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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.
Bulletin of the World Health Organization. 1956; 15:5-41.The author reviews that mortality statistics from cancer of the breast in females and from malignant neoplasms of the uterus and of the other female genital organs for nineteen countries over the years 1920-53, first considering the general trend of the mortality series for each group of diseases for all ages and then analysing for each sector of mortality the changes which have occurred in the age-specific death-rates in some pivotal years during the same period. Considerable differences in the levels of total mortality from each group of tumours for various countries are noted. The important variations among age-specific death-rates for cancer of the breast in females and for uterine neoplasms in various countries are examined and their significance is commented upon. (excerpt)
A dose escalation study of docetaxel and oxaliplatin combination in patients with metastatic breast and non-small cell lung cancer.
Anticancer Research. 2003 Jan-Feb; 23(1B):785-791.Objectives: To determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with oxaliplatin (L-OHP) as first-line treatment of patients with advanced breast (ABC) and non-small cell lung cancer (NSCLC). Patients and methods: Fifty-two patients (26 with NSCLC and 26 with ABC), who had not received prior chemotherapy for metastatic disease, were enrolled. The patients' median age was 64 years, and 42 (71%) had a performance status (WHO) 0-1. Docetaxel was given as a 1-hour infusion after standard premedication on day 1 and L-OHP as a 2 to 6-hour infusion on day 2 every 3 weeks. Doses were escalated at increments of 10mg/m2. Results: The DLT1 was reached at the doses of docetaxel 75mg/m2 and L-OHP 80mg/m2. The addition of rhG-CSF permitted further dose escalation (DLT2: docetaxel 90mg/m2 and L-OHP 130mg/m2). The dose-limiting events were grade 4 neutropenia, febrile neutropenia, grades 3 or 4 diarrhea and grade 3 fatigue. Out of 239 delivered cycles, grades 3 or 4 neutropenia occurred in 22 (9%) cycles with 5 (2%) neutropenic febrile episodes. There was one septic death. Grades 3 or 4 fatigue was observed in seven (13%) patients and grades 3-4 diarrhea in five (10%). Out of 42 patients evaluable for response, seven (27%) patients with ABC and five (19%) patients with NSCLC experienced a partial response. Conclusion: The combination of docetaxel and oxaliplatin is a feasible and well-tolerated regimen. The recommended doses for future phase II studies are 75mg/m2 for docetaxel on day 1 and 70mg/m2 for L-OHP on day 2 without rhG-CSF support and 85mg/m2 and 130mg/m2, respectively, with rhG-CSF support. (author's)
[Tamoxifen or tamoxifen in combination with chemotherapy in adjuvant therapy of breast carcinoma. Results of a multicenter randomized study] Tamoxifen nebo tamoxifen v kombinaci s chemoterapií v adjuvantní lécbe karcinomu prsu. Vysledky multicentrické randomizované studie.
Sbornik Lékarsky. 2001; 102(1):65-76.Between April 1994 and May 1997 103 breast cancer patients (pts), pT1c-3a, pN0-1, M0, were randomised after surgery to adjuvant tamoxifen (20 mg per day) or to tamoxifen plus CMF (C 500 mg/m2, M 40 mg/m2 and F 600 mg/m2 on days 1st and 8th q 28 day) in 6 cycles. The median age (49-72 years, median 58), tumour size, number of involved lymphnodes (0-3), estrogens receptor status, grade (I-III) and type of operation were well balanced among the 50 pts on tamoxifen and the 53 pts on tamoxifen plus CMF pts, preferably postmenopausal. Results. Grade of toxicity according to WHO criteria was not higher than two in both arms. Toxicity both haematological and non-haematological was higher in the group treated with chemotherapy (0 vs 32 resp. 20%) except weight gain +5% (52% in both group). After median follow-up of 42 mos five recurrences in tamoxifen and seven in tamoxifen plus CMF pts were observed (p=NS). The projected 3-y DFS is 92% for tamoxifen and 88% for tamoxifen plus CMF (p=NS). The 3-y OS is 88% for tamoxifen and 80% for tamoxifen plus CMF pts (p=NS). Conclusions. Both regimens are equally effective with higher toxicity in the group with combined chemo- and hormonal therapy. (author's)
[Unpublished] 1988. 5,  p.The World Health Organization's Special Programme of Research, Development, and Research Training in Human Reproduction, convened a meeting of scientists to discuss the correlation between longterm oral contraceptive use and breast cancer. The meeting was held in Geneva from June 27-29, 1988. The issue at hand was whether early longterm oral contraceptive use did or did not have a direct relationship to women developing breast cancer. Epidemiological data and recent unpublished reports were reviewed at the meeting and various strategies were explored. Since most of the available data at the meeting was unpublished and confidential, the report of the meeting contained a general summary of the findings. 3 hypotheses concerning breast cancer and oral contraceptives concerned the following areas: 1) latent period use of oral contraceptives, 2) their hormonal content, and 3) bias. Basic research strategies included scientific research, classification of pill preparations, use of vital statistics, ranking pill types in various studies, new case-control studies, reducing bias in new studies, and interaction between epidemiologists and other scientists.
World Health Organization Technical Report Series. 1981; (670):1-120.This report includes the collective views of a World Health Organization (WHO) Scientific Group on Research on the Menopause that met in Geneva during December 1980. It includes information on the following: 1) the endocrinology of the menopause and the postmenopausal period (changes in gonadotropins and estrogens immediately prior to the menopause and changes in gonadotropin and steroid hormone levels after the menopause); 2) the age distribution of the menopause (determining the age at menopause, factors influencing the age at menopause, and the range of ages at menopause and the definition of premature and delayed menopause); 3) sociocultural significance of the menopause in different settings; 4) symptoms associated with the menopause (vasomotor symptoms, psychological symptoms, disturbances of sexuality, and insomnia); 5) disorders resulting from, or possibly accelerated by, the menopause (osteoporosis, atherosclerotic cardiovascular disease, and arthritic disorders); 6) risks, with particular reference to neoplasia, of therapeutic estrogens and progestins given to peri- and postmenopausal women (endometrial cancer, breast cancer, and gallbladder disease); 7) fertility regulating methods for women approaching the menopause (fertility and the need for family planning in women approaching the menopause, problems of family planning in perimenopausal women, and considerations with regard to individual methods of family planning in women approaching the menopause); and 8) estrogen and the health care management of perimenopausal and postmenopausal women. At this time some controversy exists as to whether there is a menopausal syndrome of somatic and psychological symptoms and illness. There are virtually no data on the age distribution of the menopause and no information on its sociocultural significance in the developing countries. The subject of risks and benefits of estrogen therapy in peri- and postmenopausal women is of much importance in view of the large number of prescriptions issued for this medication in developed countries, which indicates their frequrnt use, and the different interpretations and opinions among epidemiologists and clinicians on both past and current studies on this subject. Specific recommendations made by the Scientific Group appear at the end of each section of the report. The following were among the general recommendations made: WHO sponsored research should be undertaken to determine the impact on health service needs of the rapidly increasing numbers of postmenopausal women in developing countries; uniform terminology should be adopted by health care workers with regard to the menopause; uniform endocrine standards should be developed which can be applied to the description of peri- and postmenopausal conditions and diseases; and descriptive epidemiological studies of the age at menopause should be performed in a variety of settings.
Geneva, Switzerland, WHO, 1978. (World Health Organization Technical Report Series No. 619) 54 pStudies 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.
FORUM. 1996 Dec; 12(2):14.While the government of St. Lucia actively supports family planning and the Ministry of Health maintains a service delivery program, the Saint Lucia Planned Parenthood Association (SLPPA) is also involved in getting family planning messages and a variety of services to the public at minimal cost. The work schedules of factory workers in St. Lucia's manufacturing sector prohibit them from visiting family planning clinics, doctors' offices, and distribution posts to obtain contraceptives. SLPPA staff members therefore go to 12 selected factories to provide female employees with family planning information and contraceptive methods. 90% of employees at these factories are female. The outreach team of one nurse midwife, a counselor, and a trained factory distributor visit the factories twice each month during which they also teach women on sexual and reproductive health, responsible family life, and relationships. More than 2000 factory workers currently have access to SLPPA services. In 1996, more than 1000 workers had individual counseling sessions on sexual and reproductive health. The SLPPA also reaches women through other non-contraception initiatives such as the early detection of cervical and breast cancer.
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.
Drs. Thomas and Noonan reply re "Comparison of Recalled and Validated Oral Contraceptive Histories" [letter]
AMERICAN JOURNAL OF EPIDEMIOLOGY. 1995 Apr 15; 141(8):791.Dr. Realini asserts in his letter that the results of the WHO Collaborative Study of Neoplasia and Steroid Contraceptives concerning oral contraceptives and breast cancer could have been biased as a result of better recall of prior oral contraceptive use by cases in comparison to controls. Although this is a possibility in any case-control study based on data collected by interviews, being able to validate positive oral contraceptive histories of more cases than controls does not necessarily mean more cases than controls who were users of oral contraceptives gave a history of such use. The issue of bias due to recall was discussed in the original paper. The medical records of women who claimed contraceptive use were checked for brand names and duration of use; the medical records of women who did not were not checked. This procedure did not alter their classification as users or nonusers. Since few combined oral contraceptives were available, and erroneous reports of use of combined or noncombined preparations were corrected, the estimated values of the relative risk of breast cancer in women who ever used combined oral contraceptives could not be appreciably influenced by any differences in the proportion of cases or controls whose oral contraceptive histories were supplemented by information from medical records. However, such differences could alter estimated values of the relative risk in relation to duration, latency, or recency. Information was obtained from the medical records of users in 27% of cases and 18% of controls. These percentages varied with center (0-94% of cases, 0-89% of controls). Information was most frequently obtained from the medical records of long-term and current or recent users in both groups. Similar results were obtained separately from countries in which information from medical records was obtained for relatively high and low proportions of users, and in individuals whose use was ascertained solely from interviews and from both interviews and medical records.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1993; 71(6):669-76.Depot-medroxyprogesterone acetate (DMPA) is a highly effective long-acting progestational contraceptive, which is administered by injection. DMPA has been widely used in Thailand and New Zealand. The licensing, acceptability, and prevalence of use have been influenced by concern that DMPA may increase the risk of cancer, in particular cancer of the breast. The results of toxicological tests in animals and epidemiological studies in humans concerning the carcinogenicity of DMPA are reviewed. Animals injected with DMPA were exposed to far greater concentrations of the progestogen than were animals tested with orally administered 19-nortestosterone derivatives. In beagle dogs, a unique response to DMPA led to increased serum growth hormone, which was probably responsible for the tumorigenic effect of DMPA on the mammary gland. However, women taking contraceptive doses of DMPA have no significant elevation of serum growth hormone. Available toxicological data do not seem to indicate that DMPA is different from other progestogens in its tumorigenic potential. Epidemiological studies reassure that use of DMPA does not increase breast cancer risk overall. Elevated risks in the same or similar subgroups were observed in the WHO and New Zealand studies, consistent with an acceleration in detection of pre-existing cancer. The data were not compatible with DMPA as an initiating agent. Research is needed on the biological mechanisms of action of progestogens on the human breast. Findings from studies of DMPA and invasive cervical cancer showed no overall increase in risk of cervical cancer and no association between DMPA and cervical cancer. Data from the WHO study provided evidence that DMPA protects against endometrial cancer and that DMPA use was not associated with either an increased or decreased risk of ovarian cancer. Therefore, restriction of DMPA use as contraceptive on the grounds of risk of neoplasia is not recommended.
AMERICAN JOURNAL OF EPIDEMIOLOGY. 1994 Nov 15; 140(10):956.A paper by Nischan and colleagues, "Comparison of Recalled and Validated Oral Contraceptive Histories," which examines the accuracy of the histories of oral contraceptive use (defined as agreement with gynecologists' records concerning duration of use, times since first and last use, and individual preparations used) in a WHO case-control study of breast cancer, "WHO Collaborative Study of Neoplasia and Steroid Contraceptives," fails to comment on the more frequent validity of the histories among those persons with breast cancer. Of 253 contraceptive histories from persons with breast cancer, for whom responses from at least 1 gynecologist were available, 234 (92.4%) were confirmed; of those from 621 controls, 524 were. The difference is statistically significant (chi-square test, p < 0.01). This better recall of ever-use of oral contraceptives among breast cancer patients creates a bias that makes an association between breast cancer and ever-use of oral contraceptives stronger than it is. The slight elevation in breast cancer risk associated with ever-use of oral contraceptives found in the WHO study may be due to this. There is no information about the accuracy of negative oral contraceptive histories.
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.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1992 Oct; 167(4 Pt 2):1171-6.The largest case control study on the association between oral contraceptive (OC) use and cancer is the US Cancer and Steroid Hormone (CASH) study. Since it did not use hospital-based patients as controls, it eliminated some biases. Since OCs suppress ovulation and suppressed ovulation is linked with reduced risk of ovarian cancer, scientists believe OCs may reduce this cancer risk. The CASH study shows that OC use indeed decreases the risk of ovarian cancer 40% (relative risk [RR]=.6 and this protection lasts for more than 10 years after OC discontinuation. Protection increases with duration of OC use (<1 year RR=.6 and >10 years RR=.2). Estrogenic stimulation of the endometrium without ample progestational protection causes endometrial cancer. Thus combined OCs which have estrogen and progestin components should reduce the risk of endometrial cancer. The CASH study reveals OC use for at least 12 months reduces this risk 50%. OCs have a protective effect for at least 15 years after stopping OC use. In addition, UK national mortality data show OC use caused the decline in ovarian cancer mortality and a 40% decrease in endometrial cancer mortality over the last 20 years. A WHO 7-county case control study indicates that OC users in developing countries have the same protective effect against ovarian and endometrial cancer as those in developed countries. Studies of OC use and cervical cancer have had conflicting results due to 3 biases: cervical cancer is associated with sexual behavior and is therefore a sexually transmitted disease; detection bias. A study in Costa Rica conducted by CDC study has addressed the 1st and 3rd biases. It found no increased risk of invasive cervical cancer or carcinoma in situ with OC use. Studies of OC use and breast cancer have also had conflicting results, but the data clearly indicate that OC use does not increase the overall risk of breast cancer. In fact, OC benefits surpass breast cancer risks.
WASHINGTON MEMO. 1992 Nov 12; (17):2-3.In October 1992, the US Food and Drug Administration (FDA) approved Depo-Provera for contraceptive use thus increasing the number of available contraceptives to women. Yet USAID has distributed it through its family planning programs in developing countries for many years. It has been available in the US since 1969 for noncontraceptive purposes such as endometrial cancer treatment. More than >30 million women around the world have used it to prevent conception. Today about 9 million women in 90 countries use it. A reason FDA did not approve Depo-Provera is that some studies revealed a link between it and breast tumors and cervical cancer in animals. More recent research conducted by WHO shows no connection with cervical cancer or ovarian cancer. In fact, it demonstrates Depo-Provera may protect against endometrial cancer. Yet it does indicate an insignificant increased risk of breast cancer in younger women. Some research suggests Depo-Provera may decrease bone density leading to osteoporosis and may increase the risk of having a low birth weight infant if the child is conceived before an injection. Evidence exists that it may lead to longer delays in becoming pregnant than other forms of contraception. Still 70% do conceive within 12 months after the last injection. Each Depo-Provera injection delivers a progestin in a water-based solution over 12 weeks resulting in suppressed ovulation. Its failure rate is <.5%/year, so Depo-Provera is one of the most effective reversible contraceptive available. The most common side effects are menstrual changes and weight gain (5-15 lbs.). Some contraindications include pregnancy, heart or liver disease, and breast cancer. As of November 1992, the FDA had not announced the cost or whether there would be a reduced price for family planning and public health clinics. Women's health and rights advocates plan on monitoring introduction of Depo-Provera to make sure that women have received comprehensive information and were not coerced to use it.
SCIENCE. 1992 Jun 26; 256:1754.Depo-Provera (DP) was unanimously recommended for approval as a contraceptive by a Food and Drug Administration (FDA) advisory committee. This had happened once before in the mid-1970s, but Congress raised concerns about DP's possible link to cervical cancer. DP has been in use for 20 years as a treatment for uterine cancer. DP is an injectable progesterone analog that induces infertility for 3 months in 99% of the women who use it. It is already in use in 90 countries and has annual sales of US$100 million. The 4 annual shots cost US$120 and is an economical alternative to Norplant. There are still many unanswered questions about its safety. A recent WHO study found that it increased breast cancer by 21%, which was almost statistically significant. However, in the <34 age group breast cancer was twice as common, which is statistically significant. DP was found to increase the number of breast cancer cases by 5.6/100,00; but, it reduced the number of uterine cancer cases by 19.2/100,000. A New Zealand Hospital study found that DP use reduced bone density by 7.5% in the lumber spine and 6.5% in the neck of the femur. Critics charge that Upjohn has had 20 years to compile data but has failed to do so. There is little or no data about its effect on developing fetuses, osteoporosis, or the mechanism that causes breast cancer. All these areas were recommended for follow-up study by the FDA advisory committee.
SOUTH AFRICAN MEDICAL JOURNAL. 1992 May 2; 81(9):444-5.The advantages and side effects of the injectable contraceptive, Depo-Provera, are highlighted. It has been available to women in South Africa and in about 90 developing and developed countries for 20 years. It is an effective and convenient contraceptive with no serious side effects. Its failure rate is 0.2-0.6/100 woman years. Nevertheless there is still concern that it may cause breast cancer because original tests of Depo-Provera using beagles indicated that it may increase breast cancer risk. WHO and the UK Committee on Safety of Medicines have since dropped the requirement of testing of beagles since they cannot predict the effects of steroids on women. A 12-year WHO multinational, hospital-based case-control study on neoplasia and hormonal contraceptives reassures Depo-Provera's safety. For example, the risk of breast cancer did not increase with duration or in women who had used it for >5 years. The risk was higher, however, among women who had used it for <4 years, particularly <35-year old women. The same holds true for oral contraceptive (OC) users. It has been suggested that this slight increase is because Depo-Provera and OCs may accelerate growth of some existing, previously undetected breast tumors. The WHO study verifies that the benefits of Depo-Provera surpass the side effects which include disturbed bleeding patterns, weight gain, and headaches. For example, it decreases the risk of ovarian and endometrial cancer. It is even more beneficial in developing countries where women often suffer from anemia because it increases hemoglobin levels. Further since women in developing countries cannot always comply and take their OCs, Depo-Provera can grant them the protection they need against pregnancy thus saving many lives. Depo-Provera should be available in developed as well as in developing countries.
CONTRACEPTION. 1992 Apr; 45(4):363-8.Researchers analyzed interview and physician records' data on 45 women with breast cancer (cases) admitted to the Central Institute of Cancer Research in Berlin, East Germany between November 1982-June 1986 and born in 1983 or later and 194 women (controls) admitted to the Klinikum Berlin-Buch also in East Germany for conditions other than breast cancer to compare recall accuracy in women who had ever used an IUD. These women were drawn from case control study of the relationship between breast cancer and oral contraceptive use was part of the WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Agreement between patient recall and physician records was exceptional for duration of IUD use (p<.001), number of IUD episodes (kappa=0.79), time since 1st IUD and time since last IUD use (p<.001). Agreement rates did not differ between cases and controls. 75% of the women could not name the IUD brand used so the researcher could not examine agreement of brand name. Thus, other than brand name, this study showed that validity of information on IUD use obtained from interviews is significant. In fact, it also pointed out that case control studies probably yield sound relative risk estimates.
The WHO Collaborative Study of Neoplasia and Steroid Contraceptives: the influence of combined oral contraceptives on risk of neoplasms in developing and developed countries.
CONTRACEPTION. 1991 Jun; 43(6):695-710.A hospital-based case-control study was conducted in 8 developing and 3 developed countries to determine whether use of combined oral contraceptives (OCs) alters risks of various cancers. An observed trend of increasing risk of invasive cervical cancer with duration of use may not represent a causal relationship and is the subject of further study. Decreased risks of ovarian and endometrial carcinomas in users likely indicate a protective effect of OCs, the degree of which was similar in developing and developed countries. A small increase in risk of breast cancer in recent and current users was found to be somewhat greater in developing countries. Both causal and noncausal interpretations of this finding have been offered. No associations were found between OCs and in situ cervical, hepatocellular, cholangio, or gallbladder carcinomas, or uterine sarcomas. However, the ability of this study to detect alterations in risks for these neoplasms in longterm users was low. (author's)
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.
CONTRACEPTIVE TECHNOLOGY UPDATE. 1992 Jan; 13(1):15-6.A recent World Health Organization (WHO) study found that women using Depo-Provera have only a slight increased risk of breast cancer. WHO examined case-control data from 5 hospitals in Africa, Mexico, and Thailand. The study revealed a 1.21 relative risk of breast cancer among all women in the study who had used Depo-Provera (a relative risk of 1.0 means that there is neither an increased or decreased likelihood to develop the disease in question). A relative risk of 1.21 indicates that there is a 21% increased likelihood of developing the disease, but any relative risk of less than 2.0 is considered slight. The study also found that among the diagnosed breast cancer cases, 12.5% had ever used Depo-Provera, compared to 12.2% among the control patients. Although an increased risk of breast cancer among women--especially women under 35--within the first 4 years of exposure to Depo-Provera was found, the risk did not increase with the duration of use, and it did not increase among women who had used the drug for more than 5 years. WHO explains that the risk of breast cancer among Depo-Provera user is similar to that found among oral contraceptives users, whose relative risk ranges from 1.0-1.42. Based on their findings, WHO investigators estimate that there would be 7-8 new cases of breast cancer per 100,000 Depo-Provera users annually, compared to 5 new cases annually among women who had not used the drug. As a recent commentary by Family Health International (FHI) points out, this increased risk of breast cancer must be weighted against the benefits provided by Depo-Provera. FHI concludes that there is a net gain for women using Depo-Provera, since despite the slight risk of breast cancer, it would result in a higher life expectancy compared to women not using contraception.
PACIFIC BASIN MATERNAL AND CHILD HEALTH RESOURCE CENTER WHAT'S NEW IN.... 1991 Dec; 3(58):1-2.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.
WORLD HEALTH STATISTICS QUARTERLY. RAPPORT TRIMESTRIEL DE STATISTIQUES SANITAIRES MONDIALES. 1987; 40(3):267-78.The primary cause of death in women in the world is cancer. In most developing countries cancer of the cervix is the most prevalent cancer. Breast cancer has this distinction in Latin America and the developed countries of North America, Europe, Australia, and New Zealand. It is also the most prevalent cancer worldwide. The most common cancer in Japan and the Soviet Union is stomach cancer. Effective early detection programs can reduce both breast and cervical cancer mortality and also the degree and duration of treatment required. In Iceland, cervical cancer mortality declined 60% between the periods of 1959-1970 and 1975-1978. Programs consist of mammography, physician breast and self examination, and Pap smear. The sophisticated early detection equipment and techniques are expensive and largely located in urban areas, however, and not accessible to urban poor women and rural women, especially in developing countries. Tobacco smoking attributes to 80-90% of all lung cancer deaths worldwide and 30% of all cancer deaths. Passive smoking increases the risk of lung cancer to 25-35% in nonsmokers who breathe in tobacco smoke. Since smoking rates of women are skyrocketing, health specialists fear that lung cancer will replace cervical and breast cancers as the most common cancer in women worldwide in 20-30 years. Tobacco use also contributes to the high incidence of oral cancer in Southern and South Eastern Asia. For example, in India, incidence of oral cancer in women is 3-7 times higher than in developed countries with the smoking and chewing of tobacco in betel quid contributing. Techniques already exist to prevent 1/3 of all cancers. If cases can be discovered early enough and adequate treatment applied, another 1/3 of the cases can be cured. In those cases where the cancer cannot be cured, drugs can relieve 80-90% of the pain.