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A potential single insertion protocol for quinacrine pellet non-surgical female sterilization.

Two preliminary single-insertion clinical trials of the quinacrine pellet method of non-surgical female sterilization were compared. Both trials used transcervical application of quinacrine, 252 mg, and diclofenac, 75 mg, as pellets. In the first trial (21 April 1992 to 17 February 1993), 58 women received oral contraceptives for three months. In the second trial (19 February 1993 to 25 May 1994), 229 women received medroxyprogesterone acetate, 150 mg IM, at the time of quinacrine insertion. At 18 months, the life-table pregnancy failure rate per 100 women of the first trial was 8.6 (SE 3.7), whereas the failure rate for the medroxyprogesterone acetate group was 0.5 (SE 0.5), p<0.05. There were no serious complications or side-effects in either group. Larger confirming trials with random allocation and long-term systematic follow-up are needed to determine whether a single injection of medroxyprogesterone improves the efficacy of quinacrine.

Cervix Uteri↗

Pituitary-ovarian activity when switching from various monophasic pills to a triphasic pill.

This study was prompted by the various recommendations given by different oral contraceptive manufacturers to women who wish to switch from a monophasic to a triphasic formulation. Ten women who switched from a variety of monophasic pills to a levonorgestrel triphasic pill formulation after a 7-day pill-free interval were studied. Follicular maturation was monitored by ultrasound scan, and the levels of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P) and estradiol (E2) measured. Pituitary-ovarian activity was suppressed in six of the ten women studied, while in the remaining four women there was some pituitary-ovarian activity during the first 10 days on the triphasic pill. These findings suggest a shorter pill-free interval, as advised in USA data sheets, may be less likely to result in pill failures when women switch from a monophasic to a triphasic preparation.

Adolescent↗

Hospital admissions due to adverse drug reactions: a comparative study from Jerusalem and Berlin.

A comparative study of adverse drug reactions (ADR) leading to hostpial admission showed that 103 (4.1%) out of 2499 medical admissions in Jerusalem and 167 (5.7%) out of 2933 admissions in Berlin were due to such reactions. Sex distribution in the two patient--populations was almost equal but the Jerusalem patients were younger. The most frequent ADRs were digitalis intoxication (in Berlin) and reactions to antibiotics (in Jerusalem). Other important differences were noted in the relative frequencies of ADRs associated anticoagulants, hypoglycemic agents and oral contraceptives. They were probably related to differences in drug usage in the two countries. The most common major side effects were arrhythmias, allergic reactions, bleeding, congestive heart failure, bronchospasm and hypoglycemia. The following risk factors were identified in both cities: old age, female sex, impaired renal function, previous history of ADR and polypragmasia.

Adult↗

Emotional reaction to sterilization.

Ninety-four patients sterilized by tubal occlusion were interviewed at the time of hospitalization for surgery and followed at scheduled intervals for a 2-year period. There were no serious problems, medical or psychologic, and all but 3 patients were pleased and satisfied at the end of 2 years. There were no technical failures. Psychosomatic symptoms do develop. They are more prominent and persist longer in the younger age group. Patients having these symptoms are those who had difficulty with contraceptive technics, have a limited understanding of the sterilization procedure, and continue to question its permanency. The need for preoperative evaluation and counseling is emphasized.

Adolescent↗

Standardization of cumulative failure rates.

A method is proposed for standardizing life table cumulative failure rates for various cohorts so that they are adjusted to the distribution of exposure by age group for a particular cohort. An approximate standard error for the standardized cumulative failure rate is presented. Application of the methodology is illustrated by a numerical example.

Age Factors↗

The 'frameless' intrauterine system for long-term, reversible contraception: a review of 15 years of clinical experience.

AIM: The development of the 'frameless' intrauterine system (IUS) is a response to the growing need to develop high-performing, long-acting, reversible, and acceptable contraceptives with a high continuation of use. METHODS: This is a review of 15 years of clinical experience in randomized controlled and non-randomized clinical trials. RESULTS: The IUS has a similar failure rate as the TCu380A Intrauterine device (IUD), considered the 'golden standard' IUD, which is attributed to the optimal target delivery of the copper ions in the upper part of the uterine cavity. Its performance is further optimized by the atraumatic design, which reduces partial and total expulsion and minimizes the side-effects and discomforts experienced with conventional 'framed' IUDs. The mini IUS is likely to further reduce the menstrual blood loss due to the very small size. The safety of the anchoring concept is beyond doubt as was demonstrated in all clinical studies covering 15,000 woman-years experience. CONCLUSIONS: Young nulliparous/nulligravid and parous women may significantly benefit from the advantages the 'frameless' IUS, which could be strategically important to help in reducing the increasing number of unintended pregnancies and induced abortions worldwide. Furthermore, the 'frameless' IUS has been shown to be highly effective for emergency contraception and for immediate postabortal insertion. The long lifespan of the IUS could constitute a cost-effective reversible alternative to irreversible female sterilization.

Female↗

Management of the lost intrauterine contraceptive device.

In order to establish that a lost IUD is within the uterine cavity, a special hook-type instrument was designed to enable removal of the device when it was located within the uterine cavity. This instrument was 100% successful in removing 17 IUDs with no visivle tails and which were within the uterine cavity. Failure to remove a lost IUD by this method in 4 other patients indicated the device's absence from the uterine cavity. The technic is simple and has not been associated with any patient discomfort or complications. X-ray procedures or operative manipulations may thereby be avoided. Therefore, when the tail of an IUD is no longer visible, immediate removal can be attempted in order to establish the intrauterine location of the device. If the patient wishes to continue using this form of contraception, a new device should be inserted.

Female↗

Microbicide acceptability research: current approaches and future directions.

With growing recognition of the potential value of microbicides for HIV/STI prevention, the importance of the acceptability of this brand-new technology has been widely acknowledged. We review the current body of microbicide acceptability research, characterize the limitations in assessment approaches, and suggest strategies for improvement. Electronic databases and abstracts of recent meetings were searched for acceptability data regarding vaginal and rectal products that may be used for HIV prevention. Of the 61 studies reviewed, more than half assessed acceptability based primarily on the description of a hypothetical microbicide, or with the demonstration of a spermicide or lubricant. Physical characteristics of microbicidal products, their effects after insertion, and their effects on sensation during intercourse (for both partners) were the dimensions most frequently assessed (measured in 77%, 49% and 49% of studies, respectively). Attention to the social context of use was inadequate. As acceptability is likely to be a key determinant in the use-effectiveness of microbicides, in-depth understanding of the social processes that shape microbicide acceptability across diverse populations will become increasingly valuable. This includes exploring the effects that sexual partners, health care providers, and key opinion leaders have on the acceptability of microbicides among women and men, including youth and people living with HIV. Future research will benefit from studies of the acceptability of other contraceptive-barrier methods (especially the female condom), use of an agreed-upon operationalization of acceptability, use of acceptability assessments within clinical trials, expansion of measurement domains, and assessment of changes in perceptions of acceptability and use over time. Failure to understand the key factors associated with microbicide acceptability is likely to hinder the adoption and continued use of products that are effective in preventing HIV infection.

Anti-Infective Agents, Local↗

Counseling issues in tubal sterilization.

Female sterilization is the number one contraceptive choice among women in the United States. Counseling issues include ensuring that the woman understands the permanence of the procedure and knowing the factors that correlate with future regret. The clinician should be aware of the cumulative failure rate of the procedure, which is reported to be about 1.85 percent during a 10-year period. Complications of tubal sterilization include problems with anesthesia, hemorrhage, organ damage, and mortality. Some women who undergo tubal ligation may experience increased sexual satisfaction. While the procedure is commonly performed postpartum, it can be done readily, without relation to recent pregnancy, by laparoscopy or, when available, by minilaparotomy. Surgery should be timed immediately postpartum, or coincide with the first half of the woman's menstrual cycle or during a time period when the woman is using a reliable form of contraception.

Contraception↗

Attitude towards family planning in Dharan, east Nepal: implications for the family planning programme.

A survey of the knowledge, attitude and practice of family planning was conducted in Dharan, Nepal. The town offers a full range of family planning services free of charge. There was a strong desire to limit family size; 52.5% of couples were currently using some modern method of family planning. Of the current users, 62.3% had been sterilized, including 92.3% of those in the lowest socioeconomic group. Health risks and incompleteness of the family were the most common reasons for non-use of contraception, the latter reason reflecting ignorance of the temporary nature of some methods. There was a strong preference for male children and couples rarely used contraception until at least one so had been born. Even in this prosperous town where couples were highly motivated towards family planning and all methods were readily available, there was heavy reliance on sterilization. This is typical of Nepal and has largely been responsible for the failure of the family planning programme--as most couples choosing sterilization are in the older age group and have completed a relatively large family. If Nepal is to succeed in meeting its target of reducing the total fertility rate (i.e., births per woman) from the current 5.8 to 4 by the year 2000 it will need not only to expand services but actively to promote temporary methods of contraception, particularly the more reliable longer acting reversible methods such as Depo-Provera, Norplant and intrauterine contraceptive devices.

Adolescent↗

Clinical experience with ethynodiol diacetate 0.5 mg daily as an oral contraceptive.

Femulen, a progestogen only oral contraceptive (ethynodiol diacetate 0.5mg), was evaluated for its contraceptive efficacy and safety in 425 women aged between 16 and 47 years. This was a multicentre open study carried out in General Practice and Family Planning clinics. Five pregnancies were reported, three of which were a result of patient failure. The net pregnancy rate at one year for method failure was 0.5%. No ectopic pregnancy was reported. The median length of the menstrual period was between four and five days and the average length of the non-bleeding interval remained between 24 and 25 days throughout the study. Blood pressure on the whole remained within normal limits. However, there was a small decrease in both systolic and diastolic blood pressure which did not reach significant levels. Body weight was unaltered and no abnormality was found in cervical smears. Femulen was shown to be an effective and acceptable contraceptive in women of varying ages.

Adolescent↗

The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

BACKGROUND: Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception. OBJECTIVE: This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg). METHODS: This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. RESULTS: Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. CONCLUSION: In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low-dose combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

Adult↗

A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception.

A prospective randomized study was conducted at the Family Planning Association of Hong Kong to compare the efficacy of the Yuzpe regimen and levonorgestrel (0.75 mg for two doses 12 h apart) in post-coital contraception. A total of 424 subjects were recruited into the Yuzpe group and 410 subjects into the levonorgestrel group; 77 subjects in the Yuzpe group and 79 subjects in the levonorgestrel group had further acts of intercourse during the treatment cycle. Fifteen pregnancies (3.5%) occurred in the Yuzpe group and 12 pregnancies (2.9%) in the levonorgestrel group. After excluding the patients who had further acts of intercourse, the failure rates in the Yuzpe group and the levonorgestrel group were 2.6 and 2.4% respectively. The incidence of nausea, vomiting and fatigue in the Yuzpe group was significantly higher than those in the levonorgestrel group. We conclude that levonorgestrel is an effective drug for post-coital contraception with a lower incidence of side-effects than the Yuzpe regimen.

Adolescent↗

Multicentre study with a new biphasic oral contraceptive containing ethinylestradiol and desogestrel. Report on efficacy, cycle control and adverse experiences with special emphasis on blood pressure and weight.

In a multicentre study 882 women were treated during a total of 12850 cycles with a new biphasic oral contraceptive: CTR 24. The study period was 18 cycles. The biphasic preparation CTR 24 contains 25 micrograms desogestrel (CAS 54024-22-5) plus 40 micrograms ethinylestradiol (CAS 57-63-6) daily for the first 7 days followed by the combination of 125 micrograms desogestrel and 30 micrograms ethinylestradiol daily for the subsequent 15 days. One pregnancy occurred. The woman had forgotten one tablet on Day 6 of Cycle 12. The Pearl Index was 0.1 (0.0-0.5) for patient failure. The combination had a good cycle control and only few side effects were reported.

Blood Pressure↗

Pitfalls inherent in retrospective time-to-event studies: the example of time to pregnancy.

Retrospective studies of time from initiation of risk (for example, transfusion of HIV-infected blood) to the occurrence of an endpoint of interest are useful in epidemiology. One example is studies of time to pregnancy, which have evaluated exposures that may affect human fertility. One can reconstruct the non-contracepting interval required for each woman's most recent pregnancy and then treat the data as if the couples had been studied prospectively. As we illustrate, however, failure-time models can be dangerously misleading when there have been trends over calendar time in exposures under study. We propose an ad hoc method for evaluating possible effects on fertility despite this bias, by making use of external data on trends in the exposure over time. This approach applies a prospective model and generates an empirical p-value, based on comparing the data-based estimated exposure coefficient with its null distribution estimated by simulation. A second method maximizes a conditional likelihood, and we show that this is equivalent to logistically modelling the relative odds for the subject's exposure as related to the reported time she required to achieve pregnancy.

Bias↗