CLINICAL TRIALS PROFILE FOR PREMARIN

505(b)(2) Clinical Trials for PREMARIN

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	NCT00380887 ↗	Study Comparing Four New Formulations for Premarin in Healthy Postmenopausal Women	Completed	Wyeth is now a wholly owned subsidiary of Pfizer		2005-06-01	The purpose of this study is to determine bioequivalence and bioavailability of four different Premarin/MPA test formulations versus the current formulation for Prempro.
New Formulation	NCT00381251 ↗	Study Comparing Bioequivalence of Two New Formulations of Premarin/MPA With Premarin/MPA Reference Formulation.	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2006-09-01	This study will compare the bioequivalence of two new investigational combination formulations of Premarin and medroxyprogesterone acetate (MPA) with a currently marketed formulation of Premarin and medroxyprogesterone, Prempro™. Prempro is indicated for use after menopause in women with a uterus to reduce moderate to severe hot flashes; to treat moderate to severe dryness, itching, and burning, in and around the vagina; and to help reduce your chances of getting osteoporosis (thin weak bones). The purpose of this study is to determine if these new formulations of Premarin and MPA provide the same levels of estrogen and MPA in the blood as Prempro in healthy postmenopausal women.
New Formulation	NCT00401219 ↗	Study Comparing Bioavailability of 3 New Formulations of Premarin/MPA With Premarin/MPA (PREMPRO) Reference Formulation	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2006-11-01	This study will compare the bioavailabity of three new investigational combination formulations of Premarin and medroxyprogesterone acetate (MPA) with a currently marketed formulation of Premarin and MPA, Prempro™. Prempro™ is indicated for use after menopause in women with a uterus to reduce moderate to severe hot flashes; to treat moderate to severe dryness, itching, and burning, in and around the vagina; and to help reduce your chances of getting osteoporosis (thin weak bones). The purpose of this study is to determine if these new formulations of Premarin/MPA provide the same levels of estrogen and MPA in the blood as Prempro in healthy postmenopausal women.
New Formulation	NCT00472927 ↗	Bioequivalence Study of 3 New Formulations of Premarin/MPA Compared With Premarin/MPA (Prempro)	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2007-05-01	To evaluate three new investigational tablet formulations of the Food and Drug Administration (FDA) approved medication Prempro™, Premarin combined with medroxyprogesterone acetate (MPA).
New Formulation	NCT00630435 ↗	Study Comparing 3 New Formulations of Premarin® 0.625 mg/MPA 2.5 mg With a Reference Formulation	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2008-02-01	The purpose of this trial is to determine the equivalence of 3 new formulations of a Premarin®/medroxyprogesterone acetate (MPA) combination tablet to the currently marketed dosage form (Prempro® [TM]). This study will be performed in healthy postmenopausal women. Each subject will participate in the study for approximately 14 weeks, including a screening evaluation within 3 weeks before the study, and four, 6-day, 5-night inpatient periods with at least a 21-day washout interval between each dose administration.
New Formulation	NCT01436513 ↗	A Study To Compare The Amount Of Premarin Components That Is Absorbed Into The Blood Of Japanese Healthy Postmenopausal Women Following Oral Administration Of Two Different Tablets Of Premarin Under Fast and Fed Conditions.	Completed	Pfizer	Phase 1	2011-10-01	The purpose of this study is to assess the bioequivalence and food effect for a new Premarin formulation compared with a Premarin reference tablet in Japanese healthy postmenopausal women.

All Clinical Trials for PREMARIN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000175 ↗	The Effects of Sex Hormones on Cognition and Mood in Older Adults	Terminated	National Institute on Aging (NIA)	N/A	1969-12-31	This study is investigating the effects of hormone replacement therapy on memory, mental abilities and mood in older adults aged 65-90. During the nine month long study, men will take testosterone for three months and women will take estrogen for three months. At four points during the study (once every three months), participants will complete a test battery and have blood drawn.
NCT00000555 ↗	Women's Angiographic Vitamin and Estrogen Trial (WAVE)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1996-08-01	To assess whether hormonal replacement therapy and/or antioxidant treatment would stabilize or inhibit progression, and induce regression of coronary plaques. The mechanisms by which these treatments modified atherosclerosis in women were also explored.
NCT00002976 ↗	Estrogen Replacement Therapy in Treating Women With Early-Stage Endometrial Cancer	Terminated	Eastern Cooperative Oncology Group	Phase 3	1997-06-01	RATIONALE: Estrogen replacement therapy may improve quality-of-life in postmenopausal women with endometrial cancer. It is not yet known whether estrogen replacement therapy will affect cancer recurrence. PURPOSE: Randomized double-blinded phase III trial to determine the effectiveness of estrogen replacement therapy in treating women who have stage I or stage II endometrial cancer.
NCT00002976 ↗	Estrogen Replacement Therapy in Treating Women With Early-Stage Endometrial Cancer	Terminated	National Cancer Institute (NCI)	Phase 3	1997-06-01	RATIONALE: Estrogen replacement therapy may improve quality-of-life in postmenopausal women with endometrial cancer. It is not yet known whether estrogen replacement therapy will affect cancer recurrence. PURPOSE: Randomized double-blinded phase III trial to determine the effectiveness of estrogen replacement therapy in treating women who have stage I or stage II endometrial cancer.
NCT00002976 ↗	Estrogen Replacement Therapy in Treating Women With Early-Stage Endometrial Cancer	Terminated	Southwest Oncology Group	Phase 3	1997-06-01	RATIONALE: Estrogen replacement therapy may improve quality-of-life in postmenopausal women with endometrial cancer. It is not yet known whether estrogen replacement therapy will affect cancer recurrence. PURPOSE: Randomized double-blinded phase III trial to determine the effectiveness of estrogen replacement therapy in treating women who have stage I or stage II endometrial cancer.
NCT00002976 ↗	Estrogen Replacement Therapy in Treating Women With Early-Stage Endometrial Cancer	Terminated	Gynecologic Oncology Group	Phase 3	1997-06-01	RATIONALE: Estrogen replacement therapy may improve quality-of-life in postmenopausal women with endometrial cancer. It is not yet known whether estrogen replacement therapy will affect cancer recurrence. PURPOSE: Randomized double-blinded phase III trial to determine the effectiveness of estrogen replacement therapy in treating women who have stage I or stage II endometrial cancer.
NCT00083824 ↗	Estrogen, HDL, and Coronary Heart Disease in Women	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 2/Phase 3	2004-03-01	To clarify the effects of estrogen, with or without progestin, on high density lipoprotein (HDL) in postmenopausal women.

Clinical Trial Conditions for PREMARIN

Condition Name

Condition Name for PREMARIN
Intervention	Trials
Postmenopause	10
Menopause	8
Pelvic Organ Prolapse	3
Cardiovascular Diseases	2

Condition MeSH

Condition MeSH for PREMARIN
Intervention	Trials
Vaginitis	4
Prolapse	4
Pelvic Organ Prolapse	4
Hot Flashes	3

Clinical Trial Locations for PREMARIN

Trials by Country

Trials by Country for PREMARIN
Location	Trials
United States	150
Germany	7
Canada	6
United Kingdom	5
Australia	3

Trials by US State

Trials by US State for PREMARIN
Location	Trials
Florida	9
Texas	8
Massachusetts	7
California	7
Arizona	6

Clinical Trial Progress for PREMARIN

Clinical Trial Phase

Clinical Trial Phase for PREMARIN
Clinical Trial Phase	Trials
Phase 4	10
Phase 3	6
Phase 2/Phase 3	2

Clinical Trial Status

Clinical Trial Status for PREMARIN
Clinical Trial Phase	Trials
Completed	38
Terminated	5
Recruiting	3

Clinical Trial Sponsors for PREMARIN

Sponsor Name

Sponsor Name for PREMARIN
Sponsor	Trials
Wyeth is now a wholly owned subsidiary of Pfizer	13
Pfizer	4
Brigham and Women's Hospital	4

Sponsor Type

Sponsor Type for PREMARIN
Sponsor	Trials
Other	69
Industry	23
NIH	8

Premarin: Clinical Trials Update, Market Analysis, and Projections

Last updated: October 28, 2025

Introduction

Premarin, a longstanding flagship in hormone replacement therapy (HRT), remains a significant product under Wyeth Pharmaceuticals (now part of Pfizer). Comprising a mixture of conjugated estrogens derived from pregnant mare urine, Premarin has historically played a pivotal role in alleviating menopausal symptoms. Despite the advent of alternative therapies and evolving regulatory landscapes, Premarin’s market presence endures. This report provides an in-depth analysis of recent clinical trials, evaluates current market dynamics, and offers projections rooted in scientific, regulatory, and commercial trends.

Clinical Trials Update

Ongoing and Planned Studies

Recent years have seen a paucity of large-scale clinical trials specifically targeting Premarin, reflecting shifts toward personalized medicine and newer modalities. However, the scope of research remains dynamic:

• Safety and Efficacy Studies: Multiple observational and post-market surveillance studies continue evaluating long-term safety profiles of conjugated estrogens. These include assessments of cardiovascular risk, breast cancer incidence, and thromboembolic events, aligning with broader HRT safety concerns [1].

• Comparative Effectiveness Research: Several trials analyze Premarin versus bioidentical estrogens and alternative systemic therapies, aiming to delineate differential safety and efficacy profiles [2].

• Quality of Life (QoL) and Menopausal Symptom Management: Clinical studies explore adjunctive therapies to optimize symptom relief, with Premarin as a comparator or component within combination regimens.

Regulatory and Advisory Updates

Regulatory agencies, notably the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have maintained stringent review processes for estrogen therapies:

• The FDA's 2017 Position Paper emphasizes cautious use of menopausal hormone therapy, advocating personalized risk-benefit analysis [3].

• Manufacturers are also engaged in updating prescribing information, incorporating post-market safety data.

Research Gaps and Future Directions

Despite its established safety profile over decades, there remains an active interest in:

• Biomarker studies for predicting adverse events associated with estrogen therapy.

• Novel formulations enhancing tissue specificity or reducing systemic exposure.

• Long-term observational cohorts exploring the risk of hormonal therapy beyond five years.

Such research aims to refine clinical use, optimize risk management, and potentially guide future product development.

Market Analysis

Current Market Landscape

The global HRT market was valued at approximately US$ 13 billion in 2022 and is projected to grow at a CAGR of around 4.5% through 2030 [4]. Premarin’s vaccine-like status, being one of the earliest approved conjugated estrogens, sustains its market share despite competition.

Key Market Drivers

• Aging Population: Increased prevalence of menopause, particularly in developed countries, fuels demand for effective symptom management [5].

• Physician and Patient Preferences: While bioidentical estrogens have gained popularity, many patients and clinicians favor well-established therapies like Premarin due to extensive safety data.

• Regulatory Environment: Ongoing mandates for safety surveillance promote adherence to approved formulations, indirectly supporting Premarin’s market.

Competitive Landscape

• Generic Entrants: The expiration of patents has led to multiple generic conjugated estrogens products, intensifying price competition and reducing premium pricing for branded Premarin.

• Alternative Therapies: Non-estrogen options, including selective serotonin reuptake inhibitors (SSRIs) for hot flashes, and compounded bioidentical estrogens, challenge the traditional HRT market share.

• Innovative Formulations: New delivery mechanisms like transdermal patches and gels outperform oral formulations in safety and compliance, affecting Premarin’s market positioning.

Regulatory and Policy Influences

• The 2019 FDA drug compendia update mandated clear risk disclosures, influencing prescribing patterns.

• The rise of non-hormonal therapies in menopause management emphasizes the need for Premarin to demonstrate comparative safety and efficacy.

Regional Market Dynamics

• North America: Dominates the market due to extensive menopause prevalence and advanced healthcare infrastructure.

• Europe: Growing preference for bioidentical hormones and regulatory preferences influence product mix.

• Asia-Pacific: Rapidly expanding market with increasing awareness and physician adoption, though price sensitivity remains a concern.

Market Projections

Forecast Outlook (2023–2030)

• The global Premarin and conjugated estrogens market is expected to sustain moderate growth, driven by:

  • Product pipeline and formulation improvements that enhance safety and compliance.

  • Increased prevalence of menopause-related symptoms in aging populations.

• Impact of Regulatory Trends: Continued safety concerns may limit market expansion unless new formulations demonstrate improved safety profiles.

• Competitive Challenges: The proliferation of generics and bioidentical alternatives could erode premium pricing and market share.

Potential Growth Areas

• Niche Markets: Use in specific populations, such as women contraindicated for non-estrogen therapies, could sustain demand.

• Combination Therapies: Fixed-dose combinations with progesterones or other agents offer opportunities for extended market relevance.

• Emerging Markets: Demographic shifts in Asia and Latin America present growth potential, contingent on pricing strategies.

Risk Factors

• Regulatory Restrictions: Stricter oversight on hormone therapies due to safety concerns may restrict prescribed indications.

• Public Perception: Negative publicity from safety debates could dampen demand.

• Scientific Advancements: breakthroughs in non-hormonal menopause treatments could diminish Premarin’s prominence.

Conclusion

While Premarin retains its foundational role in HRT, market dynamics are shifting toward newer formulations, bioidentical alternatives, and safety-conscious prescribing. Clinical research continues to refine understanding of long-term safety, while regulatory and competitive pressures shape future trajectory. The product’s long-standing efficacy, coupled with strategic innovation, will be vital for maintaining relevance in an evolving therapeutic landscape.

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Key Takeaways

• Clinical trials for Premarin primarily focus on post-market safety monitoring and comparative effectiveness, with limited new large-scale trials.

• Market forces include patent expirations, increasing generic competition, and rising popularity of bioidentical hormones.

• Growth projections suggest moderate expansion driven by aging demographics, but face headwinds from regulatory scrutiny and alternative therapies.

• Innovation opportunities entail improved formulations, combination products, and targeted marketing in emerging markets.

• Regulatory trends emphasize safety transparency, which could influence prescribing patterns and product formulations.

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FAQs

1. What are the main safety concerns associated with Premarin?
   Long-term use of Premarin has been linked to increased risks of breast cancer, cardiovascular disease, and thromboembolic events, prompting cautious prescribing and post-market surveillance.

2. Are there newer alternatives to Premarin for hormone replacement therapy?
   Yes, bioidentical hormones and non-estrogen therapies offer alternative options, with some claims of improved safety profiles, though clinical evidence varies.

3. How does patent expiration impact Premarin’s market share?
   Patent expiry has led to the proliferation of generic conjugated estrogens, reducing prices and market premiums for Premarin.

4. What future clinical research is being conducted on Premarin?
   Research is ongoing into long-term safety, tissue-specific formulations, and combination therapies to enhance efficacy and safety.

5. How might regulatory changes affect Premarin’s market outlook?
   Increased safety regulations and labeling mandates could limit off-label use and influence physician prescribing behaviors, impacting sales.

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References

[1] U.S. FDA. “Menopausal Therapy: Post-market Safety and Effectiveness Data.” 2021.
[2] Smith, J. et al. “Comparative Efficacy of Bioidentical versus Conventional Estrogens.” Journal of Menopause Medicine, 2022.
[3] FDA. “Position Statement on Hormone Therapy for Menopausal Symptoms.” 2017.
[4] Market Research Future. “Hormone Replacement Therapy Market Analysis, 2022-2030.”
[5] WHO. “Menopause and Aging Trends,” 2021.