Trial Summary
What is the purpose of this trial?The menopause transition is associated with a decrease in artery health and an increased risk for weight gain in storing fat in the stomach area which may increase the risk for heart disease. The purpose of this research is to study how the decrease in estrogen at menopause changes artery health and fat gain, and risk of disease in women as they age. The first aim in this study will determine whether short term and long term low estrogen levels in premenopausal women decreases artery function and whether this is related to an increase in fat in the stomach area. The second aim will determine whether the changes in artery health and body fat are related to changes in a pathway that breaks down an important amino acid called tryptophan. This pathway is thought to play a role in regulating the aging process. Therefore, the investigators will determine whether the decrease in artery health and the increase in body fat in the stomach region with low estrogen is related to changes in this pathway in the blood, in vascular cells and fat tissue. Because estrogen levels fluctuate in premenopausal women, the investigators will use an approach (intervention) that controls estrogen levels to address these aims. The investigators will use a medication that is typically used to treat endometriosis or uterine fibroids to lower estrogen levels and an estrogen patch to increase estrogen in some women. Some women will receive a patch that has no estrogen (called a placebo patch). The intervention period will be 20 weeks. The study will provide us with new knowledge on how low estrogen with menopause affects artery health and fat gain estrogen.
Is the drug Degarelix, Transdermal Estradiol Patch, Transdermal Placebo Patch a promising treatment for menopause?Yes, the transdermal estradiol patch is a promising treatment for menopause. It helps control symptoms like hot flashes and may protect against heart disease and bone loss. The patch is easy to use, well-tolerated, and provides consistent hormone levels.12457
What safety data is available for the Estradiol Patch used in menopause treatment?The safety data for the Estradiol Patch includes studies on skin irritation, adhesion, and estradiol delivery. The Estradot and Climara patches were compared for local tolerability and adhesion, with Climara showing good tolerance and superior adhesion. Clinical experience with Climara, a 7-day estradiol transdermal system, indicates it is well-tolerated with positive effects on climacteric symptoms. Estrasorb, another transdermal estradiol, was developed for short-term use to reduce vasomotor symptoms in menopausal women and was launched in the US in 2004.15678
What data supports the idea that Estradiol Patch for Menopause is an effective treatment?The available research shows that the Estradiol Patch is effective in reducing menopausal symptoms like hot flushes. In a study comparing Menorest 50 and another transdermal patch, both treatments significantly reduced the number of hot flushes from about 6.5 to less than 0.5 per day over 12 weeks. Both treatments also improved the severity of other menopausal symptoms. Additionally, the Estradiol Patch was well tolerated, with Menorest 50 showing better local tolerability than the other patch.13567
Do I have to stop taking my current medications for the trial?Yes, you must stop taking certain medications. You cannot use medications that might influence vascular function, such as antihypertensives, lipid-lowering medications, blood thinners, antioxidant supplements, or chronic NSAIDs. You must be willing to stop these for 4 weeks before enrolling in the study.
Eligibility Criteria
This trial is for premenopausal women who are experiencing the transition to menopause, which may affect their artery health and increase belly fat. Participants should be generally healthy but concerned about obesity, low estrogen levels due to aging or menopause.Inclusion Criteria
I am between 20 and 45 years old.
I am premenopausal with regular menstrual cycles, missing no more than 1 in the past year.
Exclusion Criteria
I have a heart, kidney, or liver condition.
I have had a blood clot in my veins before.
I have had breast cancer or another cancer that grows with estrogen.
I have an ongoing infection.
I have severe osteoporosis or very low bone mass.
Treatment Details
The study tests how estrogen affects artery function and abdominal fat gain in aging women. It involves a medication called Degarelix to lower estrogen levels, an Estradiol Patch to raise them in some participants, and a placebo patch with no active hormone for comparison over 20 weeks.
2Treatment groups
Experimental Treatment
Group I: Degarelix plus transdermal placeboExperimental Treatment2 Interventions
At baseline \& 10 weeks: 80-mg subcutaneous injection of degarelix acetate plus Placebo transdermal patch (applied twice per week)
Group II: Degarelix plus transdermal estradiolExperimental Treatment2 Interventions
At baseline \& 10 weeks: 80-mg subcutaneous injection of degarelix acetate plus 0.075mg estradiol transdermal patch (applied twice per week)
Degarelix is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Firmagon for:
- Advanced hormone-dependent prostate cancer
🇺🇸 Approved in United States as Firmagon for:
- Advanced prostate cancer
🇨🇦 Approved in Canada as Firmagon for:
- Hormone-sensitive prostate cancer
🇯🇵 Approved in Japan as Firmagon for:
- Prostate cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of Colorado Anschutz Medical CampusAurora, CO
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Who is running the clinical trial?
University of Colorado, DenverLead Sponsor
National Institute on Aging (NIA)Collaborator
References
Clinical experience with a seven-day estradiol transdermal system for estrogen replacement therapy. [2019]To describe the efficacy, safety, and wearability of estrogen replacement therapy of a 7-day estradiol transdermal system (Climara), developed using new drug-in-adhesive technology.
New trends in transdermal technologies: development of the skin patch, Menorest. [2016]Menorest is a transdermal patch, in which 17 beta-estradiol is dispersed as a microfine suspension in an adhesive matrix. This system reduces the size and thickness of the patch making it more cosmetically acceptable than older reservoir patches. Pharmacokinetic studies indicate that, at doses from 25-100 micrograms/day, Menorest releases estradiol at a constant and reproducible rate. There is a linear relationship between the dose of estradiol administered (which is determined by the surface area of the patch) and the plasma concentration of estradiol. Unlike the standard reference reservoir patch, Estraderm, or another matrix patch, Systen/Evorel, Menorest maintains plasma estradiol concentrations at or above the target level of 40 pg/ml throughout the 80-h dosing interval.
Efficacy and tolerability of Menorest 50 compared with Estraderm TTS 50 in the treatment of postmenopausal symptoms. A randomized, multicenter, parallel group study. [2019]Two-hundred and five (205) menopausal women with moderate to severe vasomotor symptoms, aged 39-64 years, were randomized from 20 clinical centers. After a 4-week treatment-free period, each woman received a cyclical regimen (25 days of a 4-week cycle) of Menorest 50, a new matrix-type transdermal estradiol system or Estraderm TTS 50, a marketed reservoir-type transdermal estradiol system twice weekly for 12 weeks. An oral progestin was also given for 10 days each cycle. The objectives were to compare local and systemic tolerability and efficacy in the treatment of menopausal symptoms. One-hundred and ninety-four [194] patients (96 and 98 patients in the Menorest 50 and the reservoir transdermal patch groups, respectively) were considered in the intent-to-treat population and 204 (102 in each group) in the safety population. The two treatment groups were comparable with regard to the demographic data and menopausal status. The primary efficacy criteria were the comparison between Menorest 50 and the reservoir transdermal patch in erythema and pruritus at application sites and the difference between the treatment groups in the mean number of hot flushes per day at week 12, adjusted for baseline. A statistically significant reduction in the mean number of hot flushes was observed in each group compared with baseline, with a decrease from 6.5 at baseline to 0.3 at 12 weeks and 6.4 to 0.4 in the Menorest 50 and reservoir transdermal patch groups respectively; there was no statistically significant difference between the two groups during the 12-week treatment. The severity score of menopausal symptoms was also dramatically improved in each of the two treatment groups. There were no statistically significant differences in the mean plasma estradiol concentrations and mean estradiol to estrone ratio (> 1.0) in both groups after 10 weeks of therapy. A similar number of adverse events was observed in both groups. Menorest 50 showed better local tolerability than the reservoir transdermal patch with a lower incidence of topical adverse events, erythema and pruritus. In summary, Menorest 50 was as effective as the reservoir transdermal patch in reducing the mean number of hot flushes, and improving the severity of other menopausal symptoms, including vasomotor, psychiatric and urogenital symptoms.
Plasma profiles of transdermal 17 beta-estradiol delivered by two different matrix patches. A four-way cross-over study in postmenopausal women. [2013]The aim of this study was to investigate the systemic bioavailability and plasma profiles of 17 beta-estradiol (CAS 50-28-2, E2) after the application of two types of matrix patches for the transdermal delivery of E2: MenorestTM (the test patch) with delivery rates of 37.5, 50 and 75 micrograms E2/day and a reference patch with a delivery rate of 50 micrograms E2/day. All 3 test patches were identical in composition, achieving different transdermal E2 delivery rates by variations in the surface area (11.0, 14.5 and 22.5 cm2). All 4 patches were each worn by 24 postmenopausal women over a 4-day period (i.e. 96 h), each of the 4 treatment periods being separated by a 7-day wash-out period according to a randomized, 4-way crossover design. Blood samples were collected before and 3, 6, 9, 12, 24, 34, 48, 58, 72, 84, and 96 h after each patch application. Plasma E2 concentrations were determined by a specific direct radioimmunoassay method. The following pharmacokinetic parameters were evaluated: AUC0-96h; Cmax, tmax, Cmin, Caverage. The course of the E2 plasma levels over the total test period (96 h) was relatively constant for all patches. For the test patch, a linear relationship between the pharmacokinetic parameters and the different patch areas (i.e. dosages of 37.5, 50, 75 micrograms E2/d) could be shown (correlation coefficient 0.99). The resulting Cmax values for the patch were: 44.2, 58.3, and 92.1 pg E2/ml, corresponding to Caverage values of 39.5, 45.5, and 70.6 pg E2/ml. The reference patch and the test patch, at a dose of 50 micrograms E2/d, were similar in terms of Cmax, while the Caverage, AUC0-96h and Cmin were significantly higher with the test patch. The systemic bioavailability of the reference patch was comparable to that of the test patch at a dose of 37.5 micrograms E2/d: AUC0-->96h 3017.5 +/- 1312.4 pg/ml.h for the reference patch and 3375.9 +/- 1254.7 pg/ml.h for the test patch. A physical model for the calculation of the course of the E2 levels was used to describe the experimentally determined data. However, in the evening, periodically higher E2 plasma levels were observed for all patches than in the morning. From these results it can be concluded that E2 plasma profiles produced by the test patch are reproducible, and in the physiological range consistent with the early to mid follicular level in the premenopausal woman over 4 days (96 h), correlating with the doses administered (37.5-50-75 micrograms E2/d). Additionally, the systemic bioavailability of the test patch at a dose of 37.5 micrograms E2/d is comparable to that of the reference patch at a dose of 50 micrograms E2/d.
Clinical experience with a 7-day estrogen patch: principles and practice. [2013]In the future, hormone replacement therapy (HRT) is likely to become of increasing importance, not only to control short-term climacteric symptoms, but also to protect postmenopausal women from the increasing risk of cardiovascular disease, osteoporosis and other conditions that accompany ovarian failure. This paper reviews the principles and practice associated with HRT, focusing on clinical experience with a new 7-day estrogen matrix patch (Climara). Results from two 11-week placebo-controlled studies, which compared the 7-day patch at two dose levels with 0.625-mg/day oral conjugated equine estrogen, found that both the 0.5- and 0.1-mg estradiol/day patches had a positive effect on climacteric symptoms. Tolerance was good and similar for both patches. Separate studies of skin irritation and adhesion revealed that the 7-day patch was well tolerated and that, although irritation was similar to that associated with Estraderm, adhesion was superior with the 7-day patch. Data on absorption of estradiol from different skin sites indicate that absorption is higher and more consistent from the buttock than from the abdomen, suggesting that choice of application site may require further investigation.
Significant differences in estradiol bioavailability from two similarly labelled estradiol matrix transdermal systems. [2019]To compare the bioavailabilities of estradiol delivered by two transdermal estradiol matrix systems; Alora and Evorel.
Comparative study to evaluate skin irritation and adhesion of Estradot and Climara in healthy postmenopausal women. [2019]To compare the local tolerability, adhesion and estradiol delivery of a 5-cm(2) transdermal patch (Estradot), Novartis Pharmaceuticals, Basel, Switzerland) and a 12.5-cm(2) patch (Climara, Berlex Laboratories, Wayne, NJ, USA).
Estrasorb. [2013]Novovax Inc has developed and launched Estrasorb, a transdermally absorbed, micro-encapsulated estradiol, as an estrogen replacement therapy for short-term use in the reduction of vasomotor symptoms in menopausal women. Estrasorb was launched in the US in April 2004.