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  1. 1

    Steroid contraception and the risk of neoplasia.

    World Health Organization [WHO]. Scientific Group

    Geneva, Switzerland, WHO, 1978. (World Health Organization Technical Report Series No. 619) 54 p

    Studies on steroid contraception (SC) and risk of neoplasia are reviewed. Methodological issues in neoplasia etiology studies include: 1) possibility of a latent period between exposure to cause and disease development; 2) cumulative effects of prolonged or repeated SC exposure; 3) discontinued drugs or dosage schedules; 4) time of exposure (adolescence or prenatal, e.g.); 5) isolation of specific causes among multiple risks; and 6) variations in neoplasma diagnoses. The 4 epidemiological approaches to SC-associated neoplasia studies have inherent shortcomings, but cohorts yield significant associations. Relative risk (ratio of disease incidence among exposed vs. nonexposed persons) is an index of association only, not evidence of cause and effect. Benign breast neoplasia risk was reduced by current SC use of >2 years, and weak evidence points to a residual protective effect, apparently associated with progestogen dose. Aggregated breast cancer data show no clear adverse or beneficial effect of SC use; however, evidence suggests SCs may increase breast cancer risk in population subgroups (e.g., young women). Only short-term evidence is available; hence, no inference of long-term SC breast cancer effects is possible. No beneficial effect of SCs on uterine fibroids is evident, but sequential SCs, no longer marketed, may have increased risk to endometrial carcinoma. Inconclusive data suggest SCs may decrease ovarian cancer risk. Increased risk of cervical dysplasia and carcinoma in situ is associated with SC use, especially long-term use by women with predisposing factors. Risk of hepatocellular adenoma of the liver increases with prolonged SC exposure, especially high dose. Relevance of existing data from more developed countries to disease risk in less developed ones is discussed, and recommendations made.
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  2. 2
    Peer Reviewed

    Preface -- updating DMPA safety.

    Meirik O

    CONTRACEPTION. 1994 Mar; 49(3):185-8.

    Depot-medroxyprogesterone acetate (DMPA) is currently used for contraception by about nine million women in more than 90 countries. DMPA injected intramuscularly at a dose of 150 mg every 3 months, is among the most effective reversible contraceptive methods. The reluctance of the US Food and Drug Administration (FDA) to approve DMPA in 1992 was attributed to the occurrence of mammary neoplasia in beagle dogs and of endometrial cancer in two of sixteen rhesus monkeys after long-term DMPA treatment. The beagle dog responds to DMPA with a release of growth hormone which is probably the cause of the tumorigenic effect of DMPA on the mammary gland. Around 1990 findings were published from a WHO multicenter study in Kenya, Mexico and Thailand and studies from Costa Rica and New Zealand. In 1993, a WHO meeting of experts reviewed the available data on use of DMPA and cancer risk in women as well as recent toxicology data. DMPA exerts a protective effect against endometrial cancer. The epidemiological studies report no association between the risk of ovarian cancer and the use of DMPA. There was a lack of an association between cervical cancer and DMPA. Two well-designed epidemiological studies did not provide evidence for an increase in overall risk of breast cancer among women having used DMPA. However, both studies reported a weak association between current and recent use of DMPA and breast cancer although there was no evidence of increased risk for women who had stopped using DMPA several years ago. Women who were less than 35 years old at diagnosis, an age at which breast cancer is rare, also showed a slightly increased risk. DMPA can cause an irregular bleeding pattern, it is not immediately irreversible, and there is a relatively slow return of fertility after discontinuation. Yet for women who wish for medium- or long-term contraception, DMPA is one of the alternatives to be considered.
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  3. 3

    Contraceptives and cancer: looking for the evidence.

    World Health Organization [WHO]. Regional Office for the Western Pacific


    The WHO has published partial results of an epidemiological study of the safety with respect to breast cancer of the injectable contraceptive depomedroxyprogesterone acetate, known as DMPA or Depo-Provera. The WHO Special Program of Research, Development and Research Training in Human Reproduction has been conducting a collaborative retrospective study of cancer and DMPA in 3 developed and 8 developing countries. Results from Kenya, Mexico and Thailand are published in Lancet on October 5, 1991. Comparing 869 women with breast cancer <64 years old and 11,890 matched hospital-based controls, the relative risk was 1.21, not statistically significant. 12.5% of the cases and 12.2% of the controls had used DMPA. Fine analysis pointed to a possibility of increased risk over the 1st 4 years of use. The data were not compatible with the hypothesis that DMPA. Fine analysis pointed to a possibility of increased risk over the 1st 4 years of use. The data were not compatible with the hypothesis that DMPA causes cancer, but only that it may speed the growth of early pre-existing cancer. When contemplating the choice of DMPA, people should evaluate their risks relative to the excellence of DMPA as a highly effective, convenient, long-acting, but reversible method.
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  4. 4
    Peer Reviewed

    Depot-medroxyprogesterone acetate (DMPA) and cancer: memorandum from a WHO meeting.

    Chutivongse S; Gray R; Hill C; Hulka B; Kenya P; Odlind V; Pardthaisong T; Petitti D; Rubin G; Shapiro S


    This memorandum from a World Health Organization (WHO) meeting held in 1985 summarizes available epidemiologic data from human studies, including the WHO Collaborative Study of Neoplasia and Steroid Contraceptives, on the association between depot-medroxyprogesterone acetate (DMPA) use and neoplasia. The WHO Collaborative Study is collecting data on cases and controls from 14 collaborating centers in 11 countries. Analysis of preliminary findings regarding cancers of the endometrium, ovary, liver, and breast suggest that there is no increased risk in DMPA users. The relative risk estimates for these sites are 0.3 for endometrial cancer, 0.7 for ovarian cancer, 1.0 for liver cancer, and 1.0 for breast cancer. The issue of a causal association between DMPA use and cervical cancer is less clear. The adjusted relative risk for cervical cancer was a nonsignificant 1.2; however, somewhat higher risks were noted in subgroups of longterm (over 4 years) users. Although the WHO study is the 1st to provide reliable data on DMPA and neoplasia, its findings must be regarded as tentative. At this point the data are insufficient to assess the influence of DMPA on risk among longterm users or risk long after initial exposure.
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  5. 5

    Breast cancer, cervical cancer, and depot medroxyprogesterone acetate. [WHO Collaborative Study of Neoplasia and Steroid Contraceptives] [letter].

    World Health Organization [WHO]. Special Programme of Research, Development and Research Training in Human Reproduction

    Lancet. 1984 Nov 24; 2(8413):1207-8.

    This letter presents the preliminary findings of a collaborative, multinational, hospital-based, case-control study being conducted under the auspices of the World Health Organization to assess the influence of depot medroxyprogesterone acetate (DMPA) on risks of mammary, gynecological, and hepatobiliary malignancies. The frequency of ever-use of DMPA was greater in breast cancer cases (15/246, or 6,0%) than in controls (381/4162, or 9.2%). When adjusted for age, center, age of birth of 1st child, and nulliparity, the relative risk in women who had ever used DMPA was 0.7. The lowest risk was noted in women who had used DMPA for 3 or more years, but no decreasing trend in risk with duration of use was evident. The reducton in risk of breast cancer in DMPA users was largely confined to women with 1st exposure after age 30 years. In terms of cervical cancer, a history of DMPA use was reported by slightly more cases (67/469, or 14.3%) than controls (269/2704, or 9.9%). Use of oral contraceptives, number of cervical smears, and number of pregnancies were the variables most strongly related to cervical or having the greatest influence on relative risk estimates for users of DMPA. When controlled for these 4 factors and age and center, the relative risk in DMPA was 1.13. The highest relative risk was found in longterm users, although there was no clear trend of increasing risk with duration of DMPA use. These preliminary findings provide no evidence that DMPA increases the risk of breast cancer. The relative risk for cervical cancer for DMPA users obtained in this study could be due to chance or to incomplete control for the confounding effect of sexual variables. Although the absence of a trend of increasing risk with duration of use tends to rule out a causal connection between DMPA use and cervical cancer, the doubling of risk in women who used DMPA for 5 years or more is of potential concern.
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  6. 6

    Depo-Provera: controversy grows, hearings scheduled.

    Intercom 6(8):2-3. August 1978.

    The injectable contraceptive Depo-Provera was discussed by the U.S. House of Representatives Select Committee on Population. In March 1978 the FDA denied approval of Depo-Provera for U.S. use. Depo-Provera is thought, but not proved, to be responsible for increased risk of breast tumor, delayed return to fertility, irregular bleeding, and birth defects. Observations and studies held in Thailand and Mexico do not show any serious side effects or unwanted pregnancies in women who were injected with Depo-Provera. It must be recognized, however, that benefit-risk considerations differ in developing countries.
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