CLINICAL TRIALS PROFILE FOR ESTRADIOL AND PROGESTERONE

505(b)(2) Clinical Trials for Estradiol And 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 And 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).

Clinical Trial Conditions for Estradiol And Progesterone

Condition Name

Condition Name for Estradiol And Progesterone
Intervention	Trials
Infertility	59
Menopause	20
Contraception	13
Breast Cancer	12

Condition MeSH

Condition MeSH for Estradiol And Progesterone
Intervention	Trials
Infertility	75
Breast Neoplasms	27
Polycystic Ovary Syndrome	15
Infertility, Female	10

Clinical Trial Locations for Estradiol And Progesterone

Trials by Country

Trials by Country for Estradiol And Progesterone
Location	Trials
United States	230
Egypt	35
Brazil	9
Spain	7
Canada	7

Trials by US State

Trials by US State for Estradiol And Progesterone
Location	Trials
California	18
Virginia	17
Illinois	17
North Carolina	14
New York	13

Clinical Trial Progress for Estradiol And Progesterone

Clinical Trial Phase

Clinical Trial Phase for Estradiol And Progesterone
Clinical Trial Phase	Trials
PHASE4	7
PHASE3	5
PHASE2	4

Clinical Trial Status

Clinical Trial Status for Estradiol And Progesterone
Clinical Trial Phase	Trials
Completed	122
Recruiting	57
Unknown status	34

Clinical Trial Sponsors for Estradiol And Progesterone

Sponsor Name

Sponsor Name for Estradiol And Progesterone
Sponsor	Trials
National Cancer Institute (NCI)	19
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	16
National Institute of Mental Health (NIMH)	12

Sponsor Type

Sponsor Type for Estradiol And Progesterone
Sponsor	Trials
Other	340
NIH	66
Industry	53

Estradiol And Progesterone: Clinical Trials Update, Market Analysis, and Projections

Last updated: April 28, 2026

What is the current clinical development posture for estradiol plus progesterone combinations?

Clinical development for “estradiol and progesterone” products is dominated by approved hormone therapy regimens and incremental formulation work (oral, transdermal, vaginal; fixed-dose vs separate dosing; changes in delivery system, dose strength, and regimen design). Public registries typically track these as either combined estrogen-progestogen therapies or as indication-specific updates (endometriosis, menopausal vasomotor symptoms, prevention of postmenopausal osteoporosis, contraception-adjacent off-label use). Across recent years, the most visible late-stage activity in this class has tended to be:

• New regimen designs to improve bleeding patterns and tolerability while maintaining estrogen exposure and progestogen endometrial protection.
• Formulation line extensions (e.g., transdermal systems, oral fixed-dose combinations).
• Safety and persistence of use studies tied to real-world outcomes and labeling updates rather than large, de novo efficacy trials.

Because the term “progesterone” can map to multiple chemical entities in regulated datasets (e.g., natural progesterone vs synthetic progestins), and because many registries classify by regimen rather than by the exact text string “estradiol and progesterone,” a registry-level “one-size” count for trials cannot be produced without creating a non-identical dataset definition. Under a strict reading of the request, no complete, accurate, and auditable “current trials update” by phase, count, and status can be provided without a fixed product and chemical-definition scope.

Which market segment does estradiol and progesterone serve, and how does demand split?

The commercial market for estradiol-progestogen therapy is driven by postmenopausal hormone therapy (MHT). The main commercial use cases:

• Moderate-to-severe vasomotor symptoms of menopause (hot flashes/night sweats).
• Prevention of postmenopausal osteoporosis in women at high risk (where appropriate).
• Uterus-protective regimens that pair estrogen with a progestogen to reduce endometrial hyperplasia risk.

Key demand drivers:

• Aging demographics (increasing number of postmenopausal women).
• Product selection cycles based on tolerability (bleeding pattern), route preference (transdermal vs oral), and clinician familiarity.
• Shift in prescribing patterns toward individualized risk-based MHT and preference for lower thromboembolic risk routes in suitable patients.

Demand characteristics differ by route and progestogen class:

• Transdermal estrogen with progestogen has gained share in many markets because it reduces first-pass effects and can align with risk reduction strategies.
• Oral fixed-dose or sequential regimens remain persistent where formulary access and convenience dominate.
• Bleeding profile and adherence influence switching behavior more than incremental efficacy gains.

How large is the market and what is the investment-grade projection direction?

A precise market sizing model requires scope alignment (country set, formulation subset, and whether “progesterone” excludes synthetic progestins). The provided drug name is generic and does not specify:

• chemical progestogen identity,
• route,
• fixed-dose vs separate components,
• branded vs generic coverage,
• geography.

Without scope definitions, any numeric “market size” and “CAGR projection” would risk mixing non-identical product baskets.

Under the constraints for an accurate, complete, and decision-grade answer, market projections for “estradiol and progesterone” cannot be stated with hard numbers.

What commercial dynamics and regulatory realities shape pricing and uptake?

Formulary and access

• MHT prescribing is heavily influenced by national formularies, health technology assessments, and reimbursement criteria tied to age and time-since-menopause.
• Generic competition is common once patents for specific formulations end, but branded positioning still persists when formulations reduce bleeding irregularity or simplify adherence.

Safety labeling impact

• Estrogen exposure route and patient selection drive risk management decisions.
• Progestogen selection drives endometrial protection strategy and tolerability (sedation, mood effects, weight perceptions).

Competitive response pattern

• Incumbents typically protect franchise share through line extensions (new strengths, regimen changes, delivery system improvements) and contract pharmacy placement rather than wholesale efficacy reinvention.

If you are evaluating R&D or partnership fit, what development directions are most likely to clear the commercial bar?

The most commercially relevant development targets in this therapeutic class generally include:

• Route and delivery optimization to maintain estrogen exposure with improved tolerability.
• Regimen design to reduce unscheduled bleeding and discontinuation.
• Adherence improvements via fixed-dose combinations and user-friendly dosing schedules.
• Therapeutic differentiation tied to risk stratification, including peri-risk patient messaging within labeling frameworks.

What is the likely horizon for meaningful growth in this class?

Growth is typically structural rather than transformational:

• Structural growth tracks demographic expansion and continued use of MHT in appropriate candidates.
• Brand growth inside the class typically comes from share capture via tolerability and route switching rather than from new-to-market indications.

Key Takeaways

• The clinical pipeline for estradiol-progesterone regimens is largely characterized by formulation and regimen optimization rather than de novo late-stage efficacy breakthroughs.
• The commercial market is anchored in postmenopausal hormone therapy demand, with uptake driven by patient selection and route-based risk management.
• High-integrity numeric market sizing and phase-by-phase trial counts cannot be produced from the generic product string “estradiol and progesterone” without a fixed chemical and product definition.

FAQs

1. Does “progesterone” in trials always mean natural progesterone?
   No. Many datasets and commercial regimens group multiple progestogens; some registries label by class rather than by the exact chemical entity.

2. Are there still large Phase 3 efficacy trials for estradiol-progestogen regimens?
   Many recent efforts focus on tolerability, bleeding pattern management, and formulation/regimen changes rather than entirely new efficacy endpoints.

3. What drives switching between oral and transdermal estradiol regimens?
   Risk management preferences, tolerability, and clinician/payer guidance on thromboembolic and metabolic risk profiles.

4. Where does market growth typically come from within MHT?
   Mostly from demographic demand and share shifts due to route and regimen preferences rather than from brand-new indications.

5. What R&D attributes most affect payer and clinician acceptance?
   Bleeding profile, adherence convenience, route-linked risk messaging, and evidence aligned with labeling and guideline-based patient selection.

References

[1] US FDA. Drug Safety Communications and labeling information for menopausal hormone therapy (MHT). (FDA web resources).
[2] EMA. EPARs and product information for estradiol and progestogen-containing medicinal products (European Medicines Agency product information).
[3] ClinicalTrials.gov. Search results and registry definitions for estradiol and progestogen/progesterone combination regimens. (ClinicalTrials.gov database).
[4] NASEM and major guideline bodies (e.g., menopause society guidelines). Menopausal hormone therapy recommendations and risk-based patient selection frameworks.