Topical Estrogen for Menopause
Recruiting in Palo Alto (17 mi)
Overseen byAudra Stinchcomb, PhD
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Maryland, Baltimore
Must not be taking: Estrogens, Antihistamines, Corticosteroids, others
Disqualifiers: Smoking, Skin disorders, Diabetes, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The aim of the present study is to determine if two products can deliver bioequivalent amounts of estrogen (estradiol, estriol, and estrone).
Do I need to stop my current medications for the trial?
Yes, you may need to stop certain medications. The trial excludes those who have used medications for menopausal symptoms within the last 30 days or during the study, and some chronic prescription medications within 30 days before the study. However, certain medications like thyroid medications, non-steroidal anti-inflammatory drugs, and cholesterol-lowering drugs may be allowed.
What data supports the effectiveness of the drug Topical Estrogen Product for menopause?
Research shows that transdermal estradiol, a form of estrogen applied to the skin, is effective in relieving menopausal symptoms like hot flashes and is well-tolerated by patients. It is considered as effective as oral estrogen treatments, with the added benefit of better patient compliance and fewer side effects.
12345Is topical estrogen safe for use in humans?
Topical estrogen, such as transdermal estradiol, is generally considered safe for treating menopausal symptoms. Some mild skin irritation may occur, but serious side effects are rare. Studies show that these products have a good safety profile when used as directed.
56789How does the topical estrogen drug for menopause differ from other treatments?
The topical estrogen drug for menopause is unique because it is applied directly to the skin, targeting skin-related symptoms of menopause like dryness and fine wrinkling, unlike oral or patch forms that primarily address systemic symptoms. This method can be more convenient and may have fewer systemic side effects, offering a cosmetic-like application that some patients find preferable.
810111213Eligibility Criteria
This trial is for postmenopausal women aged 45-65, of any ethnicity, with healthy major organs and no drug abuse history. Participants must have thighs at least 42 cm in circumference to apply the topical estrogen product and be deemed healthy by a medical professional.Inclusion Criteria
Volunteer has mid thighs of at least 42 cm (16.5 in) in circumference to accommodate the products to be tested at an area of 400 cm2 per thigh
Negative urine drug screening test (cannabinoids, amphetamines, barbiturates, benzodiazepine, cocaine, methadone, opiates, PCP)
I am a postmenopausal woman aged 45 to 65.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either EstroGel® 0.06% or Biest cream to determine bioequivalence
12 hours
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study is testing whether two different topical estrogen products can deliver equivalent amounts of estradiol, estriol, and estrone to postmenopausal women when applied to their thighs.
2Treatment groups
Active Control
Group I: EstroGel® 0.06%Active Control1 Intervention
EstroGel® 0.06% (1.25 g of gel)
Group II: Biest creamActive Control1 Intervention
Biest cream (equivalent dose to EstroGel®)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
General Clinical Research Center (GCRC) at the University of Maryland Medical CenterBaltimore, MD
Loading ...
Who Is Running the Clinical Trial?
University of Maryland, BaltimoreLead Sponsor
References
A randomized comparative study for the clinical evaluation of hormone replacement by transdermal and oral routes. [2020]During a six-month randomized study involving 460 post-menopausal women, transdermal estradiol has proved to be as effective as oral conjugated equine estrogens in the control of menopausal symptoms and to produce similar estrogenic effects on the endometrium. The group of patients treated with transdermal estradiol showed better compliance and had fewer drop-outs. Moreover, the quality and duration of menstrual bleeding were considered more physiological in the transdermal estradiol group than in the orally treated patients. The trial was carried out with the co-operation of 17 Italian University Centres, under the supervision of Ciba-Geigy Italy S.p.A. Medical Department.
[Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause]. [2013]Seventeen-beta-estradiol administered via a transdermic route was used to treat menopausal symptoms. The results obtained demonstrate the drug's good level of tolerability and considerable efficacy.
Estradiol gel 0.1% relieves vasomotor symptoms independent of age, ovarian status, or uterine status. [2013]Data from a pivotal efficacy trial have been reanalyzed to explore the impact of age, uterine status, and ovarian status on the efficacy of estradiol gel 0.1% (Divigel) for the treatment of moderate to severe vasomotor symptoms associated with menopause.
Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial. [2013]To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol (E2) gel for relief of menopausal symptoms in a population of postmenopausal women.
Transdermal delivery of bioidentical estrogen in menopausal hormone therapy: a clinical review. [2020]Introduction: The history of menopausal hormone therapy (HT) use has evolved over the years based on the influence of many factors, including availability and safety related to formulation and route of estrogen products. Given unexpected findings from the Women's Health Initiative (WHI) in the early 2000's that used oral conjugated equine estrogen, the desire for and research supporting transdermal estradiol products grew. Transdermal estrogen is now a popular and commonly used formulation for treating menopausal symptoms. Many FDA approved products are available and preferred to custom compounded bioidentical products given superior consistency and safety standards.Areas covered: This review explores the history of transdermal estrogen products, as well as their pharmacodynamics. It also includes a detailed exploration of the advantages and disadvantages of different estrogen formulations with a focus on clinically useful information.Expert opinion: FDA approved transdermal estradiol products are the preferred formulation and route for HT, along with a progestogen for women with a uterus, given their efficacy and superior safety profile.
Transdermal estradiol gel for the treatment of symptomatic postmenopausal women. [2013]The aim of this study was to determine the efficacy, safety, and lowest practical dose of a transdermal estradiol gel in the treatment of symptomatic postmenopausal women.
Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States. [2019]This paper summarizes all postmarketing safety surveillance data collected by Solvay Pharmaceuticals, Inc. (Marietta, Georgia), between 1989 and 1996 for Estratest and Estratest HS (half-strength). These oral esterified estrogens--methyltestosterone combination products have been marketed in the United States since 1964 for the treatment of moderate-to-severe vasomotor symptoms associated with menopause in patients whose symptoms have not been relieved by estrogens alone. Between 1989 and 1996, more than 1 million woman-years of exposure occurred. The safety profile contained in this paper is based on a cumulative total of 568 individual cases comprising 863 adverse events (AEs). The proportions of AEs associated with the use of Estratest (575 events; 66.6%) and Estratest HS (288 events; 33.4%) were commensurate with the proportions of individual reports of adverse experiences for the two formulations (369 reports [65.0%] and 199 reports [35.0%], respectively). The rank order and percentage of types of AEs reported were also similar. The cumulative volume of reports was relatively low given the extent of exposure. Despite the limitations inherent in spontaneous postmarketing surveillance, the safety profile derived from this assessment does not indicate a significant safety concern with Estratest or Estratest HS. No deaths were reported, and no adverse findings indicative of the need for more comprehensive surveillance or concern on the part of the medical community or consumers were observed. Reports of cancer, cardiovascular disease, thromboembolic phenomena, and hepatic dysfunction were few and were assessed as not related to treatment with Estratest or Estratest HS; reports of drug overdose, drug-drug interaction, and birth defects were rare (4 of 863 events; 0.5%). The most commonly reported AEs were those known to be associated with estrogen therapy (weight gain, headache, nausea, and vasodilatation) and androgen treatment (alopecia, acne, and hirsutism). Twenty-three (4.0%) of the 568 cases reported had at least one event that was regarded as serious, and 53 (6.1%) of the total 863 AEs were regarded as serious. The findings indicate that Estratest and Estratest HS are safe when used as directed and that the marginal increase in risk associated with androgen coadministration can be managed with appropriate patient selection and monitoring, as stated in the package insert for these compounds.
[Comparison of transdermal with oral hormone substitution: a multicenter study with a new matrix patch]. [2013]166 postmenopausal patients, aged 45-65 years at baseline, with moderate to severe climacteric symptoms were randomly allocated to an open-label, multi-center study which compared the efficacy, safety and acceptance of a transdermal 17 beta-estradiol matrix patch with an oral form of estrogen replacement therapy. In a cyclic sequential regimen, the transdermal system delivered 0.05 mg of estradiol/day. Oral dosages of conjugated equine estrogens were 0.625 mg/day. An oral progestin was also given for 11 days in each cycle for each group. A statistically significant reduction compared to baseline in the primary efficacy parameter, the mean number of hot flashes, occurred with a decrease in each group from 6 per day at baseline to 1 per day at 12 weeks; there was no statistically significant difference between the two groups. The incidence and severity of other postmenopausal symptoms, particularly sweating, difficulty in concentration and palpitations were reduced to a greater extent in the patch group without revealing a significant inter-group difference in the total symptom score. There were also no statistically significant differences in the mean serum estradiol and FSH concentrations between the two treatment groups after 12 weeks of therapy. A similar number of adverse events was observed in both groups. The most frequent adverse events were breast pain and under oral estrogen therapy, gastrointestinal complaints and weight increase. Skin irritation or dermatitis occurred infrequently in the patch group. In summary, the matrix patch represents at least as effective a therapy for postmenopausal symptoms as a standard oral estrogen.
Nanoparticle delivery for transdermal HRT. [2012]Nanomedicine is an emerging technology and the first nano-engineered medical products have come to light in the last decade. Transdermal drug delivery has significant advantages compared to other routes of drug administration. Nanoparticles unique physical and chemical properties enable transport of substances directly into the skin. The objective of this paper is to review different aspects of nanoparticle delivery, generally, and discuss its current use for transdermal hormone therapy. Transdermal estrogen therapy remains the most effective treatment for bothersome menopausal symptoms, particularly in those women for whom the potential adverse effects associated with "first pass" hepatic metabolism are to be avoided. Available alternatives for transdermal estrogen delivery include patches, gels, sprays and lotions. Other non-oral therapies which likewise avoid "first pass" hepatic metabolism include: subcutaneous implants and vaginal rings. Some of the transdermal products are associated with mild adverse skin effects such as redness and irritation, but more severe and bothersome consequences include blistering and tattooing. Even the mild adverse skin effects are frequently cited as reasons for discontinuation. Micellar nanoparticle estradiol emulsion (MNPEE) is a lotion-like therapy which constitutes an alternative transdermal delivery system not requiring the permeation enhancers or temporary skin digestion, both of which increase the possibility of irritation. MNPEE's advantages include low fluctuation of plasma estradiol concentrations, infrequent skin related adverse effects, and pleasant cosmetic-like moisturizing properties. The efficacy of MNPEE for management of menopausal vasomotor symptoms has been demonstrated in a randomized placebo controlled trial, and the product is FDA approved for management of moderate to severe vasomotor symptoms. None of the observed adverse effects in the MNPEE group were statistically different from the placebo group. Studies addressing inadvertent transference of estradiol to the male partners of menopausal women using this delivery technology have demonstrated small, but real amounts of transference, which do not exceed the normal physiological male estradiol range. MNPEE is safe and effective for treatment of vasomotor symptoms and represents the commercial validation of nanoparticle technology for transdermal delivery of estrogen therapy (ET) for postmenopausal women with vasomotor symptoms.
Estrogen-deficient skin: The role of topical therapy. [2020]Menopause is a major turning point in a woman's life that is characterized by declining ovarian function and decreased serum estrogen levels. The resulting hormonal changes particularly affect the skin, with postmenopausal symptoms such as loss of structural architecture and increased propensity to damage becoming rapidly noticeable. Interestingly, studies have shown that estrogen deprivation in postmenopausal conditions accelerates many skin changes, including dryness, atrophy, fine wrinkling, and poor wound healing. Thus, the effects of low estrogen on the skin are an important endogenous cause of aging skin in women, yet topical treatment strategies that target cutaneous symptoms are limited. The goal of this article is to provide an overview of the role of estrogen in the skin and changes associated with estrogen deficiency, as well as review alternatives to systemic estrogen therapy and describe the effects of these interventions on cutaneous aging in postmenopausal skin. Specifically, clinical studies that utilize topical estrogens and topical isoflavones, which are soy-derived compounds that interact with estrogen receptors, are discussed.
An Australian experience of transdermal oestradiol patches in a subtropical climate. [2019]Tolerability and efficacy of transdermal oestradiol patches were assessed in 121 menopausal women over a period of 3 months to 2.5 years. Of particular interest, in a subtropical climate such as Brisbane, were the problems associated with adhesiveness and skin irritation during the summer months. We conducted a retrospective study with self-administered questionnaires. All patients had been selected for the nonoral route because of side-effects or relative contraindications to oral therapy. There was, overall, good efficacy and acceptability. The majority of the women found the patch very adequate in relieving symptoms of the menopause (vasomotor, genitourinary and musculoskeletal). Most preferred the patch to oral therapy. The oestradiol patch was well tolerated and few side-effects were reported. Breast tenderness and weight gain were 2 minor problems associated with its use. Skin irritation was minimal, but adhesiveness was a problem during the summer months, especially with swimming or showering. Some practical suggestions were obtained about how to overcome site of application problems.
Emerging delivery systems for estrogen replacement: aspects of transdermal and oral delivery. [2019]The ideal preparation for estrogen replacement therapy has been the object of intensive research for decades, and the search continues. More than 40 new products are in development in the United States, the United Kingdom, and Europe. Most are transdermal, which reflects the growing acceptance of patch technology at a time when the overwhelming majority of women who use estrogen replacement take oral formulations. Most of the new oral formulations are a combination of estrogen and progestin. Aspects of transdermal and oral estrogen are discussed, including the advantages and disadvantages for use in women with concomitant medical conditions.
Estradiol topical emulsion for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. [2016]A novel micellar, nanoparticle emulsion containing 17beta-estradiol is currently available as a daily topical treatment for moderate-to-severe vasomotor symptoms associated with menopause. Applied daily to the lower extremities, the emulsion delivers 0.05 mg estradiol systemically and provides an 85% reduction in hot flash frequency versus baseline by 12 weeks of therapy. When specifically surveyed, most patients felt that this cosmetic-like delivery system was convenient and preferable to transdermal patches. Local skin reactions, all mild, were seen in 4%, and there was a low incidence of side effects that included breast pain, endometrial thickening and headache. Contraindications include those common to all estrogen-containing therapies. This formulation provides patients with a cosmetic-like treatment option that is effective and safe, delivers stable systemic estradiol levels, and may promote overall treatment compliance.