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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 -
The Lancet Regional Health. Europe Jul 2024Nomegestrol acetate (NOMAC) is a synthetic potent progestogen. This study aimed to assess the risk of intracranial meningioma associated with the prolonged use of NOMAC.
BACKGROUND
Nomegestrol acetate (NOMAC) is a synthetic potent progestogen. This study aimed to assess the risk of intracranial meningioma associated with the prolonged use of NOMAC.
METHODS
Observational cohort study using SNDS data (France). Women included had ≥ one dispensing of NOMAC between 2007 and 2017 (no dispensing in 2006). Exposure was defined as a cumulative dose >150 mg NOMAC within six months after first dispensing. A control group of women (cumulative dose ≤150 mg) was assembled. The outcome was surgery (resection or decompression) or radiotherapy for one or more intracranial meningioma(s). Poisson models assessed the relative risk (RR) of meningioma.
FINDINGS
In total, 1,060,779 women were included in the cohort (535,115 in the exposed group and 525,664 in the control group). The incidence of meningioma in the two groups was 19.3 and 7.0 per 100,000 person-years, respectively (age-adjusted RRa = 2.9 [2.4-3.7]). The RRa for a cumulative dose of more than 6 g NOMAC was 12.0 [9.9-16.0]. In the event of treatment discontinuation for at least one year, the risk of meningioma was identical to that in the control group (RRa = 1.0 [0.8-1.3]). The location of meningiomas in the anterior and middle part of the skull base was more frequent with exposure to NOMAC.
INTERPRETATION
We observed a strong dose-dependent association between prolonged use of NOMAC and the risk of intracranial meningiomas. These results are comparable to those obtained for cyproterone acetate, although the magnitude of the risk is lower. It is now recommended to stop using NOMAC if a meningioma is diagnosed.
FUNDING
The French National Health Insurance Fund (Cnam) and the French National Agency for Medicines and Health Products Safety (ANSM) via the Health Product Epidemiology Scientific Interest Group EPI-PHARE.
PubMed: 38800110
DOI: 10.1016/j.lanepe.2024.100928 -
Molecules (Basel, Switzerland) May 2024Progesterone (PROG) and estrone (E) are typical reproductive hormones in dairy cows. Assessing the levels of these hormones in vivo can aid in estrus identification. In...
Progesterone (PROG) and estrone (E) are typical reproductive hormones in dairy cows. Assessing the levels of these hormones in vivo can aid in estrus identification. In the present work, the feasibility of the qualitative and quantitative detection of PROG and E using terahertz time-domain spectroscopy (THz-TDS) and metamaterial technology was preliminarily investigated. First, the time domain spectra, frequency domain spectra, and absorption coefficients of PROG and E samples were collected and analyzed. A vibration analysis was conducted using density functional theory (DFT). Subsequently, a double-ring (DR) metamaterial structure was designed and simulated using the frequency domain solution algorithm in CST Studio Suite (CST) software. This aimed to ensure that the double resonance peaks of DR were similar to the absorption peaks of PROG and E. Finally, the response of DR to different concentrations of PROG/E was analyzed and quantitatively modeled. The results show that a qualitative analysis can be conducted by comparing the corresponding DR resonance peak changes in PROG and E samples at various concentrations. The best R for the PROG quantitative model was 0.9872, while for E, it was 0.9828. This indicates that terahertz spectral-metamaterial technology for the qualitative and quantitative detection of the typical reproductive hormones PROG and E in dairy cows is feasible and worthy of in-depth exploration. This study provides a reference for the identification of dairy cow estrus.
Topics: Cattle; Animals; Progesterone; Female; Terahertz Spectroscopy; Estrone; Dairying
PubMed: 38792227
DOI: 10.3390/molecules29102366 -
International Journal of Molecular... May 2024Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent...
Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in , causing 21-hydroxylase deficiency (21-OHD). Despite emerging treatment options for CAH, it is not always possible to physiologically replace cortisol levels and counteract hyperandrogenism. Moreover, there is a notable absence of an effective in vivo model for pre-clinical testing. In this work, we developed an animal model for CAH with the clinically relevant point mutation p.R484Q in the previously humanized mouse strain. Mutant mice showed hyperplastic adrenals and exhibited reduced levels of corticosterone and 11-deoxycorticosterone and an increase in progesterone. Female mutants presented with higher aldosterone concentrations, but blood pressure remained similar between wildtype and mutant mice in both sexes. Male mutant mice have normal fertility with a typical testicular appearance, whereas female mutants are infertile, exhibit an abnormal ovarian structure, and remain in a consistent diestrus phase. Conclusively, we show that the animal model has the potential to contribute to testing new treatment options and to prevent comorbidities that result from hormone-related derangements and treatment-related side effects in CAH patients.
Topics: Animals; Adrenal Hyperplasia, Congenital; Disease Models, Animal; Steroid 21-Hydroxylase; Mice; Female; Male; Humans; Corticosterone; Aldosterone; Adrenal Glands; Mutation; Progesterone
PubMed: 38791102
DOI: 10.3390/ijms25105062 -
Cells May 2024There are fewer investigations conducted on human primary endometrial epithelial cells (HPEECs) compared to human primary endometrial stromal cells (HPESCs). One of the...
There are fewer investigations conducted on human primary endometrial epithelial cells (HPEECs) compared to human primary endometrial stromal cells (HPESCs). One of the main reasons is the scarcity of protocols enabling prolonged epithelial cell culture. Even though it is possible to culture HPEECs in 3D over a longer period of time, it is technically demanding. In this study, we successfully established a highly pure, stable, and long-term viable human conditionally reprogrammed endometrial epithelial cell line, designated as eCRC560. These cells stained positive for epithelial markers, estrogen and progesterone receptors, and epithelial cell-cell contacts but negative for stromal and endothelial cell markers. Estradiol (ES) reduced the abundance of ZO-1 in a time- and dose-dependent manner, in contrast to the dose-dependent increase with the progestin dienogest (DNG) when co-cultured with HPESCs. Moreover, ES significantly increased cell viability, cell migration, and invasion of the eCRC560 cells; all these effects were inhibited by pretreatment with DNG. DNG withdrawal led to a significantly disrupted monolayer of eCRC560 cells in co-culture with HPESCs, yet it markedly increased the adhesion of eCRC560 to the human mesothelial MeT-5A cells. The long-term viable eCRC560 cells are suitable for in vitro analysis of HPEECs to study the epithelial compartment of the human endometrium and endometrial pathologies.
Topics: Humans; Female; Endometrium; Epithelial Cells; Progestins; Estrogens; Cell Survival; Cell Movement; Cell Line; Estradiol; Stromal Cells; Coculture Techniques; Time Factors; Cell Adhesion
PubMed: 38786035
DOI: 10.3390/cells13100811