Estradiol Matrix Research Articles

Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures.

ObjectiveTransdermal estradiol patches are primarily designed for adult women. No low-dose patches are licensed for pubertal induction in hypogonadal girls. Low doses can be achieved by cutting a matrix patch into smaller pieces. However, the manufacturers do not guarantee stability or utility of cut estradiol patches. The aim of the study was to assess 1-month stability of cut estradiol patches from four different manufacturers in the laboratory at room temperature (+21°C) and at an elevated temperature (+35°C).Design and methodsEstraderm MX 50 µg, Systen 50 µg and Oesclim 25 µg matrix patches were cut into eight pieces while Estradot 50 µg small patches were cut in half. The cut patches were stored in their respective pouches at +21°C or at +35°C for up to 1 month. The estradiol drug was extracted from the patch by ethyl acetate n-hexane and determined by radioimmunoassay.ResultsStorage at +21°C or +35°C up to 1 month did not reduce the estradiol concentration in Estraderm MX, Systen and Oesclim patches. However, although the estradiol in Estradot patches was not affected by storage at +21°C, at +35°C, estradiol decreased by 57% (±1%) in cut pieces.ConclusionsUnused Estraderm MX, Systen and Oesclim patch pieces may be stored for at least 1 month at ≤+35°C. Where estradiol patches for children are not available, cut pieces of these or similar patches can be used for pubertal induction. The Estradot patch was too small to properly cut into low doses and not stable in elevated temperatures.

An estradiol matrix transdermal system for the prevention of postmenopausal bone loss

ObjectiveThe aim of this study was to evaluate the efficacy, safety, and tolerability of 2 years' application of an estradiol matrix transdermal system for the prevention of postmenopausal bone loss. MethodsIn this multicenter, randomized, placebo-controlled, parallel-group study, 261 surgically or naturally postmenopausal women were randomized to apply the estradiol matrix transdermal system (0.025, 0.0375, 0.05, or 0.1 mg/d) or matching placebo twice a week for 2 years. The study was double blind with respect to treatment (active vs placebo) but not to the dose levels of active treatment (because of the differing sizes and shapes of the patches). In addition to receiving the assigned treatment, the 100 nonhysterectomized women received 2.5 mg medroxyprogesterone acetate daily throughout the study. ResultsThe evaluable group (n = 259) had a mean age of 52 years and a mean duration of menopause of 32 months. Following 2 years of treatment, there were significant differences in favor of estradiol between all doses of the estradiol matrix transdermal system and placebo in terms of the percentage change from baseline in the bone mineral density (BMD) of the L1-L4 anteroposterior lumbar spine (0.1 and 0.05 mg/d, P < 0.001; 0.0375 mg/d, P = 0.024; 0.025 mg/d, P = 0.002). Percentage changes from baseline in the BMD of the femoral neck after 2 years of treatment also consistently demonstrated the efficacy of the estradiol matrix transdermal system compared with placebo (all, P ≤ 0.044). The estradiol matrix transdermal system was well tolerated. ConclusionThe estradiol matrix transdermal system was effective in preventing postmenopausal bone loss at dosages of 0.025 to 0.1 mg/d, and had a safety profile consistent with the known effects of estrogen/progestin.

Low-dose 17-beta estradiol matrix transdermal system in the treatment of moderate-to-severe hot flushes in postmenopausal women

This prospective, multicenter, randomized, double-masked, parallel-group study assessed the efficacy, safety, and tolerability of a low-dose (0.0375 mg/d) estradiol matrix transdermal delivery system for the treatment of moderate-to-severe postmenopausal hot flushes. Healthy women with moderate-to-severe postmenopausal hot flushes were included in the study. Estradiol matrix or matching placebo patches were administered over three 4-week treatment cycles, and responses were assessed over a 12-week treatment period. Two hundred fifty-seven patients (130 receiving estradiol, 127 receiving placebo) were included in the intent-to-treat population, 242 of whom were assessable for efficacy. Efficacy measures, including change from baseline in mean number of hot flushes per 24 hours in the last 2 weeks of cycle 1 (weeks 3 and 4), change from baseline in mean number of hot flushes in 4 weeks of cycles 2 (weeks 5 through 8) and 3 (weeks 9 through 12), and change from baseline in mean overall severity of hot flushes in the last 2 weeks of cycle 1, the 4 weeks of cycles 2 and 3 revealed significantly greater improvement with the estradiol matrix than with placebo at all time points (P < 0.001). Patients' global assessments of treatment effectiveness also significantly favored the estradiol matrix over placebo (P < 0.001). Overall, both test patches were well tolerated, with individual adverse effects reported by similar proportions of patients in both groups. The incidence of application-site reactions was identical (3.1%) in both groups. The estradiol matrix was associated with a higher frequency of estrogen-related effects, such as breast pain (estradiol matrix, 10%; placebo, 0.8%). All other drug-related adverse effects were reported in ≤3.1% of patients in both groups. Simple endometrial hyperplasia was found in 2 patients receiving estradiol matrix but none of the patients receiving placebo. The lowest available dosage of this estradiol matrix transdermal delivery system (0.0375 mg/d) provided significant relief from moderate-to-severe postmenopausal hot flushes and was well tolerated.

Significant differences in estradiol bioavailability from two similarly labelled estradiol matrix transdermal systems

Objective To compare the bioavailabilities of estradiol delivered by two transdermal estradiol matrix systems; Alora® and Evorel®.Study design A single-center, open-label, randomized, two-period cross-over study in 33 postmenopausal women. The subjects received two successive 84-h applications of either Alora or Evorel (each labelled to deliver 50 μg/day 17β-estradiol) in a randomized sequence. Serial serum samples, collected over the 84-h period following the application of the second patch, were analyzed for estradiol using a validated radioimmunoassay method.Results The fluctuation index produced by Evorel was significantly higher than that produced by Alora (Evorel, 135%; Alora, 76%; p < 0.0005). In addition, the estradiol baseline-corrected area under the curve for Evorel was significantly lower than that for Alora (Alora, 2871.8 pg h/ml; Evorel, 1870.6 pg h/ml; p < 0.0005). Both patches were found to be generally well tolerated.Conclusion Alora delivered a higher, more consistent concentration of estradiol into the systemic circulation over the entire dosing interval than did Everol. Although the full clinical significance of these findings is currently unknown, this study demonstrates that there are significant differences in estradiol delivery from these two products, although they are labelled with the same nominal delivery rate.

Comparison of Alora® estradiol matrix transdermal delivery system with oral conjugated equine estrogen therapy in relieving menopausal symptoms

Objective To compare the efficacy of two strengths of an estradiol matrix transdermal delivery system with daily oral doses of conjugated equine estrogens in reducing the frequency of moderate-to-severe hot flushes in postmenopausal women.Design The design of the study provided for the following treatment regimens: an estradiol transdermal delivery system (Alora® 0.05 or 0.1 mg/day) administered twice weekly or oral doses of conjugated equine estrogens (CEE 0.625 or 1.25 mg) administered daily were given to 321 highly symptomatic postmenopausal women for 12 weeks following a randomized, parallel-group, double-blind, double-dummy design.Results Results indicate no statistically significant differences at any time point in mean frequency or mean percentage reduction in frequency of moderate-to-severe hot flushes between patients given Alora 0.1 mg/day and those receiving CEE 1.25 mg/day. Similarly, no significant differences were observed at any time in mean frequency of moderate-to-severe hot flushes between the Alora 0.05 mg/day and CEE 0.625 mg/day groups, although the group receiving CEE 0.625 mg/day exhibited a statistically greater percentage reduction than the Alora 0.05 mg/day group at weeks 3,4 and 8. By week 12, these two treatments were statistically indistinguishable. There were no serious or unexpected adverse events with the two transdermal systems and local skin tolerability was excellent. Other estrogenic effects such as restoration of vaginal cytology, breast tenderness and unexpected vaginal bleeding were comparable between transdermal and oral administration groups except for a lower incidence of bleeding in those women receiving the lower dose transdermal regimen.

Clinical Evaluation of Low-Dose 17-Beta Estradiol Matrix Transdermal Therapeutic System in the Management of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women

Clinical Evaluation of Low-Dose 17-Beta Estradiol Matrix Transdermal Therapeutic System in the Management of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women

Efficacy and tolerability of ®estraderm MX, a new estradiol matrix patch

Objectives: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. Methods: A multicenter, double-blin, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. Results: Estraderm MX was significantly superior to placebo ( P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6–5.5). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo ( P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. Conclusions: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.

Double-masked, multicenter study of an estradiol matrix transdermal delivery system (Alora™) versus placebo in postmenopausal women experiencing menopausal symptoms

This 12-week, double-masked, double-dummy, randomized, parallel-group study compared the efficacy and safety of an estradiol matrix transdermal delivery system (Alora™) in two strengths (50-μg/d estradiol and 100-μg/d estradiol) with placebo in postmenopausal women who were experiencing at least 60 moderate-to-severe hot flushes per week. In 273 postmenopausal women, the reduction in the frequency of moderate-to-severe hot flushes was significantly better than placebo within 2 weeks of initiating therapy in the 100-μg/d group and within 3 weeks of initiating therapy in the 50-μg/d group. The reduction in hot flushes for both active treatment groups remained significantly different from placebo throughout the 12-week trial. Improvement in vaginal cytology profile (maturation index) was observed in both active treatment groups. Serum estradiol concentrations were elevated to early-to-mid-follicular levels, in proportion to dose, and the estradiol/estrone ratio remained within the expected premenopausal range. The incidence of estrogen-related side effects was modest but greater in the active treatment groups than in the placebo group: Breast pain was reported in 4.5% of the patients in the 50-μg/d group, 5.3% of patients in the 100-μg/d group, and none of the patients in the placebo group. Breakthrough bleeding occurred in 3.4% of women in the 50-μg/d group, 20.2% of women in the 100-μg/d group, and 4.4% of women in the placebo group. Only 3 (1.1%) patients terminated treatment because of skin reactions. This study demonstrates that this estradiol matrix transdermal delivery system is effective in the treatment of menopausal symptoms, while providing the skin tolerability desired by patients.

F151 Pharmacokinetics of a new estradiol matrix patch in healthy postmenopausal volunteers and symptomatic women

F151 Pharmacokinetics of a new estradiol matrix patch in healthy postmenopausal volunteers and symptomatic women

Double-blind, Multicenter Study of a New Estradiol Matrix Transdermal Delivery System (EMTDS) Versus Conjugated Estrogens in Postmenopausal Women

Then/Tech, Inc., Salt Lake City, Utah; 1Health Decisions. Inc., Chapel Hill. North Carolina, U.S.A.

Double-blind, Multicenter Study of a New Estradiol Matrix Transdermal Delivery System (EMTDS) Versus Placebo in Women with Postmenopausal Symptoms

Double-blind, Multicenter Study of a New Estradiol Matrix Transdermal Delivery System (EMTDS) Versus Placebo in Women with Postmenopausal Symptoms

Bioavailability of Estradiol from a New Estradiol Matrix Transdermal Delivery System (EMTDS. 0.1 mg/d) Compared with Estraderm" (0.1 mg/d)

Bioavailability of Estradiol from a New Estradiol Matrix Transdermal Delivery System (EMTDS. 0.1 mg/d) Compared with Estraderm" (0.1 mg/d)

A Multicenter Randomized Parallel Group Study Comparing a New Estradiol Matrix Patch and a Registered Reservoir Patch

A new transdermal therapeutic system has been developed, in which estradiol is dispersed in the adhesive matrix. Gynecologists from 10 Swedish cities recruited 265 healthy women >50 years of age with climacteric complaints into a randomized trial. The objectives of the study were to compare the effects of treatment with the new matrix system and a registered reservoir system. Both patches administer 50 μg/day of 17-beta-estradiol transdermally. Significantly fewer women on the new patch noted erythema, itching, rubbing of the patch on clothes, rustling of the patch, and problems removing the protective lining. The matrix patch also adapted better to the skin and fell off in significantly fewer cases than the reservoir patch. The physician was unaware of the treatment allocated to the patient. Clinic visits were scheduled during treatment-free periods. Patch sites were examined by a study nurse, independently of the clinician. Overall assessment of effectiveness by the investigators favored the new matrix patch, even though efficacy variables suggested equivalence.