Associations between common contraceptive use and circulating inflammatory biomarkers.

Ovarian cancer incidence has declined in recent decades, due in part to oral contraceptive (OC) use and tubal ligation. However, intrauterine device (IUD) use has increasingly replaced OC use. As ovarian cancer is an inflammation-related disease, we examined the association of OC use, IUD use, and tubal ligation with plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor α receptor 2 (sTNFR2), in the Nurses' Health Study (NHS) and NHSII. After adjusting for reproductive, hormonal, and lifestyle factors, and mutual adjustment for other methods of contraception, there were no differences in inflammatory markers between ever and never use of each method. However, CRP levels decreased from an average 30.4% (-53.6, 4.4) with every 5 years since initial IUD use (P-trend=0.03), while CRP increased an average 9.9% (95% CI: 5.7, 14.3) with every 5 years of use of OC (P-trend<0.0001) as well as differences by BMI and menopausal status. Our results suggest IUD use and tubal ligation are not associated with higher circulating inflammatory markers long term, although long duration of OC use may increase generalized inflammation, which may in part explain why its protective effect wanes over time.

Hormonal contraceptives and behavior: Updating the potent state of the nascent science.

Hundreds of millions of people worldwide use hormonal contraceptives (HCs), which have been an essential part of women's reproductive health care for decades. Throughout that time, however, research on the neural and behavioral consequences of HCs was minimal and plagued by poor methodology. HC effects - and users - were assumed to be homogenous. Fortunately, there has been a recent upswell in the number and quality of investigations, affording tentative conclusions about the roles of HCs in spatial cognition and mental health, particularly depression. Thus, this paper leverages findings from the past few years to highlight the heterogeneous aspects of use that seem to matter for behavior - ranging from variation in hormonal contraceptive formulations and routes of administration to individual differences among users linked to age and reproductive health history. This paper closes with five tips for future research that will help capture and clarify heterogeneity in potential relations between HCs and behavior, namely data collection, regional access, lifespan factors, gender, and collaboration. HCs are sociopolitically provocative and research on their potential behavioral neuroendocrine impacts is becoming increasingly popular. It is, therefore, imperative for scientists to conduct replicable and robust empirical investigations, and to communicate findings with the nuance that the heterogeneity among users and effects requires.

Hormone-related side effects in new users of a levonorgestrel 52-mg intrauterine device.

BACKGROUND: Although the levonorgestrel 52 mg intrauterine device is locally active and has low systemic hormone exposure, hormonal intrauterine device users sometimes report hormone-related side effects. OBJECTIVE: Evaluate hormone-related adverse event rates among all participants and compare these among those who used combined hormonal or no hormonal contraception in the month before enrollment. STUDY DESIGN: A total of 1714 women aged 16 to 45 years old received a levonorgestrel 52 mg intrauterine device in a multicenter phase 3 trial to evaluate contraceptive efficacy and safety for up to 10 years. This analysis evaluated a subset of participants who used combined hormonal or no hormonal contraception in the month prior to device placement. We assessed all nonexpulsion, nonbleeding-related events with ≥1% incidence at 180 days with a plan to include weight increase regardless of incidence; we excluded events considered nonhormonal. We computed 180-day side effect frequency rates based on the number of days a side effect was reported during the study period. We created a multivariable model for side effect incidence at 180 days based on age, race, ethnicity, body mass index at enrollment, parity, and contraception use in the month before enrollment. For those side effects with a P value <.2 on univariate comparison between combined hormonal and no hormonal contraception users, we secondarily evaluated 360-day event rates. RESULTS: Overall, 644 participants used combined hormonal contraception (primarily oral [n=499, 77.5%]) and 855 used no hormonal method before intrauterine device placement. Individual side effect rates over the first 180 days did not differ between prior combined hormonal and no hormonal contraception users except for acne (84 [13.0%] vs 73 [8.5%], respectively), P=.006, odds ratio 1.61 (95% confidence interval 1.15-2.24). However, this association was weaker after adjustment for age, race, ethnicity, obesity status, and parity (adjusted odds ratio 1.40, 95% confidence interval 0.99-1.98) At 360 days, prior combined hormonal contraception users were more likely to report acne (101 [15.7%] vs 91 [10.6%], respectively, P=.005) and orgasm/libido problems (20 [3.1%] vs 12 [1.4%], respectively, P=.03). Over the first 180 days, all side effects other than acne were reported in less than 3% of days; acne was reported an average of 13 days (7.4%) per prior combined hormonal contraception user and 9 days (5.0%) per prior nonhormonal contraception user (P<.0001). Discontinuation for evaluated side effects occurred in 83 (5.5%) participants with no difference between those who used combined hormonal (36 [5.6%]) or no hormonal contraception (47 [5.5%], P=1.0) before study entry. CONCLUSION: Using combined hormonal contraception prior to levonorgestrel 52 mg intrauterine device placement is weakly associated with reporting hormonally related side effects like acne. Only a small percentage of levonorgestrel 52 mg intrauterine device users experienced potentially hormone-related side effects during the initial 6 months of use that resulted in discontinuation.

A 52-mg levonorgestrel-releasing intrauterine system vs bipolar radiofrequency nonresectoscopic endometrial ablation in women with heavy menstrual bleeding: long-term follow-up of a multicenter randomized controlled trial.

BACKGROUND: The symptom of heavy menstrual bleeding has a substantial impact on professional, physical, and social functioning. In 2021, results from a randomized controlled trial comparing a 52-mg levonorgestrel-releasing intrauterine system and radiofrequency nonresectoscopic endometrial ablation as treatments for women with heavy menstrual bleeding were published. Both treatment strategies were equally effective in treating heavy menstrual bleeding during 2-year follow-up. However, long-term results are also relevant for both patients and healthcare providers. OBJECTIVE: This study aimed to assess long-term differences in reintervention risk and menstrual blood loss in women with the symptom of heavy menstrual bleeding treated according to a strategy starting with a 52-mg levonorgestrel-releasing intrauterine system or radiofrequency nonresectoscopic endometrial ablation. STUDY DESIGN: This study was a long-term follow-up study of a multicenter randomized controlled trial (MIRA trial), in which women were allocated to either a 52-mg levonorgestrel-releasing intrauterine device (n=132) or radiofrequency nonresectoscopic endometrial ablation (n=138). Women from the original trial were contacted to fill out 6 questionnaires. The primary outcome was the reintervention rate after allocated treatment. Secondary outcomes included surgical reintervention rate, menstrual bleeding measured by the Pictorial Blood Loss Assessment Chart, (disease-specific) quality of life, sexual function, and patient satisfaction. RESULTS: From the 270 women who were randomized in the original trial, 196 (52-mg levonorgestrel-releasing intrauterine system group: n=94; radiofrequency nonresectoscopic endometrial ablation group: n=102) participated in this long-term follow-up study. Mean follow-up duration was 7.4 years (range, 6-9 years). The cumulative reintervention rate (including both medical and surgical reinterventions) was 40.0% (34/85) in the 52-mg levonorgestrel-releasing intrauterine system group and 28.7% (27/94) in the radiofrequency nonresectoscopic endometrial ablation group (relative risk, 1.39; 95% confidence interval, 0.92-2.10). The cumulative rate of surgical reinterventions only was significantly higher among patients with a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system compared with radiofrequency nonresectoscopic endometrial ablation (35.3% [30/85] vs 19.1% [18/94]; relative risk, 1.84; 95% confidence interval, 1.11-3.10). However, the hysterectomy rate was similar (11.8% [10/94] in the 52-mg levonorgestrel-releasing intrauterine system group and 18.1% [17/102] in the radiofrequency nonresectoscopic endometrial ablation group; relative risk, 0.65; 95% confidence interval, 0.32-1.34). Most reinterventions occurred during the first 24 months of follow-up. A total of 171 Pictorial Blood Loss Assessment Chart scores showed a median bleeding score of 0.0. No clinically relevant differences were found regarding quality of life, sexual function, and patient satisfaction. CONCLUSION: The overall risk of reintervention after long-term follow-up was not different between women treated according to a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system and those treated using a strategy starting with radiofrequency nonresectoscopic endometrial ablation. However, women allocated to a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system had a higher risk of surgical reintervention, which was driven by an increase in subsequent endometrial ablation. Both treatment strategies were effective in lowering menstrual blood loss over the long term. The results of this long-term follow-up study can support physicians in optimizing the counseling of women with heavy menstrual bleeding, thus promoting informed decision-making regarding choice of treatment.

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden.

BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. OBJECTIVE: We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. STUDY DESIGN: A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. RESULTS: The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years. CONCLUSION: The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

Fertility-preserving treatment for stage IA endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: The increasing use of fertility-preserving treatments in reproductive-aged patients with early-stage endometrial cancer necessitates robust evidence on the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device. We conducted a systematic review and meta-analysis to examine the outcomes following these 2 primary progestin-based therapies in reproductive-aged patients with early-stage endometrial cancer. DATA SOURCES: We conducted a systematic review of observational studies and randomized controlled trials following the Cochrane Handbook guidance. We conducted a literature search of 5 databases and 1 trial registry from inception of the study to April 16, 2024. STUDY ELIGIBILITY CRITERIA: Studies reporting complete response within 1 year in reproductive-aged patients with clinical stage IA endometrioid cancer undergoing progestin therapy treatment were included. We used data from both observational and randomized controlled studies. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary exposure assessed was the type of progestational treatment (oral progestins or LNG-IUD). The primary outcome was the pooled proportion of the best complete response (CR) within 1 year of primary progestational treatment. We performed a proportional meta-analysis to estimate the treatment response. Sensitivity analyses were performed by removing studies with extreme effect sizes or removing grade 2 tumors. The risk of bias was assessed in each study using the Joanna Briggs Institute critical appraisal checklist. RESULTS: Our analysis involved 754 reproductive-aged patients diagnosed with endometrial cancer, with 490 receiving oral progestin and 264 receiving levonorgestrel-releasing intrauterine device as their primary progestational treatment. The pooled proportion of the best complete response within 12 months of oral progestin and levonorgestrel-releasing intrauterine device treatment were 66% (95% CI, 55-76) and 86% (95% CI, 69-95), respectively. After removing outlier studies, the pooled proportion was 66% (95% CI, 57-73) for the oral progestin group and 89% (95% CI, 75-96) for the levonorgestrel-releasing intrauterine device group, showing reduced heterogeneity. Specifically, among studies including grade 1 tumors, the pooled proportions were 66% (95% CI, 54-77) for the oral progestin group and 83% (95% CI, 50-96) for the levonorgestrel-releasing intrauterine device group. The pooled pregnancy rate was 58% (95% CI, 37-76) after oral progestin treatment and 44% (95% CI, 6-90) after levonorgestrel-releasing intrauterine device treatment. CONCLUSION: This meta-analysis provides valuable insights into the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device treatment within a 12-month timeframe for patients with early-stage endometrial cancer who desire to preserve fertility. These findings have the potential to assist in personalized treatment decision-making for patients.

Immediate vs delayed postpartum insertion of long-acting reversible contraception methods: meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to conduct a meta-analysis of randomized trials comparing the immediate vs delayed provision of long-acting reversible contraceptives in postpartum subjects, focusing on short-interval pregnancies, utilization rates, and adverse events. DATA SOURCES: Cochrane Central, Embase, PubMed, and ClinicalTrials.gov were systematically searched from inception up to December 19, 2023, without filters or language limitation. STUDY ELIGIBILITY CRITERIA: We selected randomized controlled trials assessing the immediate insertion of long-acting reversible contraceptives in women during postpartum period in comparison with the delayed provision. STUDY APPRAISAL AND SYNTHESIS METHODS: We calculated relative risks with 95% confidence intervals to analyze the primary outcome of utilization rates and secondary endpoints, including initiation rates, pregnancy, any breastfeeding, exclusive breastfeeding, and serious adverse events. A random-effects model was employed in the R software. Moreover, we assessed the risk of bias of selected randomized controlled trials using version 2 of the Cochrane Risk of Bias Assessment Tool. RESULTS: We included 24 randomized trials comprising 2507 participants, of whom 1293 (51.6%) were randomized to the immediate insertion. Postpartum women in the immediate group had lower risk of pregnancy (relative risk 0.16; 95% confidence interval 0.04-0.71; P=.02) compared with delayed group, and higher rates of long-acting reversible contraceptives at 6 months of follow-up (relative risk 1.23; 95% confidence interval 1.09-1.37; P<.01). CONCLUSION: Inserting long-acting reversible contraceptives before hospital discharge was associated with a reduction in the risk of pregnancy, and increased rates of its utilization at 6 months of follow-up. This intervention may be an effective contraception strategy for postpartum women.

Mepivacaine instillation for pain reduction during intrauterine device placement in nulliparous women: a double-blinded randomized trial.

BACKGROUND: Fear of pain associated with intrauterine device (IUD) placement has been identified as a significant barrier to the adoption of long-acting reversible contraception, contributing to lower utilization of the most effective reversible contraceptive methods. OBJECTIVE: To assess whether instillation of intrauterine mepivacaine before IUD placement alleviates pain more effectively than a placebo. STUDY DESIGN: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving nulliparous women undergoing IUD placement. An intrauterine instillation of 10 mL of 20 mg/mL mepivacaine or 0.9 mg/mL sodium chloride was administrated through a hydrosonography catheter 2 minutes prior to IUD placement. Pain scores were assessed using a 100 mm visual analog scale (VAS) at prespecified time points. Primary outcome measured the difference in VAS pain scores between the intervention group and the placebo group during IUD placement. Secondary outcomes included VAS pain scores at instillation and 10 minutes after placement, tolerability of the placement pain, as well as acceptability of the analgesia method. RESULTS: We enrolled 151 participants, with 76 assigned to the mepivacaine group and 75 to the placebo group. The mean VAS pain score during IUD placement showed a difference of 13.3 mm (95% confidence interval (CI) 5.75-20.87; P<.001): the mepivacaine group had a mean of 53.9 mm (standard deviation [SD] 22.8), while the placebo group had a mean of 67.2 mm (SD 22.4). After adjusting for each individual provider's impact, the difference in mean pain scores remained statistically significant (12.2 mm 95% CI 4.85-19.62; P<.001). A greater proportion of women in the intervention group reported tolerable pain during placement with 70/75 participants (93.3%) compared to 53/66 participants (80.3%) in the placebo group (P=.021). CONCLUSION: The intrauterine instillation of mepivacaine results in statistically significant reduction in pain score among nulliparous women during IUD placement. Although the precise clinical impact of this pain reduction method remains uncertain, the observed reduction in pain score result in a higher proportion of women reporting tolerable pain. This finding and the high acceptance as a pain reduction method thereby suggests clinical relevance. Intrauterine instillation of mepivacaine is a possible strategy to increase IUD utilization, particularly among nulliparous women who are at high risk of unintended pregnancy.

Placement of an intrauterine device within 48 hours after second-trimester medical abortion: a randomized controlled trial.

BACKGROUND: International guidelines recommend placement of intrauterine devices immediately after second-trimester medical abortion, but evidence concerning the optimal time for intrauterine device placement is lacking from clinical trials. OBJECTIVE: This study aimed to investigate effectiveness, safety, and acceptability of intrauterine device placement within 48 hours, compared with placement at 2 to 4 weeks after second-trimester medical abortion. We hypothesized that intrauterine device placement within 48 hours would be superior compared with placement at 2 to 4 weeks after the abortion, in terms of the proportion of intrauterine device use after 6 months, with maintained safety and acceptability. STUDY DESIGN: In this open-label, randomized, controlled, superiority trial, we recruited participants at 8 abortion clinics in Sweden. Eligible participants were aged ≥18 years, requesting medical abortion with gestation ≥85 days, and opting for use of a postabortion intrauterine device. Participants were randomized (1:1) to intrauterine device placement either within 48 hours of complete abortion (intervention) or after 2 to 4 weeks (control). Our primary outcome was self-reported use of an intrauterine device after 6 months. Secondary outcomes included expulsion rates, pain at placement, adverse events and complications, acceptability, and subsequent pregnancies and abortions. Differences in nonnormal continuous variables were analyzed with the Mann-Whitney U test, and differences in dichotomous variables with the chi-square or Fisher exact tests. A P value <.05 was considered statistically significant. Group differences are presented by modified intention-to-treat and per-protocol analyses. RESULTS: Between January 2019 and June 2022, we enrolled 179 participants, of whom 90 were assigned to the intervention and 89 to the control arm. Enrollment was prematurely stopped after an interim analysis exceeded a predefined intrauterine device expulsion rate of 20%. According to modified intention-to-treat analysis, use of intrauterine device after 6 months was 50.7% (34/67) in the intervention group vs 71.6% (48/67) in the control group (proportion difference, 20.9%; 95% confidence interval, 4.4%-35.9%; P=.02). The intrauterine device expulsion rate was 30.1% (22/73) in the intervention group vs 2.9% (2/70; P<.001) in the control group. Other adverse events were rare and patient acceptability was high in both groups. CONCLUSION: Intrauterine device placement within 48 hours after second-trimester medical abortion was nonsuperior in terms of the proportion of intrauterine device use after 6 months when compared with placement after 2 to 4 weeks. Placement within 48 hours after second-trimester abortion can be used in selected individuals after counseling on expulsion risk.

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

Patients 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.

The suture fixation of the levonorgestrel-releasing intrauterine device with hysteroscope for the treatment of adenomyosis in patients at high risk of device expulsion-a prospective observational study.

BACKGROUND: This study aimed to investigate the safety and efficacy of suture fixation of the levonorgestrel-releasing intrauterine device (LNG-IUD) by hysteroscope for the treatment of adenomyosis in patients at high risk of device expulsion, to provide a viable treatment option for these patients. METHODS: Twenty-one patients with large symptomatic adenomyosis were sewed and fixed with the LNG-IUD in the uterus by hysteroscopy to prevent the device expulsion. RESULTS: In this prospective case series, all 21 patients were successfully sewed and fixed with the LNG-IUD in the uterus by hysteroscopy. The amount of menstruation was significantly decreased and dysmenorrhea was significantly relieved in 3, 6, and 12 months after surgery compared with before surgery. Only one patient underwent a laparoscopic hysterectomy due to dysmenorrhea which was not alleviated one month later. Serious IUD complications including expulsion and perforation were not observed. There was no development of new side effects than LNG-IUD insertion. CONCLUSION: Our findings indicate that suture fixation of the LNG-IUD by hysteroscope is a safe, effective, and minimally invasive surgical procedure to prevent the device expulsion. It is a good solution for the treatment of large symptomatic adenomyosis and has shown to be effective in managing symptoms related to adenomyosis.

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.

BACKGROUND: Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods. METHODS: In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months. RESULTS: We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p <  0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p <  0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p <  0.001 and than DMPA (mean percentage difference - 39.45, p <  0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001). CONCLUSIONS: This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study. ECHO TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users' own circulating sex hormones, both the 'female' and the 'male' sex hormones (androgens). In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.

Prospective Evaluation of Ease and Difficulties of 869 Cases of Intrauterine Devices Removals.

OBJECTIVES: The objective was to describe the ease and difficulty of removing intrauterine devices (IUDs). METHODS: We conducted a prospective study at the University of Campinas (UNICAMP), Faculty of Medical Sciences, UNICAMP. We included women who requested IUD removal. We excluded women with partial IUD expulsion in which the IUD was protruded at the external os. We identified difficult IUD removal when the removal was challenging, including the inability to visualize IUD strings extending from the cervical os. RESULTS: A total of 869 women participated. Women were aged 29.4 ± 8.0 years (mean ± SD; range 14-51) and the duration of IUD use at the time of removal was 4.3 ± 4.2 years. We found that 702 (80.8%) women had visible strings at the external os and the removals were performed at the first attempt without difficulty in 692 (79.6%) participants. The pain was more intense (>4) in cases of difficult removals. After multivariate logistic analysis, difficult removals were associated with users of IUD ≥3 years (3 times higher risk); for each previous cesarean delivery, the risk increased by 1.5 times. CONCLUSIONS: Our study showed that IUD removal is an easy and safe procedure, with only a small proportion of women reporting significant pain with IUD removal.

Association of Intrauterine Device Malposition With Previous Cesarean Delivery and Related Uterine Anatomical Changes.

OBJECTIVES: We sought to determine the association between intrauterine device (IUD) malposition and previous cesarean delivery (CD) and related uterine anatomical changes. METHODS: A retrospective cohort of all persons with an IUD presenting for two- and three-dimensional pelvic ultrasonography over 2 years, for any gynecologic indication, was compiled. IUD malposition was defined as IUD partially or completely positioned outside the endometrial cavity. Uterine position, uterine flexion, and cesarean scar defect (CSD) size were assessed. Patient characteristics and sonographic findings were compared between those with normally positioned and malpositioned IUD. Primary outcome was the rate of IUD malposition in persons with and without a history of CD. Logistic regression analysis was used to control for potential confounders. RESULTS: Two hundred ninety-six persons with an IUD had a pelvic ultrasound, 240 (81.1%) had a normally positioned IUD, and 56 (18.9%) had a malpositioned IUD. The most common location of IUD malposition was low uterine segment and cervix (67.9%). Malpositioned IUD was associated with referral for evaluation of pelvic pain (P = .001). Prior CD was significantly associated with a malpositioned IUD, after adjusting for confounders (aOR 3.50, 95% CI 1.31-9.35, P = .01). Among persons with prior CD, uterine retroflexion and a large CSD were independent risk factors for IUD malposition (aOR 4.1, 95% CI 1.1-15.9, P = .04 and aOR 5.4, 95% CI 1.4-20.9, P = .01, respectively). CONCLUSIONS: Prior CD is associated with significantly increased risk of IUD malposition. Among persons with previous CD, those with a retroflexed uterus and a large CSD are more likely to have a malpositioned IUD.

Patient Barriers to Discontinuing Long-Acting Reversible Contraception.

OBJECTIVES: To describe how frequently a national sample of patients with experience discontinuing or desiring discontinuation of long-acting reversible contraception (LARC) experienced barriers to discontinuation. METHODS: We conducted an online survey of individuals ages 18 to 50 in the United States who had previously used and discontinued or attempted to discontinue LARC. We recruited respondents using the Amazon platform MTurk. Respondents provided demographic information and answered questions regarding their experience discontinuing LARC, including reasons removal was deferred or denied. We analyzed frequency of types of barriers encountered and compared these by demographic factors. RESULTS: Of the 376 surveys analyzed, 99 (26%) described experiencing at least one barrier to removal. Barriers were disproportionately reported by those who had public health insurance, a history of abortion, and a history of birth compared to those who did not report barriers to removal. They also more frequently identified as Latinx, Asian, or Middle Eastern. Most barriers were provider-driven and potentially modifiable. CONCLUSIONS FOR PRACTICE: Barriers to LARC discontinuation are common and may be provider- or systems-driven. Providers should be mindful of biases in their counseling and practices to avoid contributing to these barriers.

Bladder Stone Formation due to Intravesical Migration of the Intrauterine Device: A Report of 2 Cases.

INTRODUCTION: Approximately 5% of bladder stones occur in women and are usually associated with foreign bodies or urinary stasis. Spontaneous migration of the intrauterine device (IUD) into the bladder is a rare complication. In this report, we present 2 cases of migrated IUD who had undergone surgery at our clinic due to bladder stones. CASE PRESENTATIONS: We detected migrated IUDs into the bladder in 2 female patients, aged 37 and 56 years, who presented with lower urinary tract symptoms and urinary tract infection. In the first case, endoscopic cystolithotripsy was performed, and the IUD was removed without complications. In the second case, the IUD could not be removed endoscopically since it had fractionally invaded the bladder wall, and the IUD was removed without complications by performing an open cystolithotomy. CONCLUSION: A comprehensive gynecological history should be taken from every female patient presenting with recurrent urinary tract infections and lower urinary tract symptoms. If these patients have a history of IUD placement, the possibility of the intravesical migration of this device should be kept in mind.

Awareness, attitude, and acceptance of post placental intra uterine contraceptive device (PPIUCD) among women in Jordan.

AIM: To assess the awareness, attitude, and acceptance of the Post Placental Intra Uterine Contraceptive Device (PPIUCD) as an immediate long-acting contraceptive method among Jordanian women. METHODS: A cross-sectional observational study was conducted at King Abdulla University Hospital among women attending antenatal clinics after 20 weeks of gestation between January 2020 and May 2021. One thousand and 30 women had completed a structured questionnaire in Arabic. RESULTS: Only 41.4% of the sample was aware of the PPIUCD. The attitude toward PPIUCD after a brief introduction was 56.3%. Women who had used interval IUCD were 5.82 times more likely to express a positive attitude toward PPIUCD, while postgraduate women were 1.35 times more prone to show the same attitude. Only 34% accepted PPIUCD if offered, whereas the main barrier to acceptance was the false fear of extra complications in 34.5% of the sample. The rate of unintended current pregnancy was 35.8%, where 53.4% were using natural methods. CONCLUSIONS: The rate of awareness of PPIUCD is low among women in Jordan. Antenatal introduction encourages attitude toward PPIUCD.

Evaluating resectoscopy and the levonorgestrel intrauterine system for intermenstrual bleeding associated with cesarean scar defects: A retrospective study of treatment outcomes.

AIM: To compare and evaluate the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUD) and resectoscopy remodeling procedure for intermenstrual bleeding associated with previous cesarean delivery scar defect (PCDS). METHODS: A retrospective comparative study was conducted on patients with PCDS receiving LNG-IUD (levonorgestrel 20 µg/24 h, N = 33) or resectoscopy remodeling (N = 27). Treatment outcomes were compared over 1, 6, and 12 months. Outcomes in patients with a retroverted or large uterus size, defect size, and local vascularization also were evaluated. RESULTS: At 12 months post-treatment, there were no significant differences between groups in efficacy rate; however, the reduction of intermenstrual bleeding days was higher in the LNG-IUD group than in the resectoscopy group (13.6 vs. 8.5 days, p = 0.015). Within the first year, both groups experienced a reduction in bleeding days, but the decrease was greater in the LNG-IUD group. Individuals exhibiting increased local vascularization at the defect site experienced more favorable outcomes in the LNG-IUD group than the resectoscopy group (p = 0.016), and who responded poorly tended to have a significantly larger uterus in the LNG-IUD group (p = 0.019). No significant differences were observed in treatment outcomes for patients with a retroverted uterus or large defect in either group. CONCLUSIONS: Our findings support that the LNG-IUD is as effective as resectoscopy in reducing intermenstrual bleeding days associated with PCDS and can be safely applied to patients without recent fertility aspirations. Patients with increased local vascularization observed during hysteroscopy may benefit more from LNG-IUD intervention than resectoscopy.

Effects of intrauterine device use on attack frequency and severity in woman of reproductive age with familial Mediterranean fever.

AIM: Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. There are known triggers to initiate an FMF attack, yet potential effects of intrauterine devices (IUD) in women of reproductive age have not been evaluated before. METHOD: Consecutive female patients with FMF who ever used IUD over the age of 18 were enrolled. Female patients with FMF were sub grouped according to the type of IUD they use. FMF attack frequency, severity, duration, presence of dysmenorrhea, severity of dysmenorrhea, having attacks during menstruation before and after IUD use were questioned. Demographic and clinical data were collected from hospital database. RESULTS: When all patients with IUD use were evaluated, it was found that the frequency of attacks increased after IUD insertion at 3rd and 12th months (median [min-max] attack frequency at 3rd month, 1 (0-3) vs 1 (0-6), p = 0.002, median [min-max] attack frequency at 12th month, 2 (0-12) vs 3.5 (0-18), p = 0.028). Attack severity measured by VAS pain was also significantly increased. Attack duration and menstrual pain was similar before and after IUD use. Attack frequency at 3rd and 12th months, attack severity and menstrual pain was all increased significantly in Cu-IUD users, whereas none of these parameters deteriorated in LNG-IUD group. CONCLUSION: IUD use, especially Cu-IUD, may increase the frequency and severity of attacks in female patients with FMF. Clinicians may benefit from considering LGN-IUD if IUDs are preferred as contraception in women of childbearing age with FMF.

Increasing utilization of intrauterine device insertion at hysteroscopic endometrial evaluation for patients with endometrial hyperplasia.

PURPOSE: To examine the utilization and characteristics related to the use of hysteroscopy at the time of endometrial evaluation for endometrial hyperplasia in the outpatient surgery setting. METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample. The study population was 3218 patients with endometrial hyperplasia who underwent endometrial evaluation from January 2016 to December 2019. Performance and clinical characteristics of hysteroscopic endometrial evaluation were assessed with multivariable binary logistic regression models. RESULTS: A total of 2654 (82.5%) patients had hysteroscopic endometrial tissue evaluation. Patients with postmenopausal bleeding, heavy menstrual bleeding, and polycystic ovary syndrome were more likely to undergo hysteroscopic endometrial evaluation in multivariable analysis (all, adjusted-P < 0.001). Uterine injury occurred in 4.9 per 1000 hysteroscopic endometrial evaluations; none had uterine injury in the non-hysteroscopy cohort. Among the 2654 patients who had hysteroscopic endometrial evaluation, 106 (4.0%) patients had intrauterine device insertion at surgery, and the utilization increased from 2.9 to 5.8% during the study period (P-trend < 0.001). Younger age, more recent year surgery, and obesity were independently associated with increased utilization of intrauterine device insertion at hysteroscopic endometrial evaluation (all, adjusted-P < 0.05). Among 2023 reproductive-age patients with endometrial hyperplasia, 1666 (82.4%) patients underwent hysteroscopic endometrial evaluation. On multivariable analysis, patients with heavy menstrual bleeding were more likely to have hysteroscopic endometrial evaluation (adjusted-P < 0.05). Intrauterine device insertion increased from 3.7% in 2016 to 8.0% in 2019 (P-trend = 0.007). CONCLUSION: This nationwide analysis suggests that the insertion of intrauterine devices at the time of hysteroscopic endometrial tissue evaluation for endometrial hyperplasia is increasing among reproductive-age population.