Estrogen Therapy for Eating Disorders

Overseen By Kamryn Eddy, Ph.D.

Age: < 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Estrogen, Progesterone

Disqualifiers: Suicidal ideation, Neurological disorders, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 12 weeks

120 Participants Needed

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. ^{1 2 3 4 5}

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. ^{1 2 4 6 7}

How is the drug 17-β estradiol transdermal patches with cyclic progesterone unique for treating eating disorders?

This drug is unique because it uses a transdermal patch to deliver hormones directly through the skin, which can mimic natural hormone levels more closely and avoid some side effects associated with oral hormone therapies, such as liver exposure and increased blood pressure. ^{1 3 8 9 10}

Research Team

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.

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.

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
• Placebo patch and pill

Trial Overview The 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

Group I: 17-β estradiol with cyclic progesterone Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

The 7-day estradiol transdermal patch (Climara) effectively reduces hot flushes in women, with a mean decline of 74.6% for the higher dose compared to 64.5% for the lower dose, showing comparable efficacy to traditional hormone therapies.

The Climara patch is well tolerated, with a low withdrawal rate due to adverse events (8.9%), primarily related to skin reactions, and it demonstrated better adhesion compared to other patches, making it a practical option for estrogen replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a seven-day estradiol transdermal system for estrogen replacement therapy. Gordon, SF.[2019]

In a study involving a once-weekly transdermal estradiol patch applied to either the buttocks or abdomen, the buttock application resulted in significantly higher estradiol levels, with a 125.1% peak concentration compared to the abdomen.

The buttocks provided better bioavailability of estradiol, which may benefit women experiencing menopausal symptoms, as it maintained higher hormone levels throughout the week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of site of application on the transcutaneous absorption of 17-beta estradiol from a transdermal delivery system (Climara). Taggart, W., Dandekar, K., Ellman, H., et al.[2019]

In a study of 29 menopausal women over 6 months, a transdermal delivery system of bioidentical 17β-estradiol and progesterone significantly improved climacteric symptoms in 93% of participants, with 88% reporting complete relief.

The treatment effectively mimicked the natural hormonal cycles of women, with no adverse health-related events reported, suggesting it is a safe option for hormone replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study. Formby, B., Schmidt, F.[2021]

The new 7-day estrogen matrix patch (Climara) effectively alleviates climacteric symptoms in postmenopausal women, showing positive results in two 11-week placebo-controlled studies with good tolerance across different doses.

The 7-day patch demonstrated superior adhesion compared to the Estraderm patch, and absorption of estradiol was found to be higher and more consistent when applied to the buttock rather than the abdomen, indicating potential for optimized application sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a 7-day estrogen patch: principles and practice. Notelovitz, M.[2013]

In a study involving 27 postmenopausal women, the transdermal delivery system Alora maintained more stable serum estradiol levels compared to Climara, with less fluctuation in hormone levels, which could be beneficial for consistent hormone therapy.

Both Alora and Climara were well tolerated, but Alora showed better skin tolerability with fewer instances of moderate skin irritation and less adhesive transfer, making it a potentially more comfortable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steady-state bioavailability of estradiol from two matrix transdermal delivery systems, Alora and Climara. Buch, A., Shen, L., Kelly, S., et al.[2013]

The transdermal therapeutic system of estrogen (Estraderm) is effective in relieving hot flushes and vaginal atrophy, showing similar efficacy to oral estrogen treatments while maintaining bone health.

The patch is well tolerated with minimal side effects, such as low incidence of endometrial hyperplasia and breast tenderness, and patients generally prefer this method over oral administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with transdermal estradiol in the treatment of the climacteric. Utian, WH.[2013]

In a study involving 33 postmenopausal women, the Alora transdermal patch delivered a higher and more consistent level of estradiol compared to the Evorel patch, despite both being labeled to deliver the same amount of the hormone.

The Evorel patch showed a significantly higher fluctuation index and a lower overall estradiol exposure, indicating that Alora may provide a more stable hormone delivery, which could be important for effective hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant differences in estradiol bioavailability from two similarly labelled estradiol matrix transdermal systems. Buch, AB., Shen, LZ., Kelly, SC., et al.[2019]

Transdermal hormone replacement therapy (HRT) using oestradiol is as effective as oral therapy for relieving menopausal symptoms and preventing osteoporosis, but it generally has fewer side effects.

The development of selective estrogen receptor modulators (SERMs) and other bleeding-free regimens may improve patient satisfaction and encourage long-term use of HRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current hormone replacement therapy: what are the shortcomings? Advances in delivery. Sturdee, DW.[2007]

Transdermal estradiol (E2) is preferred for pubertal hormone replacement therapy in girls because it avoids high liver exposure and mimics natural hormone delivery, helping to establish normal endocrine and metabolic functions.

Using specific doses of E2 patches or gels can achieve serum levels similar to those during early spontaneous puberty, allowing for effective monitoring and adjustment of hormone levels to support proper development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood. Norjavaara, E., Ankarberg-Lindgren, C., Kriström, B.[2018]

The Estraderm Transdermal System, which delivers 17-beta estradiol, is an effective method for estrogen replacement therapy, providing relief from climacteric symptoms similar to oral estrogens, with localized skin irritation as the primary side effect in about 15% of users.

Transdermal estrogen therapy may have advantages over oral estrogen, such as bypassing the liver to reduce risks associated with blood pressure elevation, but there are concerns about an increased risk of breast cancer, highlighting the need for further long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen replacement therapy and the estraderm transdermal system. Youngkin, EQ.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical experience with a seven-day estradiol transdermal system for estrogen replacement therapy. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The effect of site of application on the transcutaneous absorption of 17-beta estradiol from a transdermal delivery system (Climara). [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Clinical experience with a 7-day estrogen patch: principles and practice. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Steady-state bioavailability of estradiol from two matrix transdermal delivery systems, Alora and Climara. [2013]

6. Italy pubmed.ncbi.nlm.nih.gov

Clinical experience with transdermal estradiol in the treatment of the climacteric. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Significant differences in estradiol bioavailability from two similarly labelled estradiol matrix transdermal systems. [2019]

8. India pubmed.ncbi.nlm.nih.gov

Current hormone replacement therapy: what are the shortcomings? Advances in delivery. [2007]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Estrogen replacement therapy and the estraderm transdermal system. [2013]