drospirenone
Regulatory sources consulted
Approved indications
- Progestin-only oral contraception.
Contraindications
Absolute
- Active venous thromboembolism.
- Severe liver disease until normalization, severe renal impairment, or acute renal failure.
- Sex-steroid-sensitive neoplasm, undiagnosed vaginal bleeding, or hypersensitivity.
Clinical warnings
- Major warning · Drospirenone is potassium-sparing. Check potassium during the first cycle in renal impairment with high-normal potassium or concomitant potassium-raising treatment. — CIMA/AEMPS, ficha técnica 84603
- Major warning · Discontinue and assess if thrombosis is suspected. Bleeding-pattern changes are common; investigate heavy or persistent bleeding. — CIMA/AEMPS, ficha técnica 84603
Drug interactions
- HighEnzyme inducers such as rifampicin, carbamazepine, phenytoin, topiramate, or St John’s wort
Mechanism: They increase hormone clearance and may cause bleeding or contraceptive failure.
Recommendation: Use a barrier method during treatment and for 28 days afterward; for long-term use, choose another method.
CIMA/AEMPS, ficha técnica 84603https://cima.aemps.es/cima/dochtml/ft/84603/FT_84603.html
- ModeratePotassium-sparing or potassium-raising medicines
Mechanism: They may increase hyperkalemia risk.
Recommendation: Check potassium during the first cycle when risk is present.
CIMA/AEMPS, ficha técnica 84603https://cima.aemps.es/cima/dochtml/ft/84603/FT_84603.html
Adverse events
Common (≥1%)
Acne · Breakthrough or irregular bleeding · Headache · Breast pain · Nausea or abdominal pain
Rare but serious
Hyperkalemia · Venous thromboembolism · Severe hypersensitivity
Pregnancy and lactation
It is not indicated during pregnancy; discontinue if pregnancy occurs. Amounts in milk are negligible and it may be used while breastfeeding according to the label.
Recent literature (PubMed)
Estetrol/drospirenone is a combined oral contraceptive (COC) with a plant-synthesised foetal oestrogen (estetrol) and a well-established progestin (drospirenone). In preclinical models, estetrol has lower binding affinity for the oestrogen receptor-α (ER-α) in contrast to estradiol and has antagonistic properties against membrane ER-α in several tissues, including the breast, while retaining agonistic activity on receptors located in the nucleus. The low oestrogenicity of estetrol may potentially contribute to reduced thrombotic risk. Estetrol/drospirenone was an effective contraceptive in phase II and III clinical trials, with regular and predictable bleeding cycles maintained in the majority of women. Estetrol/drospirenone was generally well-tolerated with metrorrhagia reported as the most common treatment-related adverse event, which is consistent with other COCs. Cases of migraines with aura (or severe migraines), deep vein thrombosis, hyperkalaemia and depression were rarely reported during the phase III trials. Overall, estetrol/drospirenone is an effective and generally well-tolerated COC, with a potentially reduced risk of thrombosis. In 2019, an estimated 44% of women aged 15–49 years worldwide used modern contraception methods, and in these women using modern methods, 18% used an oral contraceptive. Estetrol/drospirenone is a combined oral contraceptive (COC) which uses estetrol, a plant-synthesised oestrogen naturally produced by the human foetal liver during pregnancy, in combination with drospirenone, a well-known progestin. Combined, these hormones suppress ovulation, which constitutes their primary mode of action in preventing pregnancy. As estetrol has weaker oestrogen-related effects, it may potentially reduce the risk for blood clots. Estetrol/drospirenone was an effective contraceptive in clinical trials, and most women had regular and predictable bleeding cycles. Metrorrhagia (i.e. abnormal bleeding) was the most commonly reported treatment-relat
Over the past decade, contraception options in the United States have expanded to include an over-the-counter progestin-only pill, a drospirenone progestin-only pill, a vaginal acidifying gel, a low-dose contraceptive patch, and a new vaginal contraceptive ring. Clinical evidence supports expanding the duration of use of the 52 mg progestin intrauterine device (IUD) and the copper IUD. Contraception counseling should center patient priorities and preferences rather than promoting methods based on the provider's beliefs. To employ a reproductive justice lens when counseling patients about their contraception options, providers should remain up to date on all available methods.
Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives (COC), which provide both progestin and oestrogen, have been examined for their ability to relieve premenstrual symptoms. A combined oral contraceptive containing drospirenone and a low oestrogen dose has been approved for treating PMDD in women who choose combined oral contraceptives for contraception. To evaluate the effectiveness and safety of COCs containing drospirenone in women with PMS. We searched the Cochrane Gynaecology and Fertility Group trial register, CENTRAL (now containing output from two trials registers and CINAHL), MEDLINE, Embase, PsycINFO, LILACS, Google Scholar, and Epistemonikos on 29 June 2022. We checked included studies' reference lists and contacted study authors and experts in the field to identify additional studies. We included randomised controlled trials (RCT) that compared COCs containing drospirenone with placebo or with another COC for treatment of women with PMS. We used standard methodological procedures recommended by Cochrane. The primary review outcomes were effects on premenstrual symptoms that were prospectively recorded, and withdrawal due to adverse events. Secondary outcomes included effects on mood, adverse events, and response rate to study medications. We included five RCTs (858 women analysed, most diagnosed with PMDD). The evidence was very low to moderate quality; the main limitations were serious risk of bias due to poor reporting of study methods, and serious inconsistency and imprecision. COCs containing drospirenone and ethinylestradiol (EE) versus placebo COCs containing drospirenone and EE may improve overall premenstrual symptoms (standardised mean difference (SMD) -0.41, 95% confidence interval (CI) -0.59 to -0.24; 2 RCTs, N = 514; I2 = 64%; low-quality evidence); and functional impairment due to premenstrual symptoms in terms of productivity (mean di
Estetrol (E4) is a natural estrogen that has recently emerged as new option for contraception and hormone replacement therapy (HRT). Unlike other estrogens, E4 primarily stimulates nuclear estrogen receptor alpha (ERα) and does not activate membrane ERα. For this reason, this novel estrogen has tissue-specific effects across various organs such as liver, vascular endothelium, mammary glands, brain, vagina, and uterus. The selective activation of the nuclear ERα results in distinct pharmacological properties that contribute to its unique therapeutic profile. Moreover, E4 shows minimal interaction with the hepatic cytochrome P450 enzyme system, leading to a favorable pharmacokinetic profile and a reduced potential for drug-drug interactions. Currently, E4 is commercially available in combination with drospirenone as a combined oral contraceptive and its application in HRT is undergoing late-stage clinical development. Many studies have demonstrated that E4 has a lower impact on hemostatic and metabolic parameters compared to other estrogens, potentially reducing the risk of adverse effects commonly associated with hormonal therapies such as thromboembolic events or dyslipidemia. Beyond its role in contraception and HRT, E4 shows promising therapeutic potential in other medical fields, including neuroprotection in neonatal hypoxic-ischemic encephalopathy, enhancement of hematopoietic stem cell transplantation outcomes and prostate cancer management. This review synthesizes the latest evidence on E4 primarily focusing on its pharmacological characteristics and clinical applications. The findings suggest that E4 versatility and peculiar mechanism of action may represent an important therapeutic option for a broad spectrum of medical conditions.