The drospirenone only pill as a contraceptive option for breastfeeding women: First data on users' acceptability and newborn development.

BACKGROUND: Progestin-only pills (POPs) have been used for contraception in breastfeeding women for years. The existing guidelines allow the use of these contraceptives. METHODS: Multicenter study with a single visit and retrospective data review. The study involved 100 women who used a drospirenone-only pill (DRSP) for contraception for at least 5 months during breastfeeding. The study aimed to analyze for those successful users the impact on new-born development, the bleeding profile and evaluate user satisfaction. RESULTS: Analysis of the newborns showed that their growth parameters length and weight, were within the expected range of standard development. The mean birth weight was 3368 g, with the lowest recorded weight being 2860 g and the highest 5040 g. The median length of the newborns was 55 cm, ranging from 35 to 65 cm. All new-borns demonstrated appropriate growth within the established percentiles. Acceptability with the bleeding profile was rated with a VAS score: the mean acceptability rating was 82.8. Women aged 35 years or older reported significantly higher acceptability compared to younger women (≥35 years: mean = 88.4, SD = 16.5; <35 years: mean = 80.3, SD = 20.2) (p = 0.02). Sixty-one patients (N = 61; 61.0%; 95% CI: 50.7 - 70.4%) expressed willingness to continue using DRSP after breastfeeding. CONCLUSION: Among those patients who continued the use of the DRSP only-pill for 5 months, this study shows no negative impact for new-borns, with no clinical influence observed on their growth. Additionally, those users expressed high satisfaction with the bleeding profile of the pill.Clinical trial registration number: DRKS00028438 .

A phase I/II study evaluating the pharmacokinetics, pharmacodynamics, and safety of drospirenone as an oral contraceptive in Japanese women.

AIM: Drospirenone (DRSP) is a synthetic progestogen approved as a progestin-only pill for contraception in both the United States and Europe. Herein, we conducted a phase I/II study to evaluate the pharmacokinetics, pharmacodynamics, and safety of DRSP in Japanese women. METHODS: Single and multiple doses of 4 mg of DRSP were orally administered to healthy premenopausal Japanese women. In the multiple-dose period, 4 mg of DRSP was administered once daily for 24 days. Pharmacokinetics, hormone levels, and adverse events (AEs) were investigated. RESULTS: Twelve Japanese women participated in this study. The single- and multiple-dose pharmacokinetics of DRSP was similar to that reported in previous studies in Caucasians. In the multiple-dose period, no subject displayed a progesterone level of more than 5.03 ng/mL. AEs were observed in 11 (91.7%) subjects. The most common AE was genital hemorrhage, which was observed in six (50.0%) subjects, followed by diarrhea and acne in four (33.3%) subjects each. All AEs resolved or improved at the end of the study, and complete recovery was confirmed in all subjects at follow-up. CONCLUSIONS: The pharmacokinetics of DRSP in Japanese women was similar to that of previous studies performed in Caucasian women. Repeated administration of DRSP maintained low plasma progesterone levels indicating effective inhibition of ovulation. No notable safety concerns were observed. In this phase I/II study, DRSP had no obvious pharmacokinetic, pharmacodynamic, or safety issues to consider in Japanese women.

The drospirenone (DRSP)-only pill: clinical implications in the daily use.

OBJECTIVES: Progestins used in contraception are either components of combined hormonal contraceptives or are used as a single active ingredient. Progestins are highly effective in long-term contraception and have a very good safety profile with very few contraindications. METHODS: An oestrogen-free ovulation inhibitor POP has been authorised in the USA and the EU. It contains 4 mg of drospirenone (DRSP). The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular- phase levels, preventing oestrogen deficiency. RESULTS: Clinical trials have demonstrated high contraceptive effectiveness, a very low risk of cardiovascular risk events and a favourable bleeding pattern. Due to the long half-life of DRSP (30-34 h), the effectiveness is maintained even in case of a forgotten pill on a single occasion. Studies involving deliberate 4 days in one cycle 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. CONCLUSIONS: This review article will describe the clinical impact in the daily use of the 4 mg DRSP only pill and the resulting data on the effectiveness and safety of this hormonal contraceptive.

The 4 mg drospirenone-only pill improves the bleeding profile in comparison to 0.075 mg desogestrel and achieves high contraceptive efficacy even with a 24 h missed pill window.

The progestin-only pills drospirenone 4 mg and desogestrel 0.075 mg as an option for the management of dysmenorrhea and mastodynia.

INTRODUCTION: Dysmenorrhea and mastodynia are the most common gynecologic pain causes in women of all ages and races during their reproductive life. The following study aimed to show the influence of two POP´s in the development of dysmenorrhea and mastodynia after nine months of use. MATERIAL AND METHODS: A total of 858 women with 6691 drospirenone (DRSP) cycles and 332 women with 2487 desogestrel (DSG) cycles were analyzed. Women included in this study were all child-bearing potentials, at risk of pregnancy, agreeing to use only the study medication for contraception for the duration of the study medication treatment, aged 18 to 45. RESULTS: At screening, 168 (19.6%) of the 858 patients using DRSP and 64 (19,3%) of the DSG patients reported that they had suffered from dysmenorrhea within six cycles prior to the first visit before starting with the medication. 20,2% of the DRSP and 10,9% of the DSG group had a sever dysmenorrhea. After 9 cycles this was reduced to 0,6% and 3,1% respectively. In total, 96 women (11.2%) in the DRSP and 49 (14,8%) experienced mastodynia within six cycles before the screening. Of these 91.6% in the DRSP group and 91,8% in the DSG group had no or mild mastodynoa at follow-up. DISCUSSION: The progestins 4 mg and desogestrel 0,075 mg showed a marked effect in the non-contraceptive aspects of dysmenorrhea and mastodynia so that new possibilities are opened for these two benign gynecological diseases. Future studies must reaffirm these first data.

Bleeding profile of women with cardiovascular risk factors using a drospirenone only pill with 4 mg over nine cycles compared to desogestrel 0.075 mg.

OBJECTIVE: Progestin-only pills are associated with irregular bleeding patterns, including amenorrhea. Desogestrel (DSG) 75 mcg, a pill that inhibits ovulation, shows poor cycle control that may harm acceptability and compliance. A Drospirenone (DRSP)-only pill was developed with 24 & 4 days of active & placebo days every 28-day cycle to improve cycle control. STUDY DESIGN: A phase III study in healthy women aged 18 to 45 years was performed to compare the bleeding profile of women taking a DRSP versus DSG over nine cycles. 249 women were older > 35 years: 173 using DRSP and 73 DSG. 259 women had a BMI > 25 kg/m2: 189 using DRSP and 70 DSG and 340 women were smokers: 237 using DRSP and 103 DSG. The amount of unscheduled bleeding/spotting days was analyzed in each of these sub-groups and compared statistically. RESULTS: Age: During cycles 2-4, the mean number of unscheduled bleeding days and spotting was 8.1 (SD10.53) for DRSP and 20.1 (19.41) for DSG; p = .0089. BMI > 25 kg/m2: During cycles 2-4 the mean number of unscheduled bleeding days and spotting was 7.8 (SD 12.18) for DRSP and 17.7 for DSG (SD 19.39); p = .0001. Smokers: During cycles 2-4, the mean number of unscheduled bleeding days and spotting was 9.6 (SD 11.69) for DRSP and 17.4 for DSG (SD 17.47); p = .0016. CONCLUSIONS: These analyses show the improvement in the bleeding profile of women with specific cardiovascular risk factors using the DRSP only oral contraceptive product compared to DSG.ImplicationsAn improvement in the bleeding profile of women with specific cardiovascular risk factors like age > 35 years, BMI > 25kg/m2, and smokers using the DRSP only oral contraceptive product is described.Herby a higher contraceptive efficacy in these patients that additionally benefit from estrogen-free contraceptive methods is expected.

Overall and bleeding-related discontinuation rates of a new oral contraceptive containing 4 mg drospirenone only in a 24/4 regimen and comparison to 0.075 mg desogestrel.

OBJECTIVES: Progestin-only pills do not increase the risk of venous thromboembolism, stroke, and myocardial infarction but are associated with poor cycle control. A novel estrogen-free pill containing only drospirenone (DRSP) to improve bleeding patterns and tolerability and reduce discontinuation rates has been introduced into the market. The present study aims to describe the improvement in the acceptability of this DRSP-only pill, e.g. regarding the bleeding profile and the reduction in discontinuation rates due to unacceptable bleeding compared to desogestrel (DSG). STUDY DESIGN: Double-blind, double-dummy prospective phase III study in healthy women aged 18-45 years evaluating a total of 858 women with 6691 DRSP and 332 women with 2487 DSG treatment cycles. RESULTS: Overall, 82 (9.6%) women in the DRSP group and 44 (13.3%) women in the DSG group experienced treatment-emergent adverse events (TEAEs) leading to premature termination of the trial meaning that 32% more women in the DRSP group finished the trial in comparison to the DSG group (based on the AUC of Kaplan-Meier's curves). Discontinuation rates due to abnormal bleeding were 3.7% for DRSP and 7.3% for DSG users. This is a 55.7% lower discontinuation rate in the DRSP group compared to the DSG group. CONCLUSIONS: This report describes the improvement in acceptability and bleeding profile of women using the new DRSP-only oral contraceptive compared to DSG, providing a better quality of life and adherence to the contraceptive method as demonstrated by lower discontinuation rates of women using the estrogen-free DRSP-only pill.

Metabolic and laboratory effects of a progestin-only pill containing drospirenone 4 mg in comparison to desogestrel 75 µg: a double-blind, double-dummy, prospective, randomised study.

Purpose: Steroid hormones in hormonal contraceptives influence a variety of metabolic parameters. Mainly, ethinyloestradiol (EE) in combined hormonal contraceptives (CHC) is a potent inducer of hepatic coagulation factors, has an impact on cholesterol and triglyceride levels and glucose tolerance. Progestins in CHC modify the oestrogen effects in different ways, depending on their pharmacologic properties. The metabolic impact of progestin-only contraceptives is generally considered low.Methods: The influence of novel drospirenone (DRSP)-only pill (4 mg DRSP in 24/4 intake) on a variety of lipid-, carbohydrate- and bone metabolic parameters and on haemostatic variables including clotting factors and D-Dimer level was evaluated in comparison to 0.075 mg desogestrel (DSG) during a multicentric, prospective, double-blind, double-dummy clinical trial with 1190 participants over nine treatment cycles.Results: For both DRSP and DSG, there was a decrease in cholesterol (total, HDL, and LDL) and triglyceride levels. No relevant influence on glucose, insulin, and c-peptide levels or bone remodelling markers were detected in both treatment groups. Considering the coagulatory parameters, there was no impact on hemostasis.Conclusions: The results confirm the beneficial properties of the drospirenone-only pill.EudraCT Number: 2011-002396-42.

Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime.

BACKGROUND: A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks. METHODS: Three European and American multicenter clinical trials have been conducted in more than 2500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9%) had a risk factor for VTE, while in the European studies, 261 patients (16.6%) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated. RESULTS: No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed. CONCLUSIONS: The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors. TRIAL REGISTRATION: EudraCT registration numbers: 2010-021787-15 & 2011-002396-42 . Clincaltrials.gov: NCT02269241 .

Correction to: A multicenter, double-blind, randomized trial on the bleeding profle of a drospirenone-only pill 4 mg over nine cycles in comparison with desogestrel 0.075 mg.

The article A multicenter, double-blind, randomized trial on the bleeding profle of a drospirenone-only pill 4 mg over nine cycles in comparison with desogestrel 0.075 mg, written by Santiago Palacios, Enrico Colli and Pedro-Antonio Regidor, was originally published Online First without Open Access.

Oestrogen-free oral contraception with a 4 mg drospirenone-only pill: new data and a review of the literature.

Purpose: The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications.Material and Methods: A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties.Results: The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30-34 h.Conclusions: Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of ovulation inhibition after scheduled 24 h delays in pill intake.

Multicenter, phase III trials on the contraceptive efficacy, tolerability and safety of a new drospirenone-only pill.

INTRODUCTION: Approximately 100 million women currently use combined oral contraceptives. Combined oral contraceptives use is associated with increased risk of venous thromboembolic events and cardiovascular disease. Progestin-only pills do not increase the risk of venous thromboembolic events, stroke and myocardial infarction but are associated with a poor cycle control. A novel estrogen-free pill containing only drospirenone (DRSP) was developed to improve bleeding pattern, tolerability and acceptance without increasing venous thromboembolic events risks in contraception. MATERIAL AND METHODS: Two prospective, multicenter Phase III studies in healthy women aged 18-45 years were performed to demonstrate the efficacy and safety of a drospirenone-only pill in a regimen of 24 days of 4 mg of drospirenone tablets followed by 4 days of placebo. A total of 1571 women (14 329 exposure cycles) were analyzed: 713 patients in the 13-cycle study 1 with 7638 exposure cycles and 858 patients in the 9-cycle study 2 with 6691 exposure cycles. The primary endpoint was the overall Pearl index, calculated for each study separately, and for both pooled. As main secondary efficacy endpoint, the "method failure Pearl index" including all pregnancies during "perfect medication cycles" was evaluated. EudraCT registration numbers: 2010-021787-15 & 2011-002396-42. RESULTS: Calculations on pooled studies 1 and 2 with 1571 patients gave an overall Pearl index (based on 14 329 cycles) of 0.7258 (95% CI 0.3133 to 1.4301). No single case of deep vein thrombosis or pulmonary embolism and only one case of hyperkalemia were reported. Additional information such as laboratory parameters, body mass index, bodyweight, heart rate and blood pressure showed no statistically significant changes due to the treatment. CONCLUSIONS: This is the first report of a new drospirenone-only oral contraceptive providing clinical efficacy similar to combined oral contraceptives, with a good safety profile, and favorable cycle control.

A multicenter, double-blind, randomized trial on the bleeding profile of a drospirenone-only pill 4 mg over nine cycles in comparison with desogestrel 0.075 mg.

PURPOSE: A typical compliance problem in the use of traditional progestin-only pills is the irregular bleeding pattern and the strict daily intake. Desogestrel 75 mg has a 12-h missed-pill window; however, its poor cycle control limits a more common use. METHODS: A drospirenone (DRSP)-only pill was developed to improve the bleeding profile. SETTING: A phase III study in healthy women aged 18-45 years was performed to compare the bleeding profile and safety of a DRSP-only pill in a regime of 24 days of 4 mg of DRSP tablets followed by 4 days of placebo versus desogestrel 0.075 mg per day continuously over nine cycles. POPULATION: A total of 858 women with 6691 drospirenone and 332 women with 2487 desogestrel treatment cycles were analyzed. MAIN OUTCOME MEASURES: The primary end point was the proportion of women with unscheduled bleeding/spotting in each cycle from cycles 2 to 9 and cumulative in cycles 2-4 and cycles 7-9. RESULTS: In each cycle, up to cycle 7, the proportion of women with unscheduled bleeding was statistically significantly lower in the DRSP group than in the DSG group (p = 0.0001, Chi-square test). CONCLUSIONS: This report describes the improvement in bleeding profile of women using the new DRSP-only oral contraceptive in comparison to DSG, providing a better quality of live and adherence to the contraceptive method. EudraCT Registration Number: 2011-002396-42.

In vitro evaluation of microbial adhesion to a contraceptive vaginal ring with a new polymer composition.

Objective: The aim of the study was to evaluate in vitro the amount of Candida albicans and Lactobacillus acidophilus adhering to the surface of Ornibel, a contraceptive vaginal ring with a new polymer composition, in comparison with NuvaRing. Methods: Ornibel and NuvaRing were tested for adhesion of microorganisms in vitro. The vaginal rings were aseptically sectioned into 1 cm segments. Suspensions of C. albicans (1-2 × 107 colony-forming units [CFU]/ml) and L. acidophilus (1-2 × 108 CFU/ml) were prepared and incubated either in monoculture or as co-culture with the ring segments. After incubation, adherent C. albicans and L. acidophilus were quantified by plate counting. Results: In monoculture, the measured amount of adhesion of C. albicans on the ring surface was significantly lower with Ornibel compared with NuvaRing (p = 6.77 × 10-5), while the adherence of L. acidophilus did not differ between the two rings. Similarly, when co-incubated with C. albicans, the number of adhering L. acidophilus microorganisms was significantly lower with Ornibel compared with NuvaRing (p = .018) . This reduction also resulted in significantly lower levels of adhering L. acidophilus in co-culture compared with L. acidophilus when incubated alone (p = .003). Conclusion: The study demonstrates that the adherence of C. albicans, as well as that of L. acidophilus when co-cultured with C. albicans, is lower with the Ornibel vaginal ring compared with NuvaRing. These in vitro findings warrant future human trials using molecular techniques to assess the vaginal microbiota composition and to establish whether Ornibel can support vaginal health.

Drospirenone as estrogen-free pill and hemostasis: coagulatory study results comparing a novel 4 mg formulation in a 24 + 4 cycle with desogestrel 75 µg per day.

INTRODUCTION: A novel estrogen free contraceptive pill, with drospirenone 4 mg in a dosing regimen of 24 + 4, has been developed with a pearl-index of 0.51 (95% CI 0.1054; 1.4922). The aim of the following study was to determine if 4 mg DRSP has an impact on coagulation factors and thrombotic risks in comparison with desogestrel 75 µg. PATIENTS AND METHODS: Thirty-nine patients received 4 mg DRSP 24 + 4 d and 29 desogestrel 75 µg per day continuously during nine complete cycles. Following hemostatic parameters were evaluated: Apc resistance, Antithrombin III, Protein C reactivity, Factor VII, Factor VIII, and d-Dimer. RESULTS: Factor VII decreased from 1.123 to 1.066 in the DRSP group and from 1.241 to 1.034 in the desogestrel group (p = 0.0088). The difference in change of mean Protein C activity from baseline to endpoint was -0.0332 in the DRSP versus -0.157 in the desogestrel group (p = 0.0249). d-Dimer values dropped in the DRSP group from baseline values of 264.9-215.0 ng/mL, whereas in the desogestrel group there was a rise from 201.4 ng/mL to 281.5 ng/mL. DISCUSSION: DRSP 4 mg was not associated with any meaningful changes on hemostatic parameters, indicating a lack of effect on hemostasis.

Degarelix versus goserelin (+ antiandrogen flare protection) in the relief of lower urinary tract symptoms secondary to prostate cancer: results from a phase IIIb study (NCT00831233).

INTRODUCTION: No studies to date have assessed the efficacy/tolerability of degarelix in the relief of lower urinary tract symptoms (LUTS) secondary to prostate cancer (PrCa). METHODS: Patients were randomised to degarelix 240/80 mg or goserelin 3.6 mg + bicalutamide flare protection (G+B); both treatments were administered for 3 months. The primary endpoint was change in International Prostate Symptom Score (IPSS) at week 12 compared with baseline. RESULTS: This study was stopped early due to recruitment difficulties. 40 patients received treatment (degarelix n = 27; G+B n = 13); most had locally advanced disease and were highly symptomatic. Degarelix was non-inferior to G+B in reducing IPSS at week 12 in the full analysis set (p = 0.20); the significantly larger IPSS reduction in the per-protocol analysis (p = 0.04) was suggestive of superior reductions with degarelix. Significantly more degarelix patients had improved quality of life (IPSS question) at week 12 (85 vs. 46%; p = 0.01). Mean prostate size reductions at week 12 were 42 versus 25% for patients receiving degarelix versus G+B, respectively (p = 0.04; post hoc analysis). Most adverse events were mild/moderate; more degarelix patients experienced injection site reactions whereas more G+B patients had urinary tract infections/cystitis. CONCLUSION: In 40 men with predominantly locally advanced PrCa and highly symptomatic LUTS, degarelix was at least non-inferior to G+B in reducing IPSS at week 12.

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.

Development and Validation of an Endometriosis Diagnostic Method Based on Serum Biomarkers and Clinical Variables.

Endometriosis affects more than 10% of women of reproductive age, significantly impacting their quality of life. Diagnosis typically takes 4 to 11 years from symptom onset. The gold standard for diagnosing this disease, laparoscopy, is invasive, contributing to this delay in diagnosis. Two studies were conducted to develop a diagnostic test based on the combination of serum biomarkers and clinical variables. Study 1, the development study, aimed to: (i) confirm the ability of CA125, BDNF and clinical variables to differentiate between cases and controls, and (ii) develop a diagnostic algorithm based on these results. Study 2 validated the clinical performance of the developed in vitro diagnostic (IVD) test in diagnosing endometriosis. Serum samples and clinical variables extracted from psychometric questionnaires were obtained from the Oxford Endometriosis CaRe Centre biobank (UK). Case/control classification was performed based on laparoscopy and histological verification of the excised lesions. Studies 1 and 2 included n = 204 and n = 79 patients, respectively. Study 1 found a statistically significant difference between cases and controls for levels of both biomarkers. Of the assessed clinical variables from the patients' medical histories, six were found to be significantly different between endometriosis cases and controls. CA125, BDNF and these six clinical variables were combined into a multivariable prediction model. In Study 2, the IVD test demonstrated sensitivity and specificity values of 46.2% (25.5-66.8%) and 100% (86.7-100%), respectively. Due to its high specificity, this IVD test is a simple and accurate rule-in test for early disease identification, even in the presence of non-specific symptoms.

Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.

UNLABELLED: Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent. The present study showed that ADT with the gonadotropin hormone-releasing hormone (GhRH) antagonist degarelix is non-inferior to combined treatment with the LHRH agonist goserelin and bicalutamide in terms of reducing prostate volume during the treatment period of 3 months. Degarelix treatment evokes, however, significantly better relief of lower urinary tract symptoms in patients having moderate and severe voiding problems. OBJECTIVE: • To assess the efficacy of monthly degarelix treatment for reduction of total prostate volume (TPV), relief of lower urinary tract symptoms (LUTS) and improvement of quality of life (QoL) in patients with prostate cancer (PCa) using monthly goserelin as active control. METHODS: • This was a randomized, parallel-arm, active-controlled, open-label, multicentre trial on 182 patients treated with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks. • For flare protection, goserelin-treated patients also received daily bicalutamide (50 mg) during the initial 28 days. • Key trial variables monitored monthly were TPV (primary endpoint), serum testosterone, prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS) and the Benign Prostate Hyperplasia Impact Index. RESULTS: • In all, 175 patients completed the trial (96.1%). • At week 12, changes in TPV for degarelix and goserelin were similar (-37.2% vs -39.0%) and met the predefined non-inferiority criterion. • Decreases in IPSS were greater in degarelix than in goserelin-treated patients, differences being statistically significant in patients with baseline IPSS > 13 (-6.7 ± 1.8 vs -4.0 ± 1.0; P = 0.02). • The number of patients with an IPSS change of ≥ 3 over baseline was also significantly higher in patients treated with degarelix (61.0 vs 44.3%, P = 0.02). • Both treatments were safe and well tolerated. CONCLUSIONS: • Medical castration reduces TPV and could also improve LUTS in patients with PCa. • While the short-term efficacy of degarelix and goserelin + bicalutamide was the same in terms of TPV reduction, degarelix showed superiority in LUTS relief in symptomatic patients, which could highlight the different actions of these drugs on extrapituitary gonadotrophin-releasing hormone (GnRH) receptors in the bladder and/or the prostate.

Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analysis of prospective clinical trials of degarelix.

PURPOSE: We investigated associations of baseline cardiovascular disease risk profile, dosing regimen and treatment duration with incident cardiovascular disease events during androgen deprivation therapy with degarelix in patients with prostate cancer. MATERIALS AND METHODS: Data on 1,704 men who participated in a total of 9 clinical trials were pooled for analysis. Patients received treatment with 1-month (20 to 240 mg) or 3-month (240 to 480 mg) doses of degarelix for an average of 22 months. End points were ischemic heart disease, cerebrovascular disorders, arterial thrombotic/embolic events and intermittent claudication. RESULTS: First time cardiovascular disease events were reported in 92 men in the year before study entry and in 168 after degarelix treatment. Event rates were similar before and after degarelix treatment in the total population (5.5 vs 6.1/100 person-years, p = 0.45) and in men without cardiovascular disease (5.6 vs 4.3/100 person-years, p = 0.11). In contrast, event rates appeared higher after degarelix treatment in men with cardiovascular disease at baseline (5.3 to 10.5 events per 100 person-years, p = 0.0013). On multivariate analysis cardiovascular disease at baseline was the strongest independent predictor of events, followed by older age, alcohol abstinence and obesity (each p <0.05). Degarelix dose and schedule were not independently associated with cardiovascular disease events. CONCLUSIONS: In men with prostate cancer observed rates of cardiovascular disease events were similar before and after degarelix treatment. Events were largely confined to men with preexisting cardiovascular disease and further modulated by age and modifiable risk factors. Randomized, controlled trials and longer followup are key to fully clarify the comparative safety of gonadotropin-releasing hormone antagonists vs agonists.

A single-arm study to evaluate the transfer of drospirenone to breast milk after reaching steady state, following oral administration of 4 mg drospirenone in healthy lactating female volunteers.

OBJECTIVE: The primary objective of this trial was to assess the transfer of drospirenone to breast milk after daily administration of an oral test preparation containing 4 mg of drospirenone at the steady state. The secondary objective of the trial was to assess safety based on clinical and laboratory measurements and reporting of adverse events and/or adverse drug reactions. PATIENTS AND METHODS: This was an open label, non-comparative single-center study. Drospirenone 4 mg per day was the first postpartum contraceptive for the study participants who were no longer breastfeeding yet were still lactating. It was administered for 7 days to achieve steady-state concentration. All participants were volunteers who planned to use oral contraceptives as their family planning method in the future. RESULTS: Twelve volunteers completed the trial according to the protocol, and the samples of all 12 study completers were analyzed. The average concentration-time curve of drospirenone in plasma 24 h after the administration of the last dose (area under the curve (0-24 h)) was 635.33 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0-120 h)) was 1180.57 ng h/mL, respectively. The average Cmax was 48.64 ng/mL.The average concentration-time curve of drospirenone in milk 24 h after the administration of the last dose (area under the curve (0-24 h)) was 134.35 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0-120 h)) was 227.17 ng h/mL, respectively. The average Cmax was 10.34 ng/mL. CONCLUSION: On average, 18.13% of plasma drospirenone made it to breast milk and the highest concentration of drospirenone in breast milk was 17.55% of that in plasma. The total quantity of drospirenone passing to breast milk is on average 4478 ng during a 24-h period representing 0.11% of the maternal daily dose. Thus, at the recommended doses, no effects on breastfed newborns/infants are anticipated with drospirenone 4 mg.