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Geneva, Switzerland, WHO, 2015.  p. (WHO/RHR/15.09)The purpose of this Statement is to reiterate and clarify the existing (current) WHO position based on published guidance that is still valid. WHO monitors the evidence in this field closely and will update its guidance as and when new evidence becomes available. The statement includes key facts about depot-medroxyprogesterone acetate (DMPA), a discussion of the safety of DMPA, and current recommendations for its use.
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.
HUMAN TOXICOLOGY. 1988 May; 7(3):235-42.The Special Program of Research, Development and Research Training in Human Reproduction of the World Health Organization held a meeting in Geneva in February of 1987 to review the results of animal and human studies analyzing contraceptive steroids. In reviewing this data, assessment of pre-clinical toxicology and human risk would be possible. The studies reviewed included: studies on steroid exposure and breast disease, the protective factor of combined oral contraceptives (OC) (against ovarian cancer), hormonal contraceptives and cervical cancer, the relationship of gall bladder disease to OC use, congenital malformations and steroid hormone, OC use and its effect on breast milk and other topics. Basic principles on pre-clinical testing were adopted. These included: 1) the establishment of safety is a joint responsibility of experimental toxicology and clinical pharmacology. 2) Testing should include detailed analysis of the hormonal effect of new types in several animal species. 3) Species specific data should be collected. 4) Studies to detect cumulative toxicity should be performed. 5) Reproductive toxicity should concentrate on exposure throughout the embryonic period. 6) In vivo and in vitro tests should be conducted to investigate the mutagenic potential of new contraceptive steroids. 7) Long-term carcinogenicity study should be performed, preferably on the rat. 8) When new delivery systems are used to administer established steroidal contraceptives, experimental safety studies should assess potential interactions with the system and on the possibility of adverse effects of the delivery system. 9) Post-registration surveillance is on integral part of the risk assessment process.
Ippf Medical Bulletin. 1983 Dec; 17(6):1-2.The response of the International Medical Advisory Panel (IMAP) of the International Planned Parenthood Federation to 2 recent papers suggesting a link between cancer and oral contraceptive (OC) use is reported. The 1st paper by Pike et al. suggested an increased risk of breast cancer in women who use OCs containing high potency progestogens before age 25 for at least 4 years. It is noted that several methodological problems with the study design could have introduced a degree of selection of ascertainment bias. These issues include the procedures used for age matching between cases and controls, the 1/3 loss to follow-up among cancer cases, and the use of telephone interviews to ascertain OC use history. Moreover, data from other studies suggest that ever-users of OCs who develop breast cancer may be more likely to survive than women with breast cancer who have never used OCs, leading to the overrepresentation of women in the former group among surviving cases. The ranking of OCs by progestogen potency does not take the estrogen content into consideration. In addition, assessment of progestogen potency by use of a delay of menses test may not correlate with the degree of effect on the breast and has produced conflicting results when used by different researchers. Finally, the numbers of women using some OC brands were too small and the possibility that women may have changed OC brand over the study period was not considered. Largescale studies such as the UK Oxford-Family Planning Association contraceptive study and the Centers for Disease Control Cancer and Steroidal Hormone Study are curently being reanalyzed, controlling for type and amount of progestogen in the OCs. Until new data become available, IMAP believes there is insufficient evidence to recommend modification of existing practice. The 2nd study by Vessey et al. suggested a higher incidence of cervical cancer in OC users as compared to IUD users. However, several key modifying factors on the risk of cervical cancer, including age at 1st sexual intercourse and number of partners, could not be controlled for. Moreover, a high proportion of OC use involved preparations containing 50 mcg or more of estrogen. Although regular cervical smears are recommended for OC users, the IMAP again does not recommend any change in current practice. The IMAP noted that the possible cancer-related risks of OCs must be weighed against the protective effects of OCs against cancers of the endometrium and ovary, pelvic inflammatory disease, and unwanted pregnancies.