Contraceptive efficacy and tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study.

BACKGROUND: The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 µg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexible(MIB)) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen. STUDY DESIGN: This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18-35 years) to the following regimens: flexible(MIB) (24-120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexible(MIB) only). RESULTS: Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexible(MIB) vs the conventional regimen [41.0±29.1 (95% CI 38.8-43.3) vs 65.8±27.0 (95% CI 62.2-69.4) days, p<0.0001; treatment difference -24.8 (95% CI -29.2 to -20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9-67.9) days. The Pearl Index for the flexible(MIB) regimen was 0.64 (95% CI 0.28-1.26). All regimens had comparable tolerability profiles. CONCLUSIONS: EE 20 µg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexible(MIB) also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexible(MIB) regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding.

Long-term tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

BACKGROUND: This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 µg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. STUDY DESIGN: In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRSP in the following regimens: flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible(MIB) regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. RESULTS: Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB), conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. CONCLUSIONS: EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.

Suppression of ovarian activity with a drospirenone-containing oral contraceptive in a 24/4 regimen.

BACKGROUND: This study was conducted to compare ovarian activity of an oral contraceptive containing drospirenone (drsp) 3 mg plus ethinylestradiol (EE) 20 mcg administered in 24/4 regimen compared with the conventional 21/7 regimen, during intended use and following predefined dosing errors. STUDY DESIGN: Women aged 18-35 years who ovulated or had a follicular diameter of >or=15 mm on or before Day 23 during a pretreatment cycle were admitted into this double-blind, randomized study. Participants underwent 3 treatment cycles with drsp 3 mg/EE 20 mcg in a 24/4 (n=52) or a 21/7 (n=52) regimen. In the third treatment cycle, the initial three pills in both groups were replaced with placebos. Ovarian activity was classified using the Hoogland scale during pretreatment and during Cycles 2 and 3. RESULTS: Suppression of ovarian activity was more pronounced with the 24/4 regimen--the odds ratio for a lower Hoogland score (i.e., greater ovarian suppression) with the 24/4 regimen compared with the conventional 21/7 regimen were 6.01 (95% CI: 2.29-17.94) and 3.06 (95% CI: 1.44-6.65) for Cycles 2 and 3, respectively. More women in the 24/4 regimen group had no ovarian activity 87.8% vs. 56.0% during Cycle 2 and 55.1% vs. 30.0% during Cycle 3. The 24/4 regimen was associated with a more consistent suppression (less fluctuation) of endogenous estradiol. CONCLUSION: The drsp 3 mg/EE 20 mcg oral contraceptive in a 24/4 regimen was associated with greater ovarian suppression (despite intentional dosing error), which results in decreased hormonal fluctuations, and may increase contraceptive efficacy with the low-dose formulation.

Efficacy and safety of 3 mg drospirenone/20 mcg ethinylestradiol oral contraceptive administered in 24/4 regimen in the treatment of acne vulgaris: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: A randomized, double-blind, parallel-group study to investigate the efficacy and safety of the 3 mg drospirenone (drsp)/20 mcg ethinylestradiol (EE) combined oral contraceptive (COC) administered in a 24/4 regimen (24 active tablets and 4 inert tablets per cycle) for the treatment of moderate acne vulgaris. STUDY DESIGN: Healthy females (aged 14-45 years old) with moderate facial acne were randomized to 3 mg drsp/20 mcg (n=266) or placebo (n=268) for six cycles of 28 days. RESULTS: Women who received the 3 mg drsp/20 mcg EE 24/4 COC had greater reductions from baseline in inflammatory, noninflammatory and total lesion counts. The odds of women in the 3 mg drsp/20 mcg EE 24/4 regimen COC group having 'clear' or 'almost clear' skin as rated by the investigators at end point was about fourfold greater than that in the placebo group (odds ratio 4.31; 95% CI: 2.11-9.60; p=.001). The 3 mg drsp/20 mcg EE 24/4 regimen COC was well tolerated and had a safety profile consistent with low-dose COC use. CONCLUSION: The 3 mg drsp/20 mcg EE 24/4 regimen COC was significantly more effective than placebo in treating moderate acne vulgaris.

A combined oral contraceptive containing 3-mg drospirenone/ 20-microg ethinyl estradiol in the treatment of acne vulgaris: a randomized, double-blind, placebo-controlled study evaluating lesion counts and participant self-assessment.

This study compared the efficacy of a low-dose combined oral contraceptive (COC) containing 3-mg drospirenone and 20-microg ethinyl estradiol (3-mg DRSP/20-microg EE) administered in a 24-day active pill/4-day inert pill (24/4) regimen and placebo in women with moderate acne vulgaris during 6 treatment cycles. A total of 534 participants were randomized and dispensed study medication (n = 266 [3-mg DRSP/20-microg EE 24/4 regimen COC group]; n = 268 [placebo group]). Women of reproductive age were eligible for inclusion in the study. Treatment with the 3-mg DRSP/20-microg EE 24/4 regimen COC was associated with a greater reduction from baseline to end point in individual lesion counts (papules, pustules, open and closed comedones) compared with placebo. The mean nodule count remained essentially constant throughout the study and was low in both treatment groups. There was a significantly higher probability that a participant had an improved assessment on the investigator's overall improvement rating scale (odds ratio [OR], 4.02; 95% CI [confidence interval], 2.29-7.31; P < .0001) and participant's overall self-assessment rating scale (OR, 2.82; 95% CI, 1.60-5.13; P = .0005) in the 3-mg DRSP/20-microg EE 24/4 regimen COC group than in the placebo group. The COC 3-mg DRSP/20-microg EE 24/4 regimen is a suitable option for women with moderate acne vulgaris who require contraception.

A comparison of the cycle control, safety, and efficacy profile of a 21-day regimen of ethinylestradiol 20mug and drospirenone 3mg with a 21-day regimen of ethinylestradiol 20mug and desogestrel 150mug.

OBJECTIVE: To compare the cycle control, efficacy, and safety of a new low-dose combined oral contraceptive containing ethinylestradiol 20mug and drospirenone 3mg with an established formulation containing ethinylestradiol 20mug and desogestrel 150mug. METHODS: This was a randomized, open-label, parallel-group, multicenter study of healthy women (aged 18-35 years) over seven treatment cycles. Both combined oral contraceptives were administered once daily for 21 consecutive days followed by a 7-day hormone-free interval. RESULTS: A total of 445 women were randomized to treatment; of these, 441 (ethinylestradiol 20mug/drospirenone 3mg, n = 220; ethinylestradiol 20mug/desogestrel 150mug, n = 221) went on to receive study medication. There was a trend towards reduced intracyclic bleeding with continued treatment in both treatment groups, consistent with clinical experience. Intracyclic bleeding was highest during the first treatment cycle in both treatment groups, but was generally much lower in subsequent cycles. More than 90% of women in each of the groups experienced withdrawal bleeding during the study. The duration of withdrawal bleeding remained fairly constant throughout the study. The maximum intensity was mainly bleeding, rather than spotting. Overall, cycle control, efficacy, and safety profiles were comparable between both groups. Adverse events were generally of mild-to-moderate intensity and were those typical of hormonal contraceptive use. CONCLUSION: In conclusion, both ethinylestradiol 20mug/drospirenone 3mg and ethinylestradiol 20mug/desogestrel 150mug are effective and well tolerated contraceptives that provide good cycle control.

Effects of two combined oral contraceptives containing ethinyl estradiol 20 microg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism.

OBJECTIVE: To compare the effect of ethinyl estradiol 20 microg/drospirenone 3 mg (EE 20 microg/DRSP 3 mg) administered according to a 24/4 regimen with ethinyl estradiol 20 microg/desogestrel 150 microg (EE 20 microg/DSG 150 microg) administered according to the conventional 21/7 regimen on lipid, carbohydrate and hemostatic parameters. STUDY DESIGN: In this open-label study, healthy women were randomized to EE 20 microg/DRSP 3 mg or EE 20 microg/DSG 150 microg for seven cycles. Mean differences in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels at cycle 7 compared to baseline were assessed. Secondary variables included changes in other lipid, hemostatic and carbohydrate parameters. RESULTS: Both treatments increased HDL-cholesterol, but decreased LDL-cholesterol by a comparable extent. Although slightly elevated in both groups, blood glucose and C-peptide levels measured during oral glucose tolerance tests were within normal reference ranges at cycle 7. Overall, the differences in lipid, hemostatic or carbohydrate parameters were not significant between the two treatments. CONCLUSION: EE 20 microg/DRSP 3 mg has a good safety profile comparable with EE 20 microg/DSG 150 microg.

Efficacy and safety of an oral contraceptive containing ethinylestradiol 20 µg/drospirenone 3 mg (24/4 regimen) in three indications in the People's Republic of China: a comparison with international studies.

While combined oral contraceptives are a popular choice in developed Western countries, they are used by only 1% of women who are married or in a relationship in the People's Republic of China. The purpose of this review is to describe the efficacy and safety of the combined oral contraceptive containing ethinylestradiol (EE) 20 µg/drospirenone 3 mg taken in a 24/4 regimen (YAZ®; Bayer HealthCare Pharmaceuticals, Berlin, Germany) by Chinese women and to compare these results with those in women assessed in the international studies. Studies of EE 20 µg/drospirenone 3 mg in three different indications (contraception, acne, and premenstrual dysphoric disorder [PMDD]) have been conducted in Chinese women. The results of these three studies indicate that the EE 20 µg/drospirenone 3 mg combined oral contraceptive is a good long-term contraceptive option in Chinese women, providing 99% contraceptive protection over the observed 1-year treatment period, and additionally had a favorable effect on moderate acne vulgaris and relieved the symptoms of PMDD. The contraceptive efficacy, improvement in acne, and relief from PMDD symptoms observed in these studies did not differ from the effects observed in other international studies of EE 20 µg/drospirenone 3 mg, indicating that EE 20 µg/drospirenone 3 mg is as effective in Chinese women as in other ethnicities. Further, EE 20 µg/drospirenone 3 mg demonstrated a similar safety and tolerability profile in women enrolled in the Chinese and international trials, with no unexpected adverse events reported in any of the three Chinese trials. Overall, the efficacy, tolerability, and degree of non-contraceptive benefits with EE 20 µg/drospirenone 3 mg appear similar in Chinese women when compared with those reported in larger studies done at other international centers.

Efficacy and safety of a low-dose 24-day combined oral contraceptive containing 20 micrograms ethinylestradiol and 3 mg drospirenone.

The aim of this open-label, multicenter, noncomparative study was to determine the efficacy, safety and bleeding profile of a new low-dose, monophasic combined oral contraceptive containing 20 micrograms ethinylestradiol and 3 mg drospirenone administered daily for 24 days followed by a 4-day hormone-free interval. Contraceptive efficacy was analyzed for 1018 women completing 11,140 treatment cycles. Eleven pregnancies occurred, giving a Pearl Index (PI) of 1.29 (upper limit of the 95% confidence interval [CI], 2.30); of these pregnancies, five were considered due to method failure, giving an adjusted PI of 0.72 (upper limit of the 95% CI, 1.69). A total of 7 (0.7%) women discontinued study medication because of irregular bleeding, suggesting a favorable bleeding profile. Overall, the treatment was well tolerated with an excellent safety profile. The majority of women (86%) stated that they were satisfied or very satisfied with the treatment and over 70% of women would have continued with the study medication.

Different Pearl Indices in studies of hormonal contraceptives in the United States: impact of study population.

OBJECTIVE: To examine the impact of subject characteristics on efficacy as measured by the Pearl Index (PI) in clinical trials and to make study populations similar by matching. METHODS: Our analysis used US data from four large Phase III studies. We compared results from one fertility control patch study with pooled data from three studies with virtually identical design on oral hormonal contraceptives. First, we identified three characteristics that had the most impact on the PI. Second, we used these three variables and matched subjects from the patch study with those from the oral contraceptive (OC) studies. Finally, we calculated the PIs for matched and unmatched subjects from both the patch study and the OC studies. RESULTS: A total of 3706 subjects were included in our analysis. The variables 'Hispanic ethnicity', 'previous pregnancy' and 'previous use of hormonal contraceptives' had the most impact on the PI. The PIs for the matched patch cohort and the matched OC cohort were 2.97 and 2.48, respectively. Those for the unmatched patch cohort and the unmatched OC cohort were 10.17 and 0.90, respectively. CONCLUSION: Subject characteristics strongly influence the PI in clinical studies of hormonal contraceptives. In particular, Hispanic ethnicity, previous pregnancies and no previous use of hormonal contraceptives result in a higher PI. IMPLICATIONS: PIs from different clinical trials cannot be meaningfully compared unless subject characteristics that have most impact on the PI are similar or are made to be similar statistically as we did here by matching.

A historical cycle control comparison of two drospirenone-containing combined oral contraceptives: ethinylestradiol 30 µg/drospirenone 3 mg administered in a 21/7 regimen versus ethinylestradiol 20 µg/drospirenone 3 mg administered in a 24/4 regimen.

OBJECTIVES: To compare the bleeding patterns and cycle control of an oral contraceptive (OC) containing ethinylestradiol (EE) 30 µg/drospirenone (drsp) 3mg administered in a 21/7 regimen versus a lower-dose OC containing EE 20 µg/drsp 3mg administered in a 24/4 regimen, using data from two identically designed studies. MATERIALS AND METHODS: In the first study, 326 healthy women (18-35 years) received EE 30 µg/drsp 3mg in a 21/7 regimen. In the second study, 1027 healthy women (17-36 years) received EE 20 µg/drsp 3mg in a 24/4 regimen. Participants recorded bleeding using daily completed diaries over 13 treatment cycles. RESULTS: During cycles 1-12, the prevalence of scheduled withdrawal bleeding was lower with EE 20 µg/drsp 3mg 24/4 than with EE 30 µg/drsp 3mg 21/7 (82.0-91.7% versus 94.8-100.0% of women, respectively); moreover, a higher proportion of women reported a maximum intensity of light scheduled withdrawal bleeding with EE 20 µg/drsp 3mg 24/4 than with EE 30 µg/drsp 3mg 21/7 (30.9-39.0% versus 13.8-20.5% of women, respectively). In cycles 2-13, unscheduled intracyclic bleeding was reported by 7.7-13.8% of EE 20 µg/drsp 3mg 24/4 recipients and 3.8-7.9% of EE 30 µg/drsp 3mg 21/7 recipients; these were mainly single bleeding days. During reference periods 1-4, the mean number of bleeding episodes was similar between groups (3.1-3.3 episodes with EE 20 µg/drsp 3mg 24/4 versus 3.2 episodes with EE 30 µg/drsp 3mg 21/7). CONCLUSIONS: A low-dose 24/4 regimen OC containing EE 20 µg/drsp 3mg is generally comparable in terms of bleeding to a higher-dose 21/7 regimen OC containing EE30 µg/drsp 3mg. Between-treatment differences in bleeding intensity and unscheduled intracyclic bleeding rates were observed.

Suppression of ovarian activity with a low-dose 21/7-day regimen oral contraceptive containing ethinylestradiol 20 mcg/drospirenone 3 mg in Japanese and Caucasian women.

BACKGROUND: Two studies assessed the effect of a low-estrogen-dose 21/7-day oral contraceptive containing ethinylestradiol and drospirenone (EE 20 mcg/drsp 3 mg) on ovarian activity in Japanese and Caucasian women. STUDY DESIGN: Study 1 was conducted in Japanese women (20-35 years), and Study 2 was conducted in Caucasian women (18-35 years). All women received EE 20 mcg/drsp 3 mg in a 21-day active pill regimen. The primary endpoint was the proportion of women with ovulation inhibition (Hoogland score <6; as assessed by transvaginal ultrasonography) during treatment cycle 2. RESULTS: Japanese (n=23) and Caucasian (n=30) women received two cycles of study treatment. During treatment cycle 2, ovulation was inhibited in 100% and 92.9% of Japanese and Caucasian women, respectively. CONCLUSIONS: EE 20 mcg/drsp 3 mg in a 21/7-day regimen provides comparable ovarian suppression in Japanese and Caucasian women, with normal ovarian function resuming shortly after treatment end in both populations.

Detailed analysis of a randomized, multicenter, comparative trial of dienogest versus leuprolide acetate in endometriosis.

OBJECTIVE: To analyze the secondary efficacy and safety outcomes from a recent trial comparing dienogest (DNG) with leuprolide acetate (LA) in women with endometriosis. METHODS: A 24-week, open-label, randomized, multicenter study of DNG versus LA in women with endometriosis-related pain was assessed for outcomes such as responder rates (using predefined thresholds of pain relief), changes in single symptoms/signs and sum scores from the Biberoglu and Behrman (B&B) scale, clinical laboratory parameters, and measures of quality of life. RESULTS: Dienogest was non-inferior to LA for treatment response using all predefined thresholds of pain relief and provided equivalent improvements in B&B symptoms and signs. No clinically relevant changes in laboratory parameters were observed during DNG treatment, whereas estrogen levels decreased in the LA group. Compared with LA, DNG was associated with pronounced improvements in specific quality-of-life measures. CONCLUSION: The analyses provide supportive evidence that the efficacy of DNG is equivalent to that of LA for treating endometriosis symptoms, with specific quality-of-life benefits and a favorable safety profile.

Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study.

BACKGROUND: This study investigated the effects of adding levomefolate calcium 0.451 mg (the calcium salt of L-5-methyltetrahydrofolate; Metafolin®) to an oral contraceptive containing ethinylestradiol (EE) 20 mcg/drospirenone (drsp) 3 mg on folate levels in healthy women seeking contraception. STUDY DESIGN: In this randomized, double-blind, multicenter US-based study, women (18-40 years) received 24 weeks (six cycles) of EE/drsp/levomefolate calcium or EE/drsp for 24 days followed by 4 days of levomefolate calcium alone or placebo, respectively. The primary efficacy variables were red blood cell (RBC) and plasma folate levels at 24 weeks. RESULTS: At week 24, increases from baseline in mean RBC (990 ± 390 nmol/L to 1406 ± 440 nmol/L) and plasma folate (45.0 ± 17.6 nmol/L to 60.8 ± 19.9 nmol/L) levels were observed in women who received EE/drsp/levomefolate calcium [per protocol set (n=262); all values are displayed as mean ± standard deviation]. In contrast, marginal fluctuations were observed with EE/drsp (p<.0001 for between-treatment differences at week 24). CONCLUSION: Clinically significant increases in folate status were observed with EE/drsp/levomefolate calcium compared with EE/drsp alone in US women of childbearing age.

Premenstrual dysphoric disorder symptom cluster improvement by cycle with the combined oral contraceptive ethinylestradiol 20 mcg plus drospirenone 3 mg administered in a 24/4 regimen.

BACKGROUND: A combined oral contraceptive comprising ethinylestradiol (EE) 20 mcg/drospirenone 3 mg in a 24/4 regimen has been clinically shown to alleviate the symptoms associated with premenstrual dysphoric disorder (PMDD). However, previous studies did not report data according to cycle-by-cycle improvement. STUDY DESIGN: This was a subanalysis of a Phase III, double-blind, multicenter, United States-based study. Women with confirmed PMDD were randomized to EE 20 mcg/drospirenone 3 mg 24/4 or placebo for three treatment cycles. Ten of the 21 emotional and physical items on the Daily Record of Severity of Problems scale were grouped to define three symptom clusters: (a) negative emotions, (b) food cravings and (c) water retention-related symptoms. The change from baseline at each treatment cycle was compared between groups using a weighted analysis of covariance model. RESULTS: The full analysis set comprised 449 women. Daily Record of Severity of Problems scores for each symptom cluster were significantly reduced from baseline with both EE 20 mcg/drospirenone 3 mg 24/4 and placebo (p<.0001 for all). The greatest symptom improvements were achieved within the first cycle of treatment and continued throughout cycles 2 to 3. The mean between-treatment difference was significant in favor of EE 20 mcg/drospirenone 3 mg 24/4 for all three symptom clusters in all three treatment cycles (p≤.0001 vs. placebo in percent change from baseline). CONCLUSION: Ethinylestradiol 20 mcg/drospirenone 3 mg 24/4 improved commonly recognizable PMDD symptom clusters relating to negative emotions, food cravings and water retention-related symptoms to a significantly greater extent than placebo during all three cycles of treatment.

Ethinyl estradiol 20µg/drospirenone 3mg 24/4 oral contraceptive for the treatment of functional impairment in women with premenstrual dysphoric disorder.

OBJECTIVE: To determine the effects of ethinyl estradiol (EE)/drospirenone in a 24/4 regimen (24days of active and 4days of inactive pills) on functional impairment (affecting work, partnership, and social activities) in women with premenstrual dysphoric disorder (PMDD). METHODS: The present study was a secondary analysis of a double-blind, randomized, parallel-design multicenter trial. Women received EE 20µg/drospirenone 3mg (n=232) or placebo (n=218) and completed the Daily Record of Severity of Problems (DRSP) scale daily. RESULTS: The decrease in mean scores for all 3 DRSP functional impairment items (work, partnership, and social activities) from baseline to cycle 3 mirrored changes in the total DRSP symptom score; the greatest decreases were observed in cycle 1 with further small reductions through to cycle 3. The proportional mean decreases from baseline to cycle 1 for the 3 functional items ranged from 47% to 48%. For all 3 functional items, the mean reductions from baseline to cycle 1 (but not from cycle 1 to cycles 2 and 3) were significantly greater with EE/drospirenone than with placebo (P<0.05). CONCLUSION: Ethinyl estradiol 20µg/drospirenone 3mg in a 24/4 regimen significantly improved functional impairment in women with PMDD. Symptoms improved in parallel.

Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 µg plus drospirenone 3mg administered in a 24/4 regimen: a pooled analysis.

OBJECTIVE: To investigate the effects of an ethinylestradiol (EE) 20 µg/drospirenone (drsp) 3mg combined oral contraceptive (COC) administered in a 24/4 regimen (24 active tablets/4 inert tablets per cycle) for the treatment of moderate acne vulgaris, based on a pooled analysis of two identically designed US studies. STUDY DESIGN: Healthy females (n=893) aged 14-45 years with moderate facial acne were randomised to EE 20 µg/drsp 3mg COC (n=451) or placebo (n=442) for six cycles. Primary outcome measures were mean percent change in acne lesion counts and the investigators' assessment of acne from baseline to endpoint. RESULTS: There were significantly greater reductions in the mean percent change from baseline to endpoint in inflammatory, non-inflammatory and total lesion counts in the EE 20 µg/drsp 3mg 24/4 COC group compared with the placebo group (P<0.0001). The odds of women in the EE 20 µg/drsp 3mg 24/4 COC group having 'clear' or 'almost clear' skin as rated by the investigators at endpoint were around three-fold greater than in the placebo group (odds ratio 3.41; 95% CI: 2.15-5.43; P<0.0001). CONCLUSIONS: A low-dose COC containing EE 20 µg/drsp 3mg (24/4) more effectively reduced acne lesions than placebo and demonstrated greater improvement in the investigator global assessment of acne.

Cycle control and bleeding pattern of a 24/4 regimen of drospirenone 3 mg/ethinylestradiol 20 µg compared with a 21/7 regimen of desogestrel 150 µg/ethinylestradiol 20 µg: a pooled analysis.

BACKGROUND AND OBJECTIVE: The degree of cycle control achieved with a hormonal contraceptive method is an important determinant of its acceptance and continuation. This study set out to compare the cycle control and bleeding profile of drospirenone (DRSP) 3 mg/ethinylestradiol (EE) 20 µg in a 24-active pill/4-inert pill (24/4) regimen (YAZ®) with those of desogestrel (DSG) 150 µg/EE 20 µg in a 21/7 regimen (Mercilon®), an established European combined oral contraceptive (COC). METHODS: Bleeding data from women aged 17-36 years who received either DRSP 3 mg/EE 20 µg in a 24/4 regimen (n = 1285) or DSG 150 µg/EE 20 µg in a 21/7 regimen (n = 471) during four clinical studies were pooled and analysed over seven treatment cycles. RESULTS: The maximum intensity of scheduled withdrawal bleeding was 'normal bleeding' for >50% of subjects in cycles 1-6 in both treatment groups. Moreover, the incidence of unscheduled intracyclic bleeding during cycles 2-7 was comparable between treatment types (10.2-14.9% in women treated with DRSP 3 mg/EE 20 µg 24/4 vs 8.6-13.8% in women treated with DSG 150 µg/EE 20 µg 21/7). Overall, similar bleeding patterns were observed with both treatments. CONCLUSION: DRSP 3 mg/EE 20 µg 24/4 is associated with a bleeding profile and cycle control that is comparable to that of an established, low-dose COC formulation.

Contraceptive efficacy of a combined oral contraceptive containing ethinyloestradiol 20 µg/drospirenone 3mg administered in a 24/4 regimen: a pooled analysis of four open-label studies.

OBJECTIVE: To determine the contraceptive efficacy of a low-dose combined oral contraceptive containing ethinyloestradiol (EE) 20 µg/drospirenone (drsp) 3mg administered for 24 days followed by a four-day hormone-free interval (24/4 regimen), by pooling data from four clinical trials. STUDY DESIGN: Data on the occurrence of pregnancy during treatment in four open-label trials that enrolled healthy female volunteers aged 17-36 years, who received EE 20 µg/drsp 3mg in a 24/4 regimen for 7 or 13 cycles, were pooled. RESULTS: Sixteen pregnancies occurred among 2386 women during 729,537 days (26,055 cycles) of treatment exposure, resulting in a Pearl Index (PI) of 0.80 (upper two-sided 95% confidence interval (CI) limit of 1.30). Of these pregnancies, seven were defined as method failures, resulting in an adjusted PI of 0.41 (upper two-sided 95% CI limit of 0.85), based on 616,607 days (22,022 cycles) of treatment. The Kaplan-Meier estimate for the one-year cumulative probability of contraceptive protection was 99.21%. CONCLUSIONS: The EE 20 µg/drsp 3mg combined oral contraceptive administered in a 24/4 regimen has acceptable contraceptive efficacy.

Bleeding pattern with drospirenone 3 mg+ethinyl estradiol 20 mcg 24/4 combined oral contraceptive compared with desogestrel 150 mcg+ethinyl estradiol 20 mcg 21/7 combined oral contraceptive.

BACKGROUND: The study was conducted to compare cycle control, bleeding pattern and efficacy of two low-dose combined oral contraceptives. STUDY DESIGN: Four hundred fifty-three women were randomized to receive a 24/4 regimen of drospirenone 3 mg/ethinyl estradiol 20 mcg (drsp 3 mg/EE 20 mcg; n=230) or a 21/7 regimen of desogestrel 150 mcg/EE 20 mcg (DSG 150 mcg/EE 20 mcg; n=223), and recorded bleeding daily over 7 treatment cycles. RESULTS: The duration [mean 4.7 (SD 1.5)-5.2 (SD 2.2) days in the drsp 3 mg/EE 20 mcg 24/4 group and 5.1 (SD 1.5)-5.4 (SD 2.1) days in the DSG 150 mcg/ EE 20 mcg group] and maximum intensity ("normal bleeding" for >50% of all subjects) of scheduled bleeding in Cycles 1-6 was comparable between treatment groups. The incidence of unscheduled bleeding during Cycles 2-6 was also similar between the two groups (drsp 3 mg/EE 20 mcg, 8.8-17.3%; DSG 150 mcg/ EE 20 mcg, 9.4-16.3%). CONCLUSION: Drsp 3 mg/EE 20 mcg 24/4 achieved an acceptable bleeding profile with reliable cycle control, comparable with an established formulation.