levonorgestrel
Regulatory sources consulted
Approved indications
- Emergency contraception within 72 hours after unprotected intercourse or contraceptive failure.
Contraindications
Absolute
- Hypersensitivity to levonorgestrel or excipients.
Clinical warnings
- Major warning · This is an occasional method and does not terminate an existing pregnancy. If menses is more than 5 days late, abnormal, or symptoms occur, exclude pregnancy and consider ectopic pregnancy. — CIMA/AEMPS, ficha técnica 78873
- Major warning · Severe hepatic impairment and severe malabsorption syndromes may reduce suitability or effectiveness; consider another option. — CIMA/AEMPS, ficha técnica 78873
- Major warning · Limited and inconclusive data suggest effectiveness may decrease with increasing body weight or BMI; it should be taken as soon as possible regardless of weight or BMI. Repeating levonorgestrel within the same menstrual cycle is discouraged because of possible cycle disturbances. — CIMA/AEMPS, ficha técnica 78873
Drug interactions
- HighCYP3A4 inducers used in the previous 4 weeks
Mechanism: They substantially reduce exposure and may lower effectiveness.
Recommendation: Prefer a copper IUD; if this is not possible or desired, use 3 mg levonorgestrel according to the label.
CIMA/AEMPS, ficha técnica 78873https://cima.aemps.es/cima/dochtml/ft/78873/FT_78873.html
- ModerateCyclosporine
Mechanism: Levonorgestrel may increase cyclosporine toxicity risk.
Recommendation: Monitor toxicity signs and levels when appropriate.
CIMA/AEMPS, ficha técnica 78873https://cima.aemps.es/cima/dochtml/ft/78873/FT_78873.html
Adverse events
Common (≥1%)
Nausea · Headache · Lower abdominal pain · Nonmenstrual bleeding · Fatigue · Dizziness · Menstrual changes
Rare but serious
Ectopic pregnancy if treatment fails · Severe hypersensitivity reaction
Pregnancy and lactation
Do not administer during a known pregnancy; it does not terminate pregnancy. To reduce exposure while breastfeeding, take immediately after a feed and avoid breastfeeding for at least 8 hours.
Recent literature (PubMed)
Abnormal uterine bleeding is a common problem in premenopausal women and refers to uterine bleeding that is abnormal in frequency, duration, volume, and/or regularity. Etiologies can be classified using the PALM-COIEN system. Patients should receive a comprehensive history and physical with special attention to menstrual, sexual, and family history. Physical examination needs to include a pelvic examination with speculum and bimanual components. All patients need to have a pregnancy test and CBC with platelets. Treatments vary by etiology. Medical treatments include levonorgestrel intrauterine devices, oral contraceptive pills, and tranexamic acid. Surgical treatment options include endometrial ablation and hysterectomy.
Long-acting reversible contraceptive (LARC) methods are effective options for pregnancy prevention. Currently available products in the United States include an etonogestrel implant, a copper intrauterine device (IUD), and several levonorgestrel IUDs. With increasing prevalence and duration of use, our understanding of efficacy, risks, and benefits has evolved. In addition to a brief discussion on nomenclature and LARC use within a framework of bodily autonomy and reproductive justice, this review covers clinical challenges with placement and removal, evidence-based duration of use, and how to mitigate side effects. Although all obstetrician-gynecologists as well as primary care clinicians can safely provide LARCs, complex family planning specialists are an expert referral source for challenging cases and evidence-based care as contraceptive technology continues to develop.
Hormonal contraceptive therapy (estrogens and/or progestogens) includes different formulations associated with varying venous thromboembolism (VTE) risks. The thrombogenicity of combined hormonal contraceptives (CHCs) is due at least in part to multiple changes in clotting factors and the vasculature and is dependent on both estrogen dose and type of progestin. Transdermal patch and vaginal ring users have similar or higher VTE risk as combined oral contraceptive users. Progestin-only agents have varying VTE risk. While depot medroxyprogesterone acetate appears to increase VTE risk, the levonorgestrel-based intrauterine system and low-dose progestin-only pills have no additional VTE risk. There are less data for the subdermal progestin-only implant. This article reviews contraceptive-related VTE risk by agent and by clinical scenario, including in patients with inherited thrombophilia, systemic lupus erythematosus with or without antiphospholipid antibodies or antiphospholipid syndrome, and sickle cell disease. Relevant clinical practice guidelines are reviewed. A multidisciplinary approach to counseling is needed for patient-focused decision-making.
Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women's health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.
To describe the current evidence-based diagnosis and management of adenomyosis. All patients with a uterus of reproductive age. Diagnostic options include transvaginal sonography and magnetic resonance imaging. Treatment options should be tailored to symptoms (heavy menstrual bleeding, pain, and/or infertility) and include medical options (non-steroidal anti-inflammatory drugs, tranexamic acid, combined oral contraceptives, levonorgestrel intrauterine system, dienogest, other progestins, gonadotropin-releasing analogues), interventional options (uterine artery embolization), and surgical options (endometrial ablation, excision of adenomyosis, hysterectomy). Outcomes of interest include reduction in heavy menstrual bleeding, reduction in pelvic pain (dysmenorrhea, dyspareunia, chronic pelvic pain), and improvement in reproductive outcomes (fertility, miscarriage, adverse pregnancy outcomes). This guideline will benefit patients with gynaecological complaints that may be caused by adenomyosis, especially those patients who wish to preserve their fertility, by presenting diagnostic methods and management options. It will also benefit practitioners by improving their knowledge of various options. Databases searched were MEDLINE Reviews, MEDLINE ALL, Cochrane, PubMed, EMBASE. The initial search was completed in 2021 and updated with relevant articles in 2022. Search terms included adenomyosis, adenomyoses, endometritis (used/indexed as adenomyosis before 2012), (endometrium AND myometrium) uterine adenomyosis/es, symptom/s/matic adenomyosis] AND [diagnosis, symptoms, treatment, guideline, outcome, management, imaging, sonography, pathogenesis, fertility, infertility, therapy, histology, ultrasound, review, meta-analysis, evaluation]. Articles included randomized controlled trials, meta-analyses, systematic reviews, observational studies, and case reports. Articles in all languages were searched and reviewed. The authors rated the quality of evidence and strength of recom