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NORELGESTROMIN

Norelgestromin is most often studied as part of a combined hormonal contraceptive patch (norelgestromin plus ethinyl estradiol). Clinical trials have looked at how well this patch prevents pregnancy, how it affects bleeding patterns (including spotting and irregular bleeding), how satisfied users are compared with other birth control methods, and how the body absorbs these hormones (pharmacokinetics). Some studies also compare the patch with pills or a vaginal ring, and one newer trial tests whether the patch can stop irregular bleeding in people who use a contraceptive implant.

Table of Contents

What is norelgestromin?

Norelgestromin is a hormone used in some contraceptive patches, usually together with ethinyl estradiol (an estrogen hormone). In one study, norelgestromin is described as the active progestin (progesterone-like) metabolite of orally administered norgestimate, meaning the body can convert norgestimate into norelgestromin when taking certain birth control pills.[1]

What is the norelgestromin/ethinyl estradiol patch?

The studied product is a transdermal contraceptive patch (a skin patch that delivers medicine through the skin). It is described in multiple trials under names such as EVRA and ORTHO EVRA, and as an ethinyl estradiol and norelgestromin transdermal patch.[2][3][4]

One trial states each EVRA patch contains 6 mg norelgestromin and 600 micrograms ethinyl estradiol, and delivers hormones over 7 days (reported as 150 micrograms norelgestromin and 20 micrograms ethinyl estradiol per 24 hours in that study).[2]

What is it used for in studies?

Across the trials provided, the patch was studied mainly for contraception (pregnancy prevention) and for managing abnormal uterine bleeding patterns (unexpected bleeding) in specific situations.[5][6]

  • Pregnancy prevention in healthy women, including evaluation of contraceptive efficacy (how well it prevents pregnancy), safety, and cycle control (how predictable bleeding is).[5]

  • Comparison of bleeding patterns using different schedules (traditional monthly cycling versus longer “extended” hormone use) in people with metrorrhagia (bleeding between periods).[7]

  • Treatment of irregular vaginal bleeding in people using contraceptive implants, by comparing an active hormonal patch to a placebo patch (a patch with no active hormones).[6]

How the patch is used (dosing schedules studied)

Most studies used a “3 weeks on, 1 week off” pattern to mimic a typical 28‑day cycle: apply one patch and wear it for 7 days, replace weekly for 3 weeks, then have a patch-free week (no patch) during week 4.[2][8][5]

  • In the European experience study, participants wore the patch for 1 week and replaced it for 3 consecutive weeks, with the fourth week patch-free, and could place it on the buttock, abdomen, upper torso, or upper arm.[2]

  • In a Canadian satisfaction study, women were instructed to apply the first patch on the first day of their next menses and then follow weekly changes for 3 weeks with week 4 patch-free, keeping the change day consistent each week; patches were applied to buttocks, abdomen, upper outer arm, or upper torso (excluding breasts).[8]

Other schedules were also studied. One trial tested an extended regimen, where patches were applied weekly for 12 consecutive weeks (84 days) followed by one patch-free week, to see whether this could reduce bleeding days compared with the standard cyclic regimen.[7]

For treating implant-related irregular bleeding, a shorter treatment course was studied: participants applied patches for 21 days, changing the patch every 7 days (3 patches total).[6]

How well it works (what studies measured)

Several trials evaluated effectiveness for pregnancy prevention using measures like the Pearl Index (a way to estimate pregnancy rates in contraception studies) and life table analysis (another method to estimate pregnancy probability over time). These were used to assess contraceptive efficacy in large studies of the patch.[5][2]

In the implant-bleeding treatment trial, effectiveness is focused on bleeding control: the main outcome is the proportion of participants who report bleeding stops during treatment and remains stopped by day 14, comparing the active patch to placebo.[6]

Bleeding patterns, spotting, and cycle control

A key topic in these trials is bleeding profile, including breakthrough bleeding and spotting (unexpected bleeding outside a planned period). In the extended-regimen trial, the main outcomes included total bleeding/spotting days and number of bleeding/spotting episodes over an 84‑day reference period.[7]

  • The extended-regimen study was designed because some people want to delay or reduce withdrawal bleeding (bleeding during the hormone-free week), and because menstrual-related symptoms like headaches or pelvic pain may occur more during the hormone-free interval; however, extended regimens can have more breakthrough bleeding, especially early on.[7]

  • Large contraceptive studies also tracked bleeding using diary cards to assess cycle control (how regular bleeding is) and compliance with patch changes.[5][9]

  • A separate randomized trial compared bleeding patterns and cycle control between EVRA and another patch (ethinylestradiol/gestodene), over 7 cycles, along with contraceptive efficacy and safety monitoring.[10]

Safety and side effects that were monitored

Across trials, safety checks commonly included recording adverse events (side effects or medical problems during the study), physical exams, gynecologic exams, vital signs, and lab tests.[7][5]

Patch studies also paid close attention to application site reaction (skin issues where the patch is placed), such as redness and swelling; in one bioequivalence study, skin was checked after patch removal for redness and swelling, and safety monitoring included these reactions plus ECGs and lab tests.[3]

One study specifically investigated blood markers related to clotting, because hormonal contraception can affect the body’s clotting system. It compared the patch to an oral pill by measuring multiple coagulation parameters (blood tests related to clot formation), such as D-dimer, factor VIII, and others, in a crossover design in healthy women.[1]

Blood levels (pharmacokinetics) and hormone exposure

Some trials focused on pharmacokinetics, meaning how much hormone gets into the blood and how it changes over time. These studies measured hormone concentrations and calculated values like Cmax (highest measured blood level), AUC (overall exposure over time), and Css (average steady level after the body reaches a stable pattern).[3]

One study compared different manufacturing lots of the patch and compared patch exposure to an oral contraceptive (CILEST), measuring blood levels of norelgestromin, norgestrel, and ethinyl estradiol across 7‑day wear periods, with washouts between periods.[11]

Another crossover study directly compared ORTHO EVRA (patch) vs CILEST (pill) over multiple cycles, measuring blood levels of norelgestromin, norgestrel, and ethinyl estradiol and also measuring hormone-related effects such as sex hormone-binding globulin (SHBG) and other binding proteins from the liver, to help interpret the hormone exposure results.[12]

A separate crossover trial comparing a patch to an oral pill reported that average weekly ethinyl estradiol exposure (AUC) was higher with transdermal use than with oral use in that study, and it also reported average steady-state concentrations and peak levels for both methods; it additionally noted that patch application location did not alter steady-state or peak levels in their referenced data.[1]

Comparisons with pills and vaginal ring

Several trials compared the patch with other contraceptive methods to understand differences in acceptability, side effects, continuation, and hormone exposure.[4][13]

  • One randomized trial compared continuation rates (staying on the method) and acceptability between the patch (OrthoEvra) and a vaginal ring (NuvaRing) over four cycles, and also looked at side effects and measures such as bacterial vaginosis scores.[4]

  • Two large trials compared the patch with oral contraceptive pills (Triphasil or Mercilon), assessing pregnancy rates (Pearl Index and life table), safety, cycle control, and compliance using diary cards.[9][14]

  • A pharmacokinetic study compared ethinyl estradiol blood levels between a patch (EVRA), a vaginal ring (NuvaRing), and an oral pill (Microgynon 30), measuring outcomes like Cmax and AUC over 21 days of active treatment and washout.[13]

  • A metabolic study compared administration routes (oral pill vs patch vs vaginal ring) over 9 weeks and measured hormone-related markers (androgens like testosterone) and glucose metabolism (how the body handles sugar) using an oral glucose tolerance test.[15]

Patch adherence (sticking) and user compliance

Trials commonly evaluated compliance (whether participants used the patch on schedule) and adhesion (how well the patch stayed stuck to the skin). Some studies checked compliance by returned patch boxes and diary cards recording dates and sites of application and any patch detachment.[2]

In the Canadian study, participants were instructed that only one patch should be worn at a time, that patches should not be taped down with extra adhesive, and that if a patch completely detached it should be replaced immediately and worn for the remainder of that week; adherence and dosing were tracked with diary cards.[8]

Bioequivalence and pharmacokinetic trials also formally scored patch adhesion and checked the skin after removal to document local reactions.[3][11]

Who was in these studies?

Many studies enrolled healthy women who needed contraception, often across multiple centers and countries, and followed them for 6–13 cycles in some large efficacy/safety studies.[5][9]

Some studies had specific eligibility criteria. For example, a bioequivalence study included healthy women with a body mass index between 16 and 29.9 kg/m² and required certain blood values like hematocrit ≥ 36%.[3]

The trial for implant-related bleeding enrolled women over age 18 who already used contraceptive implants and experienced abnormal bleeding, and compared an active hormonal patch to placebo over a 21-day treatment period with follow-up out to 3 months.[6]

Important terms explained

  • Transdermal: a method where medicine passes through the skin into the bloodstream (for example, a contraceptive patch).[2]

  • Combined hormonal contraception: contraception that uses both an estrogen (like ethinyl estradiol) and a progestin (like norelgestromin). In the implant-bleeding trial, the active patch is also called a combined hormonal contraceptive patch.[6]

  • Patch-free week: the week in a 4-week cycle when no patch is worn; bleeding during this time is often called withdrawal bleeding.[2]

  • Breakthrough bleeding: unplanned bleeding while using hormonal contraception, especially during weeks when hormones are being delivered.[7]

  • Spotting: light bleeding that may not require a pad or tampon; trials often count spotting days together with bleeding days.[7]

  • Pearl Index: a standard way to estimate how many pregnancies occur in a contraception study over a certain amount of time/exposure.[5]

  • Pharmacokinetics: how the body absorbs and processes a drug; patch studies measured blood hormone levels and values like Cmax, AUC, and Css.[3]

  • Bioequivalence: when two versions of a product provide very similar drug exposure in the body; one study tested whether a “faster equilibration” patch was bioequivalent to the marketed patch.[3]

Main drug studied Norelgestromin (usually combined with ethinyl estradiol in a transdermal patch)
Main uses studied Pregnancy prevention (contraception), bleeding/cycle control, user satisfaction and preference, pharmacokinetics (blood hormone levels), and treatment of irregular bleeding in implant users
Common patch schedule in trials 1 patch weekly for 3 weeks, then 1 patch-free week (28-day cycle); some trials tested extended continuous schedules (e.g., 12 weeks on, then 1 week off)
Key bleeding outcomes Total bleeding/spotting days and episodes over a reference period; breakthrough bleeding/spotting days; time to first bleeding/spotting; duration of menses
Key efficacy outcomes Pregnancy rates measured with Pearl Index and life table analysis
Patient experience outcomes Satisfaction with the patch and preference compared with prior methods; continuation rates (staying on the method)
Safety monitoring in trials Adverse events, physical and gynecologic exams, vital signs, lab tests; skin checks for redness/swelling in some patch studies
Examples of comparators used Oral contraceptives (e.g., CILEST, Triphasil, Mercilon, Microgynon), vaginal ring (NuvaRing), placebo patch (in an implant-bleeding study), and other patch formulations
Pharmacokinetic (PK) focus Measures like AUC, Cmax, tmax, and Css to compare exposure across patch lots, versus pills, and to test bioequivalence

FAQ

  • What is NORELGESTROMIN in these clinical trials, and how is it given? In these trials, norelgestromin is used together with ethinyl estradiol in a transdermal contraceptive patch (a patch worn on the skin). The patch is typically worn for 7 days and replaced weekly for 3 weeks, followed by 1 patch-free week (a 28-day cycle). Some trials tested extended use, such as 12 straight weeks of patches before a patch-free week.
  • What do trials measure most often with the norelgestromin/ethinyl estradiol patch? Trials commonly measured: (1) bleeding and spotting days and episodes (including breakthrough bleeding), (2) pregnancy prevention using measures like the Pearl Index and life table analysis, (3) user satisfaction and preference compared with prior methods, (4) compliance/adherence (how correctly the patch was used), (5) safety through adverse event reporting, exams, vital signs, and lab tests, and (6) pharmacokinetics (how hormone levels change in the blood over time).
  • How did trials compare “traditional” cyclic use versus “extended” use of the patch? One randomized, open-label multicenter study compared a traditional cyclic schedule (3 weekly patches then 1 patch-free week, repeated) with an extended regimen (weekly patches for 12 consecutive weeks, then 1 patch-free week). The main goal was to compare bleeding outcomes over an 84-day period, including total bleeding/spotting days and the number of bleeding/spotting episodes.
  • Are there studies where the patch is used to treat bleeding problems, not just for contraception? Yes. A randomized, double-blind, controlled trial is evaluating whether an ethinyl estradiol/norelgestromin patch can treat irregular vaginal bleeding in people using contraceptive implants. Participants apply 3 patches over 21 days (changing weekly). The main outcome is the proportion of participants whose bleeding stops and who remain bleeding-free by day 14.
  • Why do some trials focus on blood hormone levels and “bioequivalence” between patches? Some studies measured blood concentrations of norelgestromin and ethinyl estradiol to understand exposure and consistency. A bioequivalence study compared a patch lot with a faster “equilibration profile” (how quickly stable hormone levels are reached) to the marketed patch, using pharmacokinetic measures such as AUC (overall exposure over time) and Css (steady-state concentration, meaning a more stable average blood level after the body adjusts).

Ongoing Clinical Trials on NORELGESTROMIN

  • A study on ovulation inhibition with norelgestromin patch after missed applications in women who need birth control

    Recruiting

    1 1
    Investigated drugs:
    Germany

Glossary

  • Norelgestromin: A progestin hormone used in a contraceptive patch. Progestins are synthetic (man-made) versions of progesterone, a natural hormone involved in the menstrual cycle.
  • Ethinyl estradiol (EE): An estrogen hormone used in many combined hormonal contraceptives. Estrogen is a hormone that helps regulate the menstrual cycle.
  • Transdermal contraceptive patch: A medicated patch worn on the skin that releases hormones through the skin into the bloodstream. In these trials it is changed every 7 days.
  • Combined hormonal contraceptive patch: A patch that contains both a progestin (norelgestromin) and an estrogen (ethinyl estradiol). “Combined” means it has two hormone types.
  • Cyclic regimen (traditional regimen): A standard schedule that mimics a 28-day cycle: 3 weekly patches in a row (21 days of hormones) followed by 1 patch-free week.
  • Extended regimen (continuous regimen): A schedule where active hormone patches are used for longer than 21 days before a patch-free interval. In one trial this meant 12 straight weeks of patches (84 days) before a patch-free week.
  • Patch-free week (hormone-free interval): The week when no patch is worn. Bleeding can occur during this time because hormone levels drop.
  • Withdrawal bleeding: Bleeding that happens after stopping hormones for a short time (for example, during the patch-free week). It is not the same as a natural menstrual period, but it can look similar.
  • Breakthrough bleeding: Unexpected bleeding while using hormonal contraception (for example, bleeding during the weeks when the patch is on).
  • Spotting: Light bleeding that is less than a typical period.
  • Bleeding profile: A summary of bleeding patterns over time, such as how many days of bleeding/spotting occur and how often bleeding episodes happen.
  • Metrorrhagia: Bleeding at irregular times (not following a regular menstrual schedule).
  • Menstruation disturbances: Changes from usual bleeding patterns, such as irregular, heavier, lighter, or more frequent bleeding.
  • Uterine hemorrhage: Heavy bleeding from the uterus. “Hemorrhage” means significant bleeding.
  • Contraceptive efficacy: How well a method prevents pregnancy in a study.
  • Pearl Index: A way to estimate pregnancy rates in a contraceptive study. It is usually reported as the number of pregnancies per 100 women using the method for one year.
  • Life table analysis (gross cumulative probability of pregnancy): A statistical method that estimates pregnancy risk over time, taking into account when participants start, stop, or are followed in the study.
  • Compliance / adherence: How closely participants follow the dosing instructions (for example, changing the patch on schedule and recording use in a diary).
  • Diary card / bleeding diary: A participant record used in trials to track patch change dates, application sites, detachment, and daily bleeding/spotting.
  • Open-label study: A study where participants (and usually researchers) know which treatment is being used. This can affect reporting of symptoms because people know what they are taking.
  • Randomized: Participants are assigned to groups by chance, like flipping a coin. This helps make groups more similar and results more reliable.
  • Double-blind: Neither participants nor key study staff know who is receiving the active treatment versus placebo during the study, which helps reduce bias.
  • Placebo patch: A patch that looks the same as the hormone patch but has no active hormones. It is used to compare outcomes fairly.
  • Multicenter study: A study run at more than one clinic or location, which can make results more generalizable to different populations.
  • Pharmacokinetics (PK): How the body absorbs, distributes, and clears a drug. In these trials, PK was measured by taking blood samples to track hormone levels over time.
  • Bioequivalence: A finding that two products deliver very similar amounts of drug into the bloodstream. Studies often test whether exposure measures fall within a preset range (for example, 80% to 125%).
  • AUC (Area Under the Curve): A PK measure of total drug exposure over time. A larger AUC generally means more total hormone exposure during the measured period.
  • Cmax: The highest (maximum) drug concentration measured in the blood after using the patch or pill.
  • tmax: The time it takes to reach Cmax (the peak blood level).
  • Css (steady-state concentration): An average stable blood level reached when drug intake and drug clearance become balanced. For patches, this is often estimated after enough time has passed while wearing the patch.
  • Washout period: A planned break between treatments in crossover studies. It allows the first treatment to leave the body before starting the next one.
  • Crossover study: A study design where the same participant receives two different treatments at different times (with a washout period in between). This allows each person to serve as their own comparison.
  • Adverse event: Any unwanted medical problem that happens during a study, whether or not it is clearly caused by the study drug.
  • Application site reaction (erythema, swelling): Skin changes where the patch is worn. “Erythema” means redness. Swelling is puffiness or raised skin.
  • Coagulation parameters: Blood test results related to clotting. One trial compared how the patch versus an oral pill affected several clotting-related lab markers.
  • Venous thrombosis / venous thromboembolism: A blood clot in a vein. “Thromboembolism” means a clot that can travel and block blood flow elsewhere.
  • Sex hormone-binding globulin (SHBG): A protein made by the liver that binds to sex hormones in the blood. Some trials measured SHBG as part of hormone-related effects.
  • Oral glucose tolerance test (OGTT): A test that checks how the body handles sugar (glucose) over time after drinking a glucose solution. It is used to study glucose metabolism.

References

  1. https://clinicaltrials.gov/study/NCT00554632
  2. https://clinicaltrials.gov/study/NCT00261482
  3. https://clinicaltrials.gov/study/NCT00775086
  4. https://clinicaltrials.gov/study/NCT00269620
  5. https://clinicaltrials.gov/study/NCT00236769
  6. https://clinicaltrials.gov/study/NCT07083635
  7. https://clinicaltrials.gov/study/NCT00320580
  8. https://clinicaltrials.gov/study/NCT00653016
  9. https://clinicaltrials.gov/study/NCT00236795
  10. https://clinicaltrials.gov/study/NCT00984789
  11. https://clinicaltrials.gov/study/NCT00258063
  12. https://clinicaltrials.gov/study/NCT00254865
  13. https://clinicaltrials.gov/study/NCT01044056
  14. https://clinicaltrials.gov/study/NCT00236782
  15. https://clinicaltrials.gov/study/NCT01087879