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Contraceptive effects on the cervicovaginal microbiome: Recent evidence including randomized trials.American Journal of Reproductive... Nov 2023Until recently, most data regarding the effects of non-barrier contraceptives on the mucosal microbiome have derived from observational studies, which are potentially... (Review)
Review
BACKGROUND
Until recently, most data regarding the effects of non-barrier contraceptives on the mucosal microbiome have derived from observational studies, which are potentially biased due to behavioral confounders that may mask their true biological effects.
METHOD OF STUDY
This narrative review summarises recent evidence of the effect of contraceptives on the cervicovaginal microbiome, emphasising data obtained through randomized trials.
RESULTS
Good quality data describe that initiation of long-acting progestin-only contraceptives, including levonorgestrel (LNG)-implant and the injectables depot-medroxyprogesterone acetate (DMPA-IM) and norethisterone enanthate (NET-EN) do not alter the mucosal microbial environment. Likewise, no strong evidence exists that the use of oral contraceptive pills (OCPs) is associated with alterations of the vaginal microbiome or increased risk of bacterial sexually transmitted infections (STIs). Limited data on the effect of intravaginal rings (IVRs) on the mucosal environment exist and show conflicting effects on the vaginal microbiota. Copper intrauterine device (Cu-IUD) initiation has been associated with bacterial vaginosis (BV) acquisition, including in a randomized trial. LNG-IUDs may have similar affects but need to be evaluated further.
CONCLUSION
Different synthetic hormones have divergent effects on the microbiome and therefore novel hormonal methods need to be rigorously evaluated. Furthermore, the addition of antiretrovirals into multipurpose technologies may alter the effects of the hormonal component. There is thus a critical need to improve our understanding of the biological effects of contraceptive hormones and delivery methods with different pharmacokinetic and chemical properties on the mucosal microbiome in rigorous trials, to inform the development of novel contraceptives and improve individual family planning guidance.
Topics: Female; Humans; Contraceptive Agents; Contraceptive Agents, Female; Hormones; Levonorgestrel; Medroxyprogesterone Acetate; Microbiota; Randomized Controlled Trials as Topic
PubMed: 37881121
DOI: 10.1111/aji.13785 -
Journal of Epilepsy Research Dec 2023Seizure aggravation in women with epilepsy (WWE) tends to occur at two specific times during the menstrual cycle: the perimenstrual phase and the ovulation period.... (Review)
Review
Seizure aggravation in women with epilepsy (WWE) tends to occur at two specific times during the menstrual cycle: the perimenstrual phase and the ovulation period. Antiseizure drugs (ASDs), especially those that induce enzymes, can accelerate the metabolism of hormones in oral contraceptives, rendering them less effective. Estrogen in contraceptive pills increases the metabolism of lamotrigine. Physiological changes during pregnancy can significantly impact the pharmacokinetics of ASDs, potentially necessitating adjustments in dosage for women with epilepsy to maintain seizure control. The use of valproate in pregnant women is associated with the highest risk of major congenital malformations among ASDs. Risks of major congenital malformations associated with lamotrigine, levetiracetam, and oxcarbazepine were within the range reported in the general population. Exposure to valproate can lead to lower IQ in offspring. Reduced folic acid levels are linked to orofacial clefts, cardiovascular malformations, and urogenital and limb anomalies in WWE. Decreased folate levels are expected with the use of enzyme-inducing ASDs. However, a high dose of folate was associated with an increased risk of cancer in children of mothers with epilepsy. Most ASDs are generally considered safe for breastfeeding and should be encouraged. However, no single ASD is considered ideal for childbearing WWE. Lamotrigine and levetiracetam are relatively more suitable options for this situation.
PubMed: 38223363
DOI: 10.14581/jer.23005 -
PloS One 2023The efficacy of open-label placebos (OLPs) has been increasingly demonstrated and their use holds promise for applications compatible with basic ethical principles.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The efficacy of open-label placebos (OLPs) has been increasingly demonstrated and their use holds promise for applications compatible with basic ethical principles. Taking this concept one step further an imaginary pill (IP) intervention without the use of a physical pill was developed and tested in a randomized controlled trial (RCT). To explore participants' experiences and views, we conducted the first qualitative study in the field of IPs.
METHODS
A reflexive thematic analysis (RTA) of semi-structured interviews with test anxious students (N = 20) was nested in an RCT investigating an IP and OLP intervention. In addition, open-ended questions from the RCT were evaluated (N = 114) to corroborate the RTA and pill characteristics were included to more accurately capture the IP experience.
RESULTS
Four key themes were identified: (1) attitude towards the intervention, (2) applicability of the intervention, (3) experience of effects, and (4) characteristics of the imagination. The IP intervention was well-accepted, easily applicable, and various effects, pill characteristics and appearances were described. While many participants did not desire a physical pill, either due to the absence of the imagination component or aversion to pills, the approach was considered to be cognitively and time demanding, which in turn, however, encouraged the establishment of a therapeutic ritual that protected against the increase in test anxiety during the preparation phase. OLP findings were comparable, and especially the importance of a treatment rationale was stressed in both groups, counteracting an initial ambivalent attitude. The RTA findings were supported by the open-ended questions of the RCT.
CONCLUSION
IPs appear to be a well-accepted and easily applicable intervention producing a variety of beneficial effects. Thus, the IP approach might serve as an imaginary based alternative to OLPs warranting further investigations on its application to harness placebo effects without a physical pill.
Topics: Humans; Test Anxiety; Affect; Compulsive Behavior; Imagination; Moral Obligations
PubMed: 37656757
DOI: 10.1371/journal.pone.0291004 -
European Journal of Endocrinology Jul 2023To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS).
DESIGN
A systematic review and meta-analysis was performed, Prospero CRD42022345640.
METHODS
MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials.
RESULTS
A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62 kg/m2 [95% CI 0.05-1.20]) compared with conventional COCPs.There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified.
CONCLUSION
With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS.
TRIAL REGISTRATION
The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hirsutism; Hyperandrogenism; Contraceptives, Oral, Combined; Ethinyl Estradiol; Cyproterone Acetate; Testosterone
PubMed: 37440702
DOI: 10.1093/ejendo/lvad082 -
Gynecological Endocrinology : the... Dec 2023To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COC) in users over 40. (Observational Study)
Observational Study
OBJECTIVE
To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COC) in users over 40.
METHODS
In this large, observational study, new users of NOMAC-E2 and COC were recruited in Europe, Australia, and Latin America and followed-up questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/10 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight.
RESULTS
Overall, 7,762 NOMAC-E2 and 6,059 COC users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COC; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9-13.7) vs 4 COC (IR 5.9; 95% CI, 1.6-15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01-0.13) vs 5 COC (PI 0.08; 95% CI, 0.03-0.18). No differential effect on mood and weight was observed between cohorts.
CONCLUSIONS
NOMAC-E2 can be considered a valid alternative to COC in perimenopausal women.
Topics: Pregnancy; Female; Humans; Contraceptives, Oral, Combined; Ethinyl Estradiol; Estradiol; Venous Thromboembolism; Megestrol; Norpregnadienes
PubMed: 36690019
DOI: 10.1080/09513590.2023.2166032 -
Der Nervenarzt Mar 2024Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by... (Review)
Review
Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by psychological and physical symptoms causing relevant functional and social impairments. Mood swings, depression and dysphoria are associated depressive symptoms. Therefore, affective disorders should be considered as a differential diagnosis. Of women in reproductive age 3-8% suffer from premenstrual syndrome and 2% of women are affected by premenstrual dysphoric disorder. Genetic and sociobiographical risk factors are discussed. Furthermore, genetic polymorphisms of specific hormone receptors are considered to be genetic risk factors. From a pathophysiological perspective premenstrual syndrome and premenstrual dysphoric disorder are caused by a complex interaction between cyclic changes of ovarian steroids and central neurotransmitters. An imbalance of estrogen and progesterone in the luteal phase is believed to cause the symptoms. Therefore, the first treatment approach consists of regulation of the menstrual cycle or luteal support with progesterone or synthetic progestins even if their effectiveness has not yet been proven in randomized controlled studies and meta-analyses. The administration of combined oral contraceptives is also an option. Especially treatment with selective serotonin reuptake inhibitors (SSRI) represent an evidence-based approach. In severe cases the administration of gonadotropin releasing hormone (GnRH) agonists with add back treatment can also be considered. In the field of affective disorders premenstrual syndromes represent clinically relevant differential diagnoses and comorbidities, which confront the treating physician with particular clinical challenges. Therefore, this literature review gives the readership a clinical orientation for dealing with these disorders.
Topics: Female; Humans; Child, Preschool; Premenstrual Dysphoric Disorder; Progesterone; Premenstrual Syndrome; Mood Disorders; Anxiety
PubMed: 38393358
DOI: 10.1007/s00115-024-01625-5 -
Medicina (Kaunas, Lithuania) May 2024Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing... (Review)
Review
UNLABELLED
Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms.
OBJECTIVES
In this review we present all currently available treatment modalities for uterine fibroids.
METHODS
An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted.
REVIEW
Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient's age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results.
CONCLUSIONS
Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient's desire for definitive treatment or fertility preservation.
Topics: Humans; Leiomyoma; Female; Uterine Neoplasms; Hysterectomy; Uterine Artery Embolization; Uterine Myomectomy
PubMed: 38929485
DOI: 10.3390/medicina60060868 -
Current Neurology and Neuroscience... Jan 2024Given the potential for exogenous hormones to influence risk and course of MS, this narrative review aims to summarize current knowledge from observational and... (Review)
Review
PURPOSE OF REVIEW
Given the potential for exogenous hormones to influence risk and course of MS, this narrative review aims to summarize current knowledge from observational and interventional studies of exogenous hormones in humans with MS.
RECENT FINDINGS
Large randomized clinical trials for combined oral contraceptives and estriol both show modest effect on inflammatory activity, with the latter showing potential neuroprotective effect. After fertility treatment, large actively treated cohorts have not confirmed any elevated risk of relapse. Preclinical data suggest that androgens, selective estrogen receptor modulators (SERMs), and selective androgen receptor modulators (SARMs) may be neuroprotective but clinical data are lacking. Gender affirming treatment, particularly estrogen in trans-women, could possibly be associated with elevated risk of inflammation. For women with MS entering menopause, hormone therapy appears safe during the appropriate menopausal window, but its long-term effects on neuroprotection are unknown. Exogenous hormones, used in varied doses and for diverse indications, have variable effects on MS risk, inflammatory activity, and neuroprotection. Large randomized trials are needed before it is possible to determine the true effect of exogenous hormones in a condition as complex as MS.
Topics: Humans; Female; Multiple Sclerosis; Estrogens; Menopause
PubMed: 38102502
DOI: 10.1007/s11910-023-01326-7 -
Current Opinion in Pediatrics Aug 2023The diagnostic criteria for polycystic ovary syndrome (PCOS) in adults may overdiagnose PCOS in adolescents. Since 2015, three guidelines have developed... (Review)
Review
PURPOSE OF REVIEW
The diagnostic criteria for polycystic ovary syndrome (PCOS) in adults may overdiagnose PCOS in adolescents. Since 2015, three guidelines have developed adolescent-specific diagnostic criteria and treatment recommendations. In this review, we compare and contrast the recommendations to assist in the practical application to clinical practice.
RECENT FINDINGS
The guidelines agree that hyperandrogenism with menstrual irregularity be diagnostic criteria for PCOS in adolescents yet have slight differences in how to diagnose hyperandrogenism and in the definition of menstrual irregularity. The diagnostic option of 'at risk for PCOS' is recommended for those girls presenting with criteria within 3 years of menarche or with hyperandrogenism without menstrual irregularity, with re-assessment later in adolescence. Lifestyle changes is first line treatment. Treatment with combined oral contraceptives or metformin is suggested, using patient characteristics and preferences to guide decision-making.
SUMMARY
PCOS is associated with long term reproductive and metabolic complications and will present during adolescence. Yet, diagnostic features may overlap with normal adolescent physiology. The recent guidelines strove to develop criteria to accurately identify girls with PCOS allowing early surveillance and treatment yet avoid overdiagnosis of normal adolescents.
Topics: Female; Adult; Adolescent; Humans; Polycystic Ovary Syndrome; Hyperandrogenism; Menstruation Disturbances; Life Style; Metformin
PubMed: 37097290
DOI: 10.1097/MOP.0000000000001255 -
Journal of Ethnopharmacology Apr 2024Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains...
ETHNOPHARMACOLOGICAL RELEVANCE
Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains unclear.
AIM OF THE STUDY
This study aimed to explore the core molecular mechanisms of Xihuang pill in treating glioblastoma by an integrative pharmacology-based investigation.
MATERIALS AND METHODS
The main active compounds of Xihuang pill were identified from TCMSP, BATMAN-TCM, TCMID and CNKI. Glioblastoma-related therapeutic targets were retrieved from GeneCards and UniProt. Subsequently, a protein-protein interaction (PPI) network analysis was constructed using STRING. GO and KEGG enrichment were performed to analyze the intersection targets between the active compounds of Xihuang pill and glioblastoma. Based on the above analysis, we built a CTP network. The in vitro and in vivo experiments were further performed to validate the crucial molecular targets of Xihuang pill for the treatment of glioblastoma.
RESULTS
A total of sixty active compounds of Xihuang pill and ten potential targets related to glioblastoma were found. Based on topological analysis, fourteen ingredients were selected as the main active compounds, and MY11 might be the most important metabolite in Xihuang pill. PI3K/Akt signaling pathway and receptor tyrosine kinases were considered as crucial targets for Xihuang pill against glioblastoma through KEGG enrichment and CTP analysis. The present experiments indicated that Xihuang pill suppressed the activation of PI3K/Akt/mTOR signaling pathway in glioblastoma cells and mouse xenografts via modulating the expression of PTEN and Rheb proteins, the interaction between TSC2 and Rheb, and the production of PIP3. Meanwhile, after glioblastoma cells treatment with Xihuang pil, the release of IL-1β, INF-γ was increased and the production of IL-10, TGF-β1 was decreased in glioblastoma cells after incubated with Xihuang pill. In addition, the activation of the upstream positive modulators of PI3K/Akt/mTOR pathway including PDGF/PDGFR and FGF/FGFR signaling were down-regulated in glioblastoma cells and mouse xenografts after treatment with Xihuang pill.
CONCLUSION
Taken together, Xihuang pill inhibiting glioblastoma cell growth might be partly through down-regulating the activation of PDGF/PDGFR or FGF/FGFR-PI3K/Akt/mTOR signaling axis and improving immuno-suppressive micro-environment of glioblastoma.
Topics: Humans; Animals; Mice; Glioblastoma; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Molecular Docking Simulation; Drugs, Chinese Herbal; Tumor Microenvironment
PubMed: 38159819
DOI: 10.1016/j.jep.2023.117675