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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a hormone treatment to determine its effects on thinking patterns and behaviors in young women with certain eating disorders. Researchers use patches that deliver estradiol (a form of estrogen) to compare its effects with a placebo. The trial seeks females aged 14-35 with an eating disorder involving serious dieting or excessive exercise, who have experienced irregular or absent periods for some time. Participants will undergo evaluations at the start, midway, and end of the 12-week study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that 17-β estradiol, a type of estrogen used in hormone therapy, meets FDA safety standards. This estrogen is often combined with progesterone to manage symptoms like hot flashes. Studies have found that this hormone therapy is usually well-tolerated. However, some reports indicate it may increase the risk of breast cancer, though this risk can vary. Overall, many people use this therapy without major problems. These findings suggest the treatment is generally safe, but personal health factors should be considered. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for eating disorders?

Researchers are excited about using 17-β estradiol with cyclic progesterone for eating disorders because it's a fresh approach that targets hormonal imbalances, which aren't typically addressed by current treatments. Unlike standard options such as cognitive behavioral therapy and nutritional counseling, this treatment works by directly modifying hormone levels, which may play a vital role in some eating disorders. Moreover, using a transdermal patch for delivery offers a non-invasive and consistent way to administer the medication, potentially improving adherence and effectiveness.

What evidence suggests that this treatment might be an effective treatment for eating disorders?

This trial will compare the effects of 17-β estradiol transdermal patches with cyclic progesterone to a placebo in treating eating disorders. Studies have shown that estrogen therapy can help with certain aspects of eating disorders, particularly in reducing body dissatisfaction during weight gain. In teenagers with anorexia nervosa, estrogen replacement has been linked to an improved body image during recovery. Although this treatment might not significantly enhance bone health, its effects on mood and cognitive skills are under investigation. Research suggests that using 17-β estradiol patches with cyclic progesterone may improve reward processing and eating habit management. This could benefit those dealing with strict dieting and excessive exercise. ^{6 7 8 9 10}

Who Is on the Research Team?

Madhusmita Misra, M.D., M.P.H.

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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 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 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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6664444/

Estrogen Administration Improves the Trajectory of Eating ...

Abstract. Objective: Estrogen replacement prevents worsening body dissatisfaction with weight gain in adolescents with anorexia nervosa.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03740204?tab=history&a=6

Record History | ver. 6: 2020-05-29 | NCT03740204

17-β estradiol transdermal patches (100 mcg 17-β estradiol ... outcome) with 17-β estradiol versus placebo. [Time ... Change in caloric intake by 4-day food diary ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8264872/

Effect of oral and transdermal oestrogen therapy on bone ...

Systematic reviews have not found OCPs to significantly improve BMD in women with athletic FHA or anorexia nervosa (AN). However, some recent ...

4.

frontiersin.org

frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.953180/epub

Functional hypothalamic amenorrhea: Impact on bone and ...

... transdermal 17-β estradiol did not lead to a further improvement in bone outcomes (140). In contrast, in a study in adults with AN, sequential therapy with ...

5.

uptodate.com

uptodate.com/contents/functional-hypothalamic-amenorrhea-evaluation-and-management/abstract/31-33

Medline ® Abstracts for References 31-33 of 'Functional ...

METHODS 121 patients with OAA aged 14-25 years were randomised to receive: (1) a 17β-estradiol transdermal patch continuously with cyclic oral micronised ...

6.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK493191/

Hormone Replacement Therapy - StatPearls - NCBI Bookshelf

Hormone replacement therapy (HRT) replenishes women with ovarian hormones diminished during the natural menopausal transition to alleviate associated symptoms.

7.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK279050/

Menopause and Hormone Replacement - Endotext - NCBI - NIH

Data from clinical studies have refined the indications for hormone therapy. For example, estrogen remains the most effective therapy for hot flashes.

8.

emedicine.medscape.com

emedicine.medscape.com/article/276107-overview

Estrogen Therapy: Overview, Menopausal Transition ...

... 17-beta-estradiol and natural progestins became available. This product met FDA safety and efficacy standards. The study of this product was ...

9.

academic.oup.com

academic.oup.com/jcem/article/100/11/3975/2836060

Treatment of Symptoms of the Menopause: An Endocrine ...

Estrogen therapy. Most, but not all, observational studies report an increased breast cancer risk with oral or transdermal estradiol when initiated in recently ...

10.

jamanetwork.com

jamanetwork.com/journals/jama/fullarticle/198492

Commonly Used Types of Postmenopausal Estrogen for ...

Conjugated equine estrogen and 17β-estradiol have consistent and comparable effects on treatment of menopausal hot flashes and may have similar short-term ...