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 16-45 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 non-expulsion, non-bleeding-related events with ≥1% incidence at 180 days with a plan to include weight increase regardless of incidence; we excluded events considered non-hormonal. 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 <0.2 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 IUD 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%] versus 73 [8.5%], respectively), p=0.006, OR 1.61 (95% CI 1.15-2.24). However, this association was weaker after adjustment for age, race, ethnicity, obesity status, and parity (aOR 1.40, 95% CI 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=0.005) and orgasm/libido problems (20 [3.1%] vs. 12 [1.4%], respectively, p=0.03). 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 non-hormonal contraception user (p<0.0001). 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. CONCLUSIONS: Using combined hormonal contraception prior to levonorgestrel 52 mg intrauterine device placement is only 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.

Using transvaginal ultrasounds for the identification of follicle-like structures ≥10 mm in a multi-center randomized contraceptive clinical trial of three 84-day oral ulipristal acetate regimens.

PURPOSE: We examine the use of transvaginal sonography in imaging ovarian follicles among non-pregnant reproductive-aged women enrolled in a contraceptive clinical trial. METHODS: Ten sites conducted a clinical trial comparing three oral ulipristal acetate regimens for ovulation inhibition. Enrollees underwent twice weekly transvaginal sonography and hormonal blood testing throughout treatment and until the second menses post-treatment. The primary outcome of the present analysis was success in identifying follicles ≥10 mm in a subgroup of sonograms performed at times of likely follicular activity (estradiol <100 pg/ml and progesterone >3 ng/ml). Secondarily, an overall analysis assessed all sonograms regardless of timing. RESULTS: At times of likely follicular activity, 135 women underwent 969 sonograms. The proportion of sonograms without follicles ≥10 mm ranged from 8.3% to 46.3% when stratified by site (p = .01). The odds of no follicle among higher-body mass index (BMI) women were 1.91 times those among lower-BMI women after controlling for site and treatment arm (95% CI: 1.13, 3.22). Results were similar for the overall population. CONCLUSION: Sonographers were less likely to identify follicles for higher-BMI women and results varied by site. Machine quality slightly impacted sonogram results, but did not sufficiently explain site differences.

The progesterone-receptor modulator, ulipristal acetate, drastically lowers breast cell proliferation.

PURPOSE: The proliferation of breast epithelial cells increases during the luteal phase of the menstrual cycle, when they are exposed to progesterone, suggesting that ulipristal acetate, a selective progestin-receptor modulator (SPRM), may reduce breast cell proliferation with potential use in breast cancer chemoprevention. METHODS: Women aged 18-39 were randomized 1:1 to ulipristal 10-mg daily or to a combination oral contraceptive (COC) for 84 days. Participants underwent a breast biopsy and breast MRI at baseline and at end of study treatment. Proliferation of breast TDLU cells was evaluated by Ki67 immunohistochemical stain. We evaluated the breast MRIs for background parenchymal enhancement (BPE). All slides and images were masked for outcome evaluation. RESULTS: Twenty-eight treatment-compliant participants completed the study; 25 of whom had evaluable Ki67 results at baseline and on-treatment. From baseline to end of treatment, Ki67 % positivity (Ki67%+) decreased a median of 84% in the ulipristal group (N = 13; 2-sided p (2p) = 0.040) versus a median increase of 8% in the COC group (N = 12; 2p = 0.85). Median BPE scores decreased from 3 to 1 in the ulipristal group (p = 0.008) and did not decrease in the COC group. CONCLUSION: Ulipristal was associated with a major decrease in Ki67%+ and BPE. Ulipristal would warrant further investigation for breast cancer chemoprevention were it not for concerns about its liver toxicity. Novel SPRMs without liver toxicity could provide a new approach to breast cancer chemoprevention. TRIAL REGISTRATION: NCT02922127, 4 October 2016.

Update on incidence of inpatient tubal ligation and long-acting reversible contraception in the United States.

BACKGROUND: Inpatient insertion of long-acting reversible contraception and immediate postpartum tubal ligation allow women to initiate highly effective contraception before hospital discharge. OBJECTIVE: We measured rates of intrauterine device and contraceptive implant initiation and tubal ligations performed during delivery hospitalizations from 2016 to 2018 from a representative sample of US hospital discharges. STUDY DESIGN: We used the 2016 to 2018 National Inpatient Sample database, a 20% sample of all community hospital discharges in the United States, to identify delivery hospitalizations with concomitant intrauterine device insertion, contraceptive implant insertion, or tubal ligation. We performed weighted multivariable logistic regression to examine associations between possible predictors (age, delivery mode, payer, geographic region, and year) and odds of long-acting reversible contraception and tubal ligation, and to compare characteristics of users. RESULTS: This sample included 2,216,638 discharges, representing 20% of 11,083,180 delivery hospitalizations across the United States. Intrauterine device insertion increased from 2.2 per 1000 deliveries (2016) to approximately 5.0 per 1000 deliveries (2018; P<.0001); implant insertion increased from 0.3 per 1000 deliveries (2016) to 2.5 per 1000 deliveries (2018; P<.0001); tubal ligation procedures decreased (64.2 to 62.1 per 1000 deliveries; P<.0001). Women who underwent a cesarean delivery had higher odds of having a tubal ligation than those who had a vaginal delivery (adjusted odds ratio, 8.83; 95% confidence interval, 8.73-8.97). Women aged <25 years had 7 times higher odds of receiving long-acting reversible contraception than of receiving tubal ligation (adjusted odds ratio, 7.38; 95% confidence interval, 6.90-7.90). Women with public insurance had almost 5 times the odds of receiving long-acting reversible contraception compared with those with commercial insurance (adjusted odds ratio, 4.83; 95% confidence interval, 4.59-5.06). CONCLUSION: Rates of long-acting reversible contraception insertion continue to increase while the rates of inpatient postpartum tubal ligations slowly decline. Variations in patient characteristics are associated with receiving long-acting reversible contraception or tubal ligation.

Female permanent contraception trends and updates.

Permanent contraception remains one of the most popular methods of contraception worldwide. This article has reviewed recent literature related to demographic characteristics of users, prevalence of use and trends over time, surgical techniques, and barriers to obtain the procedure. We have emphasized the patient's perspective as a key element of choosing permanent contraception. This review has incorporated sections on salpingectomy, hysteroscopy, unmet need, impact of policies at religiously affiliated institutions, and reproductive coercion.

Delayed Visits for Contraception Due to Concerns Regarding Pelvic Examination Among Women with History of Intimate Partner Violence.

BACKGROUND: Concern regarding pelvic examinations may be more common among women experiencing intimate partner violence. OBJECTIVE: We examined women's attitudes towards pelvic examination with history of intimate partner violence (pressured to have sex, or verbal, or physical abuse). DESIGN: Secondary analysis of data from a cluster randomized trial on contraceptive access. PARTICIPANTS: Women aged 18-25 were recruited at 40 reproductive health centers across the USA (2011-2013). MAIN MEASURES: Delays in clinic visits for contraception and preference to avoid pelvic examinations, by history of ever experiencing pressured sex, verbal, or physical abuse from a sexual partner, reported by frequency (never, rarely, sometimes, often). We used multivariable logistic regression with generalized estimating equations for clustered data. KEY RESULTS: A total of 1490 women were included. Ever experiencing pressured sex was reported by 32.4% of participants, with 16.5% reporting it rarely, 12.1% reporting it sometimes, and 3.8% reporting it often. Ever experiencing verbal abuse was reported by 19.4% and physical abuse by 10.2% of participants. Overall, 13.2% of participants reported ever having delayed going to the clinic for contraception to avoid having a pelvic examination, and 38.2% reported a preference to avoid pelvic examinations. In multivariable analysis, women reporting that they experienced pressured sex often had significantly higher odds of delaying a clinic visit for birth control (aOR 3.10 95% CI 1.39-6.84) and for reporting a preference to avoid pelvic examinations (aOR 2.91 95% CI 1.57-5.40). We found no associations between delay of clinic visits or preferences to avoid a pelvic examination and verbal or physical abuse. CONCLUSIONS: History of pressured sex from an intimate partner is common. Among women who have experienced pressured sex, concern regarding pelvic examinations is a potential barrier to contraception. Communicating that routine pelvic examinations are no longer recommended by professional societies could potentially reduce barriers and increase preventive healthcare visits.

Experience with same-day placement of the 52 mg levonorgestrel-releasing intrauterine system.

BACKGROUND: Prescribing information for the levonorgestrel-releasing intrauterine system allows placement when the clinician is reasonably certain the patient is not pregnant. A 6 item checklist aids clinicians in determining pregnancy risk but may be too restrictive, resulting in delaying placement for many women. Same-day placement, however, may risk placement during an unrecognized luteal-phase pregnancy, that is, a preimplantation fertilized ovum not yet detectable by urine pregnancy test. OBJECTIVE: We assessed the applicability of pregnancy checklist criteria in 2 gynecology practices that routinely provide same-day placements following a negative urine pregnancy test. STUDY DESIGN: In this retrospective cohort study, we reviewed electronic medical records of all women who underwent levonorgestrel-releasing intrauterine system placement from July 2009 to August 2012. We evaluated each record to identify whether the woman met any of the checklist criteria to exclude pregnancy. We ascertained luteal-phase pregnancies and other outcomes within 12 months following placement. RESULTS: Of 885 placements, 293 (33%) were immediately after abortion. Of the remaining 592 placements, 353 (60%) met at least 1 pregnancy checklist criterion to rule out pregnancy but 239 (40%) met none. Two percent received levonorgestrel emergency contraception at the time of placement. One luteal-phase pregnancy occurred in the group not meeting pregnancy checklist criteria. Removals and expulsions were rare and similar whether or not patients met checklist criteria. CONCLUSION: In 2 practices that provide same-day intrauterine system placements, strict adherence to pregnancy checklist criteria would have resulted in 239 patients (40%) not receiving a same-day intrauterine system. Twelve month outcomes were similar whether or not patients met pregnancy checklist criteria. Providers need not withhold intrauterine system placement based on the pregnancy checklist criteria.

Hormonal contraception and breast cancer.

The recent Danish cohort study reported a 20% increased risk of breast cancer among current and recent hormonal contraception users. These results are largely consistent with previous studies. This study did not report on stage of disease at diagnosis and it is not clear to what extent the apparent increased risk may be due to a small advance in the timing of diagnosis. This study did not report on the risk associated with the use of a 20-µg ethinyl estradiol pill. They did find an increasing risk in current users of longer duration and an increased risk with use of the levonorgestrel intrauterine system-both of these potentially important findings have not been consistently found in previous studies and require further investigation. The breast cancer effects described now in multiple studies wane with time, and in the long-term hormonal contraception use has been found not to be associated with any increased total cancer risk.

Reductions in pregnancy rates in the USA with long-acting reversible contraception: a cluster randomised trial.

BACKGROUND: Unintended pregnancy remains a serious public health challenge in the USA. We assessed the effects of an intervention to increase patients' access to long-acting reversible contraceptives (LARCs) on pregnancy rates. METHODS: We did a cluster randomised trial in 40 reproductive health clinics across the USA in 2011-13. 20 clinics were randomly assigned to receive evidence-based training on providing counselling and insertion of intrauterine devices (IUDs) or progestin implants and 20 to provide standard care. Usual costs for contraception were maintained at all sites. We recruited women aged 18-25 years attending family planning or abortion care visits and not desiring pregnancy in the next 12 months. The primary outcome was selection of an IUD or implant at the clinic visit and secondary outcome was pregnancy within 12 months. We used generalised estimating equations for clustered data to measure the intervention effect on contraceptive selection, and used survival analysis to assess pregnancy rates. FINDINGS: Of 1500 women enrolled, more at intervention than control sites reported receiving counselling on IUDs or implants (565 [71%] of 797 vs 271 [39%] of 693, odds ratio 3·8, 95% CI 2·8-5·2) and more selected LARCs during the clinic visit (224 [28%] vs 117 [17%], 1·9, 1·3-2·8). The pregnancy rate was lower in intervention group than in the control group after family planning visits (7·9 vs 15·4 per 100 person-years), but not after abortion visits (26·5 vs 22·3 per 100 person-years). We found a significant intervention effect on pregnancy rates in women attending family planning visits (hazard ratio 0·54, 95% CI 0·34-0·85). INTERPRETATION: The pregnancy rate can be reduced by provision of counselling on long-term reversible contraception and access to devices during family planning counselling visits. FUNDING: William and Flora Hewlett Foundation.

Funding policies and postabortion long-acting reversible contraception: results from a cluster randomized trial.

BACKGROUND: Almost one-half of women having an abortion in the United States have had a previous procedure, which highlights a failure to provide adequate preventive care. Provision of intrauterine devices and implants, which have high upfront costs, can be uniquely challenging in the abortion care setting. OBJECTIVE: We conducted a study of a clinic-wide training intervention on long-acting reversible contraception and examined the effect of the intervention, insurance coverage, and funding policies on the use of long-acting contraceptives after an abortion. STUDY DESIGN: This subanalysis of a cluster, randomized trial examines data from the 648 patients who had undergone an abortion who were recruited from 17 reproductive health centers across the United States. The trial followed participants 18-25 years old who did not desire pregnancy for a year. We measured the effect of the intervention, health insurance, and funding policies on contraceptive outcomes, which included intrauterine device and implant counseling and selection at the abortion visit, with the use of logistic regression with generalized estimating equations for clustering. We used survival analysis to model the actual initiation of these methods over 1 year. RESULTS: Women who obtained abortion care at intervention sites were more likely to report intrauterine device and implant counseling (70% vs 41%; adjusted odds ratio, 3.83; 95% confidence interval, 2.37-6.19) and the selection of these methods (36% vs 21%; adjusted odds ratio, 2.11; 95% confidence interval, 1.39-3.21). However, the actual initiation of methods was similar between study arms (22/100 woman-years each; adjusted hazard ratio, 0.88; 95% confidence interval, 0.51-1.51). Health insurance and funding policies were important for the initiation of intrauterine devices and implants. Compared with uninsured women, those women with public health insurance had a far higher initiation rate (adjusted hazard ratio, 2.18; 95% confidence interval, 1.31-3.62). Women at sites that provide state Medicaid enrollees abortion coverage also had a higher initiation rate (adjusted hazard ratio, 1.73; 95% confidence interval, 1.04-2.88), as did those at sites with state mandates for private health insurance to cover contraception (adjusted hazard ratio, 1.80; 95% confidence interval, 1.06-3.07). Few of the women with private insurance used it to pay for the abortion (28%), but those who did initiated long-acting contraceptive methods at almost twice the rate as women who paid for it themselves or with donated funds (adjusted hazard ratio, 1.94; 95% confidence interval, 1.10-3.43). CONCLUSIONS: The clinic-wide training increased long-acting reversible contraceptive counseling and selection but did not change initiation for abortion patients. Long-acting method use after abortion was associated strongly with funding. Restrictions on the coverage of abortion and contraceptives in abortion settings prevent the initiation of desired long-acting methods.

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

OBJECTIVE: This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects. STUDY DESIGN: We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 µg ethinyl estradiol and 150 µg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. RESULTS: The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026). CONCLUSION: Limited blood sampling, including results from 2 single doses, gave highly correlated estimates of an oral contraceptive user's steady-state ethinyl estradiol exposure.

Evaluating virtual visits for contraceptive counseling: An exploratory study using the Person-Centered Contraceptive Counseling (PCCC) scale, a patient-reported outcome measure.

OBJECTIVES: To describe patient-reported quality of care for virtual contraceptive counseling, using the four-item Person-Centered Contraception Counseling (PCCC) scale. Secondary analyses evaluated PCCC scores by patient subgroups. STUDY DESIGN: From December 2021 to May 2022, we offered an anonymous web-based survey, to English and Spanish-speaking female patients 18 to 45 years old who had virtual visits through two Family Planning offices affiliated with Columbia University/New York Presbyterian Hospital in New York City. RESULTS: Among 196 respondents, 133 (68%) respondents gave the top score. The proportion who gave the top PCCC score was higher for the faculty-based practice vs. community-based practice (62% vs. 38% respectively, p = 0.02), video vs. telephone (84% vs. 16% respectively, p = 0.01), and English vs. Spanish (86% vs. 14% respectively, p = 0.02); but did not differ for ethnicity (p = 0.34). CONCLUSIONS: Patient-perceived quality of contraceptive counseling in virtual visits was high, with some disparities seen in the subgroups. IMPLICATIONS: This exploratory study about contraceptive counseling during virtual visits showed that 68% of survey respondents gave the top box PCCC score. Our work also suggests disparities in patient experiences based on several factors. Future work may expand on nuances of disparities and how these influence care.

Use of serum evaluation of contraceptive and ovarian hormones to assess reduced risk of pregnancy among women presenting for emergency contraception in a multicenter clinical trial.

OBJECTIVES: To evaluate ovulation risk among women enrolling in an emergency contraception (EC) study by measuring contraceptive steroids and ovarian hormones. STUDY DESIGN: We used standard chemiluminescent assays to evaluate endogenous hormones (estradiol, progesterone, follicle stimulating hormone, luteinizing hormone) and liquid chromatography-tandem triple quadrupole mass spectrometry to simultaneously analyze concentrations of ethinylestradiol, dienogest, norelgestromin (NGMN), norethindrone (NET), gestodene, levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate, medroxyprogesterone acetate (MPA), and drospirenone in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥80 kg reporting no recent use of hormonal contraception. RESULTS: We enrolled 532 and obtained a valid baseline blood sample from 520 women. Of these, 117 (22.5%) had detectable concentrations of progestin (MPA [n = 58, 11.2%], LNG [50, 9.6%], ENG [11, 2.1%], NET [5, 0.96%], NGMN [3, 0.06%], or drospirenone [1, 0.02%]). LNG was co-detected in all three participants with samples containing NGMN. Multiple progestins were detected in eight other women: ENG/MPA (1), ENG/LNG (2), and MPA/LNG (5). Samples from 55 (10.6%) had concentrations of one or more progestin considered above the minimum level for contraceptive (MPA ≥ 0.1 ng/mL, n = 19; NGMN/LNG ≥ 0.2 ng/mL, n = 31; ENG ≥ 0.09 ng/mL, n = 8; NET ≥ 0.35 ng/mL, n = 4). We detected concentrations of serum progesterone ≥ 3 ng/mL, indicative of luteal phase (postovulation) status, in an additional 194 (37.3%) samples. CONCLUSIONS: More than one-third of enrolled in our clinical trial of oral EC had evidence of prior ovulation at the time of enrollment. Additionally, about 23% had evidence of recent use of hormonal contraception. These results would have decreased the expected risk of pregnancy in the study. IMPLICATIONS: Many participants in a recent clinical trial of oral emergency contraception did not appear to be at risk for pregnancy or would not have benefited from intervention due to cycle timing. Investigators should consider the effects of these findings on expected pregnancy rates when determining sample size in future EC clinical trials, particularly when using noninferiority designs or historical controls.

Fertility drugs and endometrial cancer risk: results from an extended follow-up of a large infertility cohort.

STUDY QUESTION: Do fertility drugs influence the subsequent risk of endometrial cancer in a manner that is independent of other risk predictors, such as parity? SUMMARY ANSWER: In this follow-up of a large cohort of women evaluated for infertility and for whom information was captured on fertility drugs, indications for usage and other risk factors that might influence cancer risk, we found no evidence for a substantial relationship between fertility drug use and endometrial cancer risk. WHAT IS ALREADY KNOWN: Although the hormonal etiology of endometrial cancer has been well established, it remains unclear whether the use of fertility drugs has an influence on risk. Results regarding the effects of fertility drugs on endometrial cancer risk have been inconsistent, although several studies have shown some evidence for possible increases in risk. The relationship is of particular interest given that clomiphene, a commonly prescribed drug, is a selective estrogen receptor modulator, with chemical properties similar to tamoxifen, another drug linked to an increase in endometrial cancer risk. STUDY DESIGN, SIZE, DURATION: In a retrospective cohort of 12 193 women evaluated for infertility between 1965 and 1988 at five US sites, follow-up was pursued through 2010 via both passive as well as active (questionnaire) means. PARTICIPANTS, SETTING, METHODS: Among the 9832 subjects for whom follow-up was allowed and achieved, 259 346 at-risk person-years (i.e. prior to hysterectomy) were accrued, and 118 invasive endometrial cancers identified. Cox regression determined hazard ratios (HRs) and 95% confidence intervals (CIs) for fertility treatments adjusted for endometrial cancer risk factors and causes of infertility. MAIN RESULTS AND THE ROLE OF CHANCE: Although we observed slight increases in endometrial cancer risk associated with clomiphene (HR = 1.39, 95% CI: 0.96-2.01) and the less commonly prescribed gonadotrophins (1.34, 0.76-2.37), there were no convincing relationships of risk with either cycles of use or cumulative exposures for either drug. A statistically significant risk associated with the use of clomiphene among women who began use at younger ages (<30) (1.93, 1.24-3.00) may have reflected indications for drug usage rather than the effect of the drug itself. Women who received clomiphene followed by gonadotrophins were at a non-significantly elevated risk (1.77, 0.98-3.19). LIMITATIONS, REASONS FOR CAUTION: Like most studies of endometrial cancer, we were limited by sample sizes, particularly for evaluating subgroup associations. We were also unable to follow all women and were not able to obtain complete risk factor information (including hysterectomy status) for the entire cohort. WIDER IMPLICATIONS OF THE FINDINGS: Although we found no support for a relationship between fertility drugs and endometrial cancer risk, the association should continue to be monitored given that our study population was still young and had not yet reached the age of peak endometrial cancer incidence. STUDY FUNDING/COMPETING INTEREST(S): This project was supported in part by funds from the intramural research program of the National Cancer Institute, National Institutes of Health. None of the authors has any conflicting interests to declare.

A UPLC-MS/MS method for therapeutic drug monitoring of etonogestrel.

INTRODUCTION: Etonogestrel (ENG) is a progestin used in the contraceptive vaginal ring NuvaRing and the subdermal implant Implanon. A sensitive method for measuring ENG is useful for further investigating the progestin's pharmacokinetics with these alternative contraceptive formulations and generating important information about possible continued efficacy or potential failure to remove the subdermal implant. METHODS: Standards and serum samples were spiked with D8-progesterone (internal standard) and subsequently extracted with dichloromethane, dried, and reconstituted in 25% methanol with formic acid. ENG was analyzed by positive electrospray ionization in multiple reaction monitoring mode with a run time of 5.5 minutes using a C18 BEH column. The mobile phase was a gradient of water:acetonitrile, with 0.1% formic acid. The method was applied successfully to study the pharmacokinetics of ENG during vaginal ring use. The method was also used in routine patient care to assess ENG levels. RESULTS: The method is linear from 50 to 2000 pg/mL. The limits of detection and quantification are 25 and 50 pg/mL, respectively. There was no observed ionization suppression within the linear range of the assay, and the average recovery was 87%. Serum ENG levels of n = 3 subjects were all within the linear range of the assay for a total study period of 42 days after insertion of the ring. Of n = 20 patients with nonpalpable subdermal implants, n = 13 had ENG levels >25 pg/mL, whereas n = 7 had levels <25 pg/mL. CONCLUSIONS: We developed a rapid, sensitive, and robust ultra performance liquid chromatography-tandem mass spectometry (UPLC-MS/MS) method for the quantification of ENG in serum that is useful to study the progestin's pharmacokinetics and inform physicians about successful implantation or potential failure to remove a subdermal device.

Associations between contraceptive availability and rate of subsequent legal abortions in Colombia: A historical cohort analysis.

OBJECTIVE: To describe factors associated with subsequent abortions in Colombia and evaluate whether high-efficacy contraceptive availability (IUD) post-index abortion was associated with higher efficacy contraceptive initiation and fewer subsequent abortions within 2 years. METHODS: The study population comprised patients aged 15-44 years who underwent index abortion in 2017 at four clinics in Bogotá, Colombia. Using charts, we conducted a retrospective cohort study with 2-year follow-up (2017-2019) after the index abortion for outcomes of contraceptive initiation and subsequent abortion. We evaluated associations between demographic or clinical characteristics and outcomes using Pearson chi-square and multivariate logistic regression. RESULTS: Of 9175 patients with index abortion, 3409 (37.2%) initiated an intrauterine device (IUD) and 467 (5.1%) had a subsequent abortion within the study period (2017-2019). IUD availability (adjusted odds ratio [aOR], 1.64; 95% confidence interval [CI], 1.39-1.93) and insurance use (aOR, 5.03; 95% CI, 4.37-5.78) were associated with high-efficacy contraceptive initiation; medication abortion was inversely associated (aOR, 0.24; 95% CI, 0.22-0.27). Initiation of no (aOR, 4.94; 95% CI, 3.59-6.80) or moderate-efficacy (injection: aOR, 4.21 [95% CI, 3.14-5.62]; oral contraceptive pill: aOR, 4.60 [95% CI, 3.21-6.59]) methods were associated with subsequent abortion. CONCLUSION: Subsequent abortion is inversely associated with initiated postabortion contraceptive efficacy, which is modifiable on a systems level by improving access to effective postabortion contraception.

Satisfaction with a Segesterone Acetate and Ethinyl Estradiol Contraceptive Vaginal System Among Recent Oral Contraceptive or Hormonal Contraceptive Vaginal Ring Users.

Background: We evaluated satisfaction with use of a segesterone acetate and ethinyl estradiol (0.15/0.013 mg) contraceptive vaginal system (CVS) among women who had recently used a monthly contraceptive vaginal ring or contraceptive pills. The CVS is a ring-shaped device used in a 21-days-in/7-days-out regimen for 13 cycles. Materials and Methods: We analyzed post hoc satisfaction responses at cycle 3 and end of study (EOS) from a subset of participants with documented recent use of the monthly ring or daily pills before enrollment in a multinational, phase 3, 13-cycle trial evaluating the CVS. EOS included results from participants who had completed ≥10 cycles. Results were summarized descriptively. Results: We identified 128 recent ring and 219 recent pill users at cycle 3 (of 1033 survey participants), and 92 and 148, respectively, at EOS (of 622 survey participants); overall satisfaction with CVS use was high (≥90%). At EOS, most ring (89%) and pill (97%) users liked the CVS as much/better than any previous method. The two most-liked CVS features included ease of use and 1-year duration; the two most disliked features included ring insertion and feeling it coming out. At EOS, ≥88% of both groups reported no concern about using the same CVS for a year, and most (>80%) had recommended it to friends or family members. Conclusion: The CVS clinical trial participants who were recent ring/pill users reported high satisfaction and liked it as much/better than any previously used contraceptive; the CVS may be a good contraceptive option for switchers. Clinical trial registration NCT00263341.