Estrogen Therapy for Eating Disorders
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: Estrogen, Progesterone
Disqualifiers: Suicidal ideation, Neurological disorders, Pregnancy, others
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?
This is a randomized, double blind, placebo-controlled study of the effects of transdermal estradiol versus placebo on cognitive flexibility, reward processing, and eating disorder pathology in hypoestrogenemic female adolescents and young adults (ages 14-35 years) with an eating disorder characterized by extreme dietary restriction and/or excessive exercise. Subjects will be randomized 1:1 to 12 weeks of transdermal estradiol with cyclic progesterone or placebo patches and cyclic placebo pills. Study visits include a screening visit to determine eligibility and visits at baseline, 8 weeks, and 12 weeks. Study procedures comprise behavioral, neuroimaging, and endocrine assessments.
Will I have to stop taking my current medications?
The trial requires that you have not taken medications containing estrogen or progesterone in the past 3 months. If you are using a levonorgestrel-releasing intrauterine device, you may need to provide blood samples or stop if estradiol levels are too high.
What data supports the effectiveness of the drug 17-β estradiol transdermal patches with cyclic progesterone for eating disorders?
Research shows that 17-β estradiol transdermal patches, like Climara, are effective in relieving symptoms related to menopause and may help protect against conditions like cardiovascular disease and osteoporosis. While this doesn't directly relate to eating disorders, it suggests the drug can effectively deliver hormones, which might be beneficial in managing symptoms related to hormonal imbalances.12345
Is estrogen therapy using transdermal patches generally safe for humans?
Research shows that transdermal estrogen patches, like Climara and Estraderm, are generally well tolerated in humans. They have been used safely for hormone replacement therapy, with minor side effects such as skin irritation and fluid retention, but no serious adverse effects have been reported.12467
How is the drug 17-β estradiol transdermal patches with cyclic progesterone unique for treating eating disorders?
Research Team
MM
Madhusmita Misra, M.D., M.P.H.
Principal Investigator
Massachusetts General Hospital
Eligibility Criteria
This trial is for female adolescents and young adults aged 14-35 with low estrogen levels, an eating disorder characterized by extreme dietary restriction or excessive exercise, and a high drive for thinness. Participants must not be pregnant, breastfeeding, have used estrogen treatments recently, or have any health conditions that could interfere with the study.Inclusion Criteria
I am between 14 and 35 years old.
My weight is within the normal or low range for my age.
I have had irregular or no menstrual periods for more than 3 months.
See 3 more
Exclusion Criteria
I have a neurological or psychiatric condition that affects my brain's functioning.
You are not experiencing a lack of menstrual periods due to factors other than restricted eating, unless a study doctor determines that it is the cause.
You are pregnant or breastfeeding.
See 9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
1 visit (in-person)
Treatment
Participants receive 12 weeks of transdermal estradiol with cyclic progesterone or placebo patches and cyclic placebo pills
12 weeks
Visits at baseline, 8 weeks, and 12 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- 17-β estradiol transdermal patches with cyclic progesterone (Hormone Therapy)
- Placebo patch and pill (Drug)
Trial OverviewThe study tests if transdermal estradiol patches with cyclic progesterone can affect cognitive flexibility, reward processing, and eating disorder symptoms compared to placebo in participants. It's randomized and double-blind: half get real treatment; half get fake (placebo) without knowing which one they receive.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: 17-β estradiol with cyclic progesteroneExperimental Treatment1 Intervention
Group II: PlaceboPlacebo Group1 Intervention
17-β estradiol transdermal patches with cyclic progesterone is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as estradiol for:
- vasomotor symptoms of vulvar and vaginal atrophy in menopause
- hypoestrogenism
- prevention of postmenopausal osteoporosis
- treatment of breast cancer
- advanced androgen-dependent carcinoma of the prostate
🇪🇺 Approved in European Union as estradiol for:
- hormone replacement therapy for oestrogen deficiency symptoms in postmenopausal women
- prevention of osteoporosis in postmenopausal women at high risk of future fractures
🇨🇦 Approved in Canada as estradiol for:
- vasomotor symptoms of vulvar and vaginal atrophy in menopause
- hypoestrogenism
- prevention of postmenopausal osteoporosis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts General Hospital
Lead Sponsor
Trials
3066
Patients Recruited
13,430,000+
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.
The effect of site of application on the transcutaneous absorption of 17-beta estradiol from a transdermal delivery system (Climara). [2019]The effect of site of application on 17-beta estradiol bioavailability was assessed in an open-label, randomized, crossover study of a once-weekly transdermal estradiol patch (Climara).
Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study. [2021]To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system (lipophilic emulsion-type base) to relieve climacteric symptoms. The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern.
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.
Steady-state bioavailability of estradiol from two matrix transdermal delivery systems, Alora and Climara. [2013]The relative bioavailability of estradiol from two matrix transdermal delivery systems, Alora (0.05 mg/day when applied for 3-4 days) and Climara (0.05 mg/day when applied for 7 days), was evaluated in this two-period, randomized crossover study.
Clinical experience with transdermal estradiol in the treatment of the climacteric. [2013]Results of clinical studies have revealed that the transdermal therapeutic system of estrogen administration (Estraderm, Ciba Pharmaceutical Co., Summit, New Jersey) is both effective and well tolerated. Relief of hot flushes and vaginal atrophy has been shown to equal oral administration of conjugated equine estrogens and early experience suggests that the bone sparing effect is maintained. The patch has no effect on certain liver proteins; safety variables have shown no adverse biochemical changes. Moderate bleeding has occurred in some patients with an intact uterus but can be controlled by the addition of a progestogen. The incidence of endometrial hyperplasia and breast tenderness has been relatively low, and minor side effects (such as fluid retention) have been limited. Several investigators have evaluated skin irritation resulting from the systems. Some erythema has been reported but serious ulcerations or sloughing did not occur. A survey of patient attitudes comparing oral administration and transdermal systems indicated a preference for the transdermal method.
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.
Current hormone replacement therapy: what are the shortcomings? Advances in delivery. [2007]The introduction of transdermal and other parenteral delivery systems has broadened the range of options for hormone replacement therapy (HRT). Oral oestrogen is the most common initial therapy; however, direct absorption of oestradiol via the skin results in an oestradiol-oestrone ratio similar to that found in the pre-menopausal state. Both oral and transdermal oestrogen therapy have been shown to be equally effective in relieving climacteric symptoms, and in preventing osteoporosis or modifying some cardiovascular disease risk factors, although transdermal therapy tends to have fewer unwanted effects than oral. Satisfactory circulating oestradiol levels are achieved with skin patches, transdermal gel, or crystalloid oestradiol implants, and adding progestogen to protect the endometrium is well established. Sequential therapy with HRT usually produces a regular bleed, which is a major cause of patient dissatisfaction. The ideal HRT regimen is probably unobtainable, but the development of SERMs and other regimens that avoid bleeding will encourage long-term use.
Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood. [2018]The overall goal of pubertal sex hormone replacement therapy (HRT) in girls is not only about development of secondary sexual characteristics, but also to establish an adult endocrine and metabolic milieu, as well as adult cognitive function. Estradiol (E2) is the first choice for HRT compared to ethinyl estradiol (EE2). E2 is the most potent endogenous estrogen in the circulation, with established levels during spontaneous puberty. Transdermal E2, compared to oral administration, is the first choice to start pubertal HRT. Transdermal application avoids liver exposure to supraphysiologic estrogen concentrations and provides a more physiologic mechanism for hormone delivery. By cutting E2 matrix patches in doses of 0.05-0.07 µg/kg or administrate E2 gel in doses of 0.1 mg/day, serum concentrations of E2 seen in early spontaneous puberty can be obtained. Patches can be removed in the morning and thereby mimic the normal circadian rhythm. For those clinics with access to sensitive E2 determinations methods (extraction followed by radioimmunoassay or mass spectrometry) monitoring the attained E2 serum levels is recommended in order to optimally mimic the levels seen in early puberty as well as growth velocity, breast and uterus development. Mid- and late pubertal HRT is obtained by increased doses of E2, adding cyclic oral or transdermal progestin, as well as testosterone gel over the pubic area if indicated.
Estrogen replacement therapy and the estraderm transdermal system. [2013]One reliable, controlled and convenient method of delivering parenteral estrogen replacement therapy is by means of a transdermal patch known as the Estraderm Transdermal System, which contains a 17-beta estradiol formulation. The primary side effect appears to be a localized skin irritation in about 15 percent of the women using this route. Most women find this irritation annoying but not enough to necessitate stopping therapy. Studies indicate that the patch provides amelioration of climacteric symptoms that is comparable to the oral estrogens. Preliminary research shows that parenteral estrogen is as effective as oral estrogen in decreasing the risk of osteoporosis. No adverse changes in lipid-lipoprotein levels have been found. A recent Swedish study found an increased relative risk of breast cancer with estradiol and with combined estrogen-progestin use for postmenopausal therapy. Thus, more research on the long-term hormonal replacement effects of the patch is indicated. One advantage of the transdermal delivery system is a first bypass of the liver, thus decreasing the possible risk of renin substrate elevation and the potential increase in blood pressure associated with oral estrogen therapy.