In short
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.
Key points
- Clinical trials of norelgestromin mostly study it in a combined hormonal contraceptive patch with ethinyl estradiol. Studies examine how well the patch prevents pregnancy and how bleeding patterns change, including spotting and breakthrough bleeding. Researchers have compared traditional monthly cycling (3 weeks on, 1 week off) with extended regimens that use patches continuously for longer to reduce withdrawal bleeding. Several trials also focus on real-life experience, such as satisfaction, preference versus prior birth control, continuation rates, and correct weekly use. Other studies measure blood hormone levels to compare exposure between patch lots or versus pills and rings, including bioequivalence testing. A newer randomized, controlled trial is also testing whether the patch can stop irregular bleeding in contraceptive implant users over a short 21-day treatment course.
At a glance
- 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
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.
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.
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).
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.
- Pregnancy prevention in healthy women, including evaluation of contraceptive efficacy (how well it prevents pregnancy), safety, and cycle control (how predictable bleeding is).
- Comparison of bleeding patterns using different schedules (traditional monthly cycling versus longer “extended” hormone use) in people with metrorrhagia (bleeding between periods).
- 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).
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.
- 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.
- 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).
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.
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).
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.
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.
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.
- 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.
- Large contraceptive studies also tracked bleeding using diary cards to assess cycle control (how regular bleeding is) and compliance with patch changes.
- 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.
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.
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.
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.
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).
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.
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.
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.
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.
- 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.
- 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.
- 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.
- 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.
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.
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.
Bioequivalence and pharmacokinetic trials also formally scored patch adhesion and checked the skin after removal to document local reactions.
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.
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%.
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.
Important terms explained
- Transdermal: a method where medicine passes through the skin into the bloodstream (for example, a contraceptive patch).
- 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.
- Patch-free week: the week in a 4-week cycle when no patch is worn; bleeding during this time is often called withdrawal bleeding.
- Breakthrough bleeding: unplanned bleeding while using hormonal contraception, especially during weeks when hormones are being delivered.
- Spotting: light bleeding that may not require a pad or tampon; trials often count spotting days together with bleeding days.
- Pearl Index: a standard way to estimate how many pregnancies occur in a contraception study over a certain amount of time/exposure.
- Pharmacokinetics: how the body absorbs and processes a drug; patch studies measured blood hormone levels and values like Cmax, AUC, and Css.
- 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.