ethisterone and norelgestromin

Topics: Contraception; Contraceptive Agents, Female; Desogestrel; Drug Combinations; Ethisterone; Female; Humans; Levonorgestrel; Male; Medroxyprogesterone Acetate; Norgestrel; Oximes; Venous Thrombosis; Women's Health

Topics: Administration, Cutaneous; Contraception; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; Skin Absorption

Topics: Affect; Contraception; Contraception Behavior; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Delayed-Action Preparations; Desogestrel; Drug Administration Schedule; Drug Combinations; Drug Implants; Ethisterone; Female; Humans; Injections; Levonorgestrel; Medroxyprogesterone Acetate; Norgestrel; Oximes; Patient Education as Topic; Progesterone Congeners; Risk Factors; United States; Weight Gain; Women's Health

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.

Topics: Administration, Cutaneous; Animals; Clinical Trials as Topic; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Drug Combinations; Ethisterone; Female; Humans; Norgestrel; Oximes

The percutaneous route is an effective method for delivery of reproductive hormones. Several transdermal therapeutic systems (TTS) releasing estrogens, progestogens and androgens from patches attached to the skin are currently in clinical use. For women, transdermal systems have been developed for hormonal replacement therapy (HRT) and recently for contraception. HRT with patches releasing only estradiol (E2) should be supplemented with a progestogen to protect the endometrium. Patches simultaneously releasing both E2 and a progestogen are also available. Combined regimens are either continuous or sequential. In the latter, estrogen-only patches are applied for 14 days, followed by 14-day application of patches releasing both hormones. Transdermal HRT successfully treats menopausal symptoms and has a bone-sparing effect. Transdermal contraceptive patches deliver ethinyl E2 in combination with the progestogen norelgestromin. This system provides an effective contraceptive and acceptable bleeding pattern not different from that of oral contraceptives. The types of adverse events experienced are approximately the same as with oral contraceptives. Reactions at the application site cause about 3% women to discontinue the use of patches. Transdermal systems also have been designed to supplement testosterone in hypogonadal men. Testosterone released from patches produces positive effects on mood and sexual behavior and significantly increases bone mass. Men using testosterone patches have to be regularly monitored for an increase in prostate volume and changes in prostate-specific antigen. Reproductive steroids delivered by the skin avoid first-pass liver metabolism, typical of oral dosing; consequently, the liver tissue is affected to a lesser degree. Other advantages include rapid onset and termination of action, noninvasive self-administration and attainment of therapeutic hormone levels with low daily doses. Reduced frequency of dosing has the potential to improve patient compliance. While compliance is important for any hormone, it is particularly important for contraceptive purposes. Like oral delivery of sex steroids, percutaneous absorption is characterized by intra- and interindividual variability. New technologies under development, combining electronics and low-frequency ultrasound, have the potential to provide precise dosing as well as drug delivery "on demand."

Topics: Administration, Cutaneous; Contraception; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Drug Administration Schedule; Drug Combinations; Drug Delivery Systems; Equipment Design; Estradiol; Estrogen Replacement Therapy; Ethinyl Estradiol; Ethisterone; Female; Gonadal Steroid Hormones; Humans; Male; Norgestrel; Oximes; Testosterone

To present a review of a novel transdermal contraceptive patch containing norelgestromin (150 micrograms/d) and ethinylestradiol (20 micrograms/d).. Review article.. Department of Gynecology and Obstetric, 1st Medical Faculty and General Faculty Hospital, Prague.. The contraceptive patch exhibits favourable pharmakokinetic profile, maintaining efficacious serum hormone concentrations under varying conditions and without peaks and through characteristic of oral dosing. Efficacy, cycle control, tolerability and side effect profile were comparable to an established oral contraceptive. Compliance with the weekly administered contraceptive patch was significantly better than with an oral contraceptive. The reliability of adhesion of the patch is very high and consistent even under varying conditions (heat, humidity, exercise).

Topics: Administration, Cutaneous; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes

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.

Topics: Administration, Cutaneous; Clinical Trials as Topic; Contraceptive Agents, Female; Contraceptive Devices, Female; Contraceptives, Oral, Combined; Delayed-Action Preparations; Desogestrel; Drug Combinations; Drug Interactions; Estradiol; Ethinyl Estradiol; Ethisterone; Female; Humans; Injections, Intramuscular; Medroxyprogesterone; Norgestrel; Oximes

Evra (Janssen-Cilag) is the first contraceptive to be available as a skin patch. In promotional material aimed at healthcare professionals, the company claims that Evra offers a "once-weekly method of contraception" with "more than 99% effectiveness and excellent compliance". The company's website for women using Evra carries the slogan "Evra The Right Contraceptive Choice" and claims that the patch is "just as effective as the contraceptive pill". Each patch is intended to be worn for 7 days, in contrast to combined oral contraceptives (COCs), which need to be taken daily. Here we assess whether Evra offers real advantages over COCs and consider its place as a contraceptive option.

Topics: Administration, Cutaneous; Adult; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; Patient Compliance; Pregnancy; Randomized Controlled Trials as Topic

Evra is a transdermal patch releasing 20 micrograms of ethinylestradiol and 150 micrograms of norelgestromin/day during one week. The circulating levels of steroids attained are of similar amplitude though steadier than after intake of an oral combined low-dose estrogen-progestin pill. The transdermal method is user-friendly and is abided by a high degree of acceptability, and a low level of skin irritability. Its contraceptive effectiveness is similar to that conferred by oral contraceptives except if the treated woman is over 90 kg, in which case Evra should not be prescribed. Cycle control is excellent and similar to that of triphasic pills. Adverse effects and tolerance are comparable to those described with low-dose oral contraceptives with a slight estrogen dominance. Lipid and glucose metabolism as well as coagulation are influenced in the same way. Gastrointestinal disturbances (nausea, vomiting) do not prevent the efficacy of the transdermal patch. Compliance with Evra is significantly higher than with oral combined contraceptives--a major point for an effective contraception. Accordingly, Evra constitutes an useful addition to the current array of contraceptive methods.

Topics: Administration, Cutaneous; Adult; Contraception; Contraceptives, Oral; Contraceptives, Oral, Combined; Drug Combinations; Ethisterone; Female; Glucose; Humans; Lipid Metabolism; Menstrual Cycle; Nausea; Norgestrel; Oximes; Vomiting

Ethinylestradiol 20 microg/day plus norelgestromin 150 microg/day have been formulated into a transdermal patch for hormonal contraception. The predominant mechanism of action for transdermal ethinylestradiol/norelgestromin (Ortho Evra, Evra) is inhibition of ovulation by suppression of gonadotropins. It suppresses follicular development, induces changes to the endometrium that reduce the probability of implantation, and increases the viscosity of cervical mucus, which may prevent sperm penetration into the uterus. Two large randomized, nonblind efficacy studies demonstrated that transdermal ethinylestradiol/norelgestromin was as efficacious in preventing pregnancy as oral triphasic ethinylestradiol/levonorgestrel or oral ethinylestradiol/desogestrel. A large, noncomparative study also showed transdermal ethinylestradiol/norelgestromin to have good contraceptive efficacy. Moreover, in the two comparative trials, women using transdermal ethinylestradiol/norelgestromin had higher rates of perfect compliance than women using oral contraception. Age did not affect the rate of perfect compliance in women using the transdermal ethinylestradiol/norelgestromin patch, whereas the rate of compliance reduced with younger age in oral contraceptive users. Pooled results from three efficacy studies found that 1.8% of patches were replaced as a result of complete detachment and 2.9% because of partial detachment. Physical exercise, water immersion, and living in a humid climate did not affect patch adhesion. Transdermal ethinylestradiol/norelgestromin was generally well tolerated in clinical trials. The most common menstrual disturbances were breakthrough bleeding/spotting and dysmenorrhea. The incidence of discontinuation of treatment because of an adverse event was < or = 3.2%, with the most common reason being application-site reactions.. Transdermal ethinylestradiol/norelgestromin offers a well tolerated, effective, reversible, and easy-to-use method of hormonal contraception with an increased likelihood of compliance relative to oral contraceptives.

Topics: Administration, Cutaneous; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes

The pharmacokinetics of norelgestromin, the primary active metabolite of norgestimate, plus ethinyl estradiol (EE), delivered by the once-weekly contraceptive patch (Ortho Evra/Evra), have been studied in eight trials. This overview summarizes the relevant pharmacokinetic data for the contraceptive patch.. Review article.. The amount of norelgestromin and EE absorbed from the patch is proportional to patch size: the 20-cm(2) patch (Ortho Evra) delivers norelgestromin, 150 microg/d, and EE, 20 microg/d, to the systemic circulation. After single and multiple applications of the contraceptive patch, daily serum concentrations (area under the serum concentration-versus-time curve) of norelgestromin and EE were within the ranges generally seen with oral norgestimate, 250 microg/EE 35 microg (Ortho-Cyclen/Cilest), but without the peaks and troughs characteristic of oral dosing. Moreover, the contraceptive patch maintains serum concentrations of norelgestromin and EE within these ranges for up to 10 days, suggesting that clinical efficacy would be maintained even if a scheduled change is missed for as long as two full days. Regardless of the location of patch application (abdomen, buttock, upper outer arm, or torso [excluding breasts]) and even under conditions of heat, humidity, exercise, and cool-water immersion, efficacious concentrations of norelgestromin and EE are achieved. Coadministration of the patch with tetracycline did not affect the pharmacokinetics of norelgestromin and EE.. The contraceptive patch exhibits an excellent pharmacokinetic profile, maintaining efficacious serum hormone concentrations under varying conditions.

Topics: Administration, Cutaneous; Area Under Curve; Biological Availability; Contraceptives, Oral, Combined; Drug Combinations; Drug Delivery Systems; Ethinyl Estradiol; Ethisterone; Female; Half-Life; Humans; Norgestrel; Oximes

This review summarizes the clinical studies involving the once-weekly Ortho Evra/Evra contraceptive patch. The patch delivers norelgestromin (NGMN), 150 microg, and ethinyl estradiol (EE), 20 microg, daily to the systemic circulation. The contraceptive patch provided ovulation suppression and cycle control similar to that of oral norgestimate 250 microg/EE 35 microg, significantly decreased mean maximum follicular diameter following a 3-day intentional delayed dosing phase when compared with oral levonorgestrel (LNG) 50/75/125 microg/EE 30/40/30 micorg and oral LNG 100 microg/EE 20 microg, and was as effective as oral LNG 50/75/125 microg/EE 30/40/30 microg and oral desogestrel 150 microg/EE 20 microg in altering cervical mucus composition (i.e., creating a scanty, viscous consistency). The contraceptive patch provided efficacy, cycle control, and safety comparable to that seen with oral LNG 50/75/125 microg/EE 30/40/30 microg, but women were able to correctly follow the weekly dosing regimen significantly more often than the daily oral contraceptive dosing regimen. Less than 2% of patches were replaced because of complete detachment in these trials. The patch was not associated with phototoxicity or photoallergy. The contraceptive patch, the only noninvasive, weekly birth control method that a woman can self-administer, will be a valuable addition to current contraceptive options.

Topics: Administration, Cutaneous; Clinical Trials as Topic; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Drug Administration Schedule; Drug Combinations; Drug Implants; Drug Interactions; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; Pregnancy; Safety

To compare bleeding profiles and satisfaction among women using a norelgestromin/ethinyl estradiol (E2) transdermal contraceptive patch in an extended regimen to those among women using a traditional 28-day patch regimen.. Healthy, regularly menstruating women (N = 239) were randomly assigned (2:1 ratio) to receive the norelgestromin/ethinyl E2 transdermal patch in an extended regimen (weekly application for 12 consecutive weeks, 1 patch-free week, and 3 more consecutive weekly applications, n = 158) or a cyclic regimen (4 consecutive cycles of 3 weekly applications and 1 patch-free week, n = 81). Subjects recorded bleeding data daily and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens.. Extended use of the norelgestromin/ethinyl E2 transdermal patch resulted in fewer median bleeding days (6 compared with 14, P < .001), bleeding episodes (1 compared with 3, P < .001), and bleeding or spotting episodes (2 compared with 3, P < .001) compared with cyclic use during days 1-84; median numbers of bleeding or spotting days were similar between regimens (14 compared with 16, P = .407) during this time. Extended use delayed median time to first bleeding to 54 days compared with 25 days with cyclic (P < .001). Subjects were highly satisfied with both regimens. Although not statistically significant, slightly more adverse events were reported with the extended than with the 28-day regimen.. Compared with cyclic use, extended use of the norelgestromin/ethinyl E2 transdermal patch delayed menses and resulted in fewer bleeding days. This regimen may represent a useful alternative for women who prefer fewer episodes of withdrawal bleeding.

Topics: Administration, Cutaneous; Adolescent; Adult; Contraceptives, Oral, Combined; Drug Administration Schedule; Drug Combinations; Estrogens; Ethinyl Estradiol; Ethisterone; Female; Humans; Menstruation; Middle Aged; Norgestrel; Oximes; Patient Satisfaction

To document Canadian women's experience with the transdermal contraceptive patch, a method delivering 150 microg norelgestromin and 20 microg ethinyl estradiol daily.. We conducted an open-label, multicentre, descriptive cohort study of the contraceptive patch over 9 cycles in 392 women requiring contraception. A single treatment cycle consisted of 3 consecutive 7-day patch applications followed by 1 patch-free week. At the final visit, overall satisfaction and preference for the patch was rated and compared with the previously used contraceptive method.. At baseline, 80.9% of participants were either very satisfied or somewhat satisfied with their previous contraceptive method, 89% having used oral contraceptives. At final observation, 60.6% of participants preferred the patch, 9.3% had no preference; and 30% preferred their previous method (n = 376). A total of 279 participants (71.2%) completed 9 cycles of patch use. Of these, 91% were satisfied with the patch and 74.9% preferred the patch to their previous contraceptive (43% strongly preferred and 31.9% preferred); 9% had no preference; and 16.1% preferred their previous method. Of those who preferred the patch, 82.7% preferred it because of its convenience or simplicity. Across all cycles, 88% of participants recorded perfect compliance. The most common adverse event was application site reactions (most of which were mild), experienced by 49% of participants: 33.7%, 16.5%, and 14.7% at cycles 1, 4, and 9, respectively.. Both preference for and satisfaction with the transdermal contraceptive patch were high. Most participants.

Topics: Administration, Cutaneous; Adolescent; Adult; Cohort Studies; Condoms; Contraceptive Devices, Female; Contraceptives, Oral; Contraceptives, Oral, Combined; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Intrauterine Devices; Middle Aged; Norgestrel; Oximes; Patient Compliance; Patient Satisfaction; Safety; Spermatocidal Agents; Treatment Outcome

A randomized clinical trial was conducted with 239 women at nine clinical research sites to compare bleeding profile, headache frequency, and subject satisfaction with the transdermal contraceptive, ORTHO EVRA (norelgestromin/ethinyl estradiol transdermal system) used in an extended regimen (84 days) with a traditional, 28-day cyclic regimen. In a majority of women studied, compared with cyclic use, extended use of transdermal norelgestromin/ethinyl estradiol delayed menses and reduced the total incidence of mean headache days during the hormone-free interval.

Topics: Administration, Cutaneous; Adolescent; Adult; Delayed-Action Preparations; Drug Combinations; Ethisterone; Female; Headache; Humans; Middle Aged; Norgestrel; Oximes; Substance Withdrawal Syndrome; Time Factors

The purpose of this study was to compare biochemical androgen profiles in women treated with the contraceptive patch versus an oral contraceptive (OC).. Twenty-four healthy women were randomly assigned to receive 3 cycles of either the contraceptive patch (ethinyl estradiol [EE] 20 microg/d and norelgestromin 150 microg/d) or OC (EE 35 mug and norgestimate 250 microg). Blood samples were taken at baseline and end of treatment. Serum levels of sex hormone-binding globulin (SHBG), total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), and 3alpha-androstanediol glucuronide (3alpha-diol G) were quantified by immunoassay methods; free T was calculated. The paired t and Student t tests were used for statistical analysis.. Nineteen women completed the study (patch, n = 10; OC, n = 9). Despite a 1.6-fold relative increase in SHBG levels with the patch versus OC (449% vs 274%, P = .03), free T decreased equally in both groups (patch 60%, P < .0001; OC 59%, P < .0001). DHEAS decreased by 26% in the patch group (P < .01) and 32% in the OC group (P < .001). 3alpha-diol G was reduced by 52% in the patch group (P < .0001) and 51% in the OC group (P < .0001). In addition, the OC was associated with significant decreases in A and DHT.. The contraceptive patch had an effect comparable to the OC on several key androgenic markers. Given these biochemical findings, the contraceptive patch has significant potential as a therapeutic agent for disorders of androgen excess.

Topics: Administration, Cutaneous; Adolescent; Adult; Androgens; Androstenedione; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; Sex Hormone-Binding Globulin; Testosterone; Treatment Outcome

evaluation of the frequency of adverse events during the therapy with a transdermal contraceptive system (TCS) in comparison to an oral contraceptive.. 20 healthy women aged 23.8 +/- 4.1 years without contraindication to steroid hormonal therapy and a history of dermal hypersensitivity to adhesive applications. All patients were treated with either contraceptive patches containing 20 microg ethinyl estradiol (EE) and 150 microg norelgestromin (17-dNGM) or a monophasic oral contraceptive containing 20 microg EE and 150 microg desogestrel during 6 cycles. Safety evaluation was based on the frequency of adverse effects, changes in physical and gynecological examinations.. The incidence of most adverse effects was similar between the transdermal and oral contraceptive therapies, except of a higher incidence of breast pain, dysmenorrhoea and application site reactions in the patch group. 50% of patients demonstrated gastro-intestinal complaints in the oral contraceptive group. None of the patients discontinued the hormonal contraceptive therapies due to adverse effects.. The study suggests that a transdermal contraceptive system is a safe and well tolerated therapy.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Desogestrel; Dose-Response Relationship, Drug; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; Women's Health

To evaluate the acceptability and feasibility of using the new transdermal contraceptive patch in adolescents.. A 3-month longitudinal trial using the Ortho Evra transdermal contraceptive patch in 50 adolescent girls. All healthy girls aged 15-18 years were invited to participate from two San Francisco Bay Area teen clinics. Participants were followed after 1 month and 3 months of treatment. Data were collected on patch detachments, perceived advantages and disadvantages, side effects, and compliance. Data were analyzed using Student's t-test (SPSS).. Forty participants (80%) completed 1 month of treatment and 31 (62%) completed all 3 months of the study. There were no pregnancies during treatment. At the 3-month follow-up, 87.1% of participants reported perfect compliance. Ease of use, the fact that it does not require daily attention, and the ease of concealment were among the main reported advantages. Roughly 77% of participants who completed the study were planning to continue using the patch. The 35.5% rate of complete or partial detachment of at least one patch was considerably higher than reported in previous studies of adults. As in adults, the most commonly reported complaints were application site reactions and breast discomfort.. This evaluation found an overall positive impression of the new transdermal contraceptive patch, with good rates of short-term compliance and few side effects among adolescents. However, the high degree of detachment unique to this sample of adolescents is concerning and requires further evaluation.

Topics: Administration, Cutaneous; Adolescent; Analysis of Variance; Contraceptives, Oral, Combined; Drug Combinations; Ethisterone; Female; Humans; Longitudinal Studies; Norgestrel; Oximes; Patient Compliance; Patient Satisfaction; San Francisco

The transdermal contraceptive patch, Ortho Evra, was approved in December 2001 and released on the market in June 2002. In this study, we reviewed clinical data of young women who started the patch between June 2002 and December 2003 in the adolescent medicine clinic at a university-based outpatient center. A total of 62 patients started the patch in that period and two of them were lost to follow-up. Mean age of patients was 17.9 years and mean length of use was 10 cycles. Only 10 patients (16.7%) discontinued use. Reasons for discontinuation were moderate to severe skin irritation (3 patients, 5%), complete detachment (3 patients, 5%), and economic reasons (4 patients, 6.7%). Compliance was excellent overall and the side-effects profile was good. No pregnancies occurred during this period. These results confirmed that the transdermal contraceptive patch is easy to use and an effective method of birth control that may be better tolerated by young women. It also seemed to improve contraceptive compliance in this population.

Topics: Administration, Cutaneous; Adolescent; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Drug Administration Schedule; Drug Combinations; Ethisterone; Female; Humans; Norgestrel; Oximes; Patient Compliance; Time

Norelgestromin (NGMN) and levonorgestrel (LNG) are the main active metabolites of norgestimate (NGM), but their relative contributions to the pharmacological effects of NGM are unclear. We have therefore determined the serum distribution of these NGM metabolites and assessed their steady-state concentrations in women following >or=3 cycles of oral contraceptive (OC) use. The administration of 250 microg NGM/35 microg ethinyl estradiol (EE) resulted in significantly higher sex hormone-binding globulin (SHBG) levels (p = 0.002), and 30% lower serum non-protein-bound (NPB) levels of testosterone, when compared to treatment with 150 microg LNG/30 microg EE. We also confirmed that NGMN does not bind to SHBG, and found that 97.2% of this metabolite is bound to albumin while only 2.8% is in the NPB fraction. In contrast, most of the LNG was bound to SHBG (92.5% and 87.2% after NGM/EE and LNG/EE treatment, respectively), and the NPB fraction of LNG (0.7%) during NGM/EE treatment was lower (p < 0.001) than during LNG/EE treatment (1.4%). Combining these serum distributions with the C(max) and AUC(0-24h) data obtained after NGM/EE treatment gave NPB and albumin-bound values of NGMN that were much greater than the corresponding LNG values. Furthermore, the C(max) and AUC(0-24h) values for NPB LNG during NGM/EE treatment were estimated to be lower than during LNG/EE treatment. Since LNG is primarily bound by SHBG, its access to target tissues is restricted. Moreover, because SHBG does not bind NGMN, it appears to be quantitatively the more important NGM metabolite available to target tissues, and probably accounts for a substantial proportion of the progestogenic activity of NGM/EE OCs. However, it is also possible that simultaneous exposure of NGMN and LNG after treatment with NGM/EE may provide clinical benefits not seen with LNG/EE combinations.

Topics: Adolescent; Adult; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Levonorgestrel; Norgestrel; Oximes; Serum Albumin; Sex Hormone-Binding Globulin; Testosterone

To evaluate the metabolic impact on lipids of a contraceptive patch that delivers norelgestromin (primary active metabolite of norgestimate) and ethinyl estradiol to the systemic circulation as compared with a placebo patch.. In this randomized, double-blind trial, healthy women received the contraceptive patch (n = 99) or placebo patch (n = 47) for up to 9 cycles. Fasting blood samples were obtained at baseline and cycles 3, 6 and 9 for determining the serum lipid profile.. At cycles 3, 6 and 9, mean increases from baseline in high-density lipoprotein (HDL) cholesterol, HDL3 cholesterol, total cholesterol and total triglycerides, and mean decreases in calculated (Friedewald) low-density lipoprotein (LDL)/HDL were observed in the contraceptive patch group (all P < .05 vs. placebo except for total cholesterol at cycle 6). Mean changes in HDL2 and calculated LDL cholesterol were minimal and comparable between treatments. Mean body weight increased from baseline to the end of treatment by 0.8 and 0.6 kg in the 2 groups, respectively; this difference was not significant.. The lipid changes seen with the contraceptive patch are consistent with those of oral contraceptives containing norgestimate and ethinyl estradiol.

Topics: Administration, Cutaneous; Adolescent; Adult; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Contraceptives, Oral, Combined; Double-Blind Method; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Menstrual Cycle; Middle Aged; Norgestrel; Oximes; Reference Values; Time Factors; Triglycerides

To compare the effects of the contraceptive patch to oral contraceptives (OCs) on follicular size and incidence of ovulation in normal cycles and after dosing errors.. Randomized, open-label.. Twelve centers.. One hundred twenty-four ovulatory women.. Subjects received either the patch (groups 1 and 2) or one of three OCs. Correct dosing occurred in cycles 1, 2, 3, and 5. The following dosing errors were planned during cycle 4, a shortened 10-day cycle: [1] patch group 1 subjects wore one patch for 10 consecutive days; [2] for patch group 2 and OC subjects, 7 dosing days were followed by 3 drug-free days.. Follicular size, as determined at each cycle by the maximum mean follicular diameter.. After a 3-day dosing error, follicular size was significantly smaller in the patch group (mean, 7.0 mm) vs. each OC group (range of means, 11.8-17.1 mm). Similar results were seen after proper dosing. The incidence of ovulation was significantly lower for the patch users than for women using OCs.. Follicular size and incidence of ovulation were significantly reduced among contraceptive patch users compared with women using OCs in normal cycles and after planned dosing errors.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adult; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Combinations; Estradiol; Estradiol Congeners; Ethinyl Estradiol; Ethisterone; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Medication Errors; Norgestrel; Ovarian Follicle; Ovulation; Oximes; Progesterone; Ultrasonography

To present efficacy and cycle control data pooled from three pivotal studies of the contraceptive patch (Ortho Evra/Evra).. Three multicenter, open-label, contraceptive studies that included up to 13 treatment cycles.. 183 centers.. 3,319 women.. Three consecutive 7-day patches (21 days) with 1 patch-free week per cycle.. Contraceptive efficacy and cycle control.. Overall and method failure life-table estimates of contraceptive failure through 13 cycles were 0.8% (95% CI, 0.3%-1.3%) and 0.6% (95% CI, 0.2%-0.9%), respectively. Corresponding Pearl indices were 0.88 (95% CI, 0.44-1.33) and 0.7 (95% CI, 0.31-1.10). Contraceptive failure among women with a body weight < 90 kg (<198 lb) was low and uniformly distributed across the weight range. A subgroup of women with body weight > or = 90 kg (> or = 198 lb) may have increased risk of pregnancy. The incidence of breakthrough bleeding was low and decreased over time.. In contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of the patch was high and similar across age and racial groups. Among women < 90 kg (<198 lb), contraceptive failure was low and uniformly distributed across the range of body weights. In women > or = 90 kg (> or = 198 lb), contraceptive failures may be increased. Efficacy and cycle control have been shown to be comparable to an established oral contraceptive.

Topics: Administration, Cutaneous; Adolescent; Adult; Age Factors; Body Weight; Contraceptives, Oral, Combined; Drug Combinations; Drug Delivery Systems; Ethinyl Estradiol; Ethisterone; Female; Humans; Menstrual Cycle; Norgestrel; Oximes; Pregnancy; Proportional Hazards Models

To determine compliance with the contraceptive patch (Ortho Evra/Evra) overall and by age among women in North America and to compare rates of perfect use with those of an established oral contraceptive.. Data were pooled for three contraceptive studies in which women participated for up to 13 cycles; the subset of centers in North America was used in this analysis.. 76 North American centers.. Healthy women 18-45 years of age.. In all studies, the patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle.. Perfect use for the patch or oral contraceptive, defined as 21 consecutive days of drug-taking followed by a 7-day drug-free period; for contraceptive patch users, no patch could be worn for more than 7 days. Oral contraceptives were used according to package labeling.. For all contraceptive patch users in North America (n = 1,785), perfect use was consistent across age groups. The percentage of cycles with perfect use of the patch ranged within age groups from 88.1% to 91.0%. In the comparative study conducted only in North America, perfect use was also consistent across age groups for the patch (n = 812), but rates of perfect use for the oral contraceptive (n = 605) differed significantly by age.. Age did not affect compliance with the patch among all North American women studied. In a comparative study of women at North American centers, compliance with the weekly contraceptive patch was significantly better than with an established oral contraceptive. The contraceptive patch is uniformly easy to use across all ages.

Topics: Administration, Cutaneous; Adolescent; Adult; Age Factors; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Combinations; Drug Delivery Systems; Ethinyl Estradiol; Ethisterone; Female; Humans; Middle Aged; Norgestrel; North America; Oximes; Patient Compliance

To determine the pharmacokinetic profile of norelgestromin (NGMN) and ethinyloestradiol (EE) following application of the contraceptive patch, Evra/Ortho Evra, at each of four anatomic sites (abdomen, buttock, arm, and torso).. Thirty-seven healthy, nonpregnant women aged 20-45 years participated in this open-label, four-period crossover study. Subjects were randomized to one of four treatment (site of application) sequences. Each patch was worn for 7 days, with a 1 month washout between treatments. Blood samples were collected before and at various times up to 240 h after application of each patch. Serum samples were assayed for NGMN and EE by validated methods.. The serum concentration reference ranges for NGMN and EE are 0.6-1.2 ng ml-1 and 25-75 pg ml-1, respectively, based on studies of the mean Cave of oral norgestimate 250 microg and EE 35 microg. For all application sites, mean concentrations of NGMN and EE remained within these ranges during the 7 day wear period. Absorption of NGMN and EE during patch application on the buttock, arm, and torso was equivalent. Absorption of NGMN and EE during patch application on the abdomen was approximately 20% less than observed for the other three sites, although mean serum concentrations were still within reference ranges. A previous study demonstrated therapeutic equivalence of patches worn on the abdomen vs other sites.. Serum concentrations of NGMN and EE from the contraceptive patch remain within the reference ranges throughout the 7 day wear period, regardless of the site of application (abdomen, buttock, arm, or torso).

Topics: Administration, Cutaneous; Adult; Area Under Curve; Contraceptives, Oral, Combined; Cross-Over Studies; Drug Administration Schedule; Drug Combinations; Estradiol Congeners; Ethinyl Estradiol; Ethisterone; Female; Humans; Middle Aged; Norgestrel; Oximes

The primary objective of this open-label study was to determine the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE)following two consecutive applications of a contraceptive patch (ORTHO EVRA/EVRA). Twelve healthy women wore the first patch on their abdomen for 7 days and, after removal at 168 hours (day 7), wore a second patch for 10 days (i.e., 3 days beyond the intended 7-day wear period). Blood samples were collected before and at various times up to 456 hours (day 19) after application of the first patch for analysis of NGMN and EE. Mean serum concentrations of NGMN and EE remained within the reference ranges, 0.6 to 1.2 ng/ml and 25 to 75 pg/ml, respectively, during the entire 7-day wear period after application of the first patch and for 10 days after application of the second patch; reference ranges are based on studies with ORTHO-CYCLEN/ Cilest. No patch detached spontaneously. No subject discontinued or experienced a serious adverse event.

Topics: Administration, Cutaneous; Adolescent; Adult; Area Under Curve; Contraceptives, Oral, Combined; Drug Combinations; Estradiol Congeners; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; Time Factors

The objectives of this randomized, open-label, three-period, incomplete block design study were to evaluate the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE) delivered by the contraceptive patch, Ortho Evra/Evra, and to evaluate patch adhesion under conditions of heat, humidity, and exercise. During each treatment period, 30 healthy women wore Ortho Evra on the abdomen for 7 days under one of six conditions (normal activity, sauna, whirlpool, treadmill, cool water immersion, or a combination of activities). Blood samples were collected before and several times to 240 hours after patch application. Mean serum concentrations of NGMN and EE generally remained within the reference ranges, 0.6 to 1.2 ng/ml and 25 to 75 pg/ml, respectively, during the 7-day wearperiodfor all activities. Only 1 (1.1%) of 87 patches completely detached spontaneously. Peel force measurements were comparable for all activities. Ortho Evra was well tolerated. In conclusion, Ortho Evra delivers efficacious concentrations of NGMN and EE and maintains adhesive reliability through 7 days of wear even under conditions of heat, humidity, and exercise.

Topics: Adhesiveness; Administration, Cutaneous; Adult; Contraceptives, Oral, Combined; Drug Combinations; Estradiol Congeners; Ethinyl Estradiol; Ethisterone; Exercise; Female; Hot Temperature; Humans; Humidity; Middle Aged; Norgestrel; Oximes

Topics: Contraceptives, Oral, Combined; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; United States; United States Food and Drug Administration

Topics: Contraceptives, Oral, Combined; Counseling; Drug Combinations; Drug Utilization; Ethisterone; Female; Humans; Norgestrel; Oximes; Physician-Patient Relations; Practice Patterns, Physicians'; Risk Assessment; United States; United States Food and Drug Administration; Venous Thrombosis

The new combined estrogen & progestin contraceptive patch Ortho Evra was approved by the FDA in December 2001. To date, there is a paucity of data regarding its use in the adolescent age group. We examined adolescents' experience with this new contraceptive method.. Using a questionnaire designed by the authors, care providers in a hospital based adolescent clinic interviewed and reviewed the charts of adolescent girls who had initiated Ortho Evra in 2002-2003.. Twenty-eight adolescent girls (age 18 +/- 1 years, gyn age 6 +/- 1 years, onset of sexual intercourse at 14 +/- 1 years, body mass index (BMI) 27.6 +/- 1.2, 57% Hispanic, 21% Caucasian, 11% African American, 7% biracial, 4% Indian American) who had used Ortho Evra for 7 +/- 1 months were enrolled. Half (50%) were adolescent mothers, and 57% had a history of irregular menstrual periods. All (100%) girls reported regular menstrual periods while using Ortho Evra, with only 14% experiencing occasional breakthrough bleeding. Half reported a shorter duration and 36% reported a lighter flow of their periods. About a third (39%) reported a decrease and 11% reported an increase in dysmenorrhea symptoms. About a third (29%) of those with a history of recurrent headaches at initiation reported decrease in headaches, and about a third (33%) of those with acne at initiation reported decrease in facial acne while on Ortho Evra. There were no significant BMI changes during Ortho Evra use. Although condom use while on Ortho Evra was poor (only 15% reporting consistent condom use), there were no pregnancies reported. A majority (93%) reported that they remembered to apply the patches on time, and 40% stated that Ortho Evra was easier than previous contraceptive methods. Two thirds (68%) were very satisfied and 29% were somewhat satisfied with the method, and 93% stated that they would recommend the method to a friend/relative. The preferred application site was the buttock (40%) followed by the lower abdomen (32%). About a fifth (21%) experienced at least one episode of complete patch detachment and 32% reported partial peeling of the patch corners. About a third (32%) would prefer another patch color, and 25% would like a fourth week placebo patch. The most common side effects were mild temporary application site reactions (64%), some discomfort on patch removal (32%), nausea (18%), and breast tenderness (18%). Eleven girls (39%) discontinued Ortho Evra (three lost health insurance, three because of application site reactions, two found patch application schedule difficult to remember, two desired pregnancy, two because of nausea, one because of perceived weight gain).. Ortho Evra provides excellent cycle control in adolescents. Most adolescents are satisfied with this method. Intensive efforts should be made to increase condom use by adolescents on Ortho Evra.

Topics: Abdomen; Acne Vulgaris; Administration, Cutaneous; Adolescent; Attitude to Health; Breast; Buttocks; Condoms; Contraceptives, Oral, Combined; Drug Carriers; Drug Combinations; Dysmenorrhea; Ethisterone; Female; Headache; Humans; Menstrual Cycle; Menstruation; Nausea; Norgestrel; Oximes; Patient Dropouts; Patient Satisfaction

This new transdermal contraceptive system (contraceptive patch), Evra (Janssen-Cilag), received a UK product licence in 2003. In clinical trials: Consistent doses of norelgestromin and ethinyl oestradiol are released into the systemic circulation daily. Pharmacokinetic data suggest that levels are sufficient to inhibit ovulation for at least 7 days. The overall Pearl index for the contraceptive patch (1.24; 95% CI 0.19-2.33) was similar to that of a triphasic combined oral contraceptive (COC) pill (2.18; 95% CI 0.57-3.8). Self-reported "perfect" compliance was significantly better with the contraceptive patch (88.2%) than with a combined contraceptive pill (77.7%). Patch detachment, requiring replacement with a new patch, with normal daily activity is uncommon (4.6%). Breakthrough bleeding and spotting were significantly more common with the contraceptive patch than with combined oral contraception in the first two cycles but differences were not significant by cycle three. In general, reported side effects were not significantly different with contraceptive patch or combined pill use. However, breast tenderness in the first two treatment cycles was more common with patch use. Symptoms were mild to moderate in 85% of women and were rarely treatment limiting. Currently, there are limited data regarding risk of venous thromboembolism, and cervical or breast cancer with the contraceptive patch. No clinically significant alterations in metabolic or haemostatic parameters were identified with contraceptive patch use. A month's supply of the contraceptive patch costs 7.74 UK pounds. Combined oral contraception prices range from approximately 0.80 to 5.00 UK pounds and hormone replacement therapy patches range from 10.00 to 13.00 UK pounds. The contraceptive patch offers additional choice for women who wish to use a combined hormonal method of contraception.

Topics: Administration, Cutaneous; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Device Approval; Drug Combinations; Estrogens; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; United Kingdom; Women's Health

Steroid hormones regulate endometrial expression of matrix metalloproteinases (MMPs) and their inhibitors. Synthetic progestins are widely used in oral contraceptives and for hormone replacement therapy. To assess whether the synthetic progestins norgestimate and its derivative norelgestromin (17-deacetylnorgestimate) modulate the expression of MMPs, Ishikawa endometrial cancer cells were separately treated with 17 beta-estradiol, 17 alpha-hydroxyprogesterone, norgestimate and norelgestromin. Culture supernatants were assayed for MMPs 2, 3 and 9, and for tissue inhibitors of MMPs (TIMP-1 and TIMP-2) by enzyme-linked immunosorbent assays (ELISAs). No marked modulation of MMP-2 and TIMP-2 expression was observed upon incubation of the cells with the synthetic progestins. By ELISA, neither MMP-3 or MMP-9 nor TIMP-1 immunoreactivity was detected. Interestingly, TIMP-2 expression was down-regulated by 17 beta-estradiol and 17 alpha-hydroxyprogesterone.

Topics: 17-alpha-Hydroxyprogesterone; Cell Line, Tumor; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Drug Combinations; Endometrium; Enzyme-Linked Immunosorbent Assay; Estradiol; Ethisterone; Female; Humans; Matrix Metalloproteinase 2; Norgestrel; Oximes; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

Topics: Administration, Cutaneous; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Drug Combinations; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; Risk Factors

The function and clinical significance of the androgen receptor (AR) in human breast cancer are still not clear. The synthetic progestins, norgestimate and norelgestromin, were designed to minimize the adverse effects such as acne, hirsuitism and metabolic changes observed with older oral contraceptives while maintaining contraceptive effectiveness and cycle control. AR-mediated effects of these synthetic progestins were studied in an in vitro transactivation assay, employing DNA co-transfection of an AR expression vector and luciferase reporter gene construct in the MDA-MB 231 human breast cancer cell line. Testosterone acetate and 5alpha-dihydrotestosterone induced the reporter gene transcription, whereas incubation of the transfected cells with the natural progestin 17alpha-hydroxyprogesterone did not markedly induce luciferase activity. The progestins norgestimate and norelgestromin exerted a very low androgenic activity. Our data suggest that norgestimate and its metabolite norelgestromin possess weak androgen-like properties. The use of these compounds for clinical application may be of great advantage in the treatment of breast cancer as well as hyperandrogenism in women.

Topics: 17-alpha-Hydroxyprogesterone; Breast Neoplasms; Contraceptives, Oral, Combined; Dihydrotestosterone; Drug Combinations; Ethisterone; Genetic Vectors; Humans; Luciferases; Norgestrel; Oximes; Receptors, Androgen; Testosterone; Transfection; Tumor Cells, Cultured

Human breast cancer tissue contains enzymes (estrone sulfatase, 17beta-hydroxysteroid dehydrogenase, aromatase) involved in the last steps of estradiol (E(2)) formation. In this tissue, E(2) can be synthesized by two main pathways: (1) sulfatase-transforms estrogen sulfates into bioactive E(2), and the (2) aromatase-converts androgens into estrogens. Quantitative assessment of E(2) formation in human breast tumors indicates that metabolism of estrone sulfate (E(1)S) via the sulfatase pathway produces 100-500 times more E(2) than androgen aromatization. In the present study, we demonstrated in T-47D and MCF-7 human breast cancer cells that norelgestromin (NGMN) (a metabolite of norgestimate) is a potent inhibitory agent of the estrone sulfatase activity. After 24h incubation of physiological concentrations of E(1)S (5 x 10(-9)mol/l) the inhibitory effect of NGMN at concentrations of 5 x 10(-9), 5 x 10(-7) and 5 x 10(-5)mol/l was 43+/-7, 74+/-4 and 97+/-2%, respectively, in T-47D cells; 25+/-4, 57+/-5 and 96+/-2% respectively, in MCF-7 cells. Comparative studies using medroxyprogesterone acetate (MPA) showed that this progestin also has an inhibitory effect on sulfatase activity, but significantly less intense than that of NGMN. The inhibition for MPA at concentrations of 5 x 10(-9), 5 x 10(-7) and 5 x 10(-5)mol/l was 31+/-5, 47+/-3 and 61+/-3%, respectively, for T-47D cells; 6+/-3, 20+/-3 and 63+/-4%, respectively, for MCF-7 cells. In conclusion, the present data show that NGMN is a very potent inhibitory agent for sulfatase activity in the hormone-dependent breast cancer cells, resulting in decreased tissue concentration of E(2). The clinical significance of this finding remains to be elucidated.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Contraceptives, Oral, Combined; Drug Combinations; Estradiol; Ethisterone; Humans; Inhibitory Concentration 50; Medroxyprogesterone Acetate; Models, Chemical; Norgestrel; Oximes; Selective Estrogen Receptor Modulators; Sulfatases; Tumor Cells, Cultured

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Desogestrel; Drug Approval; Drug Combinations; Drug Therapy; Epoprostenol; Estradiol; Ethisterone; Filgrastim; Fondaparinux; Fulvestrant; Granulocyte Colony-Stimulating Factor; Humans; Norgestrel; Oximes; Polyethylene Glycols; Polysaccharides; Recombinant Proteins; Triptorelin Pamoate; United States; Vinyl Compounds

Topics: Administration, Cutaneous; Contraceptives, Oral, Combined; Drug Combinations; Drug Delivery Systems; Estrogens; Ethinyl Estradiol; Ethisterone; Female; Humans; Norgestrel; Oximes; Progestins

To review the safety and tolerability of the contraceptive patch (Ortho Evra/Evra) versus a standard oral contraceptive (Triphasil) and to present the pooled safety and tolerability of the patch across three pivotal studies.. Three open-label, contraceptive studies of up to 13 treatment cycles.. 183 centers.. Comparative study (812 patch, 605 oral contraceptive); pooled analysis (3,330 patch).. The patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle; the oral contraceptive was dosed according to the U.S. physician package insert.. Adverse events, laboratory tests, vital signs, and body weight.. The incidence of most events was similar between the patch and oral contraceptive groups, with the exception of a higher incidence of application site reactions, breast discomfort (cycles 1 and 2 only), and dysmenorrhea in the patch group. Pooled analysis demonstrated that most application site reactions (92%) and breast symptoms (86%) were mild or moderate in severity, and <2% of participants discontinued the patch because of either event. Only 7 (0.2%) participants experienced a serious adverse event classified as possibly, probably, or likely related to the patch. The mean change in body weight from baseline to the end of treatment was an increase of 0.3 kg.. Overall, the contraceptive patch is well tolerated and has a side effect profile similar to an established oral contraceptive.

Topics: Administration, Cutaneous; Adolescent; Adult; Contraceptives, Oral, Combined; Drug Combinations; Drug Delivery Systems; Ethinyl Estradiol; Ethinyl Estradiol-Norgestrel Combination; Ethisterone; Female; Humans; Middle Aged; Norgestrel; Oximes; Pregnancy

To assess the adhesive reliability of the contraceptive patch (Ortho Evra/Evra).. Pooled data of 3,319 women from three contraceptive studies of up to 13 treatment cycles; a subset of 325 women of the pooled data from warm and humid climates; and 30 women from a three-period, crossover exercise study.. 184 centers.. 3,349 healthy women.. In the contraceptive studies, each treatment cycle consisted of three consecutive 7-day patches (21 days) followed by one patch-free week. During each treatment period in the exercise study, women wore the patch for 7 days and participated in one of six activities (normal activity, excluding bathing; sauna; whirlpool; treadmill; cool-water immersion; or a combination of activities) each day at a supervised health center.. Patch adhesion.. In the contraceptive studies, 4.7% of patches were replaced because they fell off (1.8% [1,297 of 70,552 patches]) or became partly detached (2.9% [2,050 of 70,552 patches]); patch replacement rates in centers from a warm, humid climate were 1.7% (85 of 4,877 patches) and 2.6% (128 of 4,877 patches), respectively. Only one of 87 patches (1.1%) completely detached in the exercise study.. The reliability of adhesion of the contraceptive patch is excellent and consistent across all studies; only 1.8% and 2.9% of patches required replacement due to complete or partial detachment, respectively. Heat, humidity, and exercise do not affect adhesion.

Topics: Adhesives; Administration, Cutaneous; Adolescent; Adult; Climate; Contraceptives, Oral, Combined; Cross-Over Studies; Drug Combinations; Drug Delivery Systems; Ethinyl Estradiol; Ethisterone; Exercise; Female; Hot Temperature; Humans; Humidity; Middle Aged; Norgestrel; Oximes