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.

Hormonal contraceptives for contraception in overweight or obese women.

BACKGROUND: Obesity has reached epidemic proportions around the world. Effectiveness of hormonal contraceptives may be related to metabolic changes in obesity or to greater body mass or body fat. Hormonal contraceptives include oral contraceptives (OCs), injectables, implants, hormonal intrauterine contraception (IUC), the transdermal patch, and the vaginal ring. Given the prevalence of overweight and obesity, the public health impact of any effect on contraceptive efficacy could be substantial. OBJECTIVES: To examine the effectiveness of hormonal contraceptives in preventing pregnancy among women who are overweight or obese versus women with a lower body mass index (BMI) or weight. SEARCH METHODS: Until 4 August 2016, we searched for studies in PubMed (MEDLINE), CENTRAL, POPLINE, Web of Science, ClinicalTrials.gov, and ICTRP. We examined reference lists of pertinent articles to identify other studies. For the initial review, we wrote to investigators to find additional published or unpublished studies. SELECTION CRITERIA: All study designs were eligible. The study could have examined any type of hormonal contraceptive. Reports had to contain information on the specific contraceptive methods used. The primary outcome was pregnancy. Overweight or obese women must have been identified by an analysis cutoff for weight or BMI (kg/m(2)). DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. One entered the data into RevMan and a second verified accuracy. The main comparisons were between overweight or obese women and women of lower weight or BMI. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale. Where available, we included life-table rates. We also used unadjusted pregnancy rates, relative risk (RR), or rate ratio when those were the only results provided. For dichotomous variables, we computed an odds ratio with 95% confidence interval (CI). MAIN RESULTS: With 8 studies added in this update, 17 met our inclusion criteria and had a total of 63,813 women. We focus here on 12 studies that provided high, moderate, or low quality evidence. Most did not show a higher pregnancy risk among overweight or obese women. Of five COC studies, two found BMI to be associated with pregnancy but in different directions. With an OC containing norethindrone acetate and ethinyl estradiol (EE), pregnancy risk was higher for overweight women, i.e. with BMI ≥ 25 versus those with BMI < 25 (reported relative risk 2.49, 95% CI 1.01 to 6.13). In contrast, a trial using an OC with levonorgestrel and EE reported a Pearl Index of 0 for obese women (BMI ≥ 30) versus 5.59 for nonobese women (BMI < 30). The same trial tested a transdermal patch containing levonorgestrel and EE. Within the patch group, obese women in the "treatment-compliant" subgroup had a higher reported Pearl Index than nonobese women (4.63 versus 2.15). Of five implant studies, two that examined the six-capsule levonorgestrel implant showed differences in pregnancy by weight. One study showed higher weight was associated with higher pregnancy rate in years 6 and 7 combined (reported P < 0.05). In the other, pregnancy rates differed in year 5 among the lower weight groups only (reported P < 0.01) and did not involve women weighing 70 kg or more.Analysis of data from other contraceptive methods indicated no association of pregnancy with overweight or obesity. These included depot medroxyprogesterone acetate (subcutaneous), levonorgestrel IUC, the two-rod levonorgestrel implant, and the etonogestrel implant. AUTHORS' CONCLUSIONS: The evidence generally did not indicate an association between higher BMI or weight and effectiveness of hormonal contraceptives. However, we found few studies for most contraceptive methods. Studies using BMI, rather than weight alone, can provide information about whether body composition is related to contraceptive effectiveness. The contraceptive methods examined here are among the most effective when used according to the recommended regimen.We considered the overall quality of evidence to be low for the objectives of this review. More recent reports provided evidence of varying quality, while the quality was generally low for older studies. For many trials the quality would be higher for their original purpose rather than the non-randomized comparisons here. Investigators should consider adjusting for potential confounding related to BMI or contraceptive effectiveness. Newer studies included a greater proportion of overweight or obese women, which helps in examining effectiveness and side effects of hormonal contraceptives within those groups.

Adolescent Female Text Messaging Preferences to Prevent Pregnancy After an Emergency Department Visit: A Qualitative Analysis.

BACKGROUND: Over 15 million adolescents use the emergency department (ED) each year in the United States. Adolescent females who use the ED for medical care have been found to be at high risk for unintended pregnancy. Given that adolescents represent the largest users of text messaging and are receptive to receiving text messages related to their sexual health, the ED visit represents an opportunity for intervention. OBJECTIVE: The aim of this qualitative study was to explore interest in and preferences for the content, frequency, and timing of an ED-based text message intervention to prevent pregnancy for adolescent females. METHODS: We conducted semistructured, open-ended interviews in one urban ED in the United States with adolescent females aged 14-19 years. Eligible subjects were adolescents who were sexually active in the past 3 months, presented to the ED for a reproductive health complaint, owned a mobile phone, and did not use effective contraception. Using an interview guide, enrollment continued until saturation of key themes. The investigators designed sample text messages using the Health Beliefs Model and participants viewed these on a mobile phone. The team recorded, transcribed, and coded interviews based on thematic analysis using the qualitative analysis software NVivo and Excel. RESULTS: Participants (n=14) were predominantly Hispanic (13/14; 93%), insured (13/14; 93%), ED users in the past year (12/14; 86%), and frequent text users (10/14; 71% had sent or received >30 texts per day). All were interested in receiving text messages from the ED about pregnancy prevention, favoring messages that were "brief," "professional," and "nonaccusatory." Respondents favored texts with links to websites, repeated information regarding places to receive "confidential" care, and focused information on contraception options and misconceptions. Preferences for text message frequency varied from daily to monthly, with random hours of delivery to maintain "surprise." No participant feared that text messages would violate her privacy. CONCLUSIONS: Adolescent female patients at high pregnancy risk are interested in ED-based pregnancy prevention provided by texting. Understanding preferences for the content, frequency, and timing of messages can guide in designing future interventions in the ED.

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.

Influenza vaccine text message reminders for urban, low-income pregnant women: a randomized controlled trial.

OBJECTIVES: We evaluated the impact of influenza vaccine text message reminders in a low-income obstetric population. METHODS: We conducted a randomized controlled trial that enrolled 1187 obstetric patients from 5 community-based clinics in New York City. The intervention group received 5 weekly text messages regarding influenza vaccination starting mid-September 2011 and 2 text message appointment reminders. Both groups received standard automated telephone appointment reminders. The prespecified endpoints were receipt of either pre- or postpartum influenza vaccination calculated cumulatively at the end of each month (September-December 2011). RESULTS: After adjusting for gestational age and number of clinic visits, women who received the intervention were 30% more likely to be vaccinated as of December 2011 (adjusted odds ratio [AOR] = 1.30; 95% confidence interval [CI] = 1.003, 1.69 end of September: AOR = 1.34; 95% CI = 0.98, 1.85; October: AOR = 1.35; 95% CI = 1.05, 1.75; November: AOR = 1.27; 95% CI = 0.98, 1.65). The subgroup of women early in the third trimester at randomization showed the greatest intervention effect (December 31: 61.9% intervention vs 49.0% control; AOR = 1.88; 95% CI = 1.12, 3.15). CONCLUSIONS: In this low-income obstetric population, text messaging was associated with increased influenza vaccination, especially in those who received messages early in their third trimester.

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.

Emergency contraception for individuals weighing 80 kg or greater: A randomized trial of 30 mg ulipristal acetate and 1.5 mg or 3.0 mg levonorgestrel.

OBJECTIVES: To compare the efficacy of emergency contraception (EC) regimens used within 72 hours of unprotected intercourse in individuals weighing ≥80 kg. STUDY DESIGN: We enrolled reproductive-aged healthy women in a multicenter, single-blind, randomized study of levonorgestrel 1.5 mg (LNG1X) and 3.0 mg (LNG2X) and ulipristal acetate 30 mg (UPA) (enrollment goal 1200). Key eligibility requirements included regular cycles, weight >/= 80kg, unprotected intercourse within 72 hours, no recent use of hormonal contraception, a negative urine pregnancy test (UPT), and willingness to abstain from intercourse until next menses. To assess our primary outcome of incidence of pregnancy, participants completed home UPTs; if no menses by 2-weeks post-treatment, or a positive UPT, they returned for an in-person visit with quantitative serum human chorionic gonadotropin and ultrasound. RESULTS: We enrolled and randomized 532; 44 were not dosed or not evaluable for primary end point, leaving an analyzable sample of 488 (173 LNG1X, 158 LNG2X, 157 UPA) with similar demographics between groups (mean age 29.6 years [5.74], body mass index 37.09 kg/m2 [6.95]). Five pregnancies occurred (LNG1X n = 1, LNG2X n = 1, UPA n = 3); none occurred during the highest at-risk window (day of ovulation and the 3 days prior). We closed the study before achieving our enrollment goal because the low pregnancy rate in all groups established futility based on an interim blinded analysis. CONCLUSIONS: Although slow enrollment limited our study power, we found no differences in pregnancy rates between EC regimens among women weighing 80 kg or more. Our results are not able to refute or support differences between the treatment arms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clincialtrials.gov Clinical trials#: NCT03537768. IMPLICATIONS: Women weighing 80 kg or more experienced no differences in pregnancy rates between oral EC regimens but due to several significant study limitations including sample size and the lack of a study population at high risk of pregnancy, our results are not able to determine if differences in treatment effectiveness exist.

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.

Association of hormonal contraceptive use with reduced levels of depressive symptoms: a national study of sexually active women in the United States.

An estimated 80% of sexually active young women in the United States use hormonal contraceptives during their reproductive years. Associations between hormonal contraceptive use and mood disturbances remain understudied, despite the hypothesis that estrogen and progesterone play a role in mood problems. In this study, we used data from 6,654 sexually active nonpregnant women across 4 waves of the National Longitudinal Study of Adolescent Health (1994-2008), focusing on women aged 25-34 years. Women were asked about hormonal contraceptive use in the context of a current sexual partnership; thus, contraceptive users were compared with other sexually active women who were using either nonhormonal contraception or no contraception. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. At ages 25-34 years, hormonal contraceptive users had lower mean levels of concurrent depressive symptoms (ß = -1.04, 95% confidence interval: -1.73, -0.35) and were less likely to report a past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using low-efficacy contraception or no contraception, in models adjusted for propensity scores for hormonal contraceptive use. Longitudinal analyses indicated that associations between hormonal contraception and depressive symptoms were stable. Hormonal contraception may reduce levels of depressive symptoms among young women. Systematic investigation of exogenous hormones as a potential preventive factor in psychiatric epidemiology is warranted.

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.