In short
Clinical trials investigating Levonorgestrel are studying how it is used in different health settings, especially contraception and migraine. These studies look at effectiveness, safety, and other outcomes in groups such as healthy women, women at risk of pregnancy, and women with migraine or after abortion.
Key points
- Clinical trials of Levonorgestrel are mostly focused on contraception, including prevention of pregnancy, ovulation control, and use after medical abortion. Other studies look at migraine treatment and brain or behavior effects of oral contraceptives that include Levonorgestrel. The trials range from Phase 1 to Phase 3, with both small and large groups of women taking part. Some studies compare Levonorgestrel-based treatments with other options, while others are single-arm studies. Main outcomes include Pearl Index, ovulation, migraine days, contraceptive use, and changes in mood, cognition, or brain measures.
Clinical trials overview
The trials in this article study Levonorgestrel in different forms, including oral tablets, a vaginal delivery system, and an intrauterine system.
Most studies focus on contraception, which means preventing pregnancy, but other trials look at migraine, mood, thinking skills, brain measures, and treatment-related outcomes in endometrial cancer.
The studies include Phase 1, Phase 2, and Phase 3 trials, plus one low-intervention randomized controlled trial.
Contraception and pregnancy prevention studies
Several trials study Levonorgestrel for pregnancy prevention and contraceptive effectiveness.
One completed Phase 3 trial tested a Levonorgestrel Vaginal Delivery System for 13 cycles in non-breastfeeding women aged 18 to 35 years, and its main outcome was the Pearl Index, a standard measure of pregnancy prevention success.
Another completed Phase 3 study compared the same vaginal delivery system with desogestrel tablets over 9 cycles in non-breastfeeding women aged 35 years or younger, and it also used the Pearl Index as the main outcome.
A Phase 2 study looked at whether ovulation stayed blocked even when tablet intake was delayed on purpose, using an oral Levonorgestrel tablet for three 28-day cycles.
These studies show that researchers are not only checking whether Levonorgestrel works for contraception, but also whether it keeps working under real-life use problems such as missed or late tablets.
Migraine studies
One authorised trial studies continuous daily use of ethinylestradiol/Levonorgestrel compared with vitamin E in women with menstrually-related migraine, pure menstrual migraine, or perimenopausal migraine.
This is a randomized controlled trial with 360 participants, and the main outcome is the change in monthly migraine days over a 28-day period at the 12-week time point.
The study is split into two groups of women: one group with migraine linked to menstruation and one group with migraine around menopause.
This trial is important because it measures a clear symptom outcome that patients can understand: how often migraine happens each month.
Brain, mood, and behavior study
The BECONTRA study is a Phase 3 trial looking at the effects of common oral contraceptives that include EE/LNG, meaning ethinylestradiol/Levonorgestrel, and another oral contraceptive option, on the brain and behavior.
The study plans to enroll 600 participants and will assess mood, self-perception, cognition, brain structure, and brain function after up to 6 months of treatment.
It also studies whether these effects change back after stopping treatment, which is called reversibility upon withdrawal.
Outcomes include premenstrual symptoms, positive and negative affect, depression, anxiety, gender role, face recognition, verbal fluency, navigation, and working memory.
Drug level study in healthy women
One Phase 1 trial in healthy women studied whether BI 425809 changes the blood levels of ethinylestradiol and Levonorgestrel when taken together as the combined oral contraceptive Microgynon.
This trial had only 16 participants and measured pharmacokinetics, which means how much of the medicine is in the blood over time.
The main outcomes were area under the curve, maximum concentration, and minimum concentration at steady state, which are ways to describe blood exposure to a medicine after repeated doses.
Post-abortion contraception study
One Phase 3 trial studied immediate insertion of intrauterine contraception after medical abortion, compared with insertion 2 to 4 weeks later.
The study includes intrauterine systems such as Mirena, Kyleena, and Jaydess, and it plans to enroll 720 women.
The main outcome is the proportion of women using intrauterine contraception at 6 months after abortion, which helps show whether immediate placement improves continued contraceptive use.
Endometrial cancer study
One Phase 2 trial studies women living with endometrial adenocarcinoma, which is a cancer of the lining of the uterus, and includes Mirena as part of the treatment groups.
The trial plans to enroll 78 participants and measures pathological complete response, or pCR, at 12 months.
In this study, pCR means there is no endometrial adenocarcinoma or endometrial hyperplasia found on biopsy after treatment.
This trial shows that Levonorgestrel-related treatment is being studied not only for contraception, but also in a cancer setting where tissue changes are measured carefully.