CLINICAL TRIALS PROFILE FOR PREMPRO

505(b)(2) Clinical Trials for PREMPRO

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.

All Clinical Trials for PREMPRO

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.
NCT00027209 ↗	Hormone Replacement in Menopausal Women With Epilepsy	Completed	National Institute of Neurological Disorders and Stroke (NINDS)	Phase 2	1969-12-31	The goal of this study is to evaluate the effect of synthetic hormone replacement therapy on anti-seizure medication levels, menopausal symptom relief, and seizure frequency and safety in menopausal women with epilepsy.
NCT00302731 ↗	Bioidentical 'Natural' Hormone Evaluation in Early Menopause	Terminated	Private Foundation through KU Endowment	Phase 2	2006-02-01	Prospective double blind pilot study comparing bioidentical 'natural' hormones to low-dose PremPro. Forty participants will be enrolled. The purpose of this study is to try to gather early information about safety when "natural" or bioidentical hormones are used during early menopause.
NCT00302731 ↗	Bioidentical 'Natural' Hormone Evaluation in Early Menopause	Terminated	University of Kansas	Phase 2	2006-02-01	Prospective double blind pilot study comparing bioidentical 'natural' hormones to low-dose PremPro. Forty participants will be enrolled. The purpose of this study is to try to gather early information about safety when "natural" or bioidentical hormones are used during early menopause.

Clinical Trial Conditions for PREMPRO

Condition Name

Condition Name for PREMPRO
Intervention	Trials
Postmenopause	6
Menopause	5
Dementia Syndromes	1
Pre-Hypertension	1

Condition MeSH

Condition MeSH for PREMPRO
Intervention	Trials
Osteoporosis	2
Dementia	1
Arteriosclerosis	1
Myocardial Ischemia	1

Clinical Trial Locations for PREMPRO

Trials by Country

Trials by Country for PREMPRO
Location	Trials
United States	51
Colombia	3
Argentina	2
Australia	2
New Zealand	2

Trials by US State

Trials by US State for PREMPRO
Location	Trials
Florida	3
North Carolina	2
Connecticut	2
Nebraska	2
Virginia	2

Clinical Trial Progress for PREMPRO

Clinical Trial Phase

Clinical Trial Phase for PREMPRO
Clinical Trial Phase	Trials
Phase 3	2
Phase 2	3
Phase 1	5

Clinical Trial Status

Clinical Trial Status for PREMPRO
Clinical Trial Phase	Trials
Completed	12
Terminated	2

Clinical Trial Sponsors for PREMPRO

Sponsor Name

Sponsor Name for PREMPRO
Sponsor	Trials
Wyeth is now a wholly owned subsidiary of Pfizer	6
National Heart, Lung, and Blood Institute (NHLBI)	2
Jeanne Drisko, MD, CNS, FACN	1

Sponsor Type

Sponsor Type for PREMPRO
Sponsor	Trials
Industry	10
Other	6
NIH	4

Clinical Trials Update, Market Analysis, and Projection for Prempro

Last updated: October 30, 2025

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Introduction

Prempro, a combination hormone replacement therapy (HRT) formulated with conjugated estrogens and medroxyprogesterone acetate, has historically served millions of women worldwide for menopausal symptom relief and osteoporosis prevention. With evolving regulatory landscapes, safety concerns, and competitive dynamics, understanding its current clinical trial activity, market position, and future prospects is crucial for stakeholders. This report offers a comprehensive review of recent clinical trials, market developments, and investment outlooks related to Prempro.

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Clinical Trial Landscape and Updates

1. Shifts in Clinical Research Focus

Historically, Prempro’s clinical development centered on efficacy and safety in menopausal symptom management and osteoporosis risk mitigation. Post-2002, following the Women's Health Initiative (WHI) findings that linked combined HRT to increased breast cancer and cardiovascular risks, the landscape for Prempro trial activity declined significantly.

Recent clinical research concentrates primarily on:

• Safety profiles and alternative formulations: With safety concerns around Prempro’s traditional formulation, ongoing trials focus on risk reduction. These include evaluating lower-dose regimens and bioidentical hormone combinations.

• Long-term effects: Some recent Phase IV studies explore long-term cardiovascular outcomes, cancer risk, and cognitive function in women using hormone therapy over extended periods.

• Personalized medicine approaches: Emerging trials investigate genetic markers influencing therapy response, aiming for more tailored hormone treatments.

2. Current Clinical Trial Activity

Per ClinicalTrials.gov, as of late 2022, there are no active registration studies explicitly testing the original Prempro formulation. Instead, research has pivoted toward:

• Safety and Comparative Effectiveness Studies: Trials evaluating newer, bioidentical hormone combinations with potentially improved safety profiles are ongoing or completed. These focus on postmenopausal women with high-risk profiles.

• Repurposing and Adjunctive Therapy Investigations: Some studies examine hormone therapy's role in conjunction with other treatments, such as osteoporosis medications or cardiovascular intervention strategies.

• Biomarker-driven Trials: Research into identifying women who will benefit most from specific hormone therapies to minimize adverse effects.

3. Regulatory and Safety Considerations

Given the legacy of the WHI trials, regulatory agencies remain vigilant. The FDA’s 2017 revisions to HRT labeling underscore the importance of individualized risk assessment. While no recent trials directly aim to bring back Prempro’s original formulation, manufacturers are exploring safer derivatives, often under different brand names or as component products.

Market Analysis

1. Historical Market Dynamics

Prempro dominated the HRT market in the 1990s and early 2000s, constituting a significant revenue stream for Pfizer prior to its divestment in 2008. The market’s decline correlates with increased regulatory scrutiny and adverse safety data, prompting a shift toward selective use and alternative therapies.

2. Current Market Size and Trends

The global HRT market is projected to reach USD 21.4 billion by 2028, growing at a CAGR of 5.6% (Research and Markets, 2022). However, Prempro specifically has seen diminished market share, replaced by:

• Bioidentical Hormone Therapies (BHTs): Growing consumer demand for supposedly "natural" alternatives.
• Selective Estrogen Receptor Modulators (SERMs): Such as raloxifene for osteoporosis, reducing reliance on traditional estrogen-based therapies.
• Innovative delivery systems: Transdermal patches and gels offer improved safety and convenience, drawing patients away from oral Prempro formulations.

3. Competitive Landscape

Major players in the menopausal hormone therapy (MHT) segment include:

• AbbVie: Licensing and marketing bioidentical options.
• Eli Lilly: Developing non-hormonal alternatives.
• Compounding pharmacies: Offering personalized, bioidentical formulations outside regulatory oversight.

While generic formulations of conjugated estrogens and medroxyprogesterone acetate are available, the absence of branded Prempro limits exclusive market control for Pfizer or successors.

4. Regulatory and Reimbursement Environment

Many countries impose strict regulations on hormone therapy advertising, citing safety concerns. Reimbursement policies favor non-hormonal options unless explicitly indicated. These factors constrain market expansion of traditional Prempro-like therapies.

Market Projection and Future Outlook

1. Recovery Potential in the Context of Safety

Interest persists in developing safer, evidence-based hormone therapies. Innovations such as transdermal delivery and bioidentical compounds suggest hybrid models could reclaim some market share. Yet, the foundational safety concerns remain a barrier, restricting growth prospects under the Prempro brand.

2. Strategic Opportunities

• Development of Next-Generation HRT: Companies investing in personalized, safer formulations may overshadow traditional Prempro offerings.
• Educational Campaigns: Public awareness regarding menopausal health, if aligned with safety improvements, can sustain demand.
• Off-Label and Compounding Markets: While less regulated, these channels could maintain niche engagement, although with limited clinical validation.

3. Revenue Forecasts

Based on current market trends, the overall HRT segment will grow modestly, but the specific niche occupied by Prempro is unlikely to regain former dominance. Industry analysts predict a compound annual decline of 1-2% for traditional conjugated estrogen-progestin therapies over the next five years, barring breakthroughs in safety or delivery technology.

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Key Takeaways

• Clinical trials for Prempro have largely phased out, with focus now on safer alternatives and biomarker-driven personalized therapies. No recent initiatives aim to reintroduce Prempro’s original formulation.
• Market size and share have contracted significantly, transitioning toward bioidentical, selective, or non-hormonal strategies in menopause and osteoporosis management.
• Regulatory and safety concerns continue to constrain the growth of traditional Prempro-like therapies. These factors favor innovation in hormone delivery and composition.
• Future prospects hinge on developing safer, targeted, and personalized hormone therapies, with traditional Prempro expected to decline further unless substantial safety improvements emerge.
• Investment considerations favor entities engaged in innovation within hormone therapy safety, delivery mechanisms, and personalized medicine to carve out future market opportunities.

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FAQs

1. Why did Prempro's market share decline post-2002?
The decline resulted from the Women's Health Initiative (WHI) findings linking combined hormone therapy to increased risks of breast cancer, stroke, and cardiovascular issues, prompting regulatory scrutiny and changes in prescribing patterns.

2. Are there ongoing clinical trials testing new formulations of Prempro?
No recent trials directly test the original Prempro formulation. Current research emphasizes safer bioidentical hormone combinations, lower doses, and personalized approaches.

3. What are the primary safety concerns associated with Prempro?
The main concerns include increased risks of breast cancer, thromboembolic events, stroke, and possibly cognitive decline, as reported in landmark studies like WHI.

4. How does the current regulatory environment affect Prempro’s future?
Regulators demand strict risk-benefit assessments, limiting traditional Prempro’s usage. Future approvals depend on evidence demonstrating improved safety profiles.

5. Can Prempro’s original formulation be revived commercially?
While technically feasible, safety risks largely impede reintroduction unless new formulations or delivery methods significantly mitigate adverse effects.

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References

1. Cummings SR, et al. (2019). Long-term effects on cardiovascular events of menopausal hormone therapy: a meta-analysis. Annals of Internal Medicine.
2. ClinicalTrials.gov. (2022). Search results for hormone replacement therapy studies.
3. Research and Markets. (2022). Global Menopausal Hormone Therapy Market Analysis and Forecast.
4. U.S. Food and Drug Administration. (2017). Safety of Estrogen and Progestin Hormone Therapy.
5. Women's Health Initiative Steering Committee. (2002). Risks and benefits of estrogen plus progestin in postmenopausal women. JAMA.

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This comprehensive analysis aims to assist industry stakeholders, investors, and medical professionals in making informed decisions regarding Prempro’s current clinical, competitive, and future landscape.