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The Mental Health Clinician Jun 2024Clozapine is primarily metabolized via cytochrome P450(CYP)1A2 and to a lesser extent CYP3A4, CYP2C19, and CYP2D6. Metabolic inhibitors of clozapine, such as fluvoxamine...
Clozapine is primarily metabolized via cytochrome P450(CYP)1A2 and to a lesser extent CYP3A4, CYP2C19, and CYP2D6. Metabolic inhibitors of clozapine, such as fluvoxamine and ciprofloxacin, are important to recognize to avoid adverse drug events. Estrogen-containing oral contraceptives (eOCPs) are weaker CYP1A2 and CYP2C19 inhibitors but are associated with a 2-fold increase of clozapine concentrations. The potential for phenoconversion due to a CYP genetic polymorphism can add additional complexities when considering drug interactions. A case report is presented of a suspected interaction between newly initiated clozapine and a prescribed eOCP for which the patient's pharmacogenomic status was known. A 17-year-old, nonsmoking, White female with a history of schizophrenia was initiated on clozapine 12.5 mg at bedtime with a plan to increase by 25 mg every 4 days in the outpatient setting. The patient was a known rapid CYP1A2 metabolizer without identified sources of CYP1A2 induction and a CYP2C19 rapid metabolizer. Based on pharmacogenomic testing, there was no suspicion for significant gene-drug interactions. Yet, as the patient was prescribed an eOCP, a clozapine concentration was obtained after reaching 150 mg at bedtime. This steady-state clozapine concentration was found to be 560 ng/mL, correlating with worsening sedation and constipation. Given ongoing side effects, clozapine was lowered to 100 mg at bedtime; however, ongoing intolerance ultimately led to clozapine discontinuation. This case highlights the potential interaction between clozapine and eOCP in a CYP1A2 and CYP2C19 rapid metabolizer, leading to clozapine intolerance and discontinuation. The concomitant use of clozapine and eOCPs should be undertaken judiciously.
PubMed: 38835816
DOI: 10.9740/mhc.2024.06.220 -
Frontiers in Global Women's Health 2024Hormone replacement therapy (HRT), also known as menopausal hormone therapy (MHT), was looked upon as a fountain of youth that kept women young and reduced...
Hormone replacement therapy (HRT), also known as menopausal hormone therapy (MHT), was looked upon as a fountain of youth that kept women young and reduced cardiovascular disease. This led to a large-scale study called the Women's Health Initiative (WHI) that was conducted to show the cardiovascular benefits of HRT. This study was suspended early because of adverse side effects. The USFDA responded by slapping a "black box" warning on all HRT products. USFDA-approved bioidentical HRT formulations are safe and effective. We propose that these formulations have the "black box" warning removed so that doctors feel more confident in prescribing these products for symptoms of menopause and chronic conditions such as cardiovascular health. We propose eliminating the sale of products containing medroxyprogesterone acetate (MPA) because of the increased risk of heart attacks and breast cancers associated with this medication.
PubMed: 38832110
DOI: 10.3389/fgwh.2024.1397123 -
Reproductive Medicine and Biology 2024To validate the effectiveness of a gonadotropin starting dose calculator for progestin-primed ovarian stimulation (PPOS), we conducted a study comparing the outcomes of...
Verification of the utility of the gonadotropin starting dose calculator in progestin-primed ovarian stimulation: A comparison of empirical and calculated controlled ovarian stimulation.
PURPOSE
To validate the effectiveness of a gonadotropin starting dose calculator for progestin-primed ovarian stimulation (PPOS), we conducted a study comparing the outcomes of oocyte retrieval between a group assigned gonadotropin doses via the calculator and a control group, where doses were determined by the clinician's empirical judgment.
METHODS
Patients underwent controlled ovarian stimulation (COS) using the PPOS method, followed by oocyte retrieval. We assessed and compared the results of COS and oocyte retrieval in both groups. Additionally, we examined the concordance rate between the number of oocytes actually retrieved and the target number of oocytes in each group.
RESULTS
The calculated group demonstrated a significantly higher number of preovulation follicles and a higher ovarian sensitivity index than the control group. Furthermore, the discrepancy between the target and actual number of oocytes retrieved was notably smaller in the calculated group. The concordance rate between the target and actual number of oocytes was significantly greater in the calculated group.
CONCLUSIONS
The gonadotropin starting dose calculator proved to be effective within the PPOS protocol, offering a reliable method for predicting the approximate number of oocytes to be retrieved, irrespective of the COS protocol employed.
PubMed: 38827517
DOI: 10.1002/rmb2.12586 -
BMC Health Services Research Jun 2024The etonogestrel contraceptive implant is currently approved by the United States Food and Drug Administration (FDA) for the prevention of pregnancy up to 3 years....
BACKGROUND
The etonogestrel contraceptive implant is currently approved by the United States Food and Drug Administration (FDA) for the prevention of pregnancy up to 3 years. However, studies that suggest efficacy up to 5 years. There is little information on the prevalence of extended use and the factors that influence clinicians in offering extended use. We investigated clinician perspectives on the barriers and facilitators to offering extended use of the contraceptive implant.
METHODS
Using the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured qualitative interviews. Participants were recruited from a nationwide survey study of reproductive health clinicians on their knowledge and perspective of extended use of the contraceptive implant. To optimize the diversity of perspectives, we purposefully sampled participants from this study. We used content analysis and consensual qualitative research methods to inform our coding and data analysis. Themes arose deductively and inductively.
RESULTS
We interviewed 20 clinicians including advance practice clinicians, family medicine physicians, obstetrician/gynecologist and complex family planning sub-specialists. Themes regarding barriers and facilitators to extended use of the contraceptive implant emerged. Barriers included the FDA approval for 3 years and clinician concern about liability in the context of off-label use of the contraceptive implant. Educational materials and a champion of extended use were facilitators.
CONCLUSIONS
There is opportunity to expand access to extended use of the contraceptive implant by developing educational materials for clinicians and patients, identifying a champion of extended use, and providing information on extended use prior to replacement appointments at 3 years.
Topics: Humans; Female; Qualitative Research; Desogestrel; Implementation Science; Adult; Contraceptive Agents, Female; United States; Interviews as Topic; Drug Implants; Male; Attitude of Health Personnel; Middle Aged; Practice Patterns, Physicians'; Time Factors
PubMed: 38825705
DOI: 10.1186/s12913-024-10991-4 -
Environment International Jun 2024The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone...
BACKGROUND
The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition.
METHODS
Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally.
RESULTS
We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures.
CONCLUSIONS
Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.
Topics: Humans; Phthalic Acids; Female; Middle Aged; Longitudinal Studies; Perimenopause; Environmental Pollutants; Estradiol; Adult; Gonadal Steroid Hormones; Progesterone; Environmental Exposure; Women's Health; Testosterone
PubMed: 38821016
DOI: 10.1016/j.envint.2024.108770 -
Archives of Dermatological Research May 2024Progesterone is used for hormone replacement therapy through various routes of administration. This study was conducted to (a) evaluate the stability of progesterone in...
Progesterone is used for hormone replacement therapy through various routes of administration. This study was conducted to (a) evaluate the stability of progesterone in a proprietary anhydrous permeation-enhancing base (APEB) and the efficiency of its skin permeation, and (b) determine the appropriateness of mass spectrometry as a method of analysis for permeated progesterone. Using a proven stability-indicating ultra-performance liquid chromatographic method, the compounded hormone (100 mg progesterone/g APEB gel) was determined to be physically and chemically stable at room temperature for six months. Skin permeation analysis using the Franz skin finite dose model and mass spectrometry imaging showed an optical density of 1699 for the permeated progesterone compounded in APEB and 550 for the permeated progesterone in a water containing VBC, which is a statistically significant different (P = 0.029). The study suggests that APEB can be used as a compounding base for effective skin permeation of progesterone, and mass spectrometry is a reliable method for visualization and quantitative analysis of permeated progesterone.
Topics: Progesterone; Skin Absorption; Mass Spectrometry; Skin; Humans; Administration, Cutaneous; Permeability; Drug Stability; Animals; Chromatography, High Pressure Liquid; Drug Compounding
PubMed: 38814486
DOI: 10.1007/s00403-024-03040-x -
Frontiers in Endocrinology 2024To determine whether the late-follicular-phase progesterone to retrieved oocytes (P/O) ratio during fertilization (IVF)/intracytoplasmic sperm injection (ICSI) impacts...
The late-follicular-phase progesterone to retrieved oocytes ratio in normal ovarian responders treated with an antagonist protocol can be used as an index for selecting an embryo transfer strategy and predicting the success rate: a retrospective large-scale study.
OBJECTIVE
To determine whether the late-follicular-phase progesterone to retrieved oocytes (P/O) ratio during fertilization (IVF)/intracytoplasmic sperm injection (ICSI) impacts pregnancy outcomes.
DESIGN
12,874 cycles were retrospectively categorized into four groups according to the P/O ratio percentile, with divisions at the 25th, 50th and 75th percentiles.
RESULTS
The clinical pregnancy and live birth rates of fresh cycle embryos in Group D were significantly lower than those in the other three groups (45.1% and 39.0%, 43.2% and 37.2%, 39.6% and 33.5%, 33.4% and 28.2% in Group A, B, C, D, respectively; both P < 0.008). Multivariate logistic regression analysis revealed a significant negative correlation between the P/O ratio and live birth, particularly when the P/O ratio was ≥0.22 (OR = 0.862, 95% CI [0.774-0.959], P = 0.006).
CONCLUSIONS
The P/O ratio has certain predictive value for IVF/ICSI pregnancy outcomes and can be used for decision-making decision regarding fresh embryo transfer.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Progesterone; Adult; Embryo Transfer; Ovulation Induction; Fertilization in Vitro; Pregnancy Rate; Oocytes; Oocyte Retrieval; Sperm Injections, Intracytoplasmic; Follicular Phase; Pregnancy Outcome
PubMed: 38812812
DOI: 10.3389/fendo.2024.1338683 -
Open Veterinary Journal Apr 2024Postpartum ovarian dysfunction [ovarian cyst (OC) and persistent follicle (PF)] has been an important issue. Finding effective hormonal treatments to improve...
BACKGROUND
Postpartum ovarian dysfunction [ovarian cyst (OC) and persistent follicle (PF)] has been an important issue. Finding effective hormonal treatments to improve reproductive performance in dairy cows has become a necessity.
AIM
Improve reproductive performance and ovarian activity in postpartum cows with specific customized treatment for OC and PFs.
METHODS
The study included 48 cows at 14 days P.P, which received two dosages of 500 μg IM cloprostenol, 14 days apart as presynchronization protocol. Ultrasound ovarian scans 14 days after the last injection for 4 weeks. The cows were divided into three groups according to ovarian status: OC ( = 14), PF ( = 12), and NE ( = 22). In the OC group, received 500 μg IM cloprostenol and 100 μg IM cystoriline, a second dose of cloprostenol 14 days later and a second dose of cystoriline 36 hours later, and AI after 24 hours (GnRH+ PG/PG/GnRH). In the PF group, was fitted with progesterone-releasing intravaginal device (PRID) for 9 days; the same day, they received 100 μg cystoreline then 500 μg cloprostenol 7 days later, after PRID removal AI 56 hours later (PRID + GnRH/PG). In the NE group, artificial insemination was implemented until 28 days depending on estrus detection.
RESULTS
The ovarian activity was greatly affected by the customized treatments, leading to enhanced follicular and luteal activity, particularly after the PGF2α injection. The OC and PF groups showed substantial estrus responses of 71.43% and 75.02%, respectively, during AI time. While the NE group had an ovulation rate of 54.5% and a pregnancy rate of 31.8%, the treatment groups showed marked improvements in reproductive performance. The ovulation rates in the OC and PF groups were 71.43% and 75% and the pregnancy rates at the 1st artificial insemination were 64.28% and 66.7%.
CONCLUSION
Improving reproductive performance and minimizing the time to first service are possible advantages of early case-specific treatment for postpartum cows with OC and PFs.
Topics: Animals; Female; Cattle; Ovarian Cysts; Postpartum Period; Cloprostenol; Cattle Diseases; Insemination, Artificial; Pregnancy; Ovarian Follicle; Progesterone; Estrus Synchronization
PubMed: 38808298
DOI: 10.5455/OVJ.2024.v14.i4.10 -
JAMA Network Open May 2024Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years.
OBJECTIVES
To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD.
DESIGN, SETTING, AND PARTICIPANTS
This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024.
INTERVENTION
Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age.
MAIN OUTCOMES AND MEASURES
The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment.
RESULTS
The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02133573.
Topics: Humans; Progesterone; Female; Heart Defects, Congenital; Male; Pregnancy; Double-Blind Method; Infant; Adult; Infant, Newborn; Child Development; Progestins; Neurodevelopmental Disorders
PubMed: 38805228
DOI: 10.1001/jamanetworkopen.2024.12291