Breast cancer is a common and lethal disease in the US, and evidence suggests that gonadal steroids play a role in the development of breast cancer. Two major case control studies (one in New Zealand and the other under the auspices of the World Health Organization [WHO]) as well as a pooled analysis of these studies found no increased overall breast cancer risk in DMPA users. A currently unexplained pattern of increased risk in recent users mimics that seen with oral contraceptive (OC) use and term pregnancy. A WHO hospital-based study of the relationship between endometrial cancer and DMPA use found a protective effect of DMPA which appeared to be longterm and as great as that associated with OCs. Whereas it is plausible that DMPA, which suppresses ovulation, would lower the risk of ovarian cancer in users, a WHO case-control and hospital-based study failed to uncover such a protective effect. Studies of the routine use of DMPA in nulliparous women (who have higher risk of ovarian cancer) will shed more light on any effect DMPA may have on ovarian cancer. The unique epidemiology of cervical cancer (including number of sexual partners, use of barrier contraception, and frequent screening) makes it difficult to assess any association with contraceptive use. However, a large population-based, case-control study in Costa Rica; a WHO hospital-based, case-control study in Thailand, Mexico, and Kenya; and a study in New Zealand indicate that the risk of cervical neoplasia does not appear to be affected by DMPA use. While some issues regarding DMPA and the risk of reproductive tract carcinoma remain to be resolved, clinicians can be reassured that, for appropriately selected clients, the substantial benefits of DMPA outweigh any risks.
Long-term use of three-monthly injectable contraceptive DMPA not linked to breast cancer. News release.
Geneva, Switzerland, WHO, Special Programme of Research, Development and Research Training in Human Reproduction, 1995 Mar 20.  p. (News Release No. 1/95)According to a World Health Organization (WHO) study which was published in the March 8, 1995 issue of the Journal of the American Medical Association, women who use the injectable contraceptive, depot-medroxyprogesterone acetate (DMPA or Depo-Provera), are not at an increased risk of breast cancer, and the use of the contraceptive should not be restricted on the grounds of breast cancer risk. The study was conducted by the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction; the University of Otago Medical School, Dunedin, New Zealand; and the Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. This secondary analysis of combined data from previous studies conducted by three organizations in Kenya, Mexico, New Zealand, and Thailand compared 1768 women who had breast cancer, most under 55 years of age, with 13,905 who did not. Although women who had used DMPA more than 5 years before did not show an increase in risk (even when the period of use had been long), those women who had begun using it within the previous 5 years did. This corresponded to a relative risk estimate of 2.0. This could be due to the enhanced detection of breast tumors in women using DMPA, or to the acceleration of the growth of preexisting tumors. The analysis reconfirmed an increased risk of breast cancer with 1) early menarche; 2) being single; 3) late age at birth of first child; 4) not having had any children; 5) family history of breast cancer; and 6) history of benign breast disease. The authors recommended that patients should be warned concerning the possible accelerated growth of small, undetected tumors.
CANCER CAUSES AND CONTROL. 1991 Nov; 2(6):389-94.As part of the Who Collaborative Study of Neoplasia and Steroid Contraceptives, physicians gathered data from 2796 cases and 18,900 controls from at least 1 hospital in each country between 1979-1982 and stopped between 1982-1988 to examine the association between breast cancer in women and combined oral contraceptives (COCs), particularly around menopause. The countries included Australia, Democratic Republic of Germany, Israel, Chile, China, Colombia, Kenya, Mexico, the Philippines, and Thailand. The relative risk (RR) was higher in women who had used COCs in the last year, but the increased RR was no greater for women who would be near menopause (45-49 years) than it was for women <40 years old (1.3 vs. 1.4). In fact, the RR was highest in 40-44 year old women (2.1). Further the RRs were greater in women who began using a COC >45 years of age than they were for women who began using it <45 years of age, but the RR did not increase with duration. For example, the RR for women who began to take the COC <45 years for 12-48 months was 0.86 compared to 1.4 for those who began >45 years. The RR for women who began to take the COC at >45 years old remained at 1.4 for the other durations. In addition, the RR in women who ever used COCs was greater in women who underwent an artificially induced menopause than those who underwent a natural menopause (1.7 vs. 1.04). This higher risk in COC users occurred no matter the duration between last use of COCs and induced menopause and the method of artificial menopause. In conclusion, this study did not support the hypothesis that COCs increase the risk of breast cancer in women who use them around the time of menopause.
Family Planning Perspectives. 1992 Jan-Feb; 24(1):43-4.1 hospital in Nairobi, Kenya; Mexico City, Mexico, and Chiang Mai, Thailand and 2 hospitals in Bangkok, Thailand took part in a WHO sponsored collaborative study to examine the association between depomedroxyprogesterone acetate (DMPA) and breast cancer. The researchers compared 1979-1988 data on 869 hospitalized women with breast cancer with 11,890 hospitalized women with unrelated conditions. 12.5% of cases and 12.2% of controls had ever had an injection of DMPA. Overall ever users had no significant increased risk of breast cancer (relative risk [RR], 1.2) In addition, risk did not rise with duration. Nevertheless current users who began receiving DMPA within the past 4 years did have a significantly higher risk (RR 2.6). On the other hand, current users who began receiving DMPA >5 years earlier were not at increased risk at all. For example, the RR for those who began 8-12 years earlier was 0.8 and for those who began >12 years earlier was 0.5. Further even though the current users <35 years old who began receiving DMPA within the past 4 years were >2 times as likely to have breast cancer than their corresponding counterparts who did not use DMPA (RR 2.2), the risk according to duration was not significant. The researchers listed some possible reasons for the discrepancies. They concluded that there is only a weak association between DMPA and breast cancer--comparable to that between oral contraceptives and breast cancer. In New Zealand, a case control study of 30 25-51 year old women who used DMPA for at least 5 years showed that long term use of DMPA significantly reduced bone density. For example, for DMPA users, the spine and femoral neck bone densities were 8% and 7% respectively lower than the premenopausal controls. The researchers found the same effect even when they restricted the analysis to nonsmokers.