Inhibition ratio (I.R.) and transformation index (T.I.): new indexes to compare the effectiveness and clinical behaviour of modern progestin-only pills (POP).

Progestin-only pills (POPs) have emerged as a crucial contraceptive option for women, particularly those contraindicated to oestrogens. This opinion paper introduces two new indices, the Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.), to evaluate and compare the efficacy and clinical behaviour of modern POPs. The I.R. quantifies the ratio between the progestin dosage in a POP and the minimum dose required to inhibit ovarian function, providing insights into contraceptive efficacy. The T.I., on the other hand, assesses its clinical impact by considering the ratio between the total progestin dose and the dose required to induce endometrial luteinising changes. Both indices thus offer valuable tools for comparing progestins even at significantly different dosages and regimens, providing information on clinical characteristics and drug effects. The newest formulations of POPs (Desogestrel 28 and Drospirenone 24 + 4) have demonstrated higher I.R. and T.I. in comparison to older versions, indicating significant improvements in contraceptive efficacy and clinical impact with better menstrual cycle control. We believe that using these indices will ensure a more informed and personalised choice of progestin not only for contraceptive purposes but also for therapeutic use in gynaecology. The future goal is to develop other progestins with even more advantageous I.R. and T.I., ensuring the best contraceptive efficacy with fewer side effects, even in women at risk (obese, etc.).

The Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.) are two new proposed indexes to evaluate and compare the efficacy and clinical behaviour of modern and future POPs.

Evaluation of consumer self-selection of a proposed over-the-counter, progestin-only daily oral contraceptive.

OBJECTIVES: In an effort to switch a norgestrel 0.075 mg progestin-only pill (Opill) from prescription to over-the-counter, we conducted this study to assess whether consumers can use the drug facts label alone to guide appropriate self-selection. STUDY DESIGN: Two studies assessed self-selection: (1) an all-comers, actual-use study evaluating self-selection before purchasing and using norgestrel 0.075 mg and (2) the Targeted Breast Cancer Self-Selection Study evaluating theoretical self-selection among participants with a history of breast cancer. RESULTS: In the actual-use study, based on the label, 1670/1772 participants (94%) were appropriate for use of norgestrel 0.075 mg; 102 (6%) were not appropriate. Of the 102, 66 (65%) correctly did not select and 36 (35%) responded it was okay for them to use norgestrel 0.075 mg. Of the 36 participants who incorrectly self-selected, one had a history of breast cancer and thus might have been adversely affected had they taken norgestrel 0.075 mg. In the Targeted Breast Cancer Self-Selection Study (N = 206), 97% of participants correctly stated norgestrel 0.075 mg was not appropriate for them. CONCLUSIONS: The proposed over-the-counter label enables 98% of potential users to self-select norgestrel 0.075 mg appropriately. Only 2% of potential purchasers may have bought and started to use norgestrel 0.075 mg inappropriately. For two-thirds of these, the potential benefits of their use of the method outweighed any theoretical risks. Adverse clinical consequences of norgestrel 0.075 mg use are unlikely even in those rare cases when the drug facts label was not followed. IMPLICATIONS: The balance of the risk of inappropriate selection to the benefit of taking an over-the-counter progestin-only pill appears to be very much in favor of an overall benefit in terms of unintended pregnancy prevention.

Evaluation of adherence to a daily progestin-only pill in a simulated over-the-counter setting.

OBJECTIVE: The Adherence with Continuous Dose Oral Contraceptive: Evaluation of Self-Selection and Use (ACCESS) study assessed whether consumers can adhere to the regimen for a progestin-only pill (norgestrel 0.075 mg) in an over-the-counter (OTC) setting. STUDY DESIGN: An actual use study in a simulated OTC environment assessed adherence to directions to take norgestrel 0.075 mg every day at the same time in 883 participants for up to 24 weeks. RESULTS: Eighty-five percent (747/883) of participants reported ≥85% adherence to taking norgestrel 0.075 mg every day and reported taking their dose within three hours of their scheduled dosing time on 96% of days. When accounting for use of a condom for 48 hours if a pill was missed, participants reported correctly following the label's directed use for 97% of doses overall, with 95% of participants following label directions for ≥85% of doses. The main limitations were related to finding a balance between intensely collecting data to ensure accurate assessment of adherence and leaving users to behave as they would in a real OTC situation without healthcare practitioner intervention. We observed that some participants reported taking more doses than they could have based on the supply of medication given to them. To fully examine the situation, and the impact on the conclusions, additional post hoc sensitivity analyses were performed, and showed remarkably consistent results. CONCLUSIONS: Consumers were highly adherent to taking norgestrel 0.075 mg when using only the information provided by the proposed OTC label. IMPLICATIONS: Adherence to a daily oral contraceptive pill was high when obtained OTC. This suggests that effectiveness of an OTC pill is likely to be like that of a prescribed pill and easier access to this effective contraceptive should allow more opportunity to prevent pregnancy.

Norgestrel (Opill) Is the First Over-the-Counter Oral Contraceptive Pill Approved in the United States.

Just less than half of the pregnancies in the United States are unintended. Unintended pregnancy rates are greatest among women younger than 24 years, women of color, and those who have incomes less than 200% of the federal poverty level. Additionally, options to terminate a pregnancy are restricted or limited in some states. In July 2023, the U.S. Food and Drug Administration approved norgestrel (Opill) as the first over-the-counter oral contraceptive pill available in the United States. Norgestrel is indicated specifically for the prevention of pregnancy, contains only progesterone, and is indicated for daily oral use. This article provides an overview of over-the-counter norgestrel, including administration, adverse effects, contraindications, and practice implications for women's health nurses.

A new progestin-only pill (POP): the impact of drospirenone-only pill 4 mg 24 + 4 on coagulation markers and bleeding patterns.

PURPOSE: Progestin-only pills (POPs), compared to combined, are not associated with an increased risk of venous thromboembolism, but are associated with a poor cycle control. The aim of this study was to evaluate the impact of a new POP [4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval] on some coagulation markers (both procoagulant and fibrinolytic) and to describe its impact on bleeding patterns. MATERIALS AND METHODS: This is a prospective trial, based on serum evaluation of following coagulation markers and tests: Factor (F) X, F VIII, F V, INR, aPTT, Protein S and antithrombin III. A 'bleeding diary' was used to categorise women as having (1) unscheduled bleeding, (2) scheduled bleeding and (3) amenorrhoea. Thirty patients were followed for six 28-day intake cycles, with a follow-up at the end of the 3rd and 6th cycles. RESULTS: There was a significant decrease of F X (p = 0.03) (-5.7% at cycle 6). No significant changes have been observed for F VII, F V and INR. A significant increase in aPTT (p = 0.01 at 3 cycles), Protein S (p = 0.0006 at 3 cycles) and antithrombin III (p < 0.0001 at 3 cycles) was recorded. This non-deteriorating coagulation impact was associated with a significant and progressive reduction of days of scheduled and unscheduled bleeding in users between cycles 4 and 6 (from 1.3 ± 0.2 days at cycle 4 to 0.8 ± 0.1 days at cycle 6 and from 2.6 ± 0.4 days at cycle 4 to 0.6 ± 0.2 days at cycle 6, respectively, p < 0.0001). CONCLUSIONS: DRSP 24 + 4 use was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

Contraception with DRSP 24 + 4 was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

The efficacy, safety, and tolerability of an estrogen-free oral contraceptive drospirenone 4 mg (24/4-day regimen) in obese users.

OBJECTIVES: This study aimed to compare contraceptive efficacy and safety of drospirenone 4 mg in a 24/4-day regimen in nonobese and obese users and describe pharmacokinetics according to bodyweight. STUDY DESIGN: We analyzed data from three drospirenone 4 mg trials (2 European and 1 United States) to report outcomes in nonobese (body mass index <30 kg/m2) and obese (body mass index ≥30 kg/m2) users. We used data from the US trial to calculate the Pearl Index (pregnancies per 100 woman-years) in nonbreastfeeding participants aged ≤35 years at enrollment for confirmed pregnancies. We assessed safety outcomes from all trials based on reported treatment-emergent adverse events. We evaluated pharmacokinetics by bodyweight in the US trial. RESULTS: The three trials combined comprised 2152 nonobese and 425 obese participants, including 590 nonobese and 325 obese participants in the US trial. Eight nonobese and four obese participants had confirmed pregnancies in the US trial, resulting in Pearl Indices of 3.0 (95% CI: 1.3-5.8) and 2.9 (95% CI: 0.8-7.3), respectively. Two-hundred forty-four (11.3%) nonobese and 39 (9.2%) obese participants discontinued due to a treatment-emergent adverse event. The pharmacokinetic analysis included 814 participants with a median weight of 73 (interquartile range 61-89) kg and median plasma drospirenone exposure (AUC0-24ss) of 661.3 (interquartile range 522-828) ng∙h/mL. Changing bodyweight from the median to the fifth percentile (51 kg) or 95th percentile (118 kg) changed drospirenone exposure (AUC0-24,ss) by 22.2% and -23.6%, respectively. CONCLUSIONS: Drospirenone 4 mg demonstrated similar contraceptive efficacy for both nonobese and obese users despite a difference in exposure based on bodyweight. IMPLICATIONS: Our limited comparison between obese and nonobese users of drospirenone-only oral contraception demonstrated no evidence that efficacy or discontinuation for adverse events differs between groups. Serum drospirenone levels vary by bodyweight and may correlate with bleeding outcomes.

Drospirenone 4 mg in a 24 + 4 regimen in women with contraindications to oestrogen use for contraception: bleeding patterns according to previous menstrual characteristics.

PURPOSE: A new POP consisting of 4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval was developed to improve bleeding predictability during POP use. The aim of this study was to evaluate the effect on bleeding patterns during use of this oral contraceptive (OC) in comparison with previous menstrual cycles before the start of OC use. METHODS: This is a pilot, prospective trial. A diary was used to collect information about daily bleeding and pelvic pain before and during treatment. During OC use, women were categorised as having (1) unscheduled bleeding or spotting days (UB), (2) scheduled bleeding or spotting days (SB) and (3) absence of bleeding/spotting (AB). SF-36 and FSFI questionnaires were used to quantify health-related quality of life and the quality of sexual life in sexually active participants. RESULTS: Eighteen out of twenty-five (72%) women completed the entire follow-up. Women with UB (44.4%) were older at inclusion (p < 0.001) and had higher BMIs (p = 0.02) than those with AB (22.2%) or SB (33.4%). Women recorded a significant reduction of menstrual flow intensity during OC use (p < 0.0001). Those with UB also experienced a significant reduction of menstrual pain intensity (p = 0.006). Women with SB during OC use had a longer baseline cycle than those who reported UB during OC use (p = 0.008). Satisfaction with this OC was very high (8.4 ± 2.2 points) with no modification in SF-36 and FSFI values. CONCLUSION: A DRSP-only pill is a good OC option for women with contraindications to oestrogen use. Features of the menstrual cycle before the start of OC use may be used to predict associated changes in bleeding patterns.

Effectiveness and efficacy rates of progestin-only pills: A comprehensive literature review.

OBJECTIVES: To synthesize published literature on POP effectiveness and efficacy. STUDY DESIGN: We searched PubMed Central, PubMed, and the Cochrane library through March 07, 2022. We included articles written in English reporting a Pearl Index or life table rate for pregnancy. We excluded articles only assessing formulations that: were never marketed globally, are only sold in combination with estrogen, are currently sold only for noncontraceptive purposes, or were not given to participants continuously. Four researchers independently extracted data and two analyzed data using Excel and R. RESULTS: We included 54 studies. Among studies at low or moderate risk of bias, the median Pearl Index rate (the failure rate during typical use) was 1.63 (range 0.00-14.20, IQR 4.03) and the median method failure Pearl Index rate (the failure rate during perfect use) was 0.97 (range 0.40-6.50, IQR 0.68). Excluding the newer formulations, Desogestrel and Drospirenone, which are closer to combined oral contraceptives in that they prevent pregnancy by inhibiting ovulation, the median Pearl Index rate is 2.00 (range 0.00-14.12, IQR 2.5) and the median method failure Pearl Index rate is 1.05 (range 0.00-10.90, IQR 1.38). CONCLUSIONS: Among studies at low or moderate risk of bias, the median Pearl Index rate during typical POP use was much lower than currently estimated (7.00), while the median perfect use rate was similar to current estimates. IMPLICATIONS: Future research should investigate the possibility that POPs may be much more effective during typical use than currently believed.

Modeling the potential benefit of an over-the-counter progestin-only pill in preventing unintended pregnancies in the U.S.

OBJECTIVES: To develop a model to estimate the possible impact of use of an over-the-counter (OTC) progestin-only pill (POP) on the number of unintended pregnancies in the United States. STUDY DESIGN: Using typical use failure rates (7% for POPs), we compared the expected number of unintended pregnancies for two theoretical cohorts of 100,000 women: one which purchased and used an OTC POP exclusively for contraception, the other using contraceptive methods at proportions obtained from an actual-use clinical trial simulating OTC use of norgestrel 0.075 mg (including 35% using no method and only 19% using hormonal contraception or long-acting contraceptives). Sensitivity analyses were conducted using alternative model inputs such as different failure rates for OTC POPs and varied alternative contraceptive method mix. RESULTS: An estimated 37,624 unintended pregnancies would occur annually if 100,000 women continued their usual contraceptive method as used at baseline in the actual use trial. This would be reduced by 81% to 7,000 pregnancies with the exclusive use of an OTC POP - a net reduction of 30,624 unintended pregnancies annually. While the number of unintended pregnancies prevented varied as the model parameters were modified (ranging from 1,461 to 34,124), a net benefit of OTC POP use was observed over a wide range of input values. CONCLUSIONS: Using data from a real-world contraception user profile, our model suggests that use of an OTC POP could reduce the overall number of unintended pregnancies in the United States. This conclusion remains true across a wide range of modeled scenarios. IMPLICATIONS: The estimates suggested by this model are supportive of an OTC switch for a POP.

Mechanism of action of a 0.075 mg norgestrel progestogen-only pill 2. Effect on cervical mucus and theoretical risk of conception.

OBJECTIVE: To evaluate the cervical mucus effects of a norgestrel 0.075 mg progestin-only contraceptive pill over a 28-day cycle. STUDY DESIGN: We recruited persons ages 18 to 35 with normal cycles at 2 US academic medical centers. Participants took norgestrel 0.075 mg daily for 28 days at the same time (within a 3 hour window) daily, recorded through a text-message based e-diary. We extracted cervical mucus using a standardized aspiration technique on the day of pill initiation and then at least every 3 to 4 days over the cycle. We monitored subjects for follicular activity with transvaginal ultrasound examination and blood sampling for ovarian hormones and gonadotropins at each visit. We assessed cervical mucus scoring using a 4-category/12-point modified Insler scale (score ≥9 [favoring fertility], 5-8 [intermediate], and ≤4 [unfavorable to fertility]). We stratified cervical mucus scores by serum estradiol levels and ovulatory status based on a modified Hoogland score. RESULTS: Excluding enrollment, we collected and evaluated 413 mucus samples from 51 participants. Participants had a median mucus score of 0 (Interquartile Range 0, 2); most had scores ≤4 (samples = 385, 93%) and none had a score ≥9 favoring fertility. Seventeen (33%) participants ovulated, of which 14 (82%) had unfavorable mucus scores (≤4) at the time of ovulation and 3 (18%) had intermediate scores (5-8). CONCLUSIONS: Norgestrel 0.075 mg daily prevents mucus changes that favor fertility, even during ovulatory cycles. IMPLICATIONS: Daily administration of norgestrel 0.075 mg over an initial 28-day cycle did not result in fertile cervical mucus. Although approximately one-third of users ovulated in this first cycle of pill use, contraceptive efficacy may be maintained by mucus effects.

Adherence among a cohort taking progestin-only pills prescribed by a healthcare provider: Results of the BENCHMARK study.

OBJECTIVES: To measure adherence over six months of progestin-only pill (POP) use. STUDY DESIGN: Prospective observational cohort study measuring adherence to daily dosing and timing of dose in patients prescribed a POP, with up to six months of follow-up, conducted from January to October 2020. A pharmacy benefit manager identified potential participants with a newly prescribed POP and extended an invitation to participate. We enrolled qualified respondents by telephone, trained them to use an electronic diary to report daily whether they had taken their POP and at what time. We followed participants for up to six months. We calculated adherence to daily pill taking as the proportion of evaluable days in which a participant took a POP, and the proportion of participants reporting ≥85% adherence. We calculated adherence to same time each day as the proportion of doses taken no later than three hours after the previous dose time of day. RESULTS: The user population comprised 199 participants, 154 (77.4%) of whom completed six months of follow-up. The majority (n = 170, 85.4%) were taking norethindrone. Norethindrone users reported POP intake on 22,327 (96.4%) of 23,156 evaluable days, with 155 (91.2%) participants reporting ≥85% adherence; less than half (n = 73, 42.9%) reported 100% adherence. Participants reported adherence to same time each day on 21,698 of 22,157 (97.9%) evaluable days. CONCLUSIONS: Among participants taking a prescribed POP, participants demonstrated high adherence for daily pill taking and the same time of day, though the majority were not 100% adherent. IMPLICATIONS: This study reports data specific to adherence among those taking a progestin-only pill (POP) in the prescription setting. Clinicians who counsel patients about POP use should be aware that majority of patients were not 100% adherent, although most report ≥85% adherence.

Long-term treatment of endometriosis-related pain among women seeking hormonal contraception.

OBJECTIVE: To evaluate the different effects of a progestin-only contraceptive with desogestrel (DSG) vs combined oral contraceptives (COCs) for a first line long-term treatment of endometriosis-related pain among patients seeking hormonal contraception. METHODS: An observational retrospective cohort study was conducted in collaboration with a local outpatient clinic for endometriosis among a group of nulliparous young women (n = 216) with endometriosis-related pain and seeking contraception. The cohort was subdivided into a group (n = 73) treated as first line by DSG and another group (n = 75) treated by a COC. During the study, clinical symptoms, side effects and possible changes in OC type use were recorded. RESULTS: No significant difference was found between the two groups in terms of clinical characteristics and pain scores before treatment. After 6 months both treatments were effective in reducing endometriosis-related pain, and those treated with DSG showed lower levels of dysmenorrhea, dyspareunia and nonmenstrual pelvic pain than COCs group (p < .01). After 12 months, in DSG Group some patients (15%) switched from DSG to a COC for breakthrough bleeding, whereas in COC Group 48% of patients switched to another type of COC for reduced efficacy on pain and/or for side effects. After 3 years of OC treatment, in DSG Group 79% of patients maintained the same therapy, whereas in COC Group only 14% continued the same COC type, 37% switched to another COC and 47% to DSG. CONCLUSIONS: A progestin-only contraceptive with DSG is a valid option for long term management of endometriosis-related pain in patients seeking hormonal contraception.

The efficacy, acceptability and continuation of postpartum, post-abortive progestin-only pill: a pioneering prospective multicentric study from Turkey

Objective: The aim of this study was to evaluate the efficacy, side-effects and continuation rate of the desogestrel-progestin-only-pill (POP) in postpartum and post-abortive Turkish women and its relation with breast-feeding. Material and Methods: In this prospective multicentric study women who delivered (or had surgical abortion) and wanted to receive POP for contraception were recruited to the study. The follow-up visits were scheduled at the third, sixth and ninth months. Results: Overall A total of 7,468 women (66.5% postpartum, 33.5% post-abortive) participated in the study. The number of women who attended follow-up visits in relation to the previous visit at the third, sixth and ninth months was 944/7,468 (12.6%), 406/944 (43%) and 121/406 (29.8%) respectively. The incidence of breastfeeding at all visits was between 54.8% and 68.4%. Out of the 7,468 women recruited only 6% continued with the method at the end of the ninth month. There was a statistically significant increase in hemoglobin level at the third month compared to initial values. Oligomenorrhea, spotting and headache were the three leading side-effects. There was no pregnancy among the patients who were followed up. Conclusion: This study demonstrated that POP was an effective postpartum and post-abortive contraceptive method that had no negative impact on breast-feeding. A change in bleeding patterns was the most common side-effect. However, the possible causes of low contraceptive maintenance rates need to be investigated.

Risk factors for non-response and discontinuation of Dienogest in endometriosis patients: A cohort study.

INTRODUCTION: Progestins are commonly prescribed first-line drugs for endometriosis. High rates of non-response and intolerance to these drugs have been previously reported. However, no study to date has investigated the characteristics and comorbidities of patients taking progestins in relation to treatment outcomes, so identifying which patients will respond to or tolerate the treatment is currently impossible. The purpose of this study, therefore, was to identify risk factors for non-response and discontinuation of Dienogest (DNG) in women with endometriosis. MATERIAL AND METHODS: This is a retrospective cohort study including women currently taking, or newly prescribed, DNG for endometriosis-associated pain presenting in the Endometriosis Clinic of the University Hospital of Bern between January 2017 and May 2018. Women with initiation of treatment directly after surgery for endometriosis were excluded. For all participants the symptoms and comorbidities were documented. Effectiveness, tolerability and discontinuation of DNG were the primary end points. Univariate and multivariate binary logistic regression models were carried out to identify risk factors for non-response, intolerance and discontinuation of DNG. RESULTS: A sufficient or excellent treatment response was reported by 85/125 (68%) participants. Genital bleeding during the DNG treatment was negatively (OR 0.185, 95% CI 0.056-0.610, P = .006) and rASRM endometriosis stages III and IV were positively (OR 3.876, 95% CI 1.202-12.498, P = .023) correlated with the DNG response. When accounting for exclusively pretreatment factors, primary dysmenorrhea (OR 0.236, 95% CI 0.090-0.615, P = .003) and suspicion of adenomyosis (OR 0.347, 95% CI 0.135-0.894, P = .028) were inversely correlated with DNG response, and the latter was also correlated with treatment discontinuation (OR 3.189, 95% CI 1.247-8.153, P = .015). CONCLUSIONS: Genital bleeding during the DNG treatment and low rASRM stages are independent risk factors for DNG non-response. Before treatment initiation, primary dysmenorrhea and suspicion of adenomyosis correlate with DNG non-response. The results could assist the clinician first to provide detailed information to women before treatment initiation, second to identify and possibly modify in-therapy factors correlated to treatment effectiveness and lastly to switch treatment on time if needed.

A 1-year prospective, open-label, single-arm, multicenter, phase 3 trial of the contraceptive efficacy and safety of the oral progestin-only pill drospirenone 4 mg using a 24/4-day regimen.

OBJECTIVES: To evaluate contraceptive effectiveness and safety of oral drospirenone 4 mg 24/4-day regimen in the United States. STUDY DESIGN: We performed a prospective, single-arm, multicenter phase 3 trial in sexually active women for up to thirteen 28-day treatment cycles. Primary outcome was the Pearl index, calculated using confirmed on-drug pregnancies and evaluable cycles in nonbreastfeeding women aged ≤ 35 years. We assessed adverse events (AEs), including hyperkalemia and venous thromboembolism. RESULTS: Of 1006 women who received at least one dose of drospirenone, 352 women (35.0%) completed the trial and 654 (65.0%) women discontinued before trial end. Most participants (92.2%) were ≤ 35 years; one third had a body mass index (BMI) ≥ 30 kg/m2. Among nonbreastfeeding women aged ≤ 35 years, there were 17 pregnancies (Pearl index: 4.0; 95% confidence interval [CI], 2.3-6.4; n = 953), of which three were unconfirmed and two were from sites excluded from the main analysis for major breaches of Food and Drug Administration regulations. The Pearl index was 2.9 (95% CI: 1.5-5.1) for confirmed pregnancies among 915 nonbreastfeeding women aged ≤ 35 years from sites with no protocol violations. Nearly all (95.4%) treatment-emergent AEs were mild or moderate in intensity. No cases of venous thromboembolism were reported. The frequency of hyperkalemia was 0.5%. Women with baseline systolic/diastolic blood pressure ≥ 130/85 mmHg had a mean reduction from baseline in blood pressure at exit visit (- 8.5/- 4.9 mmHg; n = 119). No other clinically relevant changes were observed. Participant satisfaction was high. CONCLUSION: Drospirenone 4 mg 24/4 regimen provides effective contraception with a good safety/tolerability profile in a broad group of women, including overweight or obese women. IMPLICATIONS: This new progestin-only contraceptive, drospirenone 4 mg in a 24/4 regimen, provides a contraceptive option for the majority of women regardless of blood pressure or BMI.

Drospirenone 4 mg-only pill (DOP) in 24+4 regimen: a new option for oral contraception.

INTRODUCTION: The use of progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding. A new POP consisting of 4 mg drospirenone (DRSP) for 24 days plus 4-day hormone-free interval has been developed to address this need. DRSP is a potent progestin analogue of spironolactone, with antiandrogenic and antimineralocorticoid properties. AREAS COVERED: This is a narrative review of the available data on the pharmacotherapy of the new DRSP-only pill. The research includes aspects of pharmacokinetics/pharmacodynamics of the compound: the main focus is on the clinical effects of DRSP-only pill in terms of contraceptive efficacy, haemostatic effect, safety, tolerability and bleeding patterns. EXPERT OPINION: The DRSP-only pill presents a similar Pearl Index to that of common combined hormonal contraceptives: it is a POP with a better bleeding profile than traditional POPs (higher rates of scheduled bleedings and much lower rates of unscheduled intracyclic bleeding/spotting) which could increase its acceptability and the panorama of possible users. For these reasons, DRSP-only pill represents a real step forward in oral contraception with only progestins, even if the bleeding patterns during its use are still different to oestrogen-containing products (i.e. lower rates of scheduled bleedings and higher rate of amenorrhea).

Multicenter, open-label trial to assess the safety and tolerability of drospirenone 4.0 mg over 6 cycles in female adolescents, with a 7-cycle extension phase.

OBJECTIVE: To assess the safety, tolerability and bleeding patterns of drospirenone 4.0 mg. STUDY DESIGN: A multicenter, open-label, safety trial in sexually-active adolescents aged 12-17 years for six 28-day treatment cycles (Core Phase) and an optional 7-13 cycle extension with administration of drospirenone 4.0 mg in a regimen of 24 active/4 placebo tablets. RESULTS: We enrolled 111 subjects, and after eight failed Screening and one withdrew consent, 102 remained evaluable; 89 (87.3%) completed the Core Phase. Overall, treatment with drospirenone 4.0 mg was well tolerated. Possibly-related TEAEs were reported for 23 subjects (22.5% of the 102 evaluable); two serious adverse events were reported during the Extension Phase (pharyngitis and joint dislocation), neither related to treatment. The number of subjects reporting dysmenorrhea decreased from 47 prior to Screening, to 14 at the end of Cycle 6, to 8 at the end of Cycle 13. Assessments of vital signs and gynecological and physical examinations were unremarkable. We observed a trend towards less bleeding and/or spotting over the first cycles with the use of drospirenone: the proportion of subjects with both scheduled and unscheduled bleeding and spotting decreased, while the proportion with absence of bleeding or spotting increased. Only five subjects (4.9% of 102 evaluable) prematurely terminated the trial due to irregular bleeding. At the end of 6 months, 85.3% rated the tolerability of drospirenone as "excellent" or "good". CONCLUSIONS: The results indicate that 4.0 mg drospirenone over 13 treatment cycles was well tolerated, safe and acceptable for the majority of adolescents. IMPLICATIONS: Drospirenone 4.0 mg oral pills provide a well-tolerated, safe and acceptable contraceptive choice for adolescents.

Association between progestin-only contraceptive use and cardiometabolic outcomes: A systematic review and meta-analysis.

Aims The association between progestin-only contraceptive (POC) use and the risk of various cardiometabolic outcomes has rarely been studied. We performed a systematic review and meta-analysis to determine the impact of POC use on cardiometabolic outcomes including venous thromboembolism, myocardial infarction, stroke, hypertension and diabetes. Methods and results Nineteen observational studies (seven cohort and 12 case-control) were included in this systematic review. Of those, nine studies reported the risk of venous thromboembolism, six reported the risk of myocardial infarction, six reported the risk of stroke, three reported the risk of hypertension and two studies reported the risk of developing diabetes with POC use. The pooled adjusted relative risks (RRs) for venous thromboembolism, myocardial infarction and stroke for oral POC users versus non-users based on the random effects model were 1.06 (95% confidence interval (CI) 0.70-1.62), 0.98 (95% CI 0.66-1.47) and 1.02 (95% CI 0.72-1.44), respectively. Stratified analysis by route of administration showed that injectable POC with a RR of 2.62 (95% CI 1.74-3.94), but not oral POCs (RR 1.06, 95% CI 0.7-1.62), was associated with an increased risk of venous thromboembolism. A decreased risk of venous thromboembolism in a subgroup of women using an intrauterine levonorgestrel device was observed with a RR of 0.53 (95% CI 0.32-0.89). No effect of POC use on blood pressure was found, but there was an indication for an increased risk of diabetes with injectable POCs, albeit non-significant. Conclusions This systematic review and meta-analysis suggests that oral POC use is not associated with an increased risk of developing various cardiometabolic outcomes, whereas injectable POC use might increase the risk of venous thromboembolism.

Canadian Contraception Consensus (Part 3 of 4): Chapter 8 - Progestin-Only Contraception.

OBJECTIVE: To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality. OUTCOMES: Overall efficacy of cited contraceptive methods, assessing reduction in pregnancy rate, safety, ease of use, and side effects; the effect of cited contraceptive methods on sexual health and general well-being; and the relative cost and availability of cited contraceptive methods in Canada. EVIDENCE: Published literature was retrieved through searches of Medline and The Cochrane Database from January 1994 to January 2015 using appropriate controlled vocabulary (e.g., contraception, sexuality, sexual health) and key words (e.g., contraception, family planning, hormonal contraception, emergency contraception). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from January 1994 to January 2015. Searches were updated on a regular basis in incorporated in the guideline to June 2015. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of the evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). CHAPTER 8: PROGESTIN-ONLY CONTRACEPTION: Summary Statements Recommendations.

Consensus canadien sur la contraception (3(e) partie de 4) : chapitre 8 - contraception à progestatif seul.

OBJECTIF: Fournir des lignes directrices aux fournisseurs de soins quant à l'utilisation de modes de contraception pour la prévention de la grossesse et quant à la promotion d'une sexualité saine. ISSUES: Orientation des praticiens canadiens en ce qui concerne l'efficacité globale, le mécanisme d'action, les indications, les contre-indications, les avantages n'étant pas liés à la contraception, les effets indésirables, les risques et le protocole de mise en œuvre des modes de contraception abordés; planification familiale dans le contexte de la santé sexuelle et du bien-être général; méthodes de counseling en matière de contraception; et accessibilité et disponibilité des modes de contraception abordés au Canada. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans MEDLINE et The Cochrane Library entre janvier 1994 et janvier 2015 au moyen d'un vocabulaire contrôlé (p. ex. contraception, sexuality, sexual health) et de mots clés (p. ex. contraception, family planning, hormonal contraception, emergency contraception) appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre janvier 1994 et janvier 2015. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en juin 2015. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. VALEURS: La qualité des résultats a été évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau 1). CHAPITRE 8 : CONTRACEPTION à PROGESTATIF SEUL: Déclarations sommaires Recommandations.