CLINICAL TRIALS PROFILE FOR ESTRADIOL; PROGESTERONE

505(b)(2) Clinical Trials for ESTRADIOL; PROGESTERONE

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	NCT05899010 ↗	MIcronized PROgesterone in Frozen Embryo Transfer Cycles	Not yet recruiting	Fundación Santiago Dexeus Font	Phase 3	2023-06-01	This randomized trial was designed as non-inferiority trial aiming to compare ongoing pregnancy rates following LPS with 600 mg/day vs 800 mg/day vaginal VMP. All patients will undergo an artificial cycle frozen embryo transfer (AC-FET) with transdermal estradiol 6mg/day Patients undergoing an artificial cycle FET will start estrogen priming with transdermal estradiol 6mg/day (Estrogel®) on cycle D1-D3. Following 10-12 days of estrogen priming, patients will be randomized to luteal phase support with a standard formulation (200mg tid, Utrogestan®) or a new formulation (400mg bid) VMP. All patients will undergo a serum P measurement on the day before embryo transfer (ET). Patients with P

All Clinical Trials for ESTRADIOL; PROGESTERONE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
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.
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).
NCT00005108 ↗	Effects of Hormone Replacement Therapy on Inflammation and Stiffening of Artery Walls	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 2	2000-04-01	This study will determine the effects of hormone replacement therapy (estrogen alone or estrogen and progesterone) on the walls of arteries in postmenopausal women. Inflammation and stiffness of artery walls are two risk factors for atherosclerosis-deposits of fatty substances (plaques) that can block the vessel, causing a heart attack or stroke. Estrogen raises the levels of certain substances in the blood that cause vessel inflammation and lowers the levels of others. This study will measure the net effects of estrogen on artery wall inflammation and stiffness. Postmenopausal women in good health may participate in this study. Volunteers will be screened for eligibility with a complete medical history, heart examination, and blood tests. Participants will be randomly assigned to receive either: 1) hormone therapy (estradiol 2 mg daily alone for women who have had a hysterectomy or estradiol plus micronized progesterone 200 mg daily for women with an intact uterus); or 2) placebo (look-alike pills that contain no active drug). Women in both groups will take pills for 3 months, then no pills for 1 month, and then will crossover to the alternate therapy for 3 months (i.e., those in the original placebo group will take hormones, and those in the hormone group will take placebo). At the end of each 3-month treatment period, participants will undergo the following procedures to assess blood vessel inflammation and stiffness: 1. Blood tests - 60 cc (about 2 ounces) of blood will be drawn to measure levels of hormones, cholesterol, and substances in the blood that indicate inflammation of the vessels. 2. Ultrasonography - an ultrasound probe will be applied gently on the neck to image the right and left carotid arteries (arteries in the neck that lead to the brain). During the procedure, the heart's electrical activity will also be monitored with an electrocardiogram and a blood pressure cuff will be wrapped around the arm to obtain blood pressure measurements every 5 minutes. 3. Magnetic resonance imaging (MRI) - Images of the carotid arteries are taken while the volunteer lies on a table in a narrow cylinder containing a magnetic field. A padded sensor called an MRI coil is placed over the neck and earplugs are placed in the ears to muffle the loud noise of the machine during scanning. During the second half of the exam, gadolinium is injected through a catheter (thin, flexible tube) inserted into a vein. Gadolinium is a contrast agent that is used to brighten the scan images. Information from this study will increase knowledge about the effects of estrogen on vessel wall inflammation. As such, it may be used in the future to help guide decisions about chronic hormone replacement therapy in postmenopausal women.
NCT00005769 ↗	Hormone Replacement Therapy and Insulin Action: A Double-Blind, Parallel, Placebo-Controlled Hormone Intervention Study in Postmenopausal Women	Unknown status	National Center for Research Resources (NCRR)	Phase 2	1969-12-31	Considerable controversy exists regarding the effect of estrogen and progesterone on insulin sensitivity in postmenopausal women. Thus, the goal is to examine the effect of estradiol and progestin on in vivo insulin sensitivity and pathways of intracellular glucose metabolism in postmenopausal women. This will be accomplished by examining the effects of unopposed estrogen (CEE) or combination estrogen and progestin (CEE/MPA) versus placebo therapy in 30 early menopausal women (defined from 6 months to 3 years post-cessation of menses). Women will be treated for 16 weeks and the outcome measures will be: 1) insulin sensitivity and glucose oxidation as determined by euglycemic clamp, 2) assessments of insulin sensitivity on muscle biopsy cultures with the primary endpoints being glucose uptake and glycogen accumulation/synthesis, 3) protein levels of insulin action cascade steps based on muscle biopsy Western blots.

Clinical Trial Conditions for ESTRADIOL; PROGESTERONE

Condition Name

Condition Name for ESTRADIOL; PROGESTERONE
Intervention	Trials
Infertility	59
Menopause	20
Contraception	13
Breast Cancer	12

Condition MeSH

Condition MeSH for ESTRADIOL; PROGESTERONE
Intervention	Trials
Infertility	75
Breast Neoplasms	27
Polycystic Ovary Syndrome	15
Infertility, Female	10

Clinical Trial Locations for ESTRADIOL; PROGESTERONE

Trials by Country

Trials by Country for ESTRADIOL; PROGESTERONE
Location	Trials
United States	230
Egypt	35
Brazil	9
Canada	7
Vietnam	7

Trials by US State

Trials by US State for ESTRADIOL; PROGESTERONE
Location	Trials
California	18
Virginia	17
Illinois	17
North Carolina	14
New York	13

Clinical Trial Progress for ESTRADIOL; PROGESTERONE

Clinical Trial Phase

Clinical Trial Phase for ESTRADIOL; PROGESTERONE
Clinical Trial Phase	Trials
PHASE4	7
PHASE3	5
PHASE2	4

Clinical Trial Status

Clinical Trial Status for ESTRADIOL; PROGESTERONE
Clinical Trial Phase	Trials
Completed	122
Recruiting	57
Unknown status	34

Clinical Trial Sponsors for ESTRADIOL; PROGESTERONE

Sponsor Name

Sponsor Name for ESTRADIOL; PROGESTERONE
Sponsor	Trials
National Cancer Institute (NCI)	19
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	16
Cairo University	12

Sponsor Type

Sponsor Type for ESTRADIOL; PROGESTERONE
Sponsor	Trials
Other	340
NIH	66
Industry	53

ESTRADIOL; PROGESTERONE Market Analysis and Financial Projection

Last updated: April 28, 2026

Clinical Trials Update, Market Analysis, and Projection for Estradiol + Progesterone

What is the current clinical development landscape for estradiol + progesterone?

Estradiol plus progesterone is an established hormonal therapy used in menopausal hormone therapy (MHT). Clinical activity for “estradiol + progesterone” today is dominated by:

• Reformulation and delivery-system advances (improved absorption, dosing convenience, and tolerability).
• Line-extension trials in MHT subpopulations (endometrial protection, bleeding control, vaginal symptoms).
• Real-world evidence and adherence-driven endpoints that support label refreshes and payer positioning.

But current public-trial visibility for the exact pairing “estradiol; progesterone” (as a fixed combination) is limited by how registries index products. Many clinical records are filed under:

• Estradiol combined with different progestogens (e.g., medroxyprogesterone acetate) rather than micronized progesterone.
• Estradiol with sequential progesterone regimens, where the “progesterone” component is not packaged or branded as a single combination product.

As a result, global trial counts by registry search terms do not map cleanly to “estradiol + progesterone” as one development bucket. A credible update requires product-level indexing (brand, route, and regimen) and registry-to-label reconciliation. With the information available in this prompt, a complete, accurate trial update cannot be produced.

What is the market status for estradiol + progesterone?

Estradiol-based MHT products are mature and compete on route of administration, dose titration, and endometrial safety data.

Commercial reality:

• Demand concentrates on women with uterus intact, where progesterone/progestogen choice and bleeding management drive switching.
• Payer coverage tends to favor regimens with strong safety and adherence profiles, but substitution by formulary (where other progestogens are listed) remains common.
• “Progesterone” versus other progestogens matters for prescriber preference in select segments, especially where bioidentical progesterone is targeted.

Key market variables that control share:

• Route (oral vs transdermal estradiol; progesterone oral micronized vs other progestogen forms).
• Regimen design (continuous vs sequential; bleeding outcomes are a commercial lever).
• Safety communication (venous thromboembolism risk framing for route; endometrial protection evidence for progestogen).
• Brand access and rebate dynamics in major markets.

A quantitative market size, share breakdown, and forecast requires a dataset with explicit product definitions (exact combination and route) and coverage by geography. This prompt does not provide that dataset, so a complete, accurate market analysis and projection cannot be delivered.

What is the growth outlook and 5-year projection for estradiol + progesterone?

A defensible forecast depends on at least five measurable inputs:

1. Addressable population by indication (menopause prevalence and treatment penetration).
2. Route mix trends (transdermal vs oral estradiol).
3. Progestogen selection trends (micronized progesterone versus other progestogens).
4. Competitive entry and patent-expiry calendar for the specific combinations.
5. Reimbursement posture by payer and geography.

Those inputs require cited market-research figures or registry claims tied to product-level definitions. In the absence of source data, any numeric projection would be non-actionable.

What are the patent and exclusivity risks that typically shape this category?

Estradiol and progesterone each have long commercialization histories. Forecasted category economics usually hinge on:

• Formulation patents (delivery system, particle engineering, dosage form).
• Process patents (manufacturing method).
• Method-of-use claims (specific regimens, bleeding control, endometrial protection claims).
• Exclusivity events tied to regulatory filings (country-specific).

A usable risk map needs a listed claim chart or at least a patent family table tied to specific marketed products containing:

• Estradiol component (molecule form, route)
• Progesterone component (micronized progesterone vs synthetic progestins)
• Regimen and dose timing
• Jurisdictions of interest

No such patent family dataset is provided in this prompt, so a complete and accurate “risks and timeline” section cannot be produced.

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Key Takeaways

• Estradiol plus progesterone is a mature MHT category with clinical development focused on reformulation, regimen optimization, and adherence/tolerability outcomes.
• Public-trial visibility for “estradiol; progesterone” is constrained by registry indexing practices and product-level definitions, making a complete clinical trials update impossible from the information provided here.
• Market sizing and 5-year projection require product-level market inputs (route, regimen, progestogen form) and cited datasets; they are not available in this prompt.
• Patent and exclusivity analysis must be built from specific patent families tied to marketed fixed combinations or regimen packages; none are included here.

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FAQs

1) Is estradiol + progesterone still actively studied?
Yes. Activity is mostly in delivery-system and regimen optimization, plus label-supportive clinical endpoints, but product-level indexing limits a clean “estradiol; progesterone” view.

2) Does progesterone selection change commercial outcomes?
Yes. In uterine-intact populations, endometrial protection and bleeding outcomes influence formulary position, prescribing, and switching.

3) Is transdermal estradiol a growth driver in MHT?
Route trends affect share because tolerability and safety communication influence uptake, but a quantified projection needs a sourced route-mix dataset.

4) What typically drives switching between progestogens?
Bleeding profile, patient preference for “bioidentical” positioning, and payer formulary structure.

5) Can a forecast be made without product-level definitions?
No. Fixed-combination and regimen boundaries determine incidence of use, payer coverage, and competitive substitution, so forecasts require those definitions.

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References

[1] No sources were provided in the prompt to cite.