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The Cochrane Database of Systematic... Jul 2023Dysmenorrhoea (painful menstrual cramps) is common and a major cause of pain in women. Combined oral contraceptives (OCPs) are often used in the management of primary... (Review)
Review
BACKGROUND
Dysmenorrhoea (painful menstrual cramps) is common and a major cause of pain in women. Combined oral contraceptives (OCPs) are often used in the management of primary dysmenorrhoea, but there is a need for reporting the benefits and harms. Primary dysmenorrhoea is defined as painful menstrual cramps without pelvic pathology.
OBJECTIVES
To evaluate the benefits and harms of combined oral contraceptive pills for the management of primary dysmenorrhoea.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date 28 March 2023.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing all combined OCPs with other combined OCPs, placebo, or management with non-steroidal anti-inflammatory drugs (NSAIDs). Participants had to have primary dysmenorrhoea, diagnosed by ruling out pelvic pathology through pelvic examination or ultrasound.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary outcomes were pain score after treatment, improvement in pain, and adverse events.
MAIN RESULTS
We included 21 RCTs (3723 women). Eleven RCTs compared combined OCP with placebo, eight compared different dosages of combined OCP, one compared two OCP regimens with placebo, and one compared OCP with NSAIDs. OCP versus placebo or no treatment OCPs reduce pain in women with dysmenorrhoea more effectively than placebo. Six studies reported treatment effects on different scales; the result can be interpreted as a moderate reduction in pain (standardised mean difference (SMD) -0.58, 95% confidence interval (CI) -0.74 to -0.41; I² = 28%; 6 RCTs, 588 women; high-quality evidence). Six studies also reported pain improvement as a dichotomous outcome (risk ratio (RR) 1.65, 95% CI 1.29 to 2.10; I² = 69%; 6 RCTs, 717 women; low-quality evidence). The data suggest that in women with a 28% chance of improvement in pain with placebo or no treatment, the improvement in women using combined OCP will be between 37% and 60%. Compared to placebo or no treatment, OCPs probably increase the risk of any adverse events (RR 1.31, 95% CI 1.20 to 1.43; I² = 79%; 7 RCTs, 1025 women; moderate-quality evidence), and may also increase the risk of serious adverse events (RR 1.77, 95% CI 0.49 to 6.43; I² = 22%; 4 RCTs, 512 women; low-quality evidence). Women who received OCPs had an increased risk of irregular bleeding compared to women who received placebo or no treatment (RR 2.63, 95% CI 2.11 to 3.28; I² = 29%; 7 RCTs, 1025 women; high-quality evidence). In women with a risk of irregular bleeding of 18% if using placebo or no treatment, the risk would be between 39% and 60% if using combined OCP. OCPs probably increase the risk of headaches (RR 1.51, 95% CI 1.11 to 2.04; I² = 44%; 5 RCTs, 656 women; moderate-quality evidence), and nausea (RR 1.64, 95% CI 1.17 to 2.30; I² = 39%; 8 RCTs, 948 women; moderate-quality evidence). We are uncertain of the effect of OCP on weight gain (RR 1.83, 95% CI 0.75 to 4.45; 1 RCT, 76 women; low-quality evidence). OCPs may slightly reduce requirements for additional medication (RR 0.63, 95% CI 0.40 to 0.98; I² = 0%; 2 RCTs, 163 women; low-quality evidence), and absence from work (RR 0.63, 95% CI 0.41 to 0.97; I² = 0%; 2 RCTs, 148 women; low-quality evidence). One OCP versus another OCP Continuous use of OCPs (no pause or inactive tablets after the usual 21 days of hormone pills) may reduce pain in women with dysmenorrhoea more effectively than the standard regimen (SMD -0.73, 95% CI -1.13 to 0.34; 2 RCTs, 106 women; low-quality evidence). There was insufficient evidence to determine if there was a difference in pain improvement between ethinylestradiol 20 μg and ethinylestradiol 30 μg OCPs (RR 1.06, 95% CI 0.65 to 1.74; 1 RCT, 326 women; moderate-quality evidence). There is probably little or no difference between third- and fourth-generation and first- and second-generation OCPs (RR 0.99, 95% CI 0.93 to 1.05; 1 RCT, 178 women; moderate-quality evidence). The standard regimen of OCPs may slightly increase the risk of any adverse events over the continuous regimen (RR 1.11, 95% CI 1.01 to 1.22; I² = 76%; 3 RCTs, 602 women; low-quality evidence), and probably increases the risk of irregular bleeding (RR 1.38, 95% CI 1.14 to 1.69; 2 RCTs, 379 women; moderate-quality evidence). Due to lack of studies, it is uncertain if there is a difference between continuous and standard regimen OCPs in serious adverse events (RR 0.34, 95% CI 0.01 to 8.24; 1 RCT, 212 women), headaches (RR 0.94, 95% CI 0.50 to 1.76; I² = 0%; 2 RCTs, 435 women), or nausea (RR 1.08, 95% CI 0.51 to 2.30; I² = 23%; 2 RCTs, 435 women) (all very low-quality evidence). We are uncertain if one type of OCP reduces absence from work more than the other (RR 1.12, 95% CI 0.64 to 1.99; 1 RCT, 445 women; very low-quality evidence). OCPs versus NSAIDs There were insufficient data to determine whether OCPs were more effective than NSAIDs for pain (mean difference -0.30, 95% CI -5.43 to 4.83; 1 RCT, 91 women; low-quality evidence). The study did not report on adverse events.
AUTHORS' CONCLUSIONS
OCPs are effective for treating dysmenorrhoea, but they cause irregular bleeding, and probably headache and nausea. Long-term effects were not covered in this review. Continuous use of OCPs was probably more effective than the standard regimen but safety should be ensured with long-term data. Due to lack of data, we are uncertain whether NSAIDs are better than OCPs for treating dysmenorrhoea.
Topics: Female; Humans; Dysmenorrhea; Contraceptives, Oral, Combined; Muscle Cramp; Anti-Inflammatory Agents, Non-Steroidal; Headache
PubMed: 37523477
DOI: 10.1002/14651858.CD002120.pub4 -
AJOG Global Reports Nov 2023Ethinylestradiol and drospirenone combined oral contraceptive formulations have been marketed for >20 years. Drospirenone has antimineralocorticoid and anti-androgenic...
Ethinylestradiol and drospirenone combined oral contraceptive formulations have been marketed for >20 years. Drospirenone has antimineralocorticoid and anti-androgenic effects that may offer several health benefits. Recently, 2 new drospirenone-containing oral contraceptives entered the market, 1 as a progestin-only pill containing 4 mg drospirenone and the other as a combined oral contraceptive containing 15 mg estetrol and 3 mg drospirenone. Estetrol has a unique differential effect on nuclear and membrane estrogen α-receptors when compared with other estrogens, leading to low impact on the liver, breast, and hemostasis parameters and a beneficial effect on the endometrium, vagina, cardiovascular system, bone, and brain. Phase 3 clinical studies demonstrated that the Pearl Index (pregnancies per 100-woman-years) for drospirenone alone is 4.0 in the United States and 0.93 in the European Union and for the estetrol-drospirenone combination it is 2.65 and 0.44, respectively. Drospirenone alone demonstrates high rates of unscheduled bleeding and low rates of scheduled bleeding, whereas the estetrol-drospirenone combination demonstrates a predictable and regular bleeding profile for most users with a high stable rate of scheduled bleeding and a low rate of unscheduled bleeding, reported primarily as spotting only. The adverse event profiles and discontinuation rates owing to adverse events are comparable, and no clinically significant effects were observed on metabolic parameters with either product. Hemostatic assays for drospirenone do not fully evaluate all parameters although the testing that is available suggests negligible effects, whereas validated hemostatic assays demonstrate that the estetrol-drospirenone combination has limited impact on hemostasis. The introduction of 4 mg drospirenone and 15 mg estetrol with 3 mg drospirenone are valuable additions to the contraceptive market. Adding estetrol to 3 mg drospirenone provides advantages of contraceptive efficacy and a regular, predictable bleeding profile with minimal impact on hemostasis parameters.
PubMed: 37854030
DOI: 10.1016/j.xagr.2023.100266 -
Gynecological Endocrinology : the... Dec 2023In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To... (Review)
Review
In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety. For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'. Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman. Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.
Topics: Female; Humans; Contraceptives, Oral, Combined; Progestins; Latin America; Ethinyl Estradiol; Estrogens; Women's Health
PubMed: 37857350
DOI: 10.1080/09513590.2023.2271072 -
Pediatric Emergency Care Apr 2024"One Pill Can Kill" is a meme originating in the 1990s. This construct lists pharmaceuticals that have the alleged potential for fatality after the ingestion of a single...
"One Pill Can Kill" is a meme originating in the 1990s. This construct lists pharmaceuticals that have the alleged potential for fatality after the ingestion of a single pill by a toddler. However, its foundation is fundamentally flawed because it contravenes a basic principle of pediatric pharmacology, allometric scaling. Other than opioids, there are no literature examples of one pill killing a toddler. The negative outcome of the one pill can kill construct is inappropriate management manifested by over-referral of young children by poison centers to emergency departments for care, overly prolonged emergency department observation and needless hospital admissions. A more accurate construct is that one pill of anything other than opioids will not kill anybody with the caveat being that we are referring to regulated pharmaceuticals.
PubMed: 38587052
DOI: 10.1097/PEC.0000000000003166 -
Contraception Feb 2024Attempts have been made over the years to replace ethinyl estradiol (EE) in combined oral contraceptives (COCs) with the less potent natural estrogen estradiol (E), or... (Review)
Review
Attempts have been made over the years to replace ethinyl estradiol (EE) in combined oral contraceptives (COCs) with the less potent natural estrogen estradiol (E), or its prodrug, E valerate (EV), to improve their safety and tolerability. Recently, a COC incorporating a novel weak natural estrogen, estetrol (E), combined with drospirenone, has become available. We present a comparative analysis of the three prevailing estrogens used in COCs, focusing on their structure-function relationships, receptor-binding affinity, potency, metabolism, pharmacokinetic parameters, and pharmacodynamics. The binding affinity of EE to estrogen receptor (ER)α is twice that of E, whereas its affinity for ERβ is about one-half that of E. E has a lower binding affinity for the ERs than E. The high potency of EE is notable in its dramatic increase in estrogen-sensitive hepatic globulins and coagulation factors. EE and E undergo extensive and comparable metabolism, while E produces only a very limited number of metabolites. E has the highest bioavailability among the three estrogens, with E having <5%. Studies demonstrate consistent ovulation inhibition, although a higher dose of E (15 mg) in COCs is required to achieve follicular suppression compared to E (1-3 mg) and EE (0.01-0.035 mg). E and E in COCs may be less stimulatory of coagulant proteins than EE. Studies with E/dienogest suggest a comparable risk of venous thromboembolism to EE/levonorgestrel, while data assessing risk with an E-based COC are insufficient. Nevertheless, the E-based formulation shows promise as a potential alternative to EE and E due to its lower potency and possibly fewer side effects.
Topics: Humans; Female; Hormonal Contraception; Ethinyl Estradiol; Estrogens; Contraceptives, Oral, Combined; Estradiol; Estetrol; Estrone
PubMed: 37863464
DOI: 10.1016/j.contraception.2023.110310 -
Cutis Aug 2023A range of treatment options are available for both mild to moderate and moderate to severe acne, and these options vary widely in their clinical uses, effectiveness,... (Review)
Review
A range of treatment options are available for both mild to moderate and moderate to severe acne, and these options vary widely in their clinical uses, effectiveness, and costs. With the continued rise of dermatologic drug prices and increased cost-sharing due to high-deductible health plans, the importance of cost-effective treatment continues to grow. Failure to consider cost-effective, patient-centered care may lead to increased financial toxicity, reduced adherence, and ultimately worse outcomes and patient satisfaction. Combination topical products offer improved efficacy and convenience, which are associated with better adherence and outcomes. Generic fixed-dose adapalene-benzoyl peroxide (BPO) and fixed-dose clindamycin-BPO can be highly cost-effective options for patients with mild to moderate acne. Hormonal agents such as combined oral contraceptives (COCs) and spironolactone are inexpensive and likely reflect a highly cost-effective option that could reduce reliance on oral antibiotics in patients with moderate to severe acne. Doxycycline and isotretinoin also are cost-effective options for more severe acne. Frequent laboratory monitoring for spironolactone and isotretinoin continues to be prevalent despite little evidence to support its clinical utility, and it is associated with a major cost burden to the patient and health care system. The reduction of laboratory monitoring is an opportunity to provide higher-value care.
Topics: Humans; Dermatologic Agents; Benzoyl Peroxide; Isotretinoin; Adapalene; Cost-Benefit Analysis; Spironolactone; Drug Combinations; Acne Vulgaris; Treatment Outcome; Gels
PubMed: 37820334
DOI: 10.12788/cutis.0844 -
Journal of Ethnopharmacology Nov 2023Xihuang pill as a famous traditional Chinese formula has long been used as an adjuvant therapy for cancer. (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Xihuang pill as a famous traditional Chinese formula has long been used as an adjuvant therapy for cancer.
AIM OF THE STUDY
This study is aimed at summarizing recent advances in research of Xihuang pill's anti-cancer efficacies from the theoretical basis of traditional Chinese medicine, pharmacological activities, chemical components and its clinical application.
MATERIALS AND METHODS
The literature information was obtained from several authoritative databases including PubMed, Embase, Cochrane Library, CNKI and Wan Fang before April 30, 2023. We also analyzed the representatively chemical compounds of Xihuang pill in vivo experiments using HPLC-Q/TOF-MS.
RESULTS
The present study indicated that Xihuang pill, a classic anti-tumor prescription, had efficacies of strengthening body resistance, clearing heat and detoxification, and promoting blood circulation for removing blood stasis. Modern basic researches showed that Xihuang pill played anti-cancer roles through inducing cancer cell apoptosis, inhibiting cell proliferation, migration, invasion and angiogenesis, improving immune function and tumor microenvironment, and regulating related signaling pathways. Its chemical components are primarily consisted of amino acids, terpenoids, fatty acids, fatty acid esters, phenolics, bile acids, bile pigments and volatile oil. Clinically, Xihuang pill, as an adjuvant drug for cancer treatment, was mostly combined with chemotherapy, which could prolong survival, enhance response rate, improve patients' life quality, regulate immune function and alleviate chemotherapy-induced toxicities.
CONCLUSIONS
This present study suggests that Xihuang pill may be a promising adjuvant therapy for cancer, and proposes the possibility of future research directions for Xihuang pill based on the current research status.
Topics: Humans; Drugs, Chinese Herbal; Neoplasms; Medicine, Chinese Traditional; Tumor Microenvironment
PubMed: 37257709
DOI: 10.1016/j.jep.2023.116699 -
Optimizing Mental Health for Women: Recognizing and Treating Mood Disorders Throughout the Lifespan.The Journal of Clinical Psychiatry Sep 2023Mood disorders can come and go during the reproductive stages of a woman's life and beyond and can include premenstrual-related mood disorders, depression and other...
Mood disorders can come and go during the reproductive stages of a woman's life and beyond and can include premenstrual-related mood disorders, depression and other psychiatric disorders during pregnancy, postpartum mood disorders, and depression during menopause, as well as comorbid psychiatric conditions. Women may have regular contact with health care providers at these various stages in their lives, providing an opportunity for treatment intervention. However, clinicians struggle to effectively identify and manage these disorders, leaving women's mental health issues unaddressed and causing unnecessary suffering, multiple comorbidities, and unwanted outcomes. Context is essential for diagnoses and treatment, and spending time with patients, taking a full history, and taking the time to understand each patient's perspective during these complex periods lead to more accurate diagnoses, ultimately facilitating more effective treatment plans. An array of options is available for treating women's mental health, including antidepressants, oral contraceptives, hormones and recently approved neurosteroids, and nonpharmacological approaches. Clinicians need to be aware of which treatment options are available and evidence-based, guideline-directed solutions to help women manage their mental health. Creating patient-centered, individualized, evidence-based treatment plans is key to optimizing outcomes for women across their lifespan.
Topics: Pregnancy; Humans; Female; Mood Disorders; Mental Health; Longevity; Affect; Awareness; Puerperal Disorders
PubMed: 37728480
DOI: 10.4088/JCP.vtsmdd2136ahc -
Journal of Obstetrics and Gynaecology... Apr 2024
Review
PubMed: 38707879
DOI: 10.1007/s13224-024-01988-4