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Automated stability-indicating high-performance liquid chromatographic assay for ethinyl estradiol and (levo)norgestrel tablets.

An automated high-performance liquid chromatography (HPLC) assay for ethinyl estradiol and norgestrel or levonorgestrel in oral contraceptive tablets was developed. Tablets were prepared for on-line injection using a solid sampler and segmented continuous flow techniques. The active components were separated from tablet excipients, impurities, and degradation products on reversed-phase C8 and C18 columns by elution with water-acetonitrile-methanol (45:35:15). A UV detector connected in series with a fluorometric detector measured the UV absorbance of levonorgestrel and norgestrel at 240 nm and the fluorescence of ethinyl estradiol at 310 nm (excitation at 210 nm). The method employed computer control of the injection system and solid sampler for synchronization of the chromatographic and segmented flow streams. The method is applicable for content uniformity and stability testing at a rate of eight samples per hour.

Automation↗

The frameless GyneFix intrauterine implant: a major improvement in efficacy, expulsion and tolerance.

The CuFix (GyneFix), conceived in 1985, was developed to minimize three major problems frequently associated with discontinuation of IUD use: expulsion, bleeding and pain. Since the initial clinical investigations, over 10,000 woman years of experience and up to 8 years of follow-up in international multicenter, non-comparative and comparative clinical trials, including a large proportion of nulligravid/nulliparous women, have been collected. Based on new clinical information about the GyneFix from a long-term multicenter clinical trial, conducted in young nulligravid/nulliparous and parous women, the importance of this new contraceptive is discussed. The following conclusions were reached: The unique design characteristics of the GyneFix (frameless, flexible and fixed to the fundus of the uterus) have resulted in optimal tolerance and almost complete absence of expulsion. The result is enhanced effectiveness (comparable to OCs and male/female sterilization) and a high rate of continued use. The GyneFix reduces the IUD failure rate to a minimum and is, therefore, a welcome reversible alternative to OCs and female surgical contraception. Framelessness and flexibility explain the absence of side-effects and adverse events caused by dimensional incompatibility between the frame of conventional IUDs and the uterine cavity and may also explain the absence of PID and ectopic pregnancies in any of the clinical studies. The GyneFix is a promising new, highly effective and safe, contraceptive option for parous women and an equally effective and well-accepted method for nulliparous women.

Adolescent↗

Five-year experience with depot medroxy progesterone acetate injectable contraception.

BACKGROUND: The objective of this article is to describe the characteristics and experiences of clients who used depot medroxy progesterone acetate for contraception. METHODS: A retrospective review of family planning records of clients who used depo-provera between 1992 and 1996 at the family planning clinic of University of Nigerian Teaching Hospital, Enugu. RESULTS: The mean age of clients was 32.7 +/- 5.2 years. Over 71% of clients had five or more children. Clients with no education (78.7%) or primary education (75.1%) were more likely to be grand-multiparous compared to women with at least secondary education (49.6%). Among clients with 1-4 living children, 81.3% used depo-provera for child spacing. Among those with 5-8 living children, 48.8% used it for child spacing. Menstrual abnormalities were the main complications but the commonest reason given for discontinuation was "husband's wish". The continuation rate at 36 months was 82.7%. CONCLUSION: Depot medroxy progesterone acetate is an acceptable and effective method of contraception. The involvement of men in family planning programmes cannot be over-emphasised as they significantly influence the decision of women regarding contraceptive use.

Adult↗

Optimizing delivery of therapeutics: percutaneous technologies.

The purpose of this communications is to 1) demonstrate the potential of percutaneous drug-delivery on the example of female reproductive steroids, 2) point out the differences between transdermal and conventional drug dosing, and 3) outline new technologies and innovations that are looming on the horizon, specifically in the area of pain control. Transdermal delivery systems are of two basic types. The first ones employ principles of passive diffusion, and they are used for hormonal replacement therapy (HRT) and contraception. Patches for HRT, designed to release estradiol (E2) only, require a simultaneous dosing with oral progestogens. Patches employing both E2 and a progestogen release the combination either continuously or sequentially. In the latter method, estrogen-only patches are applied for 14 days, followed by a 14-day application of patches releasing both hormones. Both methods successfully cope with symptoms and signs of menopause, including bone loss. Contraceptive transdermal patches deliver ethinylestradiol in combination with the progestogen norelgestromin. This system provides high contraceptive protection with predictable withdrawal bleeding and without major adverse events and weight changes. Hormones delivered by the skin avoid first-pass liver metabolism. Other advantages include rapid onset and termination of action, self-administration, and attainment of therapeutic hormone levels with low daily doses. A disadvantage is the variable intra- and inter-individual percutaneous absorption. In some patients, patches can cause skin irritation. Active systems deliver therapeutics across intact skin non-invasively by means of an electric potential (electrotransport). A system consisting of tooth-like titanium microprojections that penetrate only the keratinized epidermis facilitates painless and needle-free transport of complex molecules to the capillaries of the dermis. Other devices use low frequency ultrasound. These systems enable precise dosage, delivery of large molecules, such as growth hormone and vaccines, and dosing of analgesics "on demand". Novel transdermal technologies are profoundly changing the current methods of pain management. (Fig. 6, Ref. 47.).

Administration, Cutaneous↗

Factors influencing the reliability of oral contraceptives.

BACKGROUND: The reliability of oral contraceptives (OC) is high but several known factors can potentially induce failures. The dose of estrogen (EE) has been reduced through the years. Interaction with concomitant use of other medicine is wellknown and gastroenteritis can reduce the uptake of EE. To further characterize and quantify these factors we have performed this study. METHODS: Among patients admitted for legal abortion we selected those who had taken OC (only combined preparations; gestagen-only preparations were excluded) according to the prescription but nevertheless became pregnant. Various parameters were noted. RESULTS: Among 8058 women 70 women were found. Twenty-nine used three-phased and 25 used low-dose OC while the rest used high-dose, two-phased or unknown OC (four, five and seven patients respectively). Five patients used other medicine concurrently (salbutamol, astemizol, mianserin, chlorcyclizin, paradryl, carbamazepin, lithium, chlorprotoxin and imipramin). Sixteen patients had symptoms of gastroenteritis at the time of conception. Forty-nine patients had failure without any known influencing factors. There was no significant difference between the various OC used by the patients compared to sales of them in Denmark. About two-thirds of the patients wanted to continue with OC as future prevention. CONCLUSIONS: Failure of OC is a rare event but can occur in case of concurrent gastroenteritis or use of other medicine but in many cases, however, no definite cause can be determined. The EE-content of the various OC was not found to have any influence. Although OC-failure had occurred two-thirds of the patients wanted to continue the use of OC.

Adolescent↗

The oral pill in the Indonesian Population/Family Planning Program.

The oral pill is the most extensively used contraceptive in Indonesia. Of new users, 64% use the pill, 20% IUDs, 8% injectables, 6% condoms and 2% voluntary sterilization. Since the continuation rate of pill use is low as compared to the other non-permanent methods, i.e. the IUD and the injectables, special steps must be taken in order to reach the goal of the program, i.e. the reduction of the crude birth rate (CBR) to 22/1000 by the year 1990. These special steps involve selecting the best pill for Indonesian women, and determining the best contraceptive combination for each region and for new pill acceptors. The role of the oral pill in the program is also discussed.

Contraceptive Devices, Male↗

Bleeding arising from the use of exogenous steroids.

A range of hormonal contraceptives and hormone replacement therapies are widely and increasingly used in most societies. These preparations result in a wide variety of scheduled and unscheduled effects on uterine bleeding patterns, some of which may be quite disconcerting for the women who use them. There is now an extensive literature on the analysis of these bleeding patterns, the way in which different hormonal methods affect these patterns and the influence which they may have on women's choice to continue or discontinue use of a method. This review has concentrated particularly on the issues related to bleeding patterns with hormonal contraceptives, but many of the issues are also relevant to menopausal hormone replacement therapy. This is particularly the case with research into the complex vascular and molecular mechanisms underlying disturbances of bleeding, where there may well be substantial overlap. Perception and tolerance are important in determining a woman's approach to a change in her menstrual pattern, and her possible acceptance of counselling and treatment approaches which may improve her symptoms.

Contraceptives, Oral, Hormonal↗

Contraceptive method switching in the United States.

CONTEXT: Switching among contraceptive method types is the primary determinant of the prevalence of use of specific contraceptive methods, and it has direct implications for women's ability to avoid unintended pregnancies. Yet, method switching among U.S. women has received little attention from researchers. METHODS: Data from the 1995 National Survey of Family Growth were used to construct multiple-decrement life tables to explore the gross switching rates of married and unmarried women. Within each group, discrete-time hazard models were estimated to determine how women's characteristics affect their switching behavior. RESULTS: Overall rates of method switching are high among both married and unmarried women (40% and 61%, respectively). Married women's two-year switching rates vary from 30% among women who use the implant, injectable, IUD or other reversible methods to 43% among nonusers, while unmarried women's rates vary from 33% among women who use the implant, injectable or IUD to 70% among nonusers. Multivariate analyses of method switching according to women's characteristics indicate that among married women, women without children are less likely than other women to adopt sterilization or a long-term reversible contraceptive (the implant, injectable or IUD). Older married women have a higher rate than their younger counterparts of switching to sterilization, but are also more likely to continue using no method. Among unmarried women, younger and more highly educated women have high rates of switching to the condom and to dual methods. CONCLUSIONS: Women's method switching decisions may be driven primarily by concerns related to level and duration of contraceptive effectiveness, health risks associated with contraceptive use and, among single women, sexually transmitted disease prevention.

Adolescent↗

Successful use of levonorgestrel intrauterine system in a HIV positive woman.

After trying other contraceptive methods a woman with HIV disease found use of the levonorgestrel intrauterine system (IUS) very satisfactory, and benefited from the amenorrhoea it induced. She continued to use condoms. Other advantages of using the IUS were freedom from regular clinic visits, no need for daily pill taking, and absence of drug interactions.

Adult↗

Two-year follow-up of changes in clinical chemistry in Singaporean Norplant acceptors: haemostatic changes.

A longitudinal study of coagulation parameters was carried out on 100 Singaporean acceptors using Norplant for contraceptive purposes. At the end of 2 years of use, results from this ongoing study indicate that these acceptors continue to have an increased predisposition to thrombosis as evidenced by significant increases in platelet count and aggregability. The shortened but stable prothrombin time and activated partial thromboplastin time and increase in certain coagulation factors indicate that Norplant acceptors still have a possible potential for hypercoagulation at the end of two years of use.

Blood Coagulation↗

The influence of spouses over each other's contraceptive attitudes in Ghana.

To what extent do spouses influence each other's reproductive goals? This question was investigated in Ghana with particular reference to family planning attitudes. Two mechanisms were identified as plausible explanations for why an individual's characteristics may affect a partner's beliefs and behavior. Quantitative evidence from the Ghana Demographic and Health Survey and qualitative information from focus-group research in Ghana were used in the analysis. Results from both data sources show that spousal influence, rather than being mutual or reciprocal, is an exclusive right exercised only by the husband. The study attributed the limited impact of family planning programs in Ghana and most of sub-Saharan Africa to the continued neglect of men as equal targets of such programs.

Adult↗

Sterilization.

Male and female sterilization is a safe and effective form of permanent contraception. The number of patients accepting this method has rapidly increased over the last ten years and is likely to continue. In some countries the rate has plateaued out: in the USA it has been 31 per cent of all married women for the last eight years. Before sterilization it is important that adequate counselling is given to both partners and that the decision is not hurried. This is emphasized by the number of women and men requesting reversal of sterilization (thought to be between 0.1 and 10 per cent of all sterilizations). These requests for reversal usually come from couples who have remarried, tend to be younger, have fewer live children, have had more abortions, less schooling and are poor users of contraception. In these high-risk patients counselling and time to make the decision is essential. Other studies indicate that regret after puerperal sterilization may be commoner, but the risks of further pregnancies have to be weighed against sterilization regret. The methodology of male sterilization has changed little in the last ten years; it is simple and usually done under local anaesthesia. In contrast, female sterilization methods are constantly being refined, from laparotomy to laparoscopy and from extensive tubal destruction or excision to minimal tubal damage. The common methods now are mini-laparotomy and laparoscopy under local or general anaesthesia, with tubal occlusion by clips, rings or bipolar or thermal coagulation. There is no place now for unipolar diathermy, because of the higher complication rate, especially for major complications such as bowel burns. Recent multicentre studies comparing different methods give low rates for immediate morbidity and surgical complications (0.8 to 2.5 per cent of cases). Technical failure is rare but often due to a pre-existing condition, for example obesity or previous pelvic disease. Some failures are due, however, to difficulties with the instruments, especially at laparoscopy; here further developments and the use of teaching aids for those in training will help to reduce problems. Mortality from female sterilization is low, at 2 to 10 per 100 000 procedures; however, half is due in part to anaesthetic complications (hypoventilation), which can be avoided by intubation, and others are due to pre-existing medical conditions. Long-term follow-up has now shown that sterilization does not cause an increase in menstrual blood loss.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Effects of continuous inhibin administration on gonadotropin secretion and subunit gene expression in immature and adult male rats.

To begin to examine inhibin as a male contraceptive, recombinant human (rh) inhibin-A was administered for 3 days via osmotic minipumps to male rats. Doses of inhibin of 0-150 mg/kg per day did not produce a concentration-dependent suppression of FSH secretion or pituitary FSH beta mRNA levels in adult rats. Treatment of immature rats at a dose of 145 micrograms/kg per day, which was without effect in adults, reduced plasma FSH levels by 49% (p < 0.01), and FSH beta mRNA levels to 47 +/- 11% of control (p < 0.01). Inhibin also decreased levels of LH beta mRNA (63 +/- 8% of control; p < 0.01), alpha-subunit mRNA (86 +/- 10% of control; p < 0.05), and GnRH-receptor mRNA (77 +/- 17% of control; p <0.01) in immature rats. Rh inhibin-A was more effective in immature than in adult animals; plasma inhibin levels were increased (p = 0.03) by rh inhibin-A treatment only in immature rats. Pharmacokinetic studies revealed that the weight-adjusted clearance was greater (p < 0.01), and the elimination half-life of rh inhibin A was shorter (p < 0.01) in adult than in juvenile rats. These data indicate that partial suppression of FSH beta mRNA inhibin is associated with a decline in GnRH receptor gene expression, suggesting that the notion that inhibin can act as a male contraceptive through selective and complete inhibition of FSH production, without effect on LH and Leydig cell function, may be mistaken. In addition, increased inhibin clearance appears to contribute to the fall in plasma inhibin levels with maturation in the male rat.

Aging↗

The Dalkon Shield contraceptive device in general practice.

The value of the Dalkon Shield as a means of birth control in general practice is reviewed, and the continuation rate is found to be disappointingly low in a well motivated group of women. These findings are at complete variance with those of Watson (1975).

Family Practice↗