Pharmaceuticals and modern statecraft in South Africa: the cases of opium, thalidomide and contraception.

This article provides a history of three pharmaceuticals in the making of modern South Africa. Borrowing and adapting Arthur Daemmrich's term 'pharmacopolitics', we examine how forms of pharmaceutical governance became integral to the creation and institutional practices of this state. Through case studies of three medicaments: opium (late 19th to early 20th century), thalidomide (late 1950s to early 1960s) and contraception (1970s to 2010s), we explore the intertwining of pharmaceutical regulation, provision and consumption. Our focus is on the modernist imperative towards the rationalisation of pharmaceutical oversight, as an extension of the state's bureaucratic and ideological objectives, and, importantly, as its obligation. We also explore adaptive and illicit uses of medicines, both by purveyors of pharmaceuticals, and among consumers. The historical sweep of our study allows for an analysis of continuities and changes in pharmaceutical governance. The focus on South Africa highlights how the concept of pharmacopolitics can usefully be extended to transnational-as well as local-medical histories. Through the diversity of our sources, and the breadth of their chronology, we aim to historicise modern pharmaceutical practices in South Africa, from the late colonial era to the Post-Apartheid present.

Effect of a Multimedia Educational Tool on Contraception Use 1 Year Postpartum.

FUNDING SOURCE: Supported in part by a research grant from Investigator-Initiated Studies program of Organon. The opinions expressed in this paper are those of the authors and do not necessarily represent Organon. CLINICAL TRIAL REGISTRAION: ClinicalTrials.gov , NCT04291040.

Educational Multimedia Tool Compared With Routine Care for the Uptake of Postpartum Long-Acting Reversible Contraception in Individuals With High-Risk Pregnancies: A Randomized Controlled Trial.

OBJECTIVE: To assess whether an intervention with a multimedia educational tool, compared with routine care, would increase the use of long-acting reversible contraceptives (LARC) at 12 weeks postpartum in individuals with high-risk pregnancies. METHODS: In this single-center randomized trial, we assigned individuals aged 13-50 years with high-risk pregnancies to either a multimedia educational tool or routine care. Participants were included during pregnancy through postpartum day 1. Those randomized to the multimedia educational tool (MET) group were provided a tablet with the preloaded 3-5-minute multimedia presentation (https://prezi.com/view/jpFrXaPnnxuqRkcI3A4a/), which was viewed without the presence of research staff and resent by secure email every 4 weeks if undelivered. The primary outcome was uptake of LARC (implant or intrauterine device) within 12 weeks of delivery. The secondary outcomes included overall use of any method of contraception and composite maternal and neonatal adverse outcomes. A priori estimates indicated that 380 participants were needed to detect a 40% difference in use of LARC (baseline 40%; alpha=0.05, power=0.8, assumed loss to follow-up 20%). Relative risk (RR) and number needed to treat (NNT), along with 95% CIs, were calculated. RESULTS: From July 2020 through December 2020, 536 persons were screened and 380 randomized as follows: 190 for the multimedia educational tool and 190 for routine care. Demographic characteristics were similar between groups. The primary outcome-available for more than 90% of participants-was higher in the MET group (32.4%) than in the routine care (RC) group (20.9%) (RR 1.55; 95% CI 1.09-2.21; NNT nine, with 95% CI 5-42). Overall use of contraception was also higher in the MET group than in the RC group (RR 1.16; 95% CI 1.03-1.32). CONCLUSION: Among individuals with high-risk pregnancies, compared with routine care, use of a multimedia-based educational tool increased the uptake of postpartum LARC by 55%. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04291040. FUNDING SOURCE: Funded in part by Investigator-Initiated studies of Organon.

The contraceptive implant.

Contraceptive implants provide long-acting, highly effective reversible contraception. Currently, the only subdermal implant available to women in the United States is the single rod etonogestrel implant, Implanon (N.V. Organon, Oss, the Netherlands) approved by the Food and Drug Administration in July 2006. Implanon is currently approved for 3 years of use, provides excellent efficacy throughout its use, and is easy to insert and remove. Similar to other progestin-only contraceptives, Implanon can cause irregular vaginal bleeding. Implanon has been shown to be safe to use during lactation, may improve dysmenorrhea, and does not significantly affect bone mineral density, lipid profile, or liver enzymes.

Canadian Consensus Guideline on Continuous and Extended Hormonal Contraception, 2007.

OBJECTIVE: To serve as a guideline for health care providers on the use of continuous and extended combined hormonal contraception regimens, to prevent pregnancy, and to delay menses that affect health-related quality of life. OPTIONS: All combined hormonal contraceptive methods available in Canada that may be used in a continuous or extended regimen are reviewed, and the implications are discussed. OUTCOMES: Efficacy of cited regimens and assessment of their side effects, patient safety, medical usage and non-contraceptive benefits, cost-effectiveness, and availability in Canada. Indications for patient counselling are also provided. EVIDENCE: Medline, PubMed, and Cochrane Database were searched for articles published in English between 1977 and May 2007. Relevant publications and position papers from appropriate reproductive health and family planning organizations were also reviewed. VALUES: The quality of evidence is rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: The guideline is intended to help reduce unintended pregnancies and improve health-related quality of life in women who find their menses problematic. Increased awareness and empowerment of women, their partners, and health care professionals will improve their ability to make appropriate choices between continuous or extended and cyclic usage of these regimens. SPONSORS: The development of this guideline has been supported by unrestricted grants from Bayer HealthCare Pharmaceuticals, Janssen Ortho, Organon Canada Ltd., Paladin Labs Inc., Pfizer Canada Inc., and Wyeth Pharmaceuticals.

New approaches for male fertility control: HE6 as an example of a putative target.

Reversible contraceptive methods for males are still not available. During the last few years several marketing studies have clearly shown that men and women would welcome a situation where men could assume responsibility for family planning. Schering AG and Organon are currently collaborating to develop a hormonal method for male fertility control based on the combination of etonogestrel as gestagenic component and testosterone undecanoate. To further optimize male contraceptives in terms of improved efficiency, rapid onset, reversibility, fewer side effects and a convenient method of application, a search for innovative non-hormonal approaches was started. During the last few years, numerous proteins were identified which play a specific role in male fertility. These proteins have first to fulfil a set of indication-specific criteria before a drug discovery process can be initiated. The most important criteria for a putative target protein are tissue-selective expression, crucial biological function in fertility, drugable properties and feasibility of assay development for high-throughput-screening and lead optimization. The G-protein-coupled receptor HE6 was selected as target and the above selection criteria were applied. HE6 displays a preferred epididymis-specific expression pattern and belongs to the superfamily of GPCRs, which are well known to be drugable with small molecules. A knockout mouse was generated which revealed an infertility phenotype with the onset occurring 6 weeks after initiation of spermatogenesis at the latest. Surprisingly, no epididymis-specific phenotype was observed. Instead, the reabsorption of testicular fluid along the efferent ducts was strongly affected. No further obvious side effects were observed in male or female mice. This study with HE6 exemplifies how targets for male contraception have to be validated before drug development can start.

[Insertion problems, removal problems, and contraception failures with Implanon]. / Implanon: difficultés d'insertion et de retrait, échecs contraceptifs.

OBJECTIVE: Analysis of the results of a national pharmacovigilance study on Implanon, a contraceptive implant containing 68 mg of etonogestrel. PATIENTS AND METHODS: This survey concerns cases of pregnancies (contraception failures), of migrations and of insertion or removal problems with Implanon reported to French Regional Drug Pharmacovigilance Centres and to Organon SA between May 2001 and September 2002. RESULTS: In France, 39 unintended pregnancies were reported over 17 months. The pregnancies were in 77% of cases (N = 30) due to an insertion technique error (implant not found when pregnancy has been diagnosed). For 3 patients (7,6%), pregnancy was due to a failure of etonogestrel contraceptive effect, explained twice by its association with an enzymatic inductor drug. For 4 patients (10%), pregnancy was due to an untimely insertion (insertion after day 5 of menstrual cycle or woman already pregnant). For two patients, no information was available. The incidence of reported pregnancies in France is estimated at 0.359 / 10(3) implants [0.246-0.482], in accordance with a typical Pearl Index of 0.06 [0.04-0.08]. Twenty-eight suspected migrations (N = 11), problems or failures in removal of the implant (N = 11) and insertion difficulties (N = 6) were notified, corresponding to an incidence of 0.257/10(3) implants [0.162-0.363]. DISCUSSION AND CONCLUSION: Occurrence of pregnancy is possible with Implanon, due to errors in the insertion technique (device not really inserted) or to a non-respect of the SPC recommendations (drug-drug interaction or untimely insertion). Insertion problems can lead to localisation problems (implant not visible by X-ray) then needing further tests and even harmful practice (removal under general anaesthesia). That is why a real and strict training is highly recommended to physicians.

Alternative methods for feline fertility control: Use of melatonin to suppress reproduction.

PRACTICAL RELEVANCE: Reversible contraceptives are highly desired by purebred cat breeders for managing estrous cycles and by scientists managing assisted reproduction programs. A variety of alternative medicine approaches have been explored as methods to control feline fertility. SCOPE: In the field of veterinary homeopathy, wild carrot seed and papaya have been used for centuries. Both appear to be safe, but their efficacy as feline contraceptives remains anecdotal. In contrast, the use of melatonin in cats has been investigated in a number of studies, findings from which are reviewed in this article. RATIONALE: Cats are seasonally polyestrous (they cycle several times during their breeding season) and are described as long-day breeders because endogenous melatonin negatively regulates estrous cyclicity. Exogenous melatonin administered parenterally also suppresses ovarian activity in cats, and long-term oral or subcutaneous melatonin administration is safe. CHALLENGES: The therapeutic use of melatonin is limited by its short biological half-life (15-20 mins), its poor oral bioavailability and its central effects in reducing wakefulness. Research is required to determine whether higher doses, longer-release formulations, repeated administration or combination implants might overcome these limitations.

Addressing unmet need for long-acting family planning in Ethiopia: uptake of single-rod progestogen contraceptive implants (Implanon) and characteristics of users.

OBJECTIVE: To describe women who accept single-rod progestogen contraceptive implants (Implanon; N.V. Organon, Oss, Netherlands) from community health workers in Ethiopia and to assess whether community-based provision addresses unmet need for contraception. METHODS: Women who accepted Implanon during training events in 4 regions were asked about their characteristics and use of family planning. They were compared with implant users nationally and women with unmet need in the Ethiopia Demographic and Health Survey (DHS). Differences between groups were tested using 2-sample comparisons of proportions and means. RESULTS: On average, Implanon acceptors were younger and had more years of education and fewer children than implant users nationally. Almost one-quarter (22.9%) of all participants had never used contraception before; this was slightly higher among women who chose Implanon (23.1% vs 16.4%; P=0.04). Acceptors were also less likely than non-acceptors to be using contraception (70.8% vs 77.3%; P<0.05) but all women interviewed were more likely to be using contraception than the rural population. Women who accepted Implanon were younger but more educated than women with unmet need for contraception in the 2005 DHS. CONCLUSION: Provision of Implanon at the community level through community health workers is effective in reaching women with the greatest need for contraception.

Effects of an estrogen-free, desogestrel-containing oral contraceptive in women with migraine with aura: a prospective diary-based pilot study.

BACKGROUND: Migraine with aura (MA) is a contraindication to the use of combined oral contraceptives (COCs) because of the increased risk of ischemic stroke. Progestogen-only contraceptive pill (POP) is a safe alternative to COCs and it is preferable in women with cerebrovascular diseases or risk factors for stroke. STUDY DESIGN: Prospective diary-based pilot study. Thirty women with MA (n = 15 who have never used COCs and n = 15 who had previously used COCs were diagnosed according to the International Headache Society criteria. The observational period lasted 9 months during which women filled in a diary with the clinical characteristics of headache attacks. After a 3-month run-in period, each subject received an estrogen-free desogestrel (DSG) (75 mcg/day)-containing OC (Cerazette(®); Schering-Plough, formerly NV Organon, Oss, The Netherlands). Follow-up evaluations were planned at the end of the third and sixth month of treatment. RESULTS: The number (mean±S.D.) of migraine attacks was significantly reduced both in previous COCs users (from 3.9±1.0 to 2.9±0.8; p<.001) and nonusers (from 3.2±0.9 to 2.6±1.3; p<.02) following 6 months of POP use in comparison with the run-in period. Duration of headache pain did not differ significantly in both groups throughout the study. Interestingly enough, a beneficial POP effect on the duration (mean±S.D.) of visual aura (from 16.3±9.5 to 11.4±5.6 min) and on the total duration (mean±S.D.) of neurological symptoms (from 33.6±23.3 to 18.6±18.0 min) was only significantly reported by previous COCs users (p<.001, for both) by the end of the study period. The POP was well tolerated by each woman and the bleeding pattern was variable with a tendency towards infrequent bleeding. CONCLUSIONS: The present study supports the use of the POP containing desogestrel in a population of women with MA and underlines a positive effect on symptoms of aura, especially in MA sensitive to previous use of COCs.

Shortened pill-free interval delivered by new 20 mcg pill. Organon's Mircette scheduled for U.S. debut this summer.

PIP: The new low-dose oral contraceptive (OC), Mircette, is the first pill to shorten the hormone-free interval. The dosing regimen begins with 21 days of 20 mcg of ethinyl estradiol and 150 mcg of desogestrel; the last 7 days start with 2 days of placebo, followed by 5 days of 10 mcg of ethinyl estradiol. These 5 days of ethinyl estradiol are expected to oppose the effect of any follicle-stimulating hormone in promoting growth of a follicle in the estimated 20% of pill takers who are close to ovulation at the end of each pill-free interval. The efficacy trial, which included more than 1000 women followed for 18 menstrual cycles, reported a Pearl index of 1.02. Breakthrough bleeding occurred in 3.5% of the 18 cycles. Less than 3% of women discontinued Mircette use because of menstruation-related side effects. The small amount of estrogen provided by Mircette during the last 5 days of the cycle helps prevent the withdrawal headaches many users of OCs with a longer hormone-free interval experience. Mircette will become available in the US in July 1998.^ieng

Reminder card helps patients remember OCs.

PIP: Organon has developed the Reminder Card to help women patients remember their regular intake of oral contraceptive (OC) pills. About 50% of women take birth control pills as prescribed, 25% miss a pill per month, and 25% miss two or more pills in the same time frame. The plastic card, about the size and shape of a credit card, contains a microchip timer. Reminder cards are available to providers who use the Starter Kits issued by the company for new-start patients on the Mircette OC. When patients begin their first pack of pills, they select the time of day they prefer to have the Reminder Card emit its tiny beep. The time is set into the microchip timer and the card is programmed to sound automatically at the pre-set time each day for the next three months. The direction for using the Reminder Card is outlined.^ieng

Vaginal contraceptive rings: option for the new millennium.

PIP: Vaginal contraceptive rings, currently in advanced clinical trials, offer a simple, long-acting, woman-controlled method of fertility control. A ring developed by the Population Council's Center for Biomedical Research, with continual release of 20 mcg of ethinyl estradiol and 1 mg of norethindrone acetate, has been accepted by a commercial partner for further studies leading to market introduction. Another Population Council-developed ring combines an even lower dose of estrogen (15 mcg) with its own patented progestin, NESTORONE. Organon is in phase III trials of a ring combining 15 mcg of ethinyl estradiol and the progestin etonogestrel and expects to complete its research by mid-1999. Of particular interest is the potential for vaginal irritation. The one-size ring is smaller than most diaphragms and does not require fitting. Once a woman has received instructions, she can insert and remove the ring herself. The ring's regimen of 3 weeks of use and 1 week of rest is similar to the schedule for oral contraceptives (OCs), but provides better cycle control than a combined OC that delivers one-third more of the same progestin and estrogen. Finally, a progestin-only vaginal ring for lactating women has been licensed for manufacture and distribution in Latin America.^ieng

Manufacturers on the fence regarding PPI revisions.

PIP: Oral contraceptive (OC) manufacturers stated that they would comply with the US Food and Drug Administration's (USFDA's) new labeling, as not responding might cause an unwanted delay in the new drug applications. New instructions on how to handle missed pills and what day to start a new cycle package concerns both manufacturers and family planning clinicians. The final version of the instructions was very different from those that Organon Inc. had drafted: the new instructions include 2 options for start days. Several confusing scenarios exist concerning missed pills, dependent upon the day a woman decided to start her package and in which week she missed the pills. A senior research associate at Family Health International in Research Triangle Park, N.C., who helped develop the guidelines, said the manufacturers' suggestions were taken into account and incorporated into a message at then end of the section on missed pills. The vice president for clinical affairs at Ortho Pharmaceuticals in Raritan, N.J., deemed the recommended approach reasonable. However, the new instructions of patient package inserts (PPIs) relating to missed pill scenarios may be too complex for some women because of USFDA's scientific thoroughness. Most individuals involved with the new guidelines believe these instructions can be amended without time-consuming problems as new information on pill use becomes available.^ieng

[Future prospects in contraception]. / Zukunftsperspektiven der Empfängnisverhütung.

PIP: Only 40% of the 1.2 billion couples in reproductive age have access to effective contraceptive methods, although only $3.0 per couple per year would suffice for contraception worldwide. Abortions are performed for 40-60 million women annually. More than 200,000 women die as a result of abortions, and another 500,000 die due to labor complications. Contraception for women comprises the following: 1) agents that prevent ovulation; prolonged breast feeding (98% safe contraception within the first 6 months); oral contraceptives containing estrogens and gestagens (60-80 million women use them worldwide; in 1968 the 50 g estrogen containing pill, in 1972 the micropill with 30 g of ethinyl estradiol [EE], and in 1992 the ultra-low-dose pill with 20 g of EE were introduced); and future developments (third generation progestagens, antigestagens, nonsteroidal natural substances, melatonin, the combination of gonadotropin-releasing hormone analogs and natural estrogens); 2) prevention of fertilization: mechanical methods (diaphragm, sterilization methods by laparoscopy or chemical means); chemical methods (spermicides such as nonoxynol); behavioral methods (temperature methods using refined measurement of the body temperature, cervical mucus resistance); hormonal methods (implants such as Norplant containing levonorgestrel [LNG], Implanon containing 3-ketodesogestrel, the vaginal ring [the WHO-ring and the Organon ring], the minipill with pure gestagen, one-month injection with Cyclofem), IUDs (copper-containing IUDs, LNG-containing IUDs with a Pearl Index of 0.2-0.5 and reduction of dysmenorrhea); and immunological contraception (ovum and spermatozoon antigens); 3) the prevention of implantation: hormonal methods (the morning-after pill with high-dose EE or the combination of estrogen and gestagen); insertion of an IUD up to the 6th day after coitus; immunological methods (human chorionic gonadotropin antibodies, antibodies against the zona pellucida glycoproteins, implantation inhibition through interaction with interleukin IL-1 receptor, and antibodies against specific proteins of the endometrium influencing implantation). Contraception for men consist of the condom, vasectomy, coitus interruptus, and medical inhibition of spermiogenesis (testosterone ester and gossypol).^ieng

Focus on managing population growth.

PIP: For the past 4 decades, the world's population growth has threatened to outstrip the planet's ability to sustain it. According to recent projections, an end to the growth of world population is finally in sight. Dr. Joseph van Arendonk, deputy executive director of the United Nations Population Fund, told an international press conference that population growth is likely to begin falling before the mid-21st century. Currently, some 87 million couples worldwide wish to use contraception but have no access to services. Van Arendonk argued that 4% of overseas aid set aside for population programs would satisfy this unmet need. He also predicted that the average family size in developing countries would stabilize at 2.1 children within the next 55 years if these needs were met. This would still mean a global population of 10 billion in the year 2050, rising to a plateau of 11.6 billion within the following century. In developing countries fertility rates fell from 6.1 to 3.3 children per woman between the mid-1960s and the mid-1980s, while use of contraception increased from 10% to 50%. However, contraceptive users in the developing world must increase from 446 million in 1994 to 603 million in 2005 to keep population growth within such projected limits. The costs of providing the contraception will increase from US $528 million to US $752 million. The contraceptive needs of 603 million users in 2005 will require: 196 million sterilizations, 436 million IUD insertions, 898 million injectables, 12.3 billion cycles of OCs, and 55 billion condoms. To this end, IPPF plans greater accessibility of services, a wider range of effective methods, and the involvement of the male partner.^ieng

[Vaginal contraception with steroids]. / La voie vaginale contraceptive par steroides ovariens.

PIP: Some scientists added the progestin levonorgestrel to the vaginal ring which must be removed every 3 weeks to address the problem of irregular bleeding, but it adversely altered lipoprotein levels and caused too many hemorrhaging problems. On the other hand, scientists in the laboratory at Organon have conducted various studies of a vaginal ring with ethinyl estradiol and 3-keto-desogestrel at different doses which have yielded favorable results. A multicenter European study was conducted with 400 women aged 18-40 years wearing a vaginal ring with 0.120 mg keto-desogestrel and 0.015 mg ethinyl estradiol every day for 9 months. 10% had slight bleeding 15 days after insertion of the vaginal ring. In 10 women tested, the plasmal levels of progesterone and estrogen decreased by 4 nmol/l and 0.010 nmol/l, respectively. The first French study was conducted at the Gynecology College of Bordeaux and the South-West in 1988 and included 40 women followed for 9 cycles. The vaginal ring consisted of 2 compartments: the biggest compartment contained only 3-keto-desogestrel and the other also contained ethinyl estradiol. It remained in the vagina for 21 days, then was removed to be rinsed, dried, and placed in a box. It was reinserted on the 5th or 7th day of the cycle. This ring reduces the volume of blood during menses and eliminates abdominal cramps, nausea, and headaches. Women tolerate the vaginal ring better than they do oral contraceptives (OCs); for example, it does not cause them to gain weight, they tolerate glucose well, it brings about favorable changes in lipoproteins, it does not bring about conditions favorable to thrombophlebitis, and it can improve the skin for acne-sufferers. Young women accept vaginal rings enthusiastically. The efficacy of vaginal rings with 2 steroids is the same as that of OCs.^ieng

[Oral contraceptives and blood platelets]. / Contraceptifs oraux et plaquettes sanguines.

PIP: This work describes a study of the effects of combined oral contraceptives (OCs) on lipid biosynthesis in platelets of female rats and women. A highly significant hypercoagulability due solely to increased activity of platelet factor 3 can be observed in women using combined OCs. The phospholipidic nature of factor 3 has been demonstrated. Phospholipids are implicated in the aggregation of platelets because they are the essential constituents of the platelet membranes and the precursors of prostaglandins. Platelets actively synthesize their own lipids, and combined OCs modify serum lipid metabolism. In each experiment, a control group of rats weighing 180-200 g received .5 ml/g body weight of olive oil once daily for 4 days. 3 groups of experimental rats received .5 ml of olive oil containing 10 mcg of ethinyl estradiol (EE) and 250 mcg of lynestrenol or 10 mcg of EE alone or 250 mcg of lynestrenol alone per 100 g of body weight. The doses were the equivalent of 1/2 that required to block ovulation in adult female rats. Platelets were studied on the 5th day. In another experiment a group of rats was given a triple dose of EE and lynestrenol on the 1st study day. Platelets were studied on days 1, 3, 5, and 8. Lipid biosynthesis was studied by incorporation of carbon 14 labelled acetate and mevalonate precursors. Radioactivity was measured for the lipids as a whole and for different lipid fractions separated by chromatography. Incorporation of carbon 14 labelled acetate was augmented by 44.6% in animals receiving EE and lynestrenol and by 43% in animals receiving EE alone, but was not modified in animals receiving lynestrenol alone. In animals receiving a triple dose of hormones, incorporation was maximal on the 3rd day, diminished on the 5th day, and normal after 8 days. The EE component thus appears to be responsible for modifications in platelet lipid metabolism during OC use. The response appears after a latency period and seems to be irreversible, since the duration of life of platelets is 4-5 days. The increased synthesis occurs mainly in cholesterol and its precursors lanosterol and dihydrolanosterol. Supplemental in vitro experiments suggested that lanosterol was responsible for the increased platelet activity. 17 nonsmoking women aged 32 years on average who took no medications were compared to 18 women aged 30 years on average who took OCs with estrogen doses of 30-40 mcg for at least 6 months. As in the rat studies, lipid biosynthesis was analyzed by incorporation of carbon 14 labelled acetate or mevalonate in the platelets. Compared to control women, the women on OCs showed an augmentation of 37% in incorporation of mevalonate and 28% of acetate. The labelled acetate showed a higher incorporation at the level of each of the lipid fractions. Mevalonate showed the highest augmentation in the lanosterol fraction. 43% of the women taking OCs showed an increased platelet sensitivity to thrombine. The increased sensitivity was correlated with increased lanosterol synthesis, but the relation was only observed in women taking OCs. The phenomenon is of interest because of its possible relationship to the increased risk of thromboembolic accidents in women taking OCs.^ieng

[The effects of MLCu 250 and VCu 200 on rural women who had experienced failure with ring IUD].

PIP: In order to study the effectiveness of different IUDs on women who had previously experienced IUD failure, 398 women were included in a clinical follow-up study using Multiload Cu 250 (MLCu) produced by Organon Company in the Netherlands, and VCu200 (VCu) produced in Shanghai, China. Among the cases, 85.6% experienced one IUD failure including 23.3% expulsion and 76.7% pregnancy with IUD in situ. 53 women had two IUD failures, and 4 had three failures. The accumulated continuation at the end of 12 months was 92.42% for MLCu and 91.41% for VCu. The accumulated expulsion at the end of 12 months was 5.07% for MLCu and 4.58% for VCu. Accumulated pregnancy with IUD in situ was 2.04% for MLCu and 1.02% for VCu. One woman using MLCu and 6 using VCu had the IUDs removed due to heavy menstrual bleeding. Age did not have a significant effect on discontinuation for either kind of IUDs. There is no significant difference on failure between the two groups, whether the IUD was inserted after menstruation or at the time of abortion. The effectiveness of these two kinds of IUDs is satisfactory. The problem of heavy bleeding resulted from VCu use needs to be solved. The insertion procedure of MLCu is relatively easy, while for VCu, it is more complicated and requires more skill. The study also showed that the expulsion of the VCu is associated with occupation and posture at work. Farmers and workers who squat a lot experience a higher rate of expulsion. Among the cases who have had one previous IUD failure, the effectiveness of these 2 IUDs is similar to that reported in the general population. While for those who have had two or more previous expulsions, the probability of another expulsion is significantly higher even with copper IUDs then in cases who had one expulsion.^ieng