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The World Health Organization multinational study of breast-feeding and lactational amenorrhea. II. Factors associated with the length of amenorrhea.
Fertility and Sterility. 1998 Sep; 70(3):461-471.The objective was to determine the relation between infant feeding practices (and other factors) and the duration of postpartum amenorrhea, and to establish whether there are real differences in the duration of postpartum amenorrhea for similar breast-feeding practices in different populations. Design: Prospective, nonexperimental, longitudinal follow-up study. Setting: Five developing and two developed countries. Patient(s): Four thousand one hundred eighteen breast-feeding mothers and their infants. Breast-feeding women collected ongoing information about infant feeding and family planning practices, plus the return of menses. Fortnightly follow-up occurred in the women's homes. A multivariate analysis explored the association between the risk of menses return and 16 infant feeding variables and 11 other characteristics. Ten factors (in addition to center effects) were significantly related to the duration of amenorrhea. Seven of these were infant feeding characteristics and the remaining three were high parity, low body mass index, and a higher frequency of infant illness. The breast-feeding stimulus is strongly linked to the duration of postpartum amenorrhea. Cross-cultural effects also are extremely important and may have caused the variations in feeding, the variation in amenorrhea, or both. (author's)
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.
The World Health Organization multinational study of breast-feeding and lactational amenorrhea. IV. Postpartum bleeding and lochia in breast-feeding women.
FERTILITY AND STERILITY.. 1999 Sep; 72(3):441-7.The main purpose of this study was to compare the duration of postpartum lochia among 7 groups of breast-feeding women, and in addition, to investigate whether age, parity, birth weight, or the amount of breast-feeding affects this duration. The participants included 4118 breast-feeding women aged 20-37 years living in China, Guatemala, Australia, India, Nigeria, Chile, or Sweden. The duration of lochia, frequency of an end-of-puerperium bleeding episode, and frequency of post-lochia bleeding episodes within 56 days of delivery were measured. This study revealed that the median duration of lochia was 27 days and varied significantly among the centers (range, 22-34 days). In about 11% of the women, lochia lasted >40 days. An end-of-puerperium bleeding episode around the 40th day postpartum was reported by 20.3% of the women. Bleeding within 56 days of delivery (separated from lochia by at least 14 days) occurred in 11.3% of the women and usually was followed by a confirmatory bleeding episode 21-70 days later. This study was able to quantify the average duration of postpartum lochia at 3-5 weeks, with significant variations by population. Lochia durations of >40 days were not unusual. A separate and distinct end-of-puerperium bleeding episode occurred in 1 out of every 4-5 women, although it is unclear how this phenomenon is clinically, socially, or culturally significant.
The World Health Organization multinational study of breast-feeding and lactational amenorrhea. III. Pregnancy during breast-feeding.
FERTILITY AND STERILITY.. 1999 Sep; 72(3):431-40.This prospective longitudinal study aimed to determine the risk of pregnancy during lactational amenorrhea relative to infant feeding status. The participants included 4118 breast-feeding mother-infant pairs, with maternal age of 20-37 years, recruited from 7 study centers located in China, Guatemala, Australia, India, Nigeria, Chile, and Sweden. Infant feeding practices, menstrual status, and the number of pregnancies were recorded. The results revealed that in the first 6 months after childbirth, cumulative pregnancy rate during amenorrhea, depending on how the end of amenorrhea was defined, ranged from 0.9% (95% confidential interval (CI) = 0-2%) to 1.2% (95% CI = 0-2.4%) during full breast-feeding, and from 0.7% (95% CI = 0.1-1.3%) to 0.8% (95% CI = 0.2-1.4%) up to the end of partial breast-feeding. At 12 months, the rates ranged from 6.6% (95% CI = 1.9-11.2%) to 7.4% (95% CI = 2.5-12.3%) during full breast-feeding, and from 3.7% (95% CI = 1.9-5.5%) to 5.2% (95% CI = 3.1-7.4%) up to the end of partial breast-feeding. Regardless of the degree of supplementation, the pregnancy rate increased with time from 6th to the 12th month postpartum. Overall, the rate of pregnancy during amenorrhea was unaffected by variations in the return of menses. This large, multicenter study found that the cumulative 6-month rate of pregnancy during lactational amenorrhea was between 0.8% (95% CI = 0-1.4%) and 1.2% (95% CI = 0-2.4%). This is equivalent to the protection provided by many nonpermanent contraceptive methods as they are actually used and upholds the 1988 Bellagio Consensus.
[Lactation-induced amenorrhea as birth control method] Lactatieamenorroe als geboorteregelingsmethode.
NEDERLANDS TIJDSCHRIFT VOOR GENEESKUNDE.. 1998 Jan 10; 142(2):60-2.In 1966 WHO published a document on improving access to quality care in family planning, which who pronounced to be a fundamental human right. According to this document, despite the assortment of reliable contraceptives worldwide 350 million people have unmet need for contraception because of lack of access or availability. Adequate reproductive health depends not only access to contraceptives, but also on adequate screening and treatment of anemia, sexually transmitted diseases, and cervical carcinoma. Among 8 groups of birth control methods studied, the lactational amenorrhea method (LAM) was dealt with in detail. The underlying mechanism lies in the stimulation that breastfeeding brings about and in breastfeeding's suppression of the release of gonadotropin- releasing hormone and of dopamine (the prolactin inhibiting factor). A 1974 investigation in Rwanda demonstrated that 50% of rural women who breast fed their children frequently got pregnant within 23 months of childbirth and that 50% of city women became pregnant 9 months postpartum. The Bellagio consensus has stated that LAM provides 98% protection against pregnancy in the first 6 months postpartum as long as breast feeding is the exclusive feeding method practiced. A 1992 analysis of 9 prospective studies reported that 6 months postpartum only 0.7% of the women using LAM became pregnant. LAM still plays a crucial role in Africa, where the average number of children per woman is 6. Without breastfeeding the estimated figure would be 10.
JOURNAL OF BIOSOCIAL SCIENCE. 1992 Jul; 24(3):379-81.WHO Simplified Methodology (1987) is being applied in several studies: the Task Force on Methods for the Natural Regulation of Fertility of the Special Program on Human Reproduction in centers in Chendu, China; Guatemala City, Guatemala; New Delhi, India; Sagamu, Nigeria; Santiago, Chile; Uppsala, Sweden; and Westmead/Sydney, Australia. 550 lactating mothers who can read and write were examined in order to provide a better understanding of the relationship between breast-feeding duration and lactational amenorrhea, and to determine whether the longitudinal study results are applicable to the general population. Protocol involved data collection of breast-feeding frequency, timing, and duration; supplementary feeding characteristics and timing; and maternal and infant health. WHO protocol is also being examined in studies in Colombo, Sri Lanka, and Sagamu, Nigeria. The study objective was to examine the effect of maternal nutritional supplementation with skimmed milk powder in Colombo and a high protein biscuit in Sagamu on the duration of lactational amenorrhea in moderately malnourished breast-feeding mothers. Followup studies are expected. Optimally, the end product should be a measure of the presence of ovulation, however, the logistics prevented this from occurring. Instead, weekly urine samples were collected and tested for the presence of estrogen and pregnanediol glucuronide. Motivation is a key determinant in the success of these projects, since detailed record keeping over a prolonged period of time is required. Motivational interventions vary between centers and may involve social contact with investigators or health care support for the mother and infant. Some preliminary results indicate that the higher the percentage receiving supplementation, the earlier the return of the menses.
ENTRE NOUS. 1991 Dec; (19):15.About 8 million women use the long acting injectable contraceptive depot-medroxy-progesterone acetate (DMPA) and norethisterone enanthate (NET-EN). These progesterone only injectables are not dependent on sexual activity and are easy to administer. Yet they are not always well accepted since they can interfere with menstrual bleeding and often induce amenorrhea. Researchers find that adding estrogen to DMPA and NET-EN treats these irregularities. They must use esters with limited action to protect the endometrium from constant estrogens, however, which requires monthly injections. Thus bleeding occurs once a month just like the normal menstrual cycle. Clinical trials in China of Injectable No. 1 (250 mg 17-alpha-hydroxyprogesterone caproate and 5 mg estradiol valerate) show that it has few side effects and is acceptable. Other trials in China are evaluating monthly injectables with NET-EN or megestrol acetate. Numerous developing countries often as WHO's Special Programme of Research in Human Reproduction for effective, safe, and fully studied monthly injectables. WHO operates under a 2 part strategy: optimum improvement of HPR 102 (50 m NET-EN and 5 mg estradiol valerate) and Cyclofem (25 mg DMPA and 5 mg estradiol cypionate) resulting in a reduction of the dose of at least 1 of the hormones and results of a study of the efficacy and side effects of these 2 injectables. It hopes the study provides the impetus to introduce them into national family planning programs. It demonstrates that they are indeed efficacious, effect fewer changes in the menstrual cycle than the progesterone only injectables, and are well accepted, even though women must go to a clinic every 27-33 days for an injection. Other studies are determining their effects on lipid and glucose metabolism, coagulation, and fibrinolysis. They are also looking at the time needed for ovulation to return. 1 study shows that menstruation returned in all women by the 3rd cycle.
CONTRACEPTION. 1988 Aug; 38(2):165-79.Researchers recruited 1216 females to study changes in amenorrhea patterns with successive injections of the long acting injectable contraceptive depot-medroxyprogesterone acetate (DMPA). The women received an injection of either 100 mg or 150 mg DMPA on the day of randomization and 3 additional injections at 90 day intervals. 1151 (94.7%) women completed a menstrual diary that could be used, but only diaries of at least 60 days were considered in each reference period (90 days). Of the 99 who received only 1 100mg injection, 23 had amenorrhea. Of the 361 receiving 4 injections, 142 experienced no amenorrhea in any of the injection intervals and 30 had amenorrhea in all 4 intervals. Overall 281 women out of 576 who received 1-4 injections of 100 mg DMPA did not experience amenorrhea at all. For those in the 150 mg sample receiving 1-4 injections, 237 out of 575 women did not have amenorrhea. Analysis of change over time suggested an increase incidence of amenorrhea following the 2nd injection. In terms of the probability of a woman accepting a injection, women who experienced amenorrhea with the 1st injection were less likely to accept a 2nd, especially in the 150 mg DMPA group. Additionally, the trend in amenorrhea pattern demonstrated that a 3rd injection was adversely affected by amenorrhea in the 2nd injection interval in the 150 mg group but not the 100 mg group. Nevertheless, the decision to have a 4th injection appeared adversely affected by amenorrhea in the 3rd injection interval in both groups. The conditional probabilities used in this research can also be applied to examine continuation or survival rates in a follow-up study based on any prognostic factors.
JAMA. 1988 Dec 9; 260(22):3286-9.In Africa, as in many developing countries where AIDS has been documented, the specific serologic test for antibody to the human immunodeficiency virus is not feasible, and the case definition of the Centers for Disease Control is impracticable because facilities for diagnosing the opportunistic infections are inadequate and the clinical spectrum of AIDS is different in tropical countries. The World Health Organization developed a clinical case definition at a 1985 AIDS workshop in the Central African Republic. It was tested to determine its generalizability in Zaire, and the present paper is a report on experience using the definition to identify AIDS in Uganda. A clinical case of AIDS is defined by the presence of at least 2 major signs and 1 minor sign. The major signs are fever for more than 1 month, weight loss greater than 10%, and chronic diarrhea for more than 1 month. The minor signs are persistent cough for more than 1 month, pruritic dermatitis, herpes zoster, oropharyngeal candidiasis, ulcerated herpes simplex, and general lymphadenopathy. The presence of disseminated Kaposi's sarcoma or disseminated cryptococcosis is sufficient by itself to diagnose AIDS. The Uganda study included 1328 patients at 15 hospitals. 562 patients (42%) tested positive by enzyme-linked immunosorbent assay, and 776 (58%) tested negative. 424 patients (32%) met the world Health Organization clinical case definition for AIDS. The World Health Organization definition had a sensitivity of 55%, a specificity of 85%, and a positive predictive value of 73%. However, so many of the patients in this sample had active tuberculosis that it was decided to substitute "persistent cough for more than 1 month without concurrent tuberculosis" as a minor sign in place of "cough for longer than 1 month." With this modification 350 patients met the clinical case definition for AIDS. Sensitivity dropped to 52%, but specificity rose to 92%, and positive predictive value rose to 83%. Moreover, 26% of the seropositive females indicated amenorrhea as a symptom. Addition of amenorrhea to the modified case definition gave it a sensitivity of 56%, a specificity of 93%, and a positive predictive value of 86%. However, this is the 1st report of amenorrhea as a symptom of AIDS, and it may only be a symptom of severe weight loss in women of childbearing age. The findings in the Ugandan experience support the generalizability of the modified World Health Organization clinical case definition of AIDS and its use for surveillance purposes in Africa.
Healthright. 1985 Aug; 4(4):9-12.The pattern of reproductive activity displayed by early hunter-gatherer ancestors, before the dawn of civilization, must have been vastly different from today's pattern. In the absence of contraception such women would have spent the greater part of their reproductive lives either pregnant or in lactational amenorrhea. In developing these ideas further it was estimated that a hunter-gatherer woman would have spent about 15 years in lactational amenorrhea, whereas just under 4 years would have been occupied by her 5 pregnancies, and she would only have had about 4 years of menstrual cycles. The total number of menstrual cycles she would experience in her entire life would be no more than about 50. This is in marked contrast to the situation today in a typical Western woman using contraceptives and experiencing menarche at 13 and the menopause at 50. Allowing her 2 years' respite from cycles during her 2 pregnancies, each followed by only a token period of breastfeeding, this leaves 35 years during which she would experience about 420 menstrual cycles. The conclusion is that an excessive number of menstrual cycles is an iatrogenic disorder of communities practicing any form of contraception. Thus, it is important to note that even the condom or vasectomy have important repercussions on the female's reproductive cycle. Since 99.9% of human existence has been spent living a nomadic hunter-gatherer life, this high frequency of menstrual cycles is a new experience, one that humans may be genetically ill-adapted to cope with. In fact, there are a number of "diseases of nulliparity" whose incidence is markedly increased in women with few or no children and who are therefore experiencing an increased number of menstrual cycles. These diseases include carcinoma of the breast, endometrium and ovaries, and endometriosis. As part of the effort to develop contraceptives that promote a healthy state of fertility, it is necessary to ask the question, "is a period really necessary?" To learn if women women accept a contraceptive method that reduced the frequency of menstruation, a clinical trial of an oral contraceptive was conducted. The OC was administered in such a way as to produce a withdrawal bleed only once every 3 months. This was termed the tricycle pill regimen. 196 women attending a family planning clinic in Edinburgh, Scotland, volunteered to participate, although 89 of them subsequently withdrew from the trial for a variety of reasons before it was completed at the end of a year. Overall, 82% of the women positvely welcomed the reduction in the number of periods; 91% of the women who completed the trial even refused to revert to a standard monthly OC regimen thereafter. The findings were in complete contrast to the results of a World Health Organization survey of patterns and perceptions of menstruation. But the WHO sample was highly biased in favor of women having regular menstrual cycles, and hence quite unrepresentative of the population as a whole. In sum, even the most pessimistic estimate of the WHO's menstruation survey shows that a proportion of women in every country investigated were prepared to accept amenorhea as a by-product of contraception. Reversible amenorrhea might become an increasingly popular form of contraception, and it might also confer significant health benefits.
In: Zatuchni GL, Goldsmith A, Shelton JD, Sciarra JJ, ed. Long-acting contraceptive delivery systems. Philadelphia, Pa., Harper and Row, 1984. 1-19. (PARFR Series on Fertility Regulation)Depo-Provera (depomedroxy-progesterone acetate, or DMPA) and NORPLANT (the Population Council's registered trade name for subdermal implants) are focused on in this literature review. Over the past 17 years, more than 1 million individual doses of Depo-Provera have been supplied in Thailand. Currently 6,000 women a month use the method. Depo-Provera has proved outstandingly successful in Bangladesh for years. The basic disadvantage of long-acting steroid systems is that return to fertility is slow and unpredictable. Other disadvantages include menstrual distrubances and weight gain. Acceptability of injectable contraceptives has been studied primarily by the World Health Organization (WHO). In 1976, the Task Force on Acceptability of Research and Family Planning explored preferences among 3 routes of contraceptive administration: 1)oral; 2)intravaginal; and 3)injection. The study was conducted in Indonesia, Korea, Pakistan, and Thailand. Although the oral route was generally preferred by most women, many respondents still chose the injectable. A WHO III multicentered trial comparing the use, effectiveness, side effects and bleeding patterns of Depo-Provera and norethisterone enanthate (NET-EN) was terminated after only 1 year because of excessively high pregnancy rates with NET-EN. A total sample of about 250 women in Manila and Alexandria were interviewed. Results indicated that the 2 most important considerations were effectiveness and menstrual bleeding. Depo-Provera did not affect menstruation. Various types of subdermal implants releasing a contraceptive Silastic implant, is placed beneath the skin of the forearm or upper arm and provides 5 or more years' protection against pregnancy. The 6 capsules are not biodegradable and require surgical removal under local anesthesia.
London, International Planned Parenthood Federation, 1984. 43 p. (IPPF Medical Publications)This booklet, for health care workers in developing countries, reviews the fertility-controlling effects of breastfeeding, its strengths and limitations as an element in family planning, and how to provide modern methods of contraception to lactating women. Breastfeeding currently provides about 30% more protection against pregnancy in developing countries than all of the organized family planning programs. The recent trend toward a falling off in the practice of breastfeeding poses a threat to infant welfare and a danger of increased fertility. Health workers are urged to reach pregnant women in the community with knowledge about the value of breastfeeding versus bottle feeding. Each country must set its own policies concerning contraception for lactating women. It is preferable for lactating women to use nonhormonal methods, but if selected, they should not be used too early. Lowest-dose preparations, especially progestogen-only pills, are preferable. Determination of when to start contraception during lactation should be based on breastfeeding patterns in the community, the age at which supplementary foods are introduced, usual birth spacing intervals, and the mean duration of lactation amenorrhea. If the usual time of resumption of menstruation in a given community is known, a rough guide to the optimal time for starting contraception is returning menstruation minus 2 months.
Multinational comparative clinical trial of long-acting injectable contraceptives: norethisterone enanthate given in two dosage regimens and depot-medroxyprogesterone acetate. A preliminary report.
Contraception. 1982 Jan; 25(1):1-11.A multicenter phase 3 clinical trial compared norethisterone enanthate (NET-EN) given by 2 different treatment regimens and depot-medroxyprogesterone acetate (DMPA). After 18 months of observation, preliminary findings are reported for 790 women who received NET-EN 200 mg every 60 days; for 796 women who recieved NET-EN every 60 days (200 mg) for 6 months, then 200 mg every 84 days, and for 1589 women who received DMPA 150 mg every 90 days. Overall discontinuation rates and discontinuation for bleeding and personal reasons were similar for all 3 groups after 18 months observation (61.8-63.5/100 women). Terminations due to amenorrhea were significantly higher among DMPA users (12.1 and 17.4/100 women at 12 and 18 months) than among both NET-EN groups (6.8-8.2/100 women at 12 months and 10.4-10.9/100 women at 18 months). The only significant difference in pregnancy rates observed among the 3 groups was a higher rate at 18 months among NET-EN (84 days) users (1.6/100 women), than among DMPA users (0.2/100 women). There was no overall significant difference between the 2 NET-EN groups, although between the 6 and 18 month follow-ups when the 2 NET-EN regimens diverged, the NET-EN (84 days) users' pregnancy rates rose significantly, whereas in the NET-EN (60 days) group, the pregnancy rate did not change. Weight gain was significantly higher in those subjects using NET-EN at 60 day intervals than at 84-day intervals. (author's modified)
Activities of the Special Program of Research, Training and Development in Human Reproduction, World Health Organization in the field of long acting contraceptives.
In: Bangladesh Fertility Research Program. Workshop on Injectable Contraceptives: Noristerat, Dacca, Bangladesh, April 25, 1980. [Dacca, Bangladesh, BFRP, 1980]. 70-80.Following a brief introduction to the World Health Organization (WHO) Special Program of Research, Development and Research Training in Human Reproduction, established in 1972, focus is on what has been achieved thus far with long-acting injectable fertility regulating agents based on steroidal hormones and possessing a duration of action of at least 1 month. Over the last 20-year period, several estrogen-progestin combinations have been developed as monthly injectable contraceptives. The Special Program has initiated a series of clinical pharmacological studies aimed at developing new and improved estrogen progestin injectable formulations. 1 preparation, composed of norethisterone enanthate (50 mg) plus 5 mg of estradiol valerate, has shown promise in preliminary clinical studies. 3 progestogen only preparations with a duration of action of several months have been tested clinically: clormadinone acetate, depo-medroxyprogesterone acetate and norethisterone-enanthate. The 1st clinical trials utilizing the heptanoic acid ester of norethisterone raised considerable hopes, for no pregnancies were observed in 70 highly fertile women given the drug every 90 days. In a WHO trial preliminary data on Depo-Provera (DMPA) bleeding irregularities were responsible for the discontinuation of 9.3 subjects/100 women-years; prolonged amenorrhea accounted for the termination of 11.5 subjects/100 women years. There are several ongoing studies to evaluate the effects of the injectables on users. Norethisterone enanthate, although not possessing the same degree of effectiveness as DMPA, when adminstered every 3 months, remains an attractive injectable because of its lower incidence of amenorrhea.
In: Raphael, D., ed. Breastfeeding and food policy in a hungry world. New York, Academic Press, 1979. p. 245-251The World Health Organization has undertaken an extensive survey of breastfeeding practises in an attempt to analyze prevalence, duration, motivation, attitude and demography of lactating mothers. A point prevalence study was implemented in 1975 in 10 locations. Mothers from 3 groups: urban elite, urban, and rural, were interviewed concerning background, medical history, pregnancy conditions, postnatal infant care, feeding schedules and diet, return of menstruation, and family planning behavior. 5 additional surveys were conducted among approximately 20,000 women. The first was a health, demographic, and socioeconomic survey. The second was an assessment of infant food marketing practises. The third survey was of health-related workers regarding their knowledge and training. The organization and delivery of health services and the social support systems for lactating mothers comprised the fourth and fifth surveys. Following these surveys WHO also conducted a cross-sectional study of the volume and composition of breast milk. The results of the studies will be input for an action program.
In: Raphael, D., ed. Breastfeeding and food policy in a hungry world. New York, Academic Press, 1979. p. 253-258UNICEF has promoted breastfeeding in developing countries through health service innovations such as nutrition rehabilitation centers and under 5s clinics. UNICEF has also helped establish departments of social pediatrics and sponsored special training programs for pediatricians in developing countries. It helped put 240 milk plants in operation in 40 countries. Skim milk powder has been distributed in the largest quantity in food-aid programs. Other milk substitutes include immature coconut milk, soy milk, whole milk powder, cheese, and butter oil. Some cases of severe malnutrition do not respond to milk unless the lactose is replaced with sucrose, some protein and fat. K-MIX-II has been distributed since 1970 and consists of skim milk powder, calcium caseinate, and sugar. Fat and water are added at the point of consumption.
Multinational comparative clinical evaluation of two long-acting injectable contraceptive steroids: norethisterone oenanthate and medroxyprogesterone acetate. 1. Use-effectiveness.
Contraception. 1977 May; 15(5):513-533.A 10-center study of the use-effectiveness of long-acting systemic contraceptive agents is reported. 200 mg of norethisterone enanthate (NET-EN) was administered every 12 weeks + or -5 days to 832 women and 150 mg of depot medroxyprogesterone acetate (DMPA) was administered to 846 women on the same schedule. The cumulative 12-month gross pregnancy rate/100 woman-years was 3.6 + or -.7 for NET-EN and .7 + or -.4 for DMRA. 54% of all the pregnancies in the NET-EN group was contributed by 2 of the 10 centers. 75% of the NET-EN pregnancies occurred during the 1st injection period, primarily in the last 4 years. The admission weight of NET-EN women who became pregnant was significantly lower than those for whom the method was successful. This difference was absent in the DMPA group. The cumulative discontinuation rate for medical reasons at 12 months was 16.9 + or -1.4/100 woman-years for NET-EN and 23.4 + or -1.7 for DMPA. The discontinuation rate for amenorrhea was significantly higher for DMPA than for NET-EN. Differences between the drugs for bleeding irregularities were insignificant as were discontinuations for nonmedical reasons. This study represents a successful attempt at comparing the use-effectiveness of 2 drugs under highly standardized conditions using a large sample drawn from a number of internationally representative settings.
Design of studies for the assessment of drugs and hormones used in the treatment of endocrine forms of female infertility.
In: Diczfalusy, E., ed. Regulation of human fertility. (Proceedings of the WHO Symposium on Advances in Fertility Regulation, Moscow, USSR, November 16-19, 1976) Copenhagen, Denmark, Scriptor, 1977. p. 135-154The lack of uniformity in diagnostic selection of women for treatment of infertility, in choice of therapy, in monitoring of therapy, and in follow-up, frequently does not allow a meaningful comparison of results reported from different centers. To design studies assessing effectiveness of therapy of endocrine forms of female infertility, it is essential to consider: 1) mechanism controlling reproductive functions (e.g., process of ovulation); 2) cause(s) responsible for infertility (mechanical factors, ovarian failure, and pituitary failure); and 3) the mechanism of action of agents used for therapy (e.g., gonadotropins stimulate gonadal function, clomiphene stimulates gonadotropin secretion, and ergoline derivatives inhibit prolactin secretion). Patients selected for therapy should be grouped according to etiology: 1) hypothalamic-pituitary failure; 2) hypothalamic-pituitary dysfunction; 3) ovarian failure; 4) congenital or acquired genital tract disorder; 5) hyperprolactinemic patients with a space-occupying lesion in the hypothalamic-pituitary region; 6) hyperprolactinemic patients with no space-occupying lesion; and 7) amenorrheic women with space-occupying lesion. Ideally, an infertile couple should be diagnosed and treated as a unit.
Multinational comparative clinical evaluation of two long-acting injectable contraceptive steroids: norethisterone oenanthate and medroxyprogesterone acetate: 2. bleeding patterns and side effects.
Contraception. 1978 May; 17(5):395-406.A WHO sponsored comparative trail (9 centers) studied the bleeding patterns and side effects experienced by 1678 women using injectable (every 12 weeks) norethisterone enanthate (NOR) and depot-medroxyprogesterone (DMPA). 388.8 women-years of menstrual experience with NOR and 372.5 with DMPA were studied. The percentage of women with total amenorrhea with DMPA was significantly higher than with NOR for all injection intervals. The porportion of women with total amenorrhea increased significantly over time with both drugs (chi-square=33.9 for NOR and 73.4 for DMPA; P < .001). After 1 year, 35% of DMPA and 8.6% of NOR users had total amenorrhea. With NOR, the cycle length distribution changed markedly over time, with the percentage of short cycles under 25 days diminishing as the percentage of long cycles in excess of 46 days increased. In contrast, DMPA held cycle length patterns more or less constant. Length of bleeding and spotting episodes were significantly greater with DMPA. The mean number of bleeding/spotting days decreased over time with both drugs; the difference from the 1st to 4th injection was statistically significant (P < .001). Though the overwhelming majority of women experienced abnormal cycles with both drugs, the percentage of normal cycles remained fairly constant during consecutive intervals. Headache was the most frequently reported complaint: 10.7% of DMPA and 6.9% of NOR users. Other nonmenstrual side effects were reported with similar frequencies in both groups.
September 1975. 41 p.Information gathered from knowledgeable sources (e.g., obstetricians, family doctors, pharmacists, nurses, family planning workers, and informal social network representatives) indicated the important position that menstrual bleeding, and the social implication related to it, holds in the life of Egyptian women. Menstrual bleeding is a sign of well-being, youth, fertility, and femininity. The majority of knowledgeable sources agreed that a normal cycle length among Eyptian women ranged from 21-32 days, whereas the normal bleeding interval ranged from 3-5 days. Abnormality, however, is a function of personal experience, i.e., a cycle is abnormal when it deviates from the woman's normal pattern. Egyptian women perceive menstrual blood as bad blood that they must lose every month, the retention is thought to result in bodily poisoning. Egyptian women are aware of specific color, smell, and texture of vaginal bleeding, and any change in quality or quantity is alarming. Illiterate women predict and recall their bleeding episodes by using a lunar calender which indicates national or religious ceremonies. Menarch is reported to be an occasion of joy signifying womanhood, whereas menopause is resented and dreaded, associated with drying or shrinking of the uterus. Menstruation is induced by various folk means, because it is believed that retention of blood causes cramping and that blood flow will alleviate that pain. The cleansing ritual after each cycle has both physical and religious importance.
Contraception. 1982 Mar; 25(3):231-41.A randomized, controlled, clinical trial comparing 6 combined oral contraceptives (OCs) with 50 mcg or less of ethinyl estradiol was undertaken in 10 WHO Collaborating Centers for Clinical Research in Human Reproduction. A total of 2430 women entered the trial and were observed for 28,077 woman-cycles. All low-dose combined OCs demonstrated equivalent efficacy with 1-year pregnancy rates of 1-6%. However, discontinuation rates for medical reasons differed significantly between the treatment groups with the preparation containing 20 mcg ethinyl estradiol and that containing 400 mcg norethisterone acetate being associated with higher discontinuation rates due to bleeding disturbances. Even among the preparations which did not differ in discontinuation rates, the reasons for discontinuation did differ. Women receiving norethisterone preparations tended to discontinue because of bleeding disturbances while those receiving the levonorgestrel-containing preparations tended to discontinue because of complaints of nausea and vomiting. (author's)