HRA Pharma (France)

ABSTRACT Almost half of the 6.1 million annual pregnancies are unintended. Barriers to accessing contraception including prescription requirements contribute to inconsistent use or nonuse. This has led to a call from major medical organizations for effective over-the-counter (OTC) contraceptives such as progestin-only pills (POPs). Studies have modeled the potential impact on an OTC POPs; however, they are based on women expressing interest versus actual use. The objective of this model was to utilize data from an actual-use clinical trial to calculate the potential impact of a POP, when they are available over the counter, on the number of unintended pregnancies in the United States. Data were obtained from a recent actual-use clinical trial that simulated OTC use of a norgestrel POP over a 6-month period. In this study, 883 women chose to pay out of pocket and use the norgestrel POP. This model compared the number of expected pregnancies among 2 cohorts of 100,000 women, one of which was based on the contraceptive mix of volunteers entering the actual-use trial, and the second was women exclusively using an OTC POP. The primary analysis set the failure rate of the OTC POP to 7%, the reported failure rate for oral contraceptive pills, and that of “no method” as 85%. The failure rate of the non-OTC POP cohort was that from the actual-use trial. A “tipping point” analysis was conducted to determine the failure rate of the OTC POP beyond which no unintended pregnancies would be prevented by OTC POP compared with the mixed-method cohort. At the 6-month time point in the actual-use trial, only 51.1% of subjects were continuing OTC POP use. A continuation-in-use analysis was conducted to determine what effect discontinuation might have on unintended pregnancy rate. According to the model, a total of 37,624 unintended pregnancies would occur if 100,000 women continued their current contraceptive method over the course of 1 year. If those 100,000 women had used the OTC POP exclusively for 1 year, 7000 unintended pregnancies would be expected. Thus, an estimated 30,624 fewer unintended pregnancies, a reduction of 80%, would be expected over 1 year by use of an OTC POP. The results of a sensitivity analysis that decreased the OTC POP failure rate from 7% to 3.5% resulted in an estimated 34,124 fewer unintended pregnancies and an increase in OTC POP failure rate to 10.5%, and reduction of “no method” failure rate to 46% resulted in an estimated 1461 fewer unintended pregnancies. The tipping point analysis identified an OTC POP typical use failure rate of 38% at the point which using the OTC actual-use trial method mix profile and a “no method” failure rate of 85% would result in equivalent unintended pregnancy rate to the OTC POP cohort. When revising estimates according to the continuation-in-use analysis, a reduction in unintended pregnancies of 59% over 6 months compared with the actual-use trial method mix profile (11,009 pregnancies prevented) was calculated. The results of this study suggest that the use of a POP when available over the counter will result in a significant reduction of unintended pregnancies in the United States.

Purpose To explore the perceived need and enthusiasm for over the counter (OTC) progestogen-only pills (POP). Materials and Methods A web-based survey of 1000 sexually active women (16–45) and 100 pharmacists in Germany, Italy and Spain. Results Despite not wanting to conceive, 5–6% of women in each country were not using contraception and 8–20% were using methods less effective than condoms. At least 74% of respondents felt knowledgeable about the different contraceptives available but at least 1/3 had experienced difficulty accessing oral contraceptive (OCs) in the past two years. The cost of contraceptives, the need to see a doctor and long waits for appointments were cited as barriers for not using OCs. The majority agreed they would discuss with their doctor the decision to buy the POP, consult about side effects and other reproductive health issues. Over 2/3 of pharmacists in each country would be very, or fairly, likely to recommend the POP, agreeing that the benefits included improved access for women, and offered them more independence. Conclusions Asked directly, women in Germany, Spain and Italy currently using contraception are positive about a POP OTC. Pharmacists are also positive, with the overwhelming majority in favour of providing POPs.

BackgroundCushing’s syndrome (CS) is a rare condition of chronically elevated cortisol levels resulting in diverse comorbidities, many of which endure beyond successful treatment affecting the quality of life. Few data are available concerning patients’ experiences of diagnosis, care and persistent comorbidities.ObjectiveTo assess CS patients’ perspectives on the diagnostic and care journey to identify unmet therapeutic needs.MethodsA 12-item questionnaire was circulated in 2019 by the World Association for Pituitary Organisations. A parallel, 13-item questionnaire assessing physician perceptions on CS patient experiences was performed.ResultsThree hundred twenty CS patients from 30 countries completed the questionnaire; 54% were aged 35–54 and 88% were female; 41% were in disease remission. The most burdensome symptom was obesity/weight gain (75%). For 49% of patients, time to diagnosis was over 2 years. Following treatment, 88.4% of patients reported ongoing symptoms including, fatigue (66.3%), muscle weakness (48.8%) and obesity/weight gain (41.9%). Comparisons with delay in diagnosis were significant for weight gain (P = 0.008) and decreased libido (P = 0.03). Forty physicians completed the parallel questionnaire which showed that generally, physicians poorly estimated the prevalence of comorbidities, particularly initial and persistent cognitive impairment. Only a minority of persistent comorbidities (occurrence in 1.3–66.3%; specialist treatment in 1.3–29.4%) were managed by specialists other than endocrinologists. 63% of patients were satisfied with treatment.ConclusionThis study confirms the delay in diagnosing CS. The high prevalence of persistent comorbidities following remission and differences in perceptions of health between patients and physicians highlight a probable deficiency in effective multidisciplinary management for CS comorbidities.

BACKGROUND Progestin-only contraceptive pills (POP) are commonly reserved for women with medical comorbidities but in actuality, POPs can be safely used by anyone wanting to prevent pregnancy. This wide safety profile makes them an ideal candidate for being available over the counter without a prescription, but adherence issues may be more common with over-the-counter use. We need a better understanding of the ability of POPs to prevent pregnancy when adherence issues occur in the form of a missed or delayed pill. OBJECTIVE This study aims to determine cervical mucus characteristics following a 6-hour delayed pill intake or after one missed pill as compared to typical daily use of norgestrel 75 mcg. METHODS This prospective, multicenter, randomized, crossover study assesses the effect of norgestrel 75 mcg (Opill) on cervical mucus and ovarian activity during reported compliant daily use, after a 6-hour delayed intake mid cycle, and after a mid-cycle missed pill. Subject participation will last approximately 4.5 months. We will recruit at 2 US sites: Oregon Health & Science University, Portland, Oregon and University of California Davis Health, Sacramento, California. Reproductive-aged subjects with regular menstrual cycles (21-35 days), BMI <32 kg/m2, and proven ovulation (screening luteal phase progesterone >3 ng/mL [>10 nmol/L]) are eligible to enroll. Participants cannot be at risk for pregnancy during the study period and not use other hormonal methods. Norgestrel 75 mcg will be taken at the same time daily except for one day in each of treatment periods 2 and 3, when the pill will be taken either 6 hours late (delayed pill) or omitted completely (missed pill). Every 3-4 days, we will monitor subjects for follicular activity with transvaginal ultrasound (TVUS) examination, cervical mucus, and blood sampling for ovarian hormones and gonadotropins. Subjects will undergo serial cervical mucus sampling on the days with missed and delayed pill intake at 8 hours after pill intake on the day before the delayed or missed pill, 3 hours following the scheduled time of pill intake if intake was delayed, 6 hours after the scheduled time if intake was omitted, and on the next day 30 minutes before the time of scheduled pill intake. The primary objective of the study is to determine the effect of a delayed or omitted pill intake on cervical mucus characteristics based on a modified Insler score compared to reported daily use. RESULTS Our protocol was successfully approved by a central institutional review board (Advarra, Columbia, MD), received ethical approval on March 23, 2018, and was registered with ClinicalTrials.gov (NCT03585712). As of January 2020, the study completed enrollment of 52 subjects. Analyses are pending. CONCLUSIONS Our protocol was approved by a central review board, and study procedures were successfully executed with completed proposed enrollment. CLINICALTRIAL ClinicalTrials.gov NCT03585712; https://clinicaltrials.gov/ct2/show/NCT03585712 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/29208

Adrenal incidentalomas (AIs) are found commonly on axial imaging. Around 30% exhibit autonomous cortisol secretion (ACS) associated with increased cardiovascular events and death. We hypothesized that AI/ACS patients have an abnormal cortisol rhythm that could be reversed by use of carefully timed short-acting cortisol synthesis blockade, with improvement in cardiovascular disease markers. In a phase 1/2a, prospective study (Eudract no. 2012-002586-35), we recruited six patients with AI/ACS and two control groups of six sex-, age-, and body mass index-matched individuals: (1) patients with AI and no ACS (AI/NoACS) and (2) healthy volunteers with no AI [healthy controls (HC)]. Twenty-four-hour circadian cortisol analysis was performed to determine any differences between groups and timing of intervention for cortisol lowering using the 11β-hydroxylase inhibitor metyrapone. Circadian profiles of serum interleukin-6 (IL-6) were assessed. Serum cortisol levels in group AI/ACS were significantly higher than both group AI/NoACS and group HC from 6 pm to 10 pm [area under the curve (AUC) difference: 0.81 nmol/L/h; P = 0.01] and from 10 pm to 2 am (AUC difference: 0.86 nmol/L/h; P < 0.001). In light of these findings, patients with ACS received metyrapone 500 mg at 6 pm and 250 mg at 10 pm, and cortisol rhythms were reassessed. Postintervention evening serum cortisol was lowered, similar to controls [6 pm to 10 pm (AUC difference: -0.06 nmol/L/h; P = 0.85); 10 pm to 2 am (AUC difference: 0.10 nmol/L/h; P = 0.76)]. Salivary cortisone showed analogous changes. IL-6 levels were elevated before treatment [10 pm to 2 pm (AUC difference: 0.42 pg/mL/h; P = 0.01)] and normalized post treatment. In AI/ACS, the evening and nocturnal cortisol exposure is increased. Use of timed evening doses of metyrapone resets the cortisol rhythm to normal. This unique treatment paradigm is associated with a reduction in the cardiovascular risk marker IL-6.