Levonorgestrel Intrauterine Device Research Articles

Correlation between steroid receptor expression and response to progestational therapy in patients with atypical endometrial hyperplasia or cancer

BackgroundConservative management of atypical endometrial hyperplasia (AEH) or endometrial cancer (EMCA) often relies on the treatment of synthetic progestins, which show varied success and response rates. We evaluate the correlation between steroid receptor expression and response to progestin therapy in patients with AEH and EMCA. MethodsRetrospective cohort study collected data for patients with AEH or EMCA who had an endometrial sample after receiving conservative therapy utilizing either Megestrol acetate or Levonorgestrel Intrauterine device (IUD). Immunohistochemistry (IHC) was performed on pre- and post- treatment biopsy samples to assess androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) expression. IHC scores (1–12) were calculated based on staining intensity and percentage of positive cells. Results and analysisWe identified 15 patients with AEH and EMCA between 2015 and 2023 with the majority of African American ethnicity (53 %). Fourteen patients (93 %) received Megestrol acetate, and 1 patient received Levonorgestrel IUD alone. Three patients ultimately underwent hysterectomy. Seven (46.6 %) endometrial samples had strong positivity for AR, PR and ER expression on pre-treatment biopsies, and only 3 (20 %) of them maintained strong positivity for the 3 receptors in the post-treatment. Patients who successfully responded to the treatment demonstrated a significantly greater decrease in IHC scores after the treatment compared to those who did not respond (p = 0.009). ConclusionSteroid receptor expression could be used as a possible biomarker for response to progestin therapy in patients undergoing conservative management for AEH and EMCA.

Block Scheduling for LARC in a Family Medicine Residency Program.

Only 20% of family physicians report providing long-acting reversible contraception (LARC). Clinician-related barriers include confidence and comfort with LARC counseling and insertion/removal, and limited availability and uptake. Training during residency may address barriers and increase access/availability of LARC to support reproductive autonomy. We sought to determine the impact of block scheduling LARC clinics on resident comfort and confidence with LARC counseling and insertion/removal. LARC block schedules were established in a Midwest family medicine residency's primary clinic (FMC) and in a federally qualified health center rotation clinic. Baseline and end-of-study surveys, compared by Mann-Whitney U and Wilcoxon signed-rank tests, were used to assess comfort and confidence with counseling and inserting LARC. The number of LARC devices placed at the FMC were collected for the intervention year and the year prior. Twenty of 30 residents completed the baseline survey; 13 completed the end-of-study survey. At the group and individual levels, comfort increased for counseling on Levonorgestrel (LNG) intrauterine devices (IUDs) and for inserting implants and LNG IUDs. Individual comfort increased for copper IUDs. Resident willingness to recommend LARC increased, and more devices were placed during the intervention year than the year prior in the FMC (all: P<.05). Block scheduling of LARC clinics was associated with increased residents' comfort and confidence with counseling and placement of implants (LNG IUDs) and with an increase in LARCs placed at one clinic. Changes to scheduling may be an effective educational strategy that may increase access/availability to LARC.

IUD Insertion Under Conscious Sedation: Patient Characteristics with Clinical Decisions

Study ObjectiveUptake of intrauterine devices (IUDs) in the adolescent population may be limited by anxiety and pain anticipated during the insertion procedure. Our institution offers conscious sedation for IUD insertion to mitigate this concern. The objective of this study was to identify characteristics and outcomes of teens choosing between two types of conscious sedation for insertion of a levonorgestrel IUD. MethodsThis was a single-site, retrospective cohort study over a one-year period reviewing the electronic medical record of patients who had an attempted IUD insertion using conscious sedation. Conscious sedation included nitrous gas (termed “light” sedation) or intravenous midazolam and fentanyl (termed “moderate” sedation). Patient demographics, medical and gynecological histories were analyzed. ResultsThere were 69 attempted IUDs insertions during the study period. Most (75.36%) were placed under light sedation, and 92.75% were successfully inserted. The only significant factor associated with choice in type of conscious sedation was prior sexual activity, which increased odds by 10.0 that they would choose light sedation (95% CI 1.23 – 81.34, p=0.031). Differences between other factors (age, history of sexual assault, tampon use, and gender identity) were not statistically significant between successful and failed insertions. ConclusionsIn conclusion, a history of sexual activity significantly differed between patients in our cohort who selected light sedation over moderate sedation. No other factors influenced choice in sedative or success of IUD insertion. Knowing the characteristics of patients who choose nitrous versus IV sedation, and how it relates to successful insertion, may help guide pre-procedural counseling for patients regarding sedation for IUD insertion.

The impact of embedment of the side arms of 52 mg levonorgestrel-intrauterine device on bleeding and pain: A prospective cohort study

PurposeThe purpose of this study was to analyse the impact of embedment of side arms of the levonorgestrel 52 mg intrauterine device (LNG-IUD) in the myometrium (assessed by three-dimensional transvaginal ultrasound (3D-TVUS)) on uterine bleeding and pain. Materials and methodsWe performed a prospective cohort study in a large Dutch teaching hospital between February 2015 and December 2016. Participants over 18 years of age who selected a LNG-IUD for contraception or because of heavy menstrual bleeding were eligible for inclusion. Six weeks after insertion, a 3D-TVUS was performed to diagnose embedment of the side arms. At that moment participants filled in questionnaires about their bleeding pattern and pelvic pain. Menstruation patterns ‘no bleeding’, ‘regular menstruation’, ‘sometimes a day of spotting (maximum once a week)’ were classified as favourable bleeding pattern. Menstruation patterns ‘heavy menstrual bleeding’, ‘several days a week bleeding days’, ‘several days a week spotting days’, ‘continuously spotting’, and ‘completely irregular cycle’ were classified as unfavourable bleeding pattern. Univariate and multivariate logistic regression analysis was used to calculate odds ratios (OR) and 95 %-confidence intervals (CI). The multivariate analysis included endometrial thickness, reason for insertion and parity. The analysis of pelvic pain additionally included previous insertion. ResultsA total of 220 participants were evaluated for the study of whom 176 returned the questionnaires. Embedment of the side arms was observed in 43 of the 176 responding participants (24.4 %). Favourable bleeding pattern was reported by 25/43 (58.1 %) participants with embedment and 53/133 (39.8 %) participants without embedment (ORadj 1.8, 95 % CI 0.9–3.9). Pelvic pain was reported by 4/43 (9.3 %) participants with embedment and 24/133 (18.1 %) participants without embedment (ORadj 0.3; CI 0.1–1.2). ConclusionsThe present study suggests that embedment of the side arms of the LNG-IUD in the myometrium assessed by 3D-TVUS is not associated with a unfavourable bleeding pattern nor pelvic pain six weeks after insertion. From this point of view, we do not recommend to perform standard 3D-TVUS for the purpose of excluding or demonstrating embedment.

Is there a difference in the clinical profile and outcome of women using levonorgestrel IUD for abnormal uterine bleeding and those using it for contraception?: A comparative cross-sectional study.

The most common indications for Levonorgestrel intrauterine device (LNG-IUD) are contraception and management of abnormal uterine bleeding (AUB). This study was conducted with the aim of exploring the differences in the clinical profile and outcome of women using LNG-IUD for contraception and AUB. This was a retrospective comparative cross-sectional study of women who underwent LNG-IUD (52 mg) between 2012 and 2017. Their electronic health records were reviewed until the last documented follow-up or until December 2021. A total of 235 women had LNG-IUD with an age range of 21 to 62 years and a mean of (37.98 years±6.76). Of these women, 153/235 (65.1%) had it for contraception and 82/235 (34.89%) had it for AUB. The follow-up was 1-94 months with (mean ± SEM) follow-up for the AUB group of (21.48±2.31) months and for contraception group was (20.74±1.76) months (p-value of 0.80). There was a significant difference between the two groups in the age and body mass index (BMI), where women who had LNG-IUD for AUB were older (mean of 42.54±6.49 years, p-value <0.001) and had higher BMI (31.88±7.52 kg/m2, p-value =0.011). All LNG-IUDs that were indicated for contraception were inserted in an outpatient setting. However, 68.3% in the AUB, the insertion was in the operating theater in conjunction with hysteroscopy. After combining both expulsion and removal of LNG-IUD during the follow-up period, there was no significant difference between the 2 groups in the overall retention rate during the follow-up (p-value =0.998). this study shows that women using LNG-IUD for the management of AUB are older and have a higher BMI compared with those using it for contraception. AUB women experienced more expulsion compared with the contraception group, but there was no difference between the 2 groups in the overall survival/retention of LNG-IUD.

Abstract B024: Immune exhaustion and reversal of progestin-related immune modulation in adaptive resistance to levonorgestrel intrauterine device for treatment of atypical hyperplasia and early endometrial cancer

Abstract Background: A growing proportion of women diagnosed with atypical hyperplasia (AH) and early-stage endometrioid endometrial cancer (EEC) require nonsurgical treatment options. Our previously published phase II clinical trial of the levonorgestrel intrauterine device (LIUD) for AH and grade 1 EEC (G1EEC) demonstrated 83% response rate at 1 year; however, prospective long-term follow-up data and determinants for duration of response to LIUD are limited. Methods: Follow-up data from patients that participated in our prospective phase II trial of LIUD as a nonsurgical approach for AH and G1EEC were collected from medical records. Duration of response and time to relapse were evaluated. Spatial transcriptomic profiling from longitudinal biopsy samples from pre-treatment (n=5), on-treatment (n=5), and disease relapse lesions (n=3) were evaluated using digital spatial profiling (DSP, Nanostring GeoMX Whole Transcriptome Atlas). In silico cell type deconvolution was performed and pathway analyses was conducted using gene set variation analysis enrichment. Results: Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen experienced disease relapse (39%) with a median time to relapse of 17 months after initial response. Clinical factors associated with shorter duration of response included age (HR 0.95, p=0.021), initial diagnosis of G1EEC (HR 3.51, p=0.014), premenopausal status (HR 3.85, p=0.039), and Hispanic ethnicity (HR 3.45, p=0.017). Pre-treatment IGF1 and IGF2 expression levels were positive predictors of duration of response (HR 0.44 and 0.45, respectively, p&amp;lt;0.05). DSP results revealed that LIUD increased NK cells (log2FC=46.13, FDR=0.004), and lymphocyte cytotoxicity signaling markers GZMB (log2FC=1.06, padj=0.023) and PRF1 (log2FC=1.62, padj=0.004), but NK cells were reduced in relapse lesions (log2FC=-55.96, FDR=0.02) as was PRF1 expression (log2FC=-1.87, padj=0.038). Multiple immune-related pathways (IFNα and IFNγ response, TGFβ signaling) were significantly upregulated in relapse lesions compared to matched pre-treatment lesions (FDR&amp;lt;0.05). IDO1 expression, a marker for immune exhaustion, was upregulated in relapse lesions compared to matched pre-treatment and on-treatment lesions (log2FC=2.56, FDR=0.01). Conclusions: While LIUD for treatment of AH or G1EEC has excellent initial response rates, upfront resistance, and relapse after initial response to LIUD impacts nearly half of patients. Our study shows progestin-related immunomodulatory effects, including increased NK cell infiltration and lymphocyte cytotoxicity. Immune mechanisms for relapse are implicated here, including reversal of progestin-related immunomodulatory effects (decreased NK cell infiltration and lymphocyte cytotoxicity) and increased immune exhaustion (prolonged IFNα and IFNγ response and increased IDO1 expression in relapse lesions). Thus, relieving immune exhaustion may increase durability of response to LIUD for treatment of AH or G1EEC. Citation Format: Mikayla B. Bowen, Brenda Melendez, Qian Zhang, Richard Yang, Bryan Fellman, Barrett Lawson, Naomi Adjei, Joseph Celestino, Tri Nguyen, Khalida Wani, Bhavana Singh, Christof Straub, Liang Zhang, Cheryl Tan, Felicia New, Diana Urbauer, Alexander Lazar, Karen Lu, Jennifer Wargo, Shannon N. Westin, Melinda S. Yates. Immune exhaustion and reversal of progestin-related immune modulation in adaptive resistance to levonorgestrel intrauterine device for treatment of atypical hyperplasia and early endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B024.

Body Mass Index and Levonorgestrel Device Expulsion in Adolescents and Young Adults

Objective: To evaluate the relationship between body mass and levonorgestrel intrauterine device (LNG-IUD) expulsion in adolescents and young adults (AYA). Methods: A retrospective chart review was conducted of nulliparous females aged 10-24 years who had a 52-milligram LNG-IUD placed between November 2017-May 2021 by pediatric and adolescent gynecology providers at a tertiary children's hospital, including those who underwent metabolic and bariatric surgery (MBS). Primary analysis focused on 10-19 year olds as they had comparable anthropometrics (namely BMI percentile [BMIP] as defined by the Centers for Disease Control). Descriptive statistics included means, standard deviations (SD), and ranges for continuous variables counts and percentages for categorical variables. Chi-square or Fisher's exact tests were used to assess associations. Logistic regressions were fit to test the associations between BMIP, MBS, and the odds of expulsion. Results: A total of 588 patients were included in the primary analysis (10-19 years). Mean age was 15.8 years (± 2.0). Using BMIP, 15.5% (n=91) of the sample was overweight and 22.3% (n=131) had obesity. Within 12 months, 33 patients (5.6%) experienced expulsion. Every one-unit increase in BMIP was associated with a 3% increase in the odds of expulsion (p=.008), and each increase in BMIP category (e.g. overweight vs average/underweight) was significantly associated with increased odds of expulsion (OR=2.77-4.28). Patients who had LNG-IUD placement during MBS (n=43) had higher odds of expulsion (OR=3.23, p=.024) than other patients. Conclusions: AYA with higher BMIP and/or who undergo MBS are at increased risk of LNG-IUD expulsion within one year of placement.

Longitudinal impact of a residency-based postplacental levonorgestrel intrauterine device insertion program: Expulsion rates in years 1, 2, and 3

ObjectiveTo evaluate expulsion rates in the first 3 years of an academic postplacental levonorgestrel intrauterine device (LNG-IUD) insertion program. Study designRetrospective case series, January 2016 to December 2018. We measured LNG-IUD expulsion rates by 12 weeks postpartum. ResultsOf 235 LNG-IUD insertions, in years 1, 2, and 3, expulsion rates were 11/39 (28%), 9/94 (10%), and 15/102 (15%) (p = 0.03). After vaginal delivery, manual insertion was associated with a higher expulsion rate than ring-forceps (10/28 [36%] vs 17/105 [16%], p = 0.04). ConclusionsLNG-IUD expulsion rates decreased after program year 1, suggesting program maturity may be associated with a lower expulsion risk.

Uptake, discontinuation, and continuation rate of long-acting contraceptive methods when offered at no cost in Campinas, Brazil

ObjectivesThis study aimed to compare the uptake, reasons for discontinuation, continuation, and satisfaction of long-acting contraceptive methods (LARC) when offered at no cost in Campinas, Brazil. Study designThis was a prospective cohort study conducted at University of Campinas, Campinas, São Paulo, Brazil, including women aged 18 to 48 years, who adopted one of three methods. Participants underwent telephone follow-up every 3 months for up to 24 months after insertion. Satisfaction was assessed at the end of 2 years of use through the Likert scale. ResultsWe invited 1222 women, and among the 971 women who volunteered to participate in follow-up, 414 (42.6%) chose the levonorgestrel 52-mg intrauterine device (IUD), 358 (36.9%) chose the etonogestrel (ENG) implant, and 199 (20.5%) chose the TCu380A IUD. Discontinuation due to bothersome bleeding was higher among users of the ENG implant (10/358; 2.4%) and the TCu380A IUD (32/199; 8.9%), and expulsion was higher for the TCu380A IUD (30/199; 15.1%). Women continued at 24 months were 340/414 (82.1%), 270/358 (75.4%), and 119/199 (59.8%) among users of the levonorgestrel 52-mg IUD, ENG implant, and TCu380A IUD, respectively. The users of the levonorgestrel 52-mg IUD (301/339, 88.8%), the ENG-implant (222/270, 82.2%), and the TCu380A IUD (105/119, 88.2%) were satisfied or very satisfied by 24 months of follow-up. ConclusionsThe three LARC methods had great uptake, high continuation, and discontinuation due to bothersome bleeding was higher among users of the ENG implant and the TCu380A IUD, and expulsion was higher for the TCu380A IUD compared to the 52-mg levonorgestrel IUD. Most of the participants reported being very satisfied. ImplicationsWhen the LARC methods were offered at no cost in a Brazilian public clinic the uptake, satisfaction and continuation were high by 24 months after device placement, and high level of satisfaction was reported by most of the participants.

Sexual and reproductive health and rights of migrant women attending primary care in England: A population-based cohort study of 1.2 million individuals of reproductive age (2009–2018)

BackgroundEvidence on the sexual and reproductive health and rights (SRHR) of migrants is lacking globally. We describe SRHR healthcare resource use and long-acting reversible contraceptives (LARCs) prescriptions for migrant versus non-migrant women attending primary care in England (2009–2018). MethodsThis population-based observational cohort study, using Clinical Practice Research Datalink (CPRD) GOLD, included females living in England aged 15 to 49. Migration was defined using a validated codelist. Rates per 100 person years at risk (pyar) and adjusted rate ratios (RRs) were measured in migrants versus non-migrants for consultations related to all-causes, six exemplar SRHR outcomes, and LARC prescriptions. Proportions of migrants and non-migrants ever prescribed LARC were calculated. FindingsThere were 25,112,116 consultations across 1,246,353 eligible individuals. 98,214 (7.9 %) individuals were migrants. All-cause consultation rates were lower in migrants versus non-migrants (509 vs 583/100pyar;RR 0.9;95 %CI 0.9–0.9), as were consultations rates for emergency contraception (RR 0.7;95 %CI 0.7–0.7) and cervical screening (RR 0.96;95 %CI 0.95–0.97). Higher rates of consultations were found in migrants for abortion (RR 1.2;95 %CI 1.1–1.2) and management of fertility problems (RR 1.39;95 %CI 1.08–1.79). No significant difference was observed for chlamydia testing and domestic violence. Of 1,205,258 individuals eligible for contraception, the proportion of non-migrants ever prescribed LARC (12.2 %;135,047/1,107,894) was almost double that of migrants (6.91 %;6,728/97,364). Higher copper intrauterine devices prescription rates were found in migrants (RR 1.53;95 %CI 1.45–1.61), whilst hormonal LARC rates were lower for migrants: levonorgestrel intrauterine device (RR 0.63;95 %CI 0.60–0.66), subdermal implant (RR 0.72;95 %CI 0.69–0.75), and progesterone-only injection (RR 0.35;95 %CI 0.34–0.36). InterpretationHealthcare resource use differs between migrant and non-migrant women of reproductive age. Opportunities identified for tailored interventions include access to primary care, LARCs, emergency contraception and cervical screening. An inclusive approach to examining health needs is essential to actualise sexual and reproductive health as a human right.

Intrauterine devices are a safe form of contraception in users with solid organ transplantation: A single‐center experience

AbstractPatients who undergo organ transplantation are advised to use contraception for health optimization, yet limited data exists on safe contraceptive options for this population. This study investigates the infection risk of intrauterine devices (IUDs) in patients who have received a solid organ transplant by evaluating the incidence of pelvic inflammatory disease (PID). We performed a retrospective chart review of subjects with a solid organ transplant who used an IUD between the years of January 2007 to February 2021. We included subjects ages 22–55 years at the time of IUD placement. We abstracted demographic information, transplant type, IUD type, immunosuppressive medications, screening for sexually transmitted infections, and diagnosis of PID. We identified 29 subjects that met the inclusion criteria. Six subjects had a copper IUD (21%) and 23 had a levonorgestrel IUD (79%). The most common organ transplanted was a kidney (n = 10) and liver (n = 10) while five subjects had multiple organs transplanted. Twenty‐five (86.2%) subjects took immunosuppressive medications at the time of IUD insertion. Twenty‐four (82.8%) patients had their IUD placed after transplantation. The average time of IUD use was 2.5 years. . In our study of IUD use in patients with solid organ transplantation, no patients developed PID. IUDs are a safe contraceptive option for immunosuppressed transplant patients. image

Progestins as a Contributing Factor to Hepatocellular Adenoma: A Case Series and Literature Review

Study objectiveTo explore the role of progestins as potential contributing factors for the development of hepatocellular adenoma (HA). MethodsWe describe three cases of adolescents and young adults who developed HA while on norethindrone (NET), and their management. In addition, we provide a comprehensive literature review on the association of progestins and HA. ResultsSince 1983, 16 cases of HA in patients on progestins have been reported. Ten patients were on norethindrone (NET), and five on a prodrug of norethindrone (four on norethindrone acetate (NETA) and one on lynestrenol). One individual had a norgestrel implant. Eight subsequently ceased all hormones: four experienced a size reduction and three had complete resolution of their HA. Among our patients, one ceased NET and instead had a levonorgestrel intrauterine device inserted and another swapped from NET to oral medroxyprogesterone acetate: both experienced complete resolution of their HA. The third ceased NET and underwent a hysterectomy, with size reduction of her HA. ConclusionThese cases and the literature review suggest an association between progestin exposure, in particular NET and its prodrugs, and the development of HA. The pathophysiology is unknown but may include peripheral conversion of NET and NETA to ethinyl estradiol or a specific action of 19-nortestosterone derivatives on hepatocytes, especially those with higher systemic doses compared to the levonorgestrel-IUD. There are no case reports relating to other forms of progestins such as 17-hydroxyprogesterone, which may be important when considering alternative therapeutic options in females requiring effective menstrual management who have comorbidities.

Does the 52-mg levonorgestrel intrauterine device have the same efficacy as the copper intrauterine device when used for postcoital (“emergency”) contraception?

Does the 52-mg levonorgestrel intrauterine device have the same efficacy as the copper intrauterine device when used for postcoital (“emergency”) contraception?

Clinical Efficacy, Pharmacokinetics, and Safety of the Available Medical Options in the Treatment of Endometriosis-Related Pelvic Pain: A Scoping Review.

In this scoping review, we sought to identify published studies evaluating the drugs currently used in the treatment of endometriosis-related pelvic pain, with reflection on their chemical properties, pharmacokinetics, safety profile, and clinical efficacy. A literature search was conducted with the use of the PubMed and EMBASE electronic databases, focusing on identifying articles published in English between January 1990 and 2023. Based on the included studies, current therapy options for the treatment of endometriosis-related pain identified and reviewed in this article were: (1) non-steroidal anti-inflammatory drugs; (2) combined oral contraceptive (COCs); (3) progestins; (4) gonadotropin-releasing hormone agonists and antagonists; (5) aromatase inhibitors (AIs); (6) selective estrogen and progesterone receptor modulators; and (7) levonorgestrel-intrauterine device. Based on the published evidence, clinicians should consider NSAIDs, COCs, and progestins as the first-line medical therapies. Compared with second-line options, such as GnRH agonists/antagonists or AIs, the abovementioned first-line options are well tolerated, efficacious, and exhibit lower overall price. Future research priorities should be to identify novel target therapies and to evaluate the effects of available drugs through different routes of administration.

Disparities in oncofertility referral, treatment utilization, and fertility outcomes among women with atypical hyperplasia or early endometrioid endometrial cancer treated with the levonorgestrel intrauterine device (2228)

Disparities in oncofertility referral, treatment utilization, and fertility outcomes among women with atypical hyperplasia or early endometrioid endometrial cancer treated with the levonorgestrel intrauterine device (2228)

Predictors of long-term response in prospective phase II trial of levonorgestrel intrauterine device for atypical hyperplasia and early endometrial cancer (1247)

Predictors of long-term response in prospective phase II trial of levonorgestrel intrauterine device for atypical hyperplasia and early endometrial cancer (1247)

Comparison of Mirena and Liletta levonorgestrel intrauterine device for the treatment of endometrial intraepithelial neoplasia and low risk early-stage endometrial cancer (1193)

Comparison of Mirena and Liletta levonorgestrel intrauterine device for the treatment of endometrial intraepithelial neoplasia and low risk early-stage endometrial cancer (1193)

Changes in hair cortisol concentration in intrauterine device initiators: A prospective cohort study

ObjectivesPrior studies found increased hair cortisol concentration (a surrogate marker for hypothalamic-pituitary-adrenal axis activation) in users of the levonorgestrel intrauterine device (LNG 52 mg IUD). We evaluated change in hair cortisol and psychometric tests in women initiating a copper (CuT380 IUD) or LNG 52 mg IUD. Study designWe prospectively enrolled healthy women initiating an LNG 52 mg IUD or CuT380 IUD. Participants provided hair and blood samples and completed psychometric inventories (Patient Health Questionnaire-9, Positive and Negative Affect Schedule, and Psychological General Well-Being Index) after IUD insertion and at 6 and 12 months. We used liquid chromatography with tandem mass spectrometry to measure hair cortisol concentrations. We compared hair cortisol concentrations and psychometric test changes from baseline to 6 and 12 months using independent two-sample t tests. ResultsWe enrolled 39 of our targeted 86 participants (LNG 52 mg IUD 26, CuT380 IUD 13). Thirty-eight subjects (LNG 52 mg IUD 25, CuT380 IUD 13) completed 6 months of follow-up. We found no difference between cohorts in the mean change in hair cortisol concentrations at 6 months (LNG 52 mg IUD n = 21 [−0.01 pg/mg (95% CI −1.26, 1.23); CuT380 IUD n = 13 [−1.31 pg/mg (−3.36, 0.73)]). While psychometric inventory results remained within normal ranges, LNG 52 mg IUD users reported a trend toward more favorable changes over time. ConclusionsWe did not find clinically important differences in hair cortisol concentrations following initiation of a CuT380 IUD or LNG 52 mg IUD; psychometric inventories demonstrated no adverse effect of hormonal IUDs on mood. ImplicationsOur findings of similar hair cortisol concentrations following the initiation of either the LNG 52 mg IUD or CuT380 IUD suggest that hormonal IUDs do not increase cortisol concentrations or alter stress reactivity, and favorable effects on psychometric inventories provide further reassurance that the LNG 52 mg IUD has no adverse impact on mood. Trial registration numberClinicalTrials.gov NCT03499379

Levonorgestrel intrauterine device and depression: A Swedish register-based cohort study

BackgroundThe levonorgestrel intrauterine device (LNG-IUD) is traditionally viewed as a safe contraceptive with limited systemic effects. However, three recent studies have indicated an increased risk of depression subsequent to LNG-IUD use. This study aimed to examine the potential associated risk between LNG-IUDs and depression, and determine which women are at risk. MethodsThis longitudinal cohort study was based on data from seven Swedish national population-based registers. All Nordic-born women aged 15–24 years residing in Sweden between 2010 and 2017 were included. Cox regression was implemented to estimate the adjusted hazard ratio (AHR) for developing depression, defined as first depression diagnosis or redeemed prescription for antidepressant treatment. We adjusted for age, education level, parental country of origin, parental psychiatric health, previous hormonal contraceptive use and medical indications for contraceptive use. Findings703,157 women were included in the analysis. The LNG-IUD was associated with 57 % increased risk of depression [AHR 1.57 (95 % CI 1.51–1.64)]. The greatest risk increase was seen in adolescent women [AHR 2.57, (95 % CI 2.36–2.80)] and women who used the LNG-IUD as their first hormonal contraceptive method [AHR 1.63, (95 % CI 1.50–1.78)]. The risk of depression decreased at the end of study period [AHR 1.43, (95 % CI 1.36–1.51)], once the LNG-IUD became more widely accessible among nulliparous women. ConclusionsAdolescent women who use the LNG-IUD as their first-ever hormonal contraceptive are at increased risk of developing depression. However, additional impact from confounding factors is likely as risk estimates decreased over the study period. Further research needs to determine if there is a causal relationship between LNG-IUDs and depression.

Comparison of Mirena and Liletta levonorgestrel intrauterine devices for the treatment of endometrial intraepithelial neoplasia and grade 1 endometrioid endometrial cancer

ObjectiveCurrent standard nonsurgical management of endometrial intraepithelial neoplasia (EIN) and grade 1 endometrioid endometrial cancer (g1EEC) is the Mirena levonorgestrel intrauterine device (M−IUD). This retrospective study was designed primarily to determine noninferiority of the Liletta IUD (L-IUD) for pathologic regression of EIN and g1EEC compared to the M−IUD at 6 months of continuous use. Secondary objectives include to determine noninferiority as above at 3, 9, and 12 months of continuous use and to identify factors including DNA mismatch repair (MMR) status associated with pathologic regression after LNG-IUD use. MethodsA retrospective observational study was performed with patients treated for EIN or g1EEC and managed continuously with M- or L-IUD. Patients with recent (within 6 months) or concurrent progesterone use were excluded. For the EIN group, the noninferiority margin of odds ratio was predetermined to be 0.58, and for the g1EEC group it was 0.64. Results62 patients from an academic center and a safety-net hospital were identified with continuous M−IUD (n = 44) or L-IUD (n = 18) use for EIN or g1EEC. 85% of patients treated with L-IUD were from a safety-net hospital, which had 63% with public insurance. At 3/6/9 months, 54/71/73% of patients with M−IUD and 80/83/100% with L-IUD had pathologic regression of EIN (95% confidence interval of estimated odds ratio 1.00–2.07/0.84–2.03/0.69–2.10). Lifetime smoking status, not MMR status, was significantly associated with pathologic regression. ConclusionsL-IUD is an effective fertility-sparing treatment for EIN. L-IUD is noninferior to M−IUD for pathologic regression of EIN after 3,6, and 9 months. Further larger studies are warranted to validate findings in EIN and g1EEC.