CLINICAL TRIALS PROFILE FOR ESTRADIOL

505(b)(2) Clinical Trials for ESTRADIOL

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT00649896 ↗	Evaluation of Adhesion Quality of a New Formulation of the Mylan Estradiol Transdermal System 0.025 mg/Day and Climara® Transdermal System 0.025 mg/Day	Completed	Mylan Pharmaceuticals	Phase 1	2003-08-01	The primary objective of this study was to compare the adhesive quality of a new formulation of the Mylan Estradiol Transdermal System with that of Climara® Transdermal System following a single system application in 80 healthy postmenopausal female volunteers. As a secondary objective, primary dermal irritation was assessed after removal of each transdermal system.
New Formulation	NCT02253173 ↗	Estradiol Vaginal Softgel Capsules in Treating Symptoms of Vulvar and Vaginal Atrophy in Postmenopausal Women	Completed	TherapeuticsMD	Phase 3	2014-09-01	This study will assess the safety and efficacy of a new formulation of vaginal estradiol for the treatment of symptoms of vulvar and vaginal atrophy in postmenopausal women.
OTC	NCT02516202 ↗	The Vaginal Health Trial	Completed	Group Health Cooperative	Phase 3	2016-04-01	This is a new application from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Clinical Trials network. Here we propose to conduct a large multicenter trial comparing two common treatments, a vaginal hormone tablet and an over-the-counter gel, with placebo to evaluate their effects on bothersome vaginal symptoms and sexual function, and to create a biorepository of specimens for future translational, mechanistic research on the etiology of vaginal symptoms.
OTC	NCT02516202 ↗	The Vaginal Health Trial	Completed	Kaiser Permanente	Phase 3	2016-04-01	This is a new application from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Clinical Trials network. Here we propose to conduct a large multicenter trial comparing two common treatments, a vaginal hormone tablet and an over-the-counter gel, with placebo to evaluate their effects on bothersome vaginal symptoms and sexual function, and to create a biorepository of specimens for future translational, mechanistic research on the etiology of vaginal symptoms.
OTC	NCT02516202 ↗	The Vaginal Health Trial	Completed	Massachusetts General Hospital	Phase 3	2016-04-01	This is a new application from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Clinical Trials network. Here we propose to conduct a large multicenter trial comparing two common treatments, a vaginal hormone tablet and an over-the-counter gel, with placebo to evaluate their effects on bothersome vaginal symptoms and sexual function, and to create a biorepository of specimens for future translational, mechanistic research on the etiology of vaginal symptoms.
OTC	NCT02516202 ↗	The Vaginal Health Trial	Completed	University of California, San Diego	Phase 3	2016-04-01	This is a new application from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Clinical Trials network. Here we propose to conduct a large multicenter trial comparing two common treatments, a vaginal hormone tablet and an over-the-counter gel, with placebo to evaluate their effects on bothersome vaginal symptoms and sexual function, and to create a biorepository of specimens for future translational, mechanistic research on the etiology of vaginal symptoms.
OTC	NCT02516202 ↗	The Vaginal Health Trial	Completed	University of Minnesota	Phase 3	2016-04-01	This is a new application from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Clinical Trials network. Here we propose to conduct a large multicenter trial comparing two common treatments, a vaginal hormone tablet and an over-the-counter gel, with placebo to evaluate their effects on bothersome vaginal symptoms and sexual function, and to create a biorepository of specimens for future translational, mechanistic research on the etiology of vaginal symptoms.

All Clinical Trials for ESTRADIOL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000559 ↗	Women's Estrogen/Progestin Lipid Lowering Hormone Atherosclerosis Regression Trial (WELL-HART)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1995-03-01	To determine the effects, in postmenopausal women, of hormone replacement therapy on progression/regression of coronary heart disease, as measured by quantitative angiography.
NCT00000897 ↗	A Study to Evaluate the Effects of Different Methods of Birth Control on the Drug Actions of Zidovudine (an Anti-HIV Drug) in HIV-Positive Women and to Compare Zidovudine Metabolism in Men and Women	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	The purpose of this study is to look at the effects of different methods of birth control (oral and injectable) on how the body absorbs, makes available, and removes zidovudine (ZDV). This study will also evaluate the differences in men and women in how the body absorbs, makes available, and removes ZDV. Past research has shown that the effectiveness of ZDV as an anti-HIV drug might be decreased in individuals who use certain methods of birth control. ZDV may also have different effects in men compared to women.
NCT00001202 ↗	Treatment of Boys With Precocious Puberty	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	1985-01-01	This study is a continuation of two previous studies conducted at the NIH. The first study , "Treatment of True Precocious Puberty with a Long-Acting Lutenizing Hormone Releasing Hormone Analog (D-Trp(6)-Pro(9)-Net-LHRH)" had less than optimal results. Some patients, all of whom were diagnosed with familial isosexual precocious puberty, had an inadequate response to the medication and were observed to have high levels of testosterone, advanced bone aging, and other complications of the disease. As a result these patients were enrolled in a second study In the second study, "Spironolactone Treatment for Boys with Familial Isosexual Precocious Puberty", - the patients received another medication, spironolactone (Aldactone). The drug blocked the effects of testosterone, -but bone age advancement did not improve. Some patients began experiencing gynecomastia (an abnormal growth of the male breasts). Researchers believe these may be the effects of elevated levels of estrodiol (a form of the female hormone, estrogen). In the present study, testolactone is added to the drug regimen to block the production of estrogen. The study therefore uses spironolactone to prevent the action of the male hormones (androgen) and testolactone to block the production of female hormones (estrogen). Deslorelin, an LHRH analog which works by turning off true (central) puberty, is added to the drug regimen once true puberty begins. This is because it is know that boys with familial male precocious puberty go into true puberty too early (despite treatment with spironolactone and testolactone), and when that happens, the spironolactone and testolactone are no longer as effective. The goal of the treatment is to delay sexual development until a more appropriate age and prevent short adult stature (height).
NCT00001221 ↗	Effect of Biosynthetic Growth Hormone and/or Ethinyl Estradiol on Adult Height in Patients With Turner Syndrome	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	1987-09-01	Turners Syndrome is a genetic condition in females that is a result of abnormal chromosomes. Girls with Turner syndrome are very short as children and as adults. Although their growth hormone secretion is almost always normal, giving injections of growth hormone to Turner syndrome girls may increase their rate of growth. In addition, most girls with Turner syndrome do not have normal ovaries. In normal girls the ovaries begin producing small amounts of the female sex hormone, estrogen at about 11 - 12 years of age. As girls grow older the level of estrogen increases. Estrogen is responsible for the changes in girls known as feminization. During feminization the hips grow wider, the breasts develop, there is an increase in the rate of growth, and eventually girls experience their first menstrual period. This study was designed to evaluate the effect of low dose estrogen, growth hormone, and the combination of low dose estrogen and growth hormone on adult height in girls with Turner syndrome. Patients will be entered into the study from ages 5 to 12 and will be randomly placed into one of four groups. 1. Group one will receive low dose estrogen 2. Group two will receive growth hormone 3. Group three will receive both low dose estrogen and growth hormone 4. Group four will receive a placebo "sugar pill" Once started, the treatment will continue until the patients approach their adult height, and growth slows to less than 1/2 inch over the preceding year. This usually occurs by the age of 15 or 16. Patients will be seen at the outpatient clinic every 6 months during the study and will receive a routine check-up with blood and urine tests, and hand/wrist X-rays to determine bone age. On patient's yearly visits they will have the density of bone measured in their spine and forearm.
NCT00001259 ↗	A Treatment Study for Premenstrual Syndrome (PMS)	Completed	National Institute of Mental Health (NIMH)	Phase 1	1992-08-11	This study examines the effects of estrogen and progesterone on mood, the stress response, and brain function and behavior in women with premenstrual syndrome. Previously this study has demonstrated leuprolide acetate (Lupron (Registered Trademark)) to be an effective treatment for PMS. The current purpose of this study is to evaluate how low levels of estrogen and progesterone (that occur during treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and progesterone (given during individual months of hormone add-back) on a variety of physiologic measures (brain imaging, stress testing, etc.) in women with PMS. PMS is a condition characterized by changes in mood and behavior that occur during the second phase of the normal menstrual cycle (luteal phase). This study will investigate possible hormonal causes of PMS by temporarily stopping the menstrual cycle with leuprolide acetate and then giving, in sequence, the menstrual cycle hormones progesterone and estrogen. The results of these hormonal studies will be compared between women with PMS and healthy volunteers without PMS (see also protocol 92-M-0174). At study entry, participants will undergo a physical examination. Blood, urine, and pregnancy tests will be performed. Cognitive functioning and stress response will be evaluated during the study along with brain imaging and genetic studies.
NCT00001322 ↗	The Effects of Reproductive Hormones on Mood and Behavior	Completed	National Institute of Mental Health (NIMH)	N/A	1994-06-09	This study evaluates the effects of estrogen and progesterone on mood, the stress response, and brain function in healthy women. The purpose of this study is to evaluate how low levels of estrogen and progesterone (that occur during treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and progesterone (given during individual months of hormone add-back) on a variety of physiologic measures (brain imaging, stress testing, etc.) in healthy volunteer women without PMS. This study will investigate effects of reproductive hormones by temporarily stopping the menstrual cycle with leuprolide acetate and then giving, in sequence, the menstrual cycle hormones progesterone and estrogen. Tests (such as brain imaging or stress testing, etc.) will be performed during the different hormonal conditions (low estrogen and progesterone, progesterone add-back, estrogen add-back). The results of these studies will be compared between women without PMS and women with PMS (see also protocol 90-M-0088). At study entry, participants will undergo a physical examination. Blood, urine, and pregnancy tests will be performed. Cognitive functioning and stress response will be evaluated during the study along with brain imaging and genetic studies.
NCT00001481 ↗	The Role of Hormones in Postpartum Mood Disorders	Recruiting	National Institute of Mental Health (NIMH)	Phase 2	1996-04-26	Determine whether postpartum depression is triggered by the abrupt withdrawal of estrogen and progesterone. The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major effective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estrogen and progesterone for an additional month. Outcome measures will include mood, behavioral and hormonal parameters (a separate protocol done in collaboration with NICHD).

Clinical Trial Conditions for ESTRADIOL

Condition Name

Condition Name for ESTRADIOL
Intervention	Trials
Infertility	91
Contraception	82
Menopause	68
Breast Cancer	59

Condition MeSH

Condition MeSH for ESTRADIOL
Intervention	Trials
Infertility	130
Breast Neoplasms	100
Atrophy	35
Syndrome	35

Clinical Trial Locations for ESTRADIOL

Trials by Country

Trials by Country for ESTRADIOL
Location	Trials
Germany	82
China	79
Canada	65
Egypt	59
Poland	56

Trials by US State

Trials by US State for ESTRADIOL
Location	Trials
California	111
Florida	93
Texas	85
Pennsylvania	78
New York	78

Clinical Trial Progress for ESTRADIOL

Clinical Trial Phase

Clinical Trial Phase for ESTRADIOL
Clinical Trial Phase	Trials
PHASE4	21
PHASE3	11
PHASE2	20

Clinical Trial Status

Clinical Trial Status for ESTRADIOL
Clinical Trial Phase	Trials
Completed	601
Recruiting	155
Unknown status	96

Clinical Trial Sponsors for ESTRADIOL

Sponsor Name

Sponsor Name for ESTRADIOL
Sponsor	Trials
National Cancer Institute (NCI)	52
Bayer	47
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	41

Sponsor Type

Sponsor Type for ESTRADIOL
Sponsor	Trials
Other	1016
Industry	469
NIH	191

Estradiol (Systemic Estrogen) Clinical Trials Update, Market Analysis, and Projection

Last updated: April 25, 2026

What is estradiol and how is it positioned commercially?

Estradiol is the primary natural human estrogen. Commercial products span multiple delivery systems (oral, transdermal, vaginal, implants). Market access is dominated by brand portfolios and payer formularies by route and indication, with biosimilar-like dynamics largely limited to specific branded products rather than a single “platform” category.

Key market segmentation (route/in-market use):

• Transdermal estradiol (patches, gels): common for menopausal symptom management and longer-term use where clinicians target avoidance of first-pass metabolism.
• Oral estradiol: includes tablets; clinical use remains material, particularly where cost and formulary fit favor oral dosing.
• Vaginal estradiol (low-dose local therapy): addresses vulvovaginal atrophy/dyspareunia associated with menopause.
• Other systemic formulations (e.g., implants in some markets): lower switching rates but region-dependent availability.

Strategic implication: competitive intensity depends more on formulation, dosing convenience, and label-specific payer coverage than on “molecular novelty,” because estradiol is not a new chemical entity in the way typical late-stage pipeline drugs are.

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What clinical trial activity exists for estradiol right now?

Estradiol trial activity is dominated by one of three patterns:

1. Route optimization and formulation development (same active, different delivery)
2. New dosing regimens within approved indications (dose titration, frequency changes)
3. Expanded use cases around menopause-related indications (including local estrogen and symptom subdomains)

What you should expect in trial reporting for estradiol assets:

• High volume of small-to-mid size studies compared with oncology/rare disease pipelines.
• Frequent use of non-inferiority or pharmacokinetic endpoints, especially for transdermal and vaginal products.
• Endpoints aligned with symptom scales and surrogate exposure measures rather than disease-modifying outcomes.

Where trials cluster most:

• Menopausal vasomotor symptoms
• Genitourinary syndrome of menopause (vaginal atrophy, dyspareunia)
• Pharmacokinetics and comparative bioavailability for formulation line extensions

Decision impact for R&D and licensing: the dominant “value creation” path is label differentiation and payer acceptance by route, dose regimen, and tolerability profile (skin reactions for patches, systemic exposure profiles, and local tolerability for vaginal therapy), not new estrogen biology.

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How does the competitive landscape look for estradiol?

Who competes

Competition is primarily brand-to-generic within each route:

• Transdermal: multiple branded originators and generic patch lines
• Oral: generic tablets with residual brand differentiation in some geographies
• Vaginal: brand-to-generic dynamics vary by country and product form (cream/tablet/ring)

Competitive drivers

• Formulary tiering and rebate intensity (payer behavior)
• Switching friction (patient preference and stability of dosing)
• Adherence (patch/gels vs pills)
• Safety and tolerability by route (localized vs systemic adverse event burden)

What this means for IP

For estradiol, patent portfolios typically focus on:

• Formulation-specific patents
• Manufacturing and composition of matter variants
• Device delivery technology for patches/implants or specialized dispensers
• Specific dosing regimens (where enforceable)

This structure limits the number of true “blockbuster-molecule” bets and increases the importance of route-specific defensibility.

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What is the market size, growth rate, and demand profile?

Estradiol is a core estrogen therapy within the global menopausal hormone therapy and genitourinary syndrome of menopause market. Market growth is driven by:

• Aging demographics
• Increased diagnosis and symptom reporting
• Broader guideline acceptance of individualized hormone therapy regimens
• Continued uptake of low-dose local therapy for vulvovaginal atrophy

Market behavior characteristics

• Mature market with incremental growth
• Route-dependent shares
• Price pressure where generics are prevalent
• Payer-managed adoption with seasonal and adherence effects

Projection framework for estradiol markets A practical projection approach uses:

• Population over 45-65 cohorts in key markets
• Treatment penetration rate for menopause symptoms and genitourinary syndrome
• Share by delivery route (transdermal vs oral vs vaginal)
• Average annual treatment cost (blended by coverage and rebates)
• Switching and persistence rates by route

Business interpretation: the near-term upside is more likely to come from route mix (transdermal and vaginal low-dose) and persistence/adherence improvements than from step-change demand.

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What is the market projection for estradiol through the next 5 to 10 years?

Base-case projection (directional, route-mix driven)

• Moderate growth in total demand in most large markets.
• Transdermal and vaginal segments typically hold stronger growth vs oral where clinical practice emphasizes tolerability and individualized systemic exposure.
• Generic pressure sustains price erosion, offset by unit volume growth and improved adherence.

Scenario logic

• Base case: gradual volume growth plus continued price erosion; stable to slightly higher share for transdermal/vaginal with localized symptom focus.
• Upside case: faster uptake of local vaginal therapies for genitourinary syndrome and increased transdermal prescribing under preference for reduced first-pass effects.
• Downside case: payer restrictions or tighter utilization management reduce persistence and new starts, with generics deepening price pressure.

Commercial takeaway: revenue growth is most sensitive to (1) route mix changes and (2) formulary positioning rather than to new molecular differentiation.

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Which clinical endpoints and regulatory expectations matter for estradiol line extensions?

Across estradiol trials and submissions, the recurring endpoint set is:

• Pharmacokinetics: exposure and time-to-peak for systemic delivery (transdermal/oral)
• Symptom response: standardized menopausal symptom measures (vasomotor symptoms) and local symptom scales (vaginal atrophy)
• Safety/tolerability: endometrial safety considerations for systemic therapy, local tolerability for vaginal products, and application-site reactions for transdermal systems

Regulatory expectations for estradiol variants typically revolve around:

• Bioequivalence/comparability where appropriate
• Consistent systemic exposure for systemic indications
• Demonstrated clinical relevance of local effect for vaginal indications

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What are the highest-value R&D targets for estradiol programs?

For investors and licensing teams, the most bankable R&D themes are not new estrogen pathways, but:

• Improved delivery that reduces clinically meaningful adverse events (e.g., transdermal skin reactions)
• Simplified dosing to raise persistence and adherence
• Route-specific differentiation that supports formulary positioning (transdermal for systemic symptoms, vaginal for genitourinary syndrome)
• Demonstrable exposure consistency for systemic therapies to reduce “real-world variability” in dosing

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Key Takeaways

• Estradiol is a mature, route-diverse estrogen therapy where commercial outcomes depend on formulation, dosing regimen, payer access, and adherence.
• Current clinical trial activity centers on formulation and regimen optimization and on trials designed around pharmacokinetics and symptom endpoints rather than disease modification.
• The market outlook is moderate growth with ongoing price pressure where generics are prevalent; upside aligns with transdermal and vaginal low-dose mix shifts and improved persistence.
• For pipeline and licensing strategy, route-specific differentiation and defensible product patents matter more than molecular innovation.

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FAQs

1) Is estradiol currently treated as a “pipeline” category like novel small molecules?

No. Estradiol’s pipeline is typically formulation- and regimen-based, with clinical development focused on comparability, exposure, and symptom response in approved indication areas.

2) Which estradiol delivery routes are most sensitive to payer coverage?

Transdermal systemic and vaginal local therapies are the most sensitive to payer formulary placement because they compete across multiple branded and generic options with route-specific tolerability narratives.

3) What typically drives switching in estradiol therapy?

Switching is driven by formulary changes, cost, dosing convenience, and tolerability. Route changes often face higher persistence resistance than within-route substitutions.

4) What endpoints are most common in estradiol trials?

Pharmacokinetics for systemic delivery and validated symptom measures for menopausal and genitourinary syndrome indications, paired with route-specific safety and tolerability assessments.

5) Where do commercial opportunities tend to concentrate?

Opportunities concentrate in route mix optimization, adherence and tolerability improvements, and label/regimen differentiation that supports payer acceptance.

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References

[1] U.S. Food and Drug Administration. Drug Trials Snapshots. https://www.accessdata.fda.gov/scripts/cder/daf/ (accessed 2026-04-25).
[2] European Medicines Agency. Medicines and information for the public. https://www.ema.europa.eu/ (accessed 2026-04-25).
[3] NAMS (North American Menopause Society). Menopause-related clinical guidance and position statements. https://menopause.org/ (accessed 2026-04-25).
[4] ClinicalTrials.gov. Search results for estradiol. https://clinicaltrials.gov/ (accessed 2026-04-25).