Transdermal Estrogen for Anorexia Nervosa

Overseen By Pouneh Fazeli, MD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: Pouneh K. Fazeli, MD

Must not be taking: Glucocorticoids, Bisphosphonates

Disqualifiers: Thyroid dysfunction, Diabetes, Breast cancer, 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: Unknown

Duration: 18 months

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a skin patch with estrogen to improve low bone mass in women with anorexia nervosa. Anorexia nervosa can weaken bones, and the study aims to determine if estrogen can strengthen them. Participants will receive either the estrogen patch or a placebo patch for comparison. Suitable candidates have anorexia nervosa, experience missed periods, and have low bone density. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications known to affect bone metabolism, such as certain steroids or bisphosphonates, for specific periods before starting the trial. If you're on these medications, you may need to stop them for a while before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that estrogen patches applied to the skin are generally safe for women with anorexia nervosa. One study found that short-term use of these patches improved bone strength, which is encouraging. The treatment involves placing a patch on the skin to deliver a steady amount of estrogen.

No serious side effects have been reported in the studies, suggesting the treatment is safe for most individuals. However, monitoring for any possible side effects remains important, as with any treatment. This study is still in the early stages, so researchers continue to explore its safety and effectiveness. So far, the results appear promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anorexia nervosa?

Transdermal estrogen is unique because it offers a new delivery method for addressing anorexia nervosa. Unlike traditional treatments, which often focus on nutritional rehabilitation and psychotherapy, this treatment uses a hormone patch applied to the skin. Researchers are excited because transdermal delivery may provide a steady, controlled release of estrogen, potentially improving bone health and mood without the need for oral medications. This method also bypasses the digestive system, which can be particularly beneficial for individuals with anorexia nervosa.

What evidence suggests that transdermal estrogen might be an effective treatment for low bone mass in anorexia nervosa?

Research has shown that estrogen patches applied to the skin can increase bone strength in women with anorexia nervosa. In this trial, participants may receive a transdermal estrogen/progesterone patch. Previous studies have found this leads to a 2% increase in bone strength in the lower back over six months. Another study showed improvement in bone strength in both the spine and hip. These findings suggest that this treatment effectively addresses low bone mass in women with anorexia nervosa. ^{1 2 3 6 7}

Who Is on the Research Team?

Pouneh Fazeli, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adult women aged 19-45 with anorexia nervosa, specifically those who are underweight according to specific tables and have low bone mass. Participants must not be pregnant or planning pregnancy soon, should not have a history of certain blood or bone disorders, no recent use of medications affecting bone metabolism, and no severe illnesses like diabetes or untreated thyroid issues.

Inclusion Criteria

<85% of ideal body weight as defined by the 1983 Metropolitan Life Insurance Height and Weight Tables

The T-score of your bone scan is less than -1.0 at spine or hip.

I have been diagnosed with anorexia nervosa.

Exclusion Criteria

I or my close family member had breast cancer.

25-OH vitamin D level < 20 ng/mL

Pregnant or breastfeeding (or desiring pregnancy within the next 18 months)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a transdermal estrogen/progesterone patch or a placebo patch applied weekly for 18 months

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transdermal estrogen

Trial Overview The study is testing the effects of transdermal estrogen patches compared to placebo on improving bone density in women with anorexia nervosa. It's a randomized trial meaning participants will be randomly assigned to either the treatment group receiving estrogen or the control group receiving a placebo.

How Is the Trial Designed?

Group I: Transdermal estrogen/progesterone Experimental Treatment 1 Intervention

Transdermal estradiol (0.045mg)/levonorgestrel (0.015mg) patch applied weekly for 18 months

Group II: Placebo Placebo Group 1 Intervention

Placebo patch applied weekly for 18 months

Transdermal estrogen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Estradiol patch for:

• Menopause symptoms
• Osteoporosis prevention
• Hormone replacement therapy

Approved in European Union as Estradiol patch for:

• Menopause symptoms
• Osteoporosis prevention
• Hormone replacement therapy

Approved in Canada as Estradiol patch for:

• Menopause symptoms
• Osteoporosis prevention
• Hormone replacement therapy

Who Is Running the Clinical Trial?

Pouneh K. Fazeli, MD

Lead Sponsor

Trials

1

Recruited

70+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

The estradiol transdermal therapeutic system effectively delivers estradiol to maintain premenopausal levels in postmenopausal women, helping to protect against osteoporosis and reduce fracture risk with minimal dosages.

This method of delivery is well-tolerated, with local irritation being the most common side effect, and it offers similar benefits for menopausal symptoms as oral estrogens, making it a promising alternative for estrogen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal estradiol. A review of its pharmacological profile, and therapeutic potential in the prevention of postmenopausal osteoporosis. Balfour, JA., McTavish, D.[2018]

The new estradiol transdermal patch, applied once weekly, effectively increased plasma estradiol levels in postmenopausal women, achieving average concentrations proportional to the patch strength (25, 50, and 75 micrograms/day) over a 7-day period.

The patches were well tolerated with only mild and transient skin reactions, and they showed good systemic tolerability, making them a practical option for long-term estrogen replacement therapy to manage postmenopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol and estrone plasma levels during application of three strengths of a 7-day estradiol transdermal patch. Setnikar, I., Rovati, LC., Santoro, A., 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 of 13 patients with anorexia nervosa, significant hormonal deficiencies were observed, with estradiol, LH, and FSH levels markedly lower than those in a control group, indicating a disruption in reproductive hormone regulation due to the condition.

Administration of LH-RH resulted in a significant increase in LH and FSH levels, suggesting that hormonal response mechanisms are still functional in these patients, which could have implications for treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The adenohypophyseal gonadotropins in patients with anorexia nervosa]. Smiljanić, N., Ciglar, S., Kasnar, V., et al.[2015]

In a 12-month study involving 70 adolescent girls with anorexia nervosa, the combination of DHEA and estrogen replacement therapy did not significantly improve bone mineral density compared to a placebo.

Among participants with open growth plates, those receiving DHEA + estrogen actually experienced a greater decline in bone density than those on placebo, indicating that this treatment may be ineffective for preserving bone health in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Adrenal Hormone Supplementation on Bone Geometry in Growing Teens With Anorexia Nervosa. DiVasta, AD., Feldman, HA., O'Donnell, JM., et al.[2021]

The transdermal therapeutic system for estrogen administration (Estraderm) is effective and well tolerated, showing no adverse effects on liver proteins compared to oral conjugated estrogens, based on both single- and multicenter clinical studies.

While moderate bleeding occurred in some patients, it can be managed with progestogen, and the overall incidence of serious side effects like endometrial hyperplasia and breast tenderness is low, with patients generally preferring the transdermal method over oral administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal estradiol overall safety profile. Utian, WH.[2019]

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]

In a study of 104 postmenopausal women, the Systen estradiol patch was found to have better tolerability and adhesion compared to the Estraderm patch, with 79% of Systen users rating their treatment as 'good' or 'very good'.

Overall satisfaction with therapy was higher for Systen (53%) compared to Estraderm (46%), indicating that Systen may be a more effective option for estrogen replacement therapy in terms of patient acceptance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative multicenter study of two transdermal estradiol replacement therapies in the treatment of postmenopausal symptoms. Van Leusden, HA., Albertyn, G., Verlaine, C., et al.[2013]

In a 96-week study involving 124 postmenopausal women, the transdermal patch containing estradiol/norethisterone acetate (E(2)/NETA) significantly increased bone mineral density (BMD) at the lumbar spine compared to placebo, indicating its efficacy in reducing bone loss.

The E(2)/NETA patch not only prevented bone loss but also reduced the frequency of bone remodeling, showing effects on the hip similar to those seen with higher doses of estrogen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of low-dose transdermal E2/NETA on the reduction of postmenopausal bone loss in women. Rubinacci, A., Peruzzi, E., Modena, AB., et al.[2019]

In a study of 296 transgender individuals on feminizing hormone therapy, those aged 45 and older were more likely to be treated with transdermal estradiol, which is recommended for this age group due to potential cardiovascular risks.

Despite similar serum estradiol levels between age groups, older individuals receiving oral estradiol were prescribed lower doses, highlighting the need for tailored cardiovascular risk management in aging transgender populations, especially given the high prevalence of conditions like hypertension and obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feminizing Hormone Therapy Prescription Patterns and Cardiovascular Risk Factors in Aging Transgender Individuals in Australia. Balcerek, MI., Nolan, BJ., Brownhill, A., et al.[2021]

In a 6-month study involving 11 women with anorexia nervosa, treatment with transdermal estradiol and levonorgestrel resulted in significant increases in bone mineral density (BMD) at the lumbar spine, indicating potential benefits for bone health in this population.

The treatment also led to a significant decrease in bone marrow adipose tissue (BMAT) after 3 months, suggesting that physiologic doses of estrogen may help improve bone quality in women with anorexia nervosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal Estrogen in Women With Anorexia Nervosa: An Exploratory Pilot Study. Resulaj, M., Polineni, S., Meenaghan, E., et al.[2020]

Estrogen preparations (EP) have a moderate positive effect on bone mineral density in the lumbar spine of women with anorexia nervosa, but no significant effect on the femoral neck, based on a systematic review of two cohort studies and four randomized clinical trials.

The evidence regarding the benefits of EPs is low quality, and they should generally be avoided in women with anorexia nervosa, especially when the focus is on achieving weight and nutritional rehabilitation rather than just resuming menstrual cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect on bone health of estrogen preparations in premenopausal women with anorexia nervosa: a systematic review and meta-analyses. Sim, LA., McGovern, L., Elamin, MB., et al.[2018]

In a study involving 70 adolescent girls with anorexia nervosa, treatment with DHEA combined with estrogen/progestin for 12 months significantly reduced bone marrow fat in the distal femur compared to a placebo, indicating a potential to prevent bone loss.

The treatment was particularly effective in girls with a body mass index (BMI) above 18 kg/m², suggesting that higher BMI may enhance the therapeutic benefits of DHEA and hormone therapy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa. Vajapeyam, S., Ecklund, K., Mulkern, RV., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6957987/

Transdermal Estrogen in Women With Anorexia Nervosa We have shown that short‐term treatment with transdermal, physiologic estrogen treatment increases spine BMD in adult women with anorexia nervosa. We have also ...

2. jpbs.hapres.com jpbs.hapres.com/htmls/JPBS_1487_Detail.html

Estrogen for the Treatment of Low Bone Mineral Density in ... Six months of treatment with a transdermal estradiol patch (45 mcg/24 h) resulted in a mean 2% increase in lumbar spine bone mineral density [35].

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3304439/

Physiologic Estrogen Replacement Increases Bone ... Physiological estradiol replacement increases spine and hip BMD in girls with AN. Keywords: Anorexia nervosa, adolescents, bone density, bone turnover, bone ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03875378

Transdermal Estrogen in Women With Anorexia Nervosa This 18-month randomized, placebo-controlled study will investigate in women (ages 20 to 45 years old) with anorexia nervosa whether treatment with transdermal ...

5. mdpi.com mdpi.com/2072-6643/14/13/2557

Physiologic Transdermal Estradiol Replacement Mimics ... This is the first study to demonstrate that transdermal physiologic estrogen replacement in adolescent girls and young women with anorexia ...

6. massgeneral.org massgeneral.org/children/anorexia-nervosa/effective-therapy-identified-for-improving-bone-density-adolescent-girls

Effective Therapy Identified for Improving Bone Density in ... The results were promising. Girls with anorexia nervosa who received the transdermal estrogen treatment had greater increases in BMD Z-scores at ...

7. monash.edu monash.edu/news/articles/breaking-new-ground-with-trials-targeting-the-biology-of-anorexia-nervosa

Breaking new ground with trials targeting the biology of ... Melbourne researchers are using transcranial magnetic stimulation (TMS) or estrogen to treat people living with anorexia nervosa.