Effects of levonorgestrel: A Synthesis of Findings from 13 Studies

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Original Abstract of the Article

Main Research Findings

Levonorgestrel, a progestin, is widely used in various contraceptive methods, including oral contraceptives, emergency contraceptives, and intrauterine devices. Research has investigated the contraceptive efficacy, side effects, and metabolic effects of levonorgestrel. 2 found that low-dose oral contraceptives containing levonorgestrel had poorer cycle control compared to those containing norethisterone. 8 demonstrated that a single mid-cycle dose of levonorgestrel, similar to emergency contraception, did not alter the expression of markers related to endometrial receptivity. Furthermore, 13 suggested that levonorgestrel, when administered as a hormonal emergency contraceptive, resulted in an endometrial gene expression profile associated with receptivity. 1 confirmed the contraceptive efficacy of levonorgestrel as an emergency contraceptive, but also highlighted the potential risk of menstrual cycle disturbances and side effects. 4 compared the effects of progestin-only pills containing desogestrel or levonorgestrel on carbohydrate metabolism, adrenal, and thyroid function, concluding that there were minimal differences between the two. 12 systematically reviewed the adverse effects of levonorgestrel emergency oral contraceptives, finding that most adverse reactions were common and not serious, although rare serious adverse events were reported. 9 indicated that levonorgestrel used alone may have fewer side effects and be more effective than the Yuzpe regimen. 7 compared the metabolic effects of a contraceptive vaginal ring containing etonogestrel with an oral contraceptive containing levonorgestrel, suggesting that the vaginal ring had fewer adverse metabolic effects. 3 compared levonorgestrel and mifepristone for emergency contraception, finding that mifepristone was more effective. 6 investigated the skeletal effects of desogestrel and levonorgestrel in oral contraceptives, suggesting that levonorgestrel might have a more beneficial effect on bone formation. 10 compared the effects of levonorgestrel-releasing intrauterine systems with systemic progestins for endometrial protection, finding that the intrauterine system was comparable to other systemic progestins except for sequential medroxyprogesterone acetate. 11 analyzed the pharmacokinetics of different doses of levonorgestrel-releasing intrauterine systems, finding that lower doses resulted in lower systemic exposure to levonorgestrel and lower incidence of anovulation while maintaining similar progestogen effects. 5 assessed the impact of a one-third dose reduction of ethinyl estradiol and levonorgestrel in oral contraceptives, finding that the reduction resulted in slightly lower changes in lipid and carbohydrate variables.

Benefits and Risks

Benefits Summary

Levonorgestrel is a widely used contraceptive that offers both short-term and long-term options, including emergency contraception, oral contraceptives, and intrauterine devices. It is generally considered effective in preventing pregnancy and has been shown to be well-tolerated. Levonorgestrel also offers additional benefits such as menstrual cycle regulation, endometrial protection, and potential hormonal balance benefits.

Risks Summary

While levonorgestrel is generally safe, it is important to understand potential risks and side effects. The most common side effects include menstrual irregularities, nausea, headache, and breast tenderness. While rare, serious adverse events have been reported. Levonorgestrel is not recommended for use during pregnancy. It is important to consult with a healthcare professional to discuss potential risks and benefits and to determine if levonorgestrel is suitable for individual circumstances. It is also essential to follow prescribed guidelines and instructions for safe and effective use.

Comparison Across Studies

Similarities Among Studies

Most studies have consistently demonstrated that levonorgestrel is an effective contraceptive agent. Additionally, across different research studies, levonorgestrel has shown potential benefits related to menstrual cycle regulation, endometrial protection, and hormonal balance.

Differences Among Studies

While research has consistently demonstrated the effectiveness of levonorgestrel, there are differences observed in the magnitude of effects and the type of side effects. For example, 2 indicated poorer cycle control with levonorgestrel-containing oral contraceptives compared to those containing norethisterone. 4 reported minimal differences between desogestrel and levonorgestrel in their effects on carbohydrate metabolism, adrenal, and thyroid function. These variations highlight the need for individual considerations and personalized approaches when using levonorgestrel.

Consistency and Contradictions in Findings

Research on levonorgestrel has yielded both consistent and contradictory findings. For example, 8 and 13 indicated that levonorgestrel, when used for emergency contraception, did not negatively impact endometrial receptivity. However, 1 suggested a potential risk of menstrual cycle disturbances and side effects associated with emergency levonorgestrel use. These discrepancies could be attributed to differences in study design, participant characteristics, dosage, and methods used to assess side effects.

Practical Considerations and Implications

Levonorgestrel is a valuable tool for contraception and for managing menstrual cycle issues and endometrial protection. However, it is not suitable for everyone. Prior to starting any levonorgestrel-based contraceptive method, it is essential to consult with a healthcare professional to determine its suitability and to discuss potential benefits and risks. Following prescribed guidelines for use is crucial for safe and effective contraception.

Limitations of Current Research

There are limitations to current research on levonorgestrel, such as the relatively small sample sizes of some studies, variations in study design, and limited long-term data. Further research is needed to address these limitations and to gain a more comprehensive understanding of levonorgestrel's long-term effects.

Future Research Directions

To enhance our understanding of levonorgestrel's effects and safety, future research should focus on investigating its long-term effects, exploring its efficacy and safety across various administration methods and dosages, and examining its impact on specific populations. Additionally, research efforts should be directed towards refining methods for accurately assessing side effects and potential risks.

Conclusion

Levonorgestrel is a widely used and generally effective contraceptive agent. It offers several benefits, including menstrual cycle regulation, endometrial protection, and hormonal balance. However, it is not suitable for all individuals. Consulting with a healthcare professional to determine suitability and to discuss potential benefits and risks is essential. Following prescribed guidelines for safe and effective use is paramount. As research continues to evolve, we can expect a deeper understanding of levonorgestrel's long-term effects and a more nuanced approach to its application in various contraceptive settings.

Literature analysis of 13 papers
Positive Content
12
Neutral Content
0
Negative Content
1
Article Type
10
3
2
1
13
1.

A multicenter clinical study on two types of levonorgestrel tablets administered for postcoital contraception.

Author: HeC H, ShiY E, XuJ Q, Van LookP F

Contraceptive efficacy
Cycle disturbances
Side effects

Two types of levonorgestrel tablets were tested for their effectiveness as emergency contraception in 361 women. Both types were found to be effective, with a failure rate of 1.4%. Common side effects included menstrual irregularities and spotting.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

A prospective randomized study comparing the clinical effects of a norethisterone and a levonorgestrel containing low dose oestrogen oral contraceptive pills.

Author: AnsteeP, KovacsG T

Improved cycle control

Norethisterone-containing low-dose oral contraceptives were less effective in cycle control compared to levonorgestrel-containing pills.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

3.

[A randomized, double-blind, multicentre study on comparing levonorgestrel and mifepristone for emergency contraception].

Author: WuS, WangC, WangY

Emergency contraception
Side effects

Levonorgestrel and low-dose mifepristone were both found to be effective and safe for emergency contraception, but mifepristone was more effective at preventing pregnancy. The failure rate was 3.1% for levonorgestrel and 1.4% for mifepristone.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

4.

The effects of two progrestogen-only pills containing either desogestrel (75 microgram/day) or levonorgestrel (30 microgram/day) on carbohydrate metabolism and adrenal and thyroid function.

Author: KiveläA, RuuskanenM, AgrenU, DiebenT

Minimal effects

Both desogestrel and levonorgestrel progestogen-only pills had minimal effects on carbohydrate metabolism. There was a trend for higher glucose and insulin values in the levonorgestrel group, but these changes were not considered clinically relevant. Both treatments were well tolerated.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel.

Author: SkoubySven O, EndrikatJan, DüsterbergBernd, SchmidtWerner, GerlingerChristoph, WesselJens, GoldsteinHenri, JespersenJoergen

Reduce lipid and carbohydrate changes

A one-third dose reduction in ethinyl estradiol (EE) and levonorgestrel (LNG) in oral contraceptives caused slightly lower, but insignificant, changes in lipid and carbohydrate variables compared to the reference treatment.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

6.

Comparison of the skeletal effects of the progestogens desogestrel and levonorgestrel in oral contraceptive preparations in young women: controlled, open, partly randomized investigation over 13 cycles.

Author: HartardManfred, KleinmondChristine, LuppaPeter, ZelgerOtto, EggerKathrin, WisemanMichael, WeissenbacherErnst Rainer, FelsenbergDieter, ErbenReinhold G

Bone health
Bone density loss

This study evaluated the skeletal effects of two monophasic oral contraceptives containing 20 mug of ethinylestradiol and 100 mug of levonorgestrel (LEVO) or 150 mug of desogestrel (DESO) in young women. The results showed that the LEVO group did not lose vertebral bone mineral density (BMD), whereas women in the DESO group lost 1.5%. LEVO also induced an increase in total cross-sectional area at the distal radius and tibia, suggesting increased periosteal bone formation. The study concluded that the skeletal effects of oral contraceptives may be influenced by progestogenic components in young women.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive.

Author: Elkind-HirschKaren E, DarensbourgCarmen, OgdenBeverly, OgdenLauren F, HindelangPhilip

Contraception

Metabolic, hormonal, and lipid profiles were compared in women using a contraceptive vaginal ring (NuvaRing) versus a low-dose oral contraceptive (Aviane).

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

A single midcycle dose of levonorgestrel similar to emergency contraceptive does not alter the expression of the L-selectin ligand or molecular markers of endometrial receptivity.

Author: PalominoWilder Alberto, KohenPaulina, DevotoLuigi

No ovulation disruption
No progesterone production disruption

Levonorgestrel, given as emergency contraception on the day of LH surge, did not disrupt ovulation or progesterone production. It did not affect endometrial receptivity biomarkers, suggesting that its contraceptive mechanism does not involve alterations in these factors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

A randomized clinical trial of two emergency contraceptive pill regimens in a Ugandan population.

Author: ByamugishaJosaphat K, MirembeFlorence M, FaxelidElisabeth, TumwesigyeNazarius M, Gemzell-DanielssonKristina

Emergency contraception
Side effects

This review discusses the effectiveness and side effects of different methods of emergency contraception. Levonorgestrel is more effective and has fewer side effects than the Yuzpe regimen.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Effects of the levonorgestrel-releasing intrauterine system plus estrogen therapy in perimenopausal and postmenopausal women: systematic review and meta-analysis.

Author: SomboonpornWoraluk, PannaSunida, TemtanakitpaisanTeerayut, KaewrudeeSrinaree, SoontrapaSukree

Endometrial protection
Relief of climacteric symptoms
Spotting
Vaginal bleeding

This review of six randomized controlled trials compared the effects of the LNG-IUS with those of systemic progestogen in perimenopausal and postmenopausal women taking ET. The LNG-IUS was found to be comparable with other systemic progestogen regimens for endometrial protection, except for sequential medroxyprogesterone acetate, for which the LNG-IUS was more effective.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

11.

Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies.

Author: ApterDan, Gemzell-DanielssonKristina, HauckBrian, RosenKimberly, ZurthChristian

Lower LNG exposure
Lower anovulation incidence

Pooled pharmacokinetic and pharmacodynamic analyses of phase II and III studies comparing levonorgestrel intrauterine system (LNG-IUS) 13.5 mg and LNG-IUS 19.5 mg to LNG-IUS 20 μg/24 h found that LNG-IUS 13.5 mg and LNG-IUS 19.5 mg resulted in lower systemic exposure to LNG, lower incidence of anovulation, and similar progestin impact on the endometrium and cervical function.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive.

Author: LeelakanokNattawut, MethaneethornJanthima

Effective
Well tolerated
Serious adverse events

This study found that the most common side effects of levonorgestrel oral emergency contraceptives are not serious. However, multiple serious adverse events have been reported, including convulsions, ectopic pregnancy, and suicidal ideation. More research is needed to ensure the safety of repeated use of levonorgestrel emergency contraception.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

13.

Analysis of the Endometrial Transcriptome at the Time of Implantation in Women Receiving a Single Post-Ovulatory Dose of Levonorgestrel or Mifepristone.

Author: Barrios-HernándezAna E, Durand-CarbajalMarta, VegaClaudia C, LarreaFernando

Endometrial receptivity
LNG contraceptive safety

This study found that levonorgestrel (LNG) as a hormonal emergency contraceptive resulted in an endometrial gene expression profile associated with receptivity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

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