Ethinylestradiol + etonogestrel contraceptive vaginal ring: new drug. Possibly useful in some situations

(1) The standard hormonal contraception consists of a combined oral contraceptive containing about 30 micrograms of ethinylestradiol and a well-evaluated and widely used progestin such as levonorgestrel or norethisterone. (2) A vaginal ring delivering about 120 micrograms of etonogestrel and 15 micrograms of ethinylestradiol daily for 3 consecutive weeks per cycle, which is then removed for one week, is now marketed in France as a contraceptive. Etonogestrel, a desogestrel metabolite, is classified as a 'third-generation' progestin. (3) On the basis of 2 non-comparative trials involving a total of 2322 women, the vaginal ring's contraceptive efficacy, as measured by the Pearl index, is about 1 per 100 woman-years, a value similar to that of other available combined hormonal contraceptives. (4) In total, 41% and 29.6% of women withdrew early from each of the two trials. In the two trials combined, 15.6% of women withdrew due to adverse events. (5) A comparative trial versus oral ethinylestradiol + levonorgestrel showed no difference in adherence rates, and similar Pearl index scores. (6) The most frequent adverse effects, occurring in about 20% of women using the vaginal ring, were gynecological disorders (vaginitis, leukorrhea or local discomfort). The other adverse effects were those common to all hormonal contraceptives. (7) The thromboembolic risk of etonogestrel, when administered in a contraceptive ring, has not been evaluated. (8) In practice, the standard hormonal contraceptive remains a combined oral contraceptive containing about 30 micrograms of ethinylestradiol plus a well-evaluated progestin such as levonorgestrel or norethisterone. The vaginal ring offers no advantage in terms of efficacy, adverse effects or adherence. However, it is an additional effective contraceptive and may be preferred by some women, at least temporarily, in certain situations.     

New hormonal contraceptives: a comprehensive review of the literature

Over 16 million women in the United States take oral hormonal contraceptives, yet approximately 5% experience an unintended pregnancy during the first year of use. Compliance with the regimen is important in maintaining cycle control and preventing pregnancy. New hormonal contraceptive agents, norelgestromin-ethinyl estradiol patch, etonogestrel-ethinyl estradiol vaginal ring, and medroxyprogesterone-estradiol cypionate injection, were designed to increase compliance and decrease adverse effects while maintaining efficacy. Each one has potential advantages for women seeking alternatives to traditional oral contraceptives or for those who have trouble remembering to take a daily pill. Each agent also may have its own disadvantages, including application site reactions, need for monthly injections, and device-related events; however, all have similar efficacy and adverse-effect profiles compared with current oral hormonal contraceptives.     

Pros and cons of vaginal rings for contraceptive hormone delivery

The capacity of the vaginal epithelium to absorb hormonal steroids and the ability of silicone elastomers to release these hormones at an almost constant rate form the basis for the use of synthetic rubber vaginal rings for therapeutic purposes. The first prototypes were made for contraception purposes but were later used for hormone replacement therapy (HRT) and, more recently, for the release of antiviral drugs. We have limited this article to contraceptive vaginal rings (CVRs), as their use in HRT was recently extensively reviewed and there are no publications on microbicide-delivering vaginal rings, available to date. Numerous models of CVRs have been studied, but only two have reached the market: NuvaRing® that releases ethinylestradiol and etonogestrel; and Progering® that releases progesterone, for use in lactating women. The main advantages of CVRs are: their effectiveness (similar or slightly better than the pill); ease of use, negating the need to remember a daily routine; the user’s ability to control initiation and discontinuation; the nearly constant release rate allowing for lower doses; and, the good cycle control with the combined ring. It was expected that the CVRs would also allow avoidance of the first-pass effect on liver metabolism, but that hypothesis has not yet been confirmed. The main disadvantages are related to the mode of delivery: vaginal insertion may be unpleasant for some women; ring expulsion is not uncommon; the ring may be felt during coitus and be unpleasant for some partners; and, it may cause vaginal discharge and complaints. Although one ring model was associated with disruption of the vaginal mucosa, other studies with different models have not shown conclusive evidence that the ring causes vaginal lesions. CVRs are new methods of hormonal contraception that are likely to be used by many women, particularly in countries where there is greater cultural acceptance of women touching their own genitals.     

Hormonal contraception,thrombosis and age

Introduction: This paper reviews the risk of thrombosis with use of different types of hormonal contraception in women of different ages.

Areas covered: Combined hormonal contraceptives with desogestrel, gestodene, drospirenone or cyproterone acetate (high-risk products) confer a sixfold increased risk of venous thromboembolism as compared with nonusers, and about twice the risk as compared with users of products with norethisterone, levonorgestrel or norgestimate (low-risk products). Transdermal patches and vaginal ring belong to high-risk products. The risk of thrombotic stroke and myocardial infarction is increased 50 – 100% with use of combined products, with little difference in risk between different progestins. Progestin-only products do not confer any increased risk of venous or arterial thrombosis, except for progestin depot, which may double the risk of venous thrombosis.

Expert opinion: First choice in women below 35 years should be a combined low-risk pill, that is, with a second-generation progestin, with the lowest compliable dose of estrogen. Young women with risk factors of thrombosis such as age above 35 years, genetic predispositions, adiposity, polycystic ovary syndrome, diabetes, smoking, hypertension or migraine with aura should not use high-risk products, but should primarily consider progestin-only products, and be careful to use low-risk combined products.     

871例育龄妇女5种节育措施避孕效果的临床研究

目的了解分析5种常用避孕方式的避孕失败率和不良反应,为避孕节育方法的选择提供临床依据。方法对采用安全期、避孕套、宫内节育器、口服短效避孕药、口服紧急避孕药等5种常用避孕方式的871例育龄妇女进行调查,其中采用安全期避孕法105例,采用避孕套避孕法300例,采用宫内节育器203例。采用口服短效避孕药212例,采用口服紧急避孕药51例。结果使用安全期、避孕套、宫内节育器、口服短效避孕药、口服紧急避孕药等5种避孕方式的避孕失败率,以安全期避孕为最高（15．2％）,口服短效避孕药为最低（2-4％）,差异有统计学意义（P〈0．05）。不良反应发生率由高到低依次为宫内节育器、口服紧急避孕药、口服短效避孕药、安全套、安全期避孕。宫内节育器不良反应以腰腹酸痛的发生为主,发生率为13．8％;口服紧急避孕药不良反应以不规则阴道流血的发生为主．发生率为7．8％;口服短效避孕药不良反应以胃肠道反应的发生为主,发生率为5．7％;10例采用避孕套避孕妇女曾有过敏情况,发生率为3．3％;安全期避孕法无精液过敏情况出现。结论5种常用避孕方法中,VI服短效避孕药有效性较高、不良反应较低。     

Awareness and perceptions of emergency contraception among retail pharmacists in Kuwait

Objective To describe the awareness and perceptions of hormonal emergency contraception (EC) among retail pharmacists.Setting Private retail pharmacies in Kuwait City.Method A self-administered questionnaire was developed to elicit pertinent demographic information as well as awareness of and concerns about EC and administered to the senior pharmacist in 51 randomly selected private retail pharmacies.Main outcome measure Proportion of pharmacists aware of EC and who had recommended EC.Results The respondents had a mean (SD) age of 34.2 (7.7) years; 58.8% were male, and all but one were non-Kuwaiti. The median practice experience of the pharmacists was 6 years. Oral contraceptives and male condoms were universally available in the pharmacies, but none stocked emergency contraceptives, female condoms, or diaphragms. Twenty respondents (39.2%; 95% confidence intervals 25.5–53.9%) said they were aware of EC, and 4 (7.8%) that they had ever offered EC. Nine (17.6%) respondents saw EC as offering no advantages over other contraceptive measures and effectiveness was perceived to be low. Most cited concerns were of encouraging irresponsible behaviour and women relying on EC in place of regular contraceptive measures. Religious opposition (41.2%), lack of awareness by clients (51.0%) and lack of awareness by health providers (35.3%) were seen as the most significant obstacles to provision of EC.Conclusion Knowledge of EC is poor among community pharmacists in Kuwait. Action is needed to address this deficit and to make EC more accessible to women who wish to use it.     

Menopausal status and factors affecting cessation of menses in the region of Bonn, Germany

Because of the high prevalence of hormone use and reproductive surgeries in Western women natural menopause is a less frequent condition. Our aim was to examine the influences of hormonal and other factors on timing of cessation of menses. We analysed population controls of a German case-control study on breast cancer risks. The sample comprised N=829 women without hysterectomy or bilateral oophorectomy. We estimated the risk for the occurrence of last menses by Cox proportional hazard modelling. For calculating hazard rate ratios (HRR) and 95% confidence intervals (CI) women with menstrual cycles up to one year before interview were censored at that age. Median age at cessation of menses was 50 years (inter-quartile range 47–53 years). A significant later cessation of menses resulted from oral contraceptive use (HRR 0.74, 95% CI 0.59–0.93 for up to 10 years), and hormone therapy use until last menses (HRR 0.57, 95% CI 0.47–0.70). Also, thyroidal medications were associated with a delayed cessation of menses (HRR 0.64, 95% CI 0.42–0.96 for more than 10 years of use). Smoking until at least two years before last menses and allergies revealed an earlier cessation of bleedings (HRR 1.50, 95% CI 1.22–1.83 and HRR 1.28, 95% CI 1.07–1.53 respectively). Natural menopause is difficult to determine. Factors affecting the ovaries or the endocrine system can modulate timing of menopause. Endocrine biomarkers should be additionally taken into account when defining menopausal status.     

The combined etonogestrel/ethinyl estradiol contraceptive vaginal ring

Many factors influence the effectiveness of contraceptive methods. Oral contraceptives are the second most popular contraceptive method after female sterilization in the US. A total of 25% of women do not use their oral contraceptives correctly; 30% of women do not use them consistently. Several new contraceptive methods with alternate routes of delivery and less frequent dosing are available. The combined etonogestrel/ethinyl estradiol contraceptive vaginal ring is marketed under the name of NuvaRing. This is the only contraceptive ring approved by the FDA. The administration of steroids by the vaginal route may offer many advantages. Because of less frequent dosing, self-administration, and possibly, an improved side effect profile, the ring has the potential to increase successful use.     

Comprehensive overview of the recently FDA-approved contraceptive vaginal ring releasing segesterone acetate and ethinylestradiol: A new year-long,patient controlled,reversible birth control method

ABSTRACT

Introduction: This is an overview of the recently FDA-approved silicone elastomer combined hormonal contraceptive vaginal ring (CVR), which is used cyclically for up to 1 year, eliminating resupply challenges. This ring requires no refrigeration, simplifying the supply chain. Developed by the Population Council, this CVR will soon be marketed in the United States as Annovera? by TherapeuticsMD.

Areas Covered: The composition of the elastomer ring and the chemical, pharmacokinetic and pharmacodynamic properties of both hormonal components are discussed. Results of the clinical trials of its efficacy, tolerability, safety, and acceptability follow. Finally, subanalyses from the clinical trials are presented to guide clinicians in counseling potential users.

Expert Opinion: This CVR introduces a new progestin – segesterone acetate (SA) – that has no androgenic or estrogenic action in vitro or in vivo, but has the highest anti-ovulatory potential of all available progestins. SA is paired with EE in an intravaginal elastomer ring, that is used cyclically (21 days in place/7 days removed) to provide 12 months (13 cycles) of contraception. This once-a-month, self-applied CVR offers a convenient, rapidly reversible, year-long contraception with efficacy and side effect profiles similar to other combined hormonal methods, for women with BMI < 29 kg/m².     

Information sources used by women in Finland who use hormonal contraceptives

Objective The aim of this study was to examine information sources used by women who use hormonal contraceptives (HCs), and how information source affected women’s attitudes and perceptions in 2001 and 2007. Setting The questionnaires were distributed from university pharmacies in 12 large cities across Finland. Method The data were collected with two questionnaire surveys among women who used hormonal contraceptives in 2001 and 2007. In the 2001 survey the response rate was 53% (n = 264) and in the 2007 survey 55% (n = 436). Results The number of respondents who considered professional information sources the most important information sources was markedly bigger in 2007 than in 2001 (P = 0.005). The most common source of information concerning the benefits of hormonal contraceptives was a physician (2001: 43%, 2007: 53%). The most common source of information concerning the risks of hormonal contraceptives was friends and relatives (43%) in 2001 and physician in 2007 (35%). Only a few percent of the respondents considered a pharmacy the most important information source both the 2001 and 2007 surveys. Conclusion The importance of health care professionals as sources of information concerning hormonal contraceptives has increased. However, role of pharmacists as information source was surprisingly small. Women who use hormonal contraceptives need more information from professional sources to alleviate possible fears associated with use.     

Male hormonal contraception

Although women have traditionally shouldered the responsibility of contraception, up to a third of couples worldwide employ a male form of contraception (e.g., condoms or vasectomy). Some women are unable to use hormonal contraception; vasectomy is best considered irreversible; and long-term use of condoms is associated with a relatively high failure rate (pregnancy). Thus, a need exists for a safe, effective, reversible, well-tolerated male hormonal contraceptive agent. Two large multi-centre, multi-national trials sponsored by the World Health Organization in the 1990s showed that high-dosage exogenous testosterone provided contraceptive efficacy similar to existing female oral contraceptives. However, the supraphysiological dosages of testosterone used resulted in androgen-related adverse effects such as weight gain and suppression of high-density lipoprotein cholesterol levels. Subsequent efforts have been directed at combining testosterone with other agents, such as progestogens or gonadotropin-releasing hormone analogues, to decrease the dosage of testosterone (and thus androgen-related side effects) while achieving uniform azoospermia. This review discusses the latest developments in male hormonal contraception.     

Safety of hormonal contraception for obese women

Introduction: Obese women have special safety requirements for contraceptive choice, but the evidence supporting such decision is dispersed and sometimes conflicting. Despite being effective, well tolerated and safe for most women, hormonal contraceptives are underused by obese women due to fear of contraceptive failure, weight gain and venous thrombosis.

Areas covered: We performed a comprehensive literature search to identify studies about hormonal contraception in overweight and obese women, including safety concerns. We considered the safety of hormonal contraceptives for otherwise healthy obese women and for those with comorbidities such as hypertension, diabetes, vascular disease, or a history of deep venous thrombosis.

Expert opinion: Over time there is no convincing evidence that obesity increases the risk of contraceptive failure. Hormonal contraceptive users may have a modest weight gain that is comparable to that of non-users. Current evidence supports the safe use of combined hormonal contraceptives by obese women after detailed clinical screening to exclude comorbidities that may contraindicate the use of estrogens. Progestin-only methods are generally safe, and long-acting reversible contraceptives hold the best combination of efficacy, safety and convenience for this group, although individualization is advisable.     

Male hormonal contraceptives

As the world human population continues to explode, the need for effective, safe and convenient contraceptive methods escalates. Historically, women have borne the brunt of responsibility for contraception and family planning. Except for the condom, there are no easily reversible, male-based contraceptive options. Recent surveys have confirmed that the majority of men and women would consider using a hormonal male contraceptive if a safe, effective and convenient formulation were available. Investigators have sought to develop a male hormonal contraceptive based on the observation that spermatogenesis depends on stimulation by gonadotropins, follicle-stimulating hormone (FSH) and luteinising hormone (LH). Testosterone (T) and other hormones such as progestins suppress circulating gonadotropins and spermatogenesis and have been studied as potential male contraceptives. Results from two large, multi-centre trials demonstrated that high-dosage T conferred an overall contraceptive efficacy comparable to female oral contraceptives. This regimen was also fully reversible after discontinuation. However, this regimen was not universally effective and involved weekly im. injections that could be painful and inconvenient. In addition, the high dosage of T suppressed serum high-density lipoprotein (HDL) cholesterol levels, an effect that might increase atherogenesis. Investigators have attempted to develop a hormonal regimen that did not cause androgenic suppression of HDL cholesterol and that was uniformly effective by suppressing spermatogenesis to zero in all men. Studies of combination regimens of lower-dosage T and a progestin or a gonadotropin-releasing hormone analogue have demonstrated greater suppression of spermatogenesis than the WHO trials of high-dosage T but most of these regimens cause modest weight gain and suppression of serum HDL cholesterol levels. Overall, the data suggest that we are close to developing effective male hormonal contraceptives. The focus is now on developing effective oral regimens that could be safely taken daily or long-acting depot formulations of a male hormonal contraception that could be conveniently injected every 3 - 6 months. In this article, we shall review the exciting new developments in male hormonal contraception.     

Drug stimulated biotransformation of hormonal steroid contraceptives: clinical implications.

On the basis of well documented biochemical and pharmacological data about the influence of drug mediated enzyme induction on the biotransformation of natural and synthetic sex steroids, practical consequences for hormonal steroid contraception are described and discussed. Clinical reports dealing with this problem are still sparse. The clinical symptoms of drug stimulated biotransformation of hormonal steroid contraceptives are characteristic. Spotting or breakthrough bleeding are observed and in the extreme case conception may occur despite the regular intake of the contraceptive. The appearance of these symptoms differs from one individual to another. With a strong enzyme inducer, bleeding disorders can be provoked artifically in 50 to 60% of the women receiving hormonal contraceptive treatment. The range of drugs which stimulate biotransformation of hormonal contraceptives with consequent loss of their biological effectiveness is not completely known. For practical purposes, it is recommended that bleeding disturbances under hormonal steroid contraception in a previously regular cycle be regarded as loss of reliability; they should be remedied and taken as a sign to search for uncontrolled drug taking.     

Development and validation of an acceptability and satisfaction questionnaire for a contraceptive vaginal ring, NuvaRing

OBJECTIVE: To validate an acceptability questionnaire for NuvaRing, a new combined contraceptive vaginal ring. METHODS: A 21-item questionnaire was developed covering: ease of ring use, ease of package use, clarity of instructions, sexual comfort, cycle-related characteristics, compliance and satisfaction. A total of 2145 women completed the questionnaire after 3, 6 or 13 cycles of NuvaRing use. The psychometric properties and predictive value of the questionnaire were assessed using cycle 3 data (n = 1950). The quality of completed questionnaires, item content analysis, construct validity, internal consistency reliability, known groups validity and predictive validity were evaluated. RESULTS: Excluding non-ordinal items, 0.6% of the data were missing. Principal component analysis of 15 ordinal items indicated that two hypothesised dimensions ('ease of package use' and 'clarity of instructions') were consistently linked and so were combined into a single 'ease of comprehension' scale. Item convergent validity (the degree of correlation between an item and its own scale) was 100% for 'ease of ring use' (r = 0.44) and 'satisfaction' (r = 0.58), 83% for 'ease of comprehension' (r = 0.25-0.62) and 67% (r = 0.38-0.54) for 'sexual comfort', but 0% for 'cycle-related characteristics' (r = 0.31). Item discriminant validity (the degree to which an item correlates with its own scale compared with other scales) was >/=96% for all dimensions. Internal consistency reliability was acceptable for all dimensions (adjusted Cronbach's alpha coefficient >0.70). Satisfaction was higher than in the complementary groups for respondents who had no adverse events, chose NuvaRing as the best method of contraception or completed the study; this indicated good known groups validity. Low satisfaction with the method was a good predictor of early discontinuation after cycle 3, indicating that the questionnaire had good predictive validity. CONCLUSIONS: The acceptability questionnaire has good psychometric properties and can predict early discontinuation of the NuvaRing vaginal ring method of contraception.     

Risks and benefits, advantages and disadvantages of levonorgestrel-releasing contraceptive implants.

Levonorgestrel-releasing implants are long acting contraceptives, approved for 5 years of continuous use. Two marketed systems, the six capsule Norplant use of tradenames is for product identification purposes only and does not imply endorsement. and the two rod Jadelle, have essentially equal rates of drug release, pregnancy and adverse events over 5 years of use. Randomised clinical trials and controlled cohort observations indicate that for the first 3 years, when pregnancy rates are at or almost zero, no other contraceptive system is more effective, although etonogestrel implants provide equal effectiveness. Annual pregnancy rates rise in the fifth year of continuous use but remain below 1 per 100 women. Annual pregnancy rates of Norplant users remain below 1 per 100 throughout 7 years of continuous use. Levonorgestrel implants provide low progestogen doses; 40-50 microg/day at 1 year of use, decreasing to 25-30 microg/day in the fifth year. Serum levels of levonorgestrel at 5 years are 60-65% of those levels measured at 1 month of use. Adverse effects with levonorgestrel implants are similar to those observed with progestogen only and combined oral contraceptives. Risks of ectopic pregnancy, other pregnancy complications and pelvic inflammatory disease are reduced in comparison with those of women using copper or non-medicated intrauterine devices. Risks of developing gallbladder disease and hypertension or borderline hypertension, although small, are about 1.5 and 1.8 times greater, respectively, in women using levonorgestrel implants than in women not using hormonal contraception. Other serious diseases have not been found to occur significantly more frequently in levonorgestrel implant users than in women not using hormonal contraception. The great majority of levonorgestrel implant users experience menstrual problems, but serious bleeding problems are not more frequent than in controls. Other health problems reported more frequently by levonogestrel implant users than by women not using hormonal contraception in a study of 16000 women included skin conditions, headache, upper limb neuropathies, dizziness, nervousness, malaise, minor visual disturbances, respiratory conditions, arthropathies, weight change, anxiety and non-clinical depression. Clinical depression is not more frequent in women using implants compared with those not using hormonal contraception (i.e. using intrauterine devices, sterilisation). Removal problems occur less frequently with Jadelle than with Norplant. The mean removal time for Jadelle is half that of Norplant. Levonorgestrel implants in nationally representative scientific samples, in randomised trials, and in controlled cohort studies have continuation rates as high as or higher than any other reversible contraceptive over a duration of 5 years. This would imply that the satisfaction women derive from the contraceptive effectiveness of levonorgestrel implants greatly outweighs the dissatisfaction that may accompany menstrual disturbances and other adverse effects associated with implants.     

Pharmacovigilance in psychiatry: pharmacogenetic tests and therapeutic drug monitoring are promising tools

Contraceptive management in women with epilepsy is critical owing to the potential maternal and fetal risks if contraception or seizure management fails. This article briefly describes the pharmacokinetic interactions between antiepileptic drugs (AEDs) and hormonal contraceptives and the rational strategies that may overcome these risks. Hormonal contraception, including the use of oral contraceptives (OCs), is widely used in many women with epilepsy – there is no strong evidence of seizures worsening with their use. AEDs are the mainstay for seizure control in women with epilepsy. However, there are many factors to consider in the choice of AED therapy and hormonal contraception, since some AEDs can reduce the efficacy of OCs owing to pharmacokinetic interactions. Estrogens and progestogens are metabolized by cytochrome P450 3A4. AEDs, such as phenytoin, phenobarbital, carbamazepine, felbamate, topiramate, oxcarbazepine and primidone, induce cytochrome P450 3A4, leading to enhanced metabolism of either or both the estrogenic and progestogenic component of OCs, thereby reducing their efficacy in preventing pregnancy. OCs can also decrease the concentrations of AEDs such as lamotrigine and, thereby, increase the risk of seizures. Increased awareness of AED interactions may help optimize seizure therapy in women with epilepsy.     

Enhanced Metabolism of Levonorgestrel During Phenobarbital Treatment and Resultant Pregnancy

Levonorgestrel implants (Norplant) are an alternative to oral contraceptives and medroxyprogesterone acetate intramuscular injections. An interaction may exist between levonorgestrel and agents that induce the hepatic microsomal enzyme system. A 21-year-old woman with a history of a seizure disorder, treated with phenobarbital, who received levonorgestrel implants became pregnant. After a normal delivery, she took oral contraceptives concomitantly with phenobarbital. Although she was educated about the importance of a backup method of contraception, the woman again became pregnant and delivered twins. A recent national survey of neurologists and obstetricians was conducted evaluating prescriber knowledge of interactions between oral contraceptives and anticonvulsants. Only 4% of neurologists and zero percent of obstetricians knew all the interactions between the six most commonly prescribed anticonvulsants and oral contraceptives. This case supports the importance of continued patient and prescriber education regarding the possibility of drug-drug interactions in women taking anticonvulsants and hormonal contraceptives.     

Vaginal rings for menopausal symptom relief

The vagina is an alternative delivery site of sex steroids for menopausal women. New ring technology provides continuous and consistent delivery of steroids for up to 3 months. Rings rest on the pelvic floor muscles in a nearly horizontal position and are usually imperceptible. Steroid is delivered directly into the systemic circulation which may result in less alteration of coagulation/fibrinolysis pathways as seen with transdermal hormone therapy. Fewer adverse effects are noted when progesterone is applied vaginally, possibly due to lower serum levels of metabolites such as alloprenanolone. Women often switch to a ring for the longer dosing interval but also appreciate the reduced messiness. Over 5700 healthy US women who evaluated an unmedicated ring as a drug delivery platform found it very acceptable independent of age or prior use of barrier contraceptives. Marketed rings in the US include: (i) a ring for systemic and vaginal menopausal therapy that provides average serum estradiol levels of 40.6 pg/mL for the 0.05 mg and 76 pg/mL for the 0.1 mg dose; (ii) a ring for urogenital menopausal symptoms only that minimally elevates serum estradiol, usually within the menopausal range, treating atrophic vaginitis and urethritis; and (iii) a ring labelled for contraception that provides ethinyl estradiol 15 microg and etonogestrel 120 microg appropriate for nonsmoking perimenopausal women. A ring for combination hormone therapy and another releasing progesterone for contraception in lactating women have been reported in the literature, but are not yet available commercially. These may offer future options for hormone therapy. Women with a uterus receiving estrogen, even in low doses, should be given progestogen to prevent endometrial hyperplasia or carcinoma. Even women who have had an endometrial ablation are likely to have some endometrial tissue remaining since long-term amenorrhoea is uncommon. Since no marketed combination ring product is available, other forms of progestogen are necessary. Vaginal rings offer a novel approach to menopausal hormone therapy producing consistent serum levels sustained for up to 3 months per unit dose with lower adverse effects than other vaginal products and high acceptability among users.     

Ortho Evra,a new contraceptive patch

Ortho Evra is the first transdermal patch approved for the prevention of pregnancy. Comparative trials have shown that Ortho Evra has efficacy similar to the oral contraceptives Mercilon (not available in the United States) and Triphasil for the prevention of pregnancy when used as directed. Adverse effects with Ortho Evra are similar to those reported with combined oral contraceptives, with the exceptions of mild-to-moderate application-site reactions and an increased frequency of breast symptoms. The most commonly reported adverse reactions were breast symptoms, headache, application-site reactions, nausea and vomiting, dysmenorrhea, and abdominal pain. Approximately 5% of study subjects had at least one patch that did not stay attached to their skin, and about 2% of women withdrew from clinical trials due to irritation from the patch. In clinical studies, the patch appeared to be less effective in women weighing more than 90 kg than in women with lower body weights. More research is needed on the relationship between body weight and contraceptive patch efficacy. In two clinical trials, compliance was greater with the patch than with oral contraceptives. Whether this will result in reduced pregnancy rates in general use is unknown. Additional studies are warranted to determine if the patch offers any significant efficacy or safety advantages over current methods of hormonal contraception.