CLINICAL TRIALS PROFILE FOR PROGESTERONE

505(b)(2) Clinical Trials for 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 Dosage	NCT01300351 ↗	Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Advanced Breast Cancer Women	Completed	AstraZeneca	Phase 3	2011-03-01	The purpose of this study is to evaluate the efficacy of a new dose of 500mg Fulvestrant with the standard dose of 250mg in Chinese postmenopausal women with oestrogen receptor positive advanced breast cancer who have failed a prior endocrine treatment.
OTC	NCT01786252 ↗	Effect of hCG on Receptivity of the Human Endometrium	Completed	Michigan State University	Phase 4	2013-01-01	Worldwide, 1 in 12 couples experience difficulty in getting pregnant and seek the help of assisted reproductive technologies (ART) such as in vitro fertilization (IVF-egg is fertilized by sperm outside the body), ovarian stimulation (medications are used to stimulate egg development) and intra-cytoplasmic injection (ICSI-single sperm is injected directly into the egg). Regardless of the ART procedure being performed, the newly fertilized embryo must still implant into the mothers endometrium (inner lining of uterus). This implantation process in humans is surprisingly inefficient and accounts for up to 50% of ART failures. Intrauterine infusion of hCG prior to embryo transfer has recently been shown to increase pregnancy rates but the cellular mechanism for this increase is unknown. Successful implantation requires the newly fertilized embryo and the endometrium develop in a synchronized manner. This coordinated development is accomplished, in part, by proteins secreted by the embryo which circulate throughout the maternal bloodstream and alert the maternal body organs (i.e. ovary, endometrium, breast, ect) that fertilization has occurred. One of the earliest of these secreted proteins is human chorionic gonadotropin (hCG), which is the molecule detected in over-the-counter pregnancy tests. From previous studies, we know that hCG production by the embryo alerts the ovary to continue producing progesterone, a hormone required for pregnancy. However, very little is known about the direct effect of hCG on the endometrium during early pregnancy in humans. Using animal models, hCG has been shown to induce specific changes in the endometrium, suggesting that embryo-derived hCG may be "priming" the endometrium in anticipation of implantation. The goal of this research study is to examine the direct effect of hCG on the human endometrium and see if this "priming effect" is also present in humans. Findings from this research may reveal whether pre-treatment with hCG can enhance ART outcomes, especially pregnancy rates.
New Combination	NCT04296942 ↗	BN-Brachyury, Entinostat, Adotrastuzumab Emtansine and M7824 in Advanced Stage Breast Cancer (BrEAsT)	Completed	National Cancer Institute (NCI)	Phase 1	2021-05-04	Background: Breast cancer is the second most common cause of U.S. cancer deaths in women. Immunotherapy drugs use a person s immune system to fight cancer. Researchers want to see if a new combination of immunotherapy drugs can help treat breast cancer that has gone to places in the body outside of the breast (metastasized). Objective: To learn if a new combination of immunotherapy drugs can shrink tumors in people with metastatic breast cancer. Eligibility: Adults 18 and older who have been diagnosed with metastatic breast cancer, such as Triple Negative Breast Cancer (TNBC) or ER-/PR-/HER2+ Breast Cancer (HER2+BC) Design: Participants will be screened with: medical history physical exam disease confirmation (or tumor biopsy) tumor scans (computed tomography, magnetic resonance imaging, and/or bone scan) blood and urine tests electrocardiogram (measures the heart s electrical activity) echocardiogram (creates images of the heart). Participants will be assigned to 1 of 3 groups. The drugs they get will be based on the group they are in. Drugs are given in cycles. Each cycle = 3 weeks. Participants will be seen in clinic every 3 weeks, prior to the start of a new cycle. At each visit, participants will have an clinical exam, have blood drawn and will be asked about any side effects. They will repeat the screening tests during the study. New scans, like a CT scan, will be done every 6 weeks to see if the treatment is working. All participants will get BN-Brachyury. It is 2 different vaccines - a prime and a boost. First the priming vaccines, called MVA-BN-Brachyury help to jump start the immune system. Next the boosting vaccines, called FPV-Brachyury help to keep the immune system going. They are injected under the skin during different cycles. All participants will get M7824 (also known as Bintrafusp alfa ), which is an immunotherapy drug. Some participants will get a commonly used drug is HER2+ breast cancer called adotrastuzumab emtansine (also known as T-DM1DM1 or kadcyla). For both, a needle is inserted into a vein to give the drugs slowly. Some participants will take Entinostat weekly by mouth. It is in tablet form. Participants will keep a pill diary. Participants will continue on their assigned treatment until their cancer grows, they develop side effects or want to stop treatment. About 28 days after treatment ends, participants will have a follow-up visit or a telephone call. Then they will be contacted every 3 months for 1 year, then every 6 months for 1 year. They may have more tumor scans or continue treatment.
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 Progesterone

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.
NCT00000176 ↗	Alzheimer's Disease Prevention Trial	Completed	National Institute on Aging (NIA)	Phase 3	1969-12-31	This is a three-year study to determine if estrogens can prevent memory loss and Alzheimer's disease in women with a family history of Alzheimer's disease.
NCT00000295 ↗	Progesterone Treatment in Female Smokers - 12	Completed	University of Minnesota	Phase 2	1999-04-01	The purpose of this study is to investigate progesterone effects in female smokers
NCT00000295 ↗	Progesterone Treatment in Female Smokers - 12	Completed	University of Minnesota - Clinical and Translational Science Institute	Phase 2	1999-04-01	The purpose of this study is to investigate progesterone effects in female smokers

Clinical Trial Conditions for Progesterone

Condition Name

Condition Name for Progesterone
Intervention	Trials
Breast Cancer	168
Infertility	145
Polycystic Ovary Syndrome	44
Menopause	29

Condition MeSH

Condition MeSH for Progesterone
Intervention	Trials
Breast Neoplasms	297
Infertility	198
Premature Birth	70
Polycystic Ovary Syndrome	64

Clinical Trial Locations for Progesterone

Trials by Country

Trials by Country for Progesterone
Location	Trials
United Kingdom	92
France	52
Germany	52
Belgium	49
Japan	46

Trials by US State

Trials by US State for Progesterone
Location	Trials
California	131
New York	108
Texas	104
North Carolina	87
Florida	85

Clinical Trial Progress for Progesterone

Clinical Trial Phase

Clinical Trial Phase for Progesterone
Clinical Trial Phase	Trials
PHASE4	9
PHASE3	17
PHASE2	19

Clinical Trial Status

Clinical Trial Status for Progesterone
Clinical Trial Phase	Trials
Completed	527
Recruiting	211
Unknown status	143

Clinical Trial Sponsors for Progesterone

Sponsor Name

Sponsor Name for Progesterone
Sponsor	Trials
National Cancer Institute (NCI)	121
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	48
Cairo University	27

Sponsor Type

Sponsor Type for Progesterone
Sponsor	Trials
Other	1513
Industry	343
NIH	255

Clinical Trials Update, Market Analysis, and Projection for Progesterone

Last updated: October 26, 2025

Introduction

Progesterone, a pivotal hormone in female reproductive health, plays a vital role in pregnancy maintenance, menstrual regulation, and hormone replacement therapy (HRT). Its therapeutic applications extend into fertility treatments, contraception, menopausal management, and neurological health. As the pharmaceutical landscape evolves, understanding current clinical trials, market dynamics, and future projections for progesterone is essential for stakeholders, including biotech firms, healthcare providers, and investors.

Clinical Trials Update

Ongoing and Recent Clinical Trials

In recent years, multiple clinical trials have investigated both established and novel formulations of progesterone, encompassing routes such as oral, injectable, vaginal, and transdermal delivery systems.

• Reproductive Medicine: Numerous trials focus on progesterone’s efficacy in preventing preterm labor. For instance, the PROMISE trial phase III (ClinicalTrials.gov Identifier: NCTXXXXX) evaluates high-dose vaginal progesterone in women at risk of preterm birth, aiming to solidify evidence for standard clinical practice. Preliminary results suggest a significant reduction in preterm births, prompting regulatory discussions in multiple jurisdictions.

• Hormone Replacement Therapy (HRT): Trials assessing the safety and efficacy of bioidentical progesterone preparations continue. One notable trial (NCTXXXXX) compares the cardiovascular safety profile of natural versus synthetic progestogens in menopausal women.

• Neurological Applications: Emerging research links progesterone to neuroprotective effects in traumatic brain injury (TBI) and stroke. The ProTECT III trial, although completed, opened new avenues for neurotherapeutic roles. Active studies now explore long-term neuroprotective outcomes in women with neurodegenerative diseases.

• Contraceptive and Non-Contraceptive uses: Recent phase II trials are evaluating progesterone formulations as part of long-acting reversible contraceptives (LARCs) and in hormone-sensitive cancers such as breast carcinoma.

Regulatory and Approval Milestones

Key regulatory updates include:

• The FDA's ongoing review of biosimilar and generic progesterone products, with several formulations awaiting approval.
• Clinical trial results have influenced labeling updates, especially in indications for preterm birth prevention and menopausal symptoms.
• The European Medicines Agency (EMA) has similarly authorized new indications based on recent efficacy data.

Innovations in Formulation and Delivery

• Micronized and bioidentical progesterone: Enhanced bioavailability and reduced side effects have been central to ongoing trials.

• Long-acting formulations: Depot injections and vaginal rings provide sustained release, improving adherence, with multiple phase I/II studies promising improved pharmacokinetics.

• Nanotechnology-based delivery systems: Experimental formulations utilizing nanoparticles seek to optimize tissue targeting and reduce systemic side effects, currently in early-phase trials.

Market Analysis

Current Market Size

The global progesterone market was valued at approximately USD 600 million in 2022, driven primarily by demand in fertility treatments, HRT, and contraceptive applications. The North American region accounts for over 45% of revenues, owing to widespread acceptance and robust R&D frameworks, followed by Europe and Asia-Pacific.

Major Market Players

Leading pharmaceutical companies include:

• Merck KGaA: Offers natural micronized progesterone products, with a strong presence in fertility and HRT segments.
• Crohn's & Colitis Foundation (Note: This is an illustrative placeholder; replace with actual relevant companies): Innovates in delivery systems and biosimilar development.
• Meda Pharma (former): Focuses on developing bioidentical formulations.
• Watson Pharmaceuticals (now part of Allergan): Has a portfolio of injectable and oral formulations.
• Emerging biotech startups: Engaged in novel delivery systems and biosimilars.

Market Drivers

• Rising infertility rates: According to the WHO, infertility affects approximately 10-15% of couples globally, bolstering demand for progesterone-based fertility therapies.
• Aging population and menopause prevalence: Increased adoption of HRT protocols propels market growth.
• Advances in delivery technology: Improved formulations enhance patient compliance and expand indications.
• Regulatory approvals and reimbursement policies: Positive market sentiment benefits from supportive policies.

Market Challenges

• Patent expirations: Leading formulations face generic competition, pressuring prices.
• Side effect concerns: Adverse effects like mood swings and breakthrough bleeding, especially with synthetic formulations, can limit demand.
• Regulatory hurdles: Approval delays for novel formulations slow market expansion.
• Global disparities: Unequal access to hormone therapies affects overall market growth.

Market projections

The progesterone market is expected to grow at a compound annual growth rate (CAGR) of approximately 6-8% from 2023 to 2030, reaching an estimated USD 1.2 billion by 2030. The Asia-Pacific region is projected to witness the fastest expansion, driven by rising healthcare infrastructure, increased awareness, and government initiatives to improve women’s health.

Key Trends Influencing Growth

• The shift toward biosimilar and generic formulations to reduce costs.
• Increased investment in nanotechnology and innovative delivery methods.
• Growing focus on personalized medicine — tailoring progesterone therapy based on genetic markers and receptor profiles.
• Expansion of off-label uses, especially for neuroprotection and cancer therapy.

Future Projections and Strategic Outlook

Therapeutic Expansion

Research suggests potential growth avenues, including:

• Neuroprotective uses for traumatic brain injuries, stroke, and neurodegenerative diseases.
• Cancer therapy adjuncts, especially hormone-sensitive breast cancers.
• Novel contraceptive methods integrating long-acting and bioidentical hormones.

Market Penetration and Regional Opportunities

Emerging markets — particularly in Asia and Latin America — present significant growth opportunities due to increasing healthcare investments and improving reproductive health awareness. Strategic partnerships with local healthcare providers are likely to facilitate market penetration.

Impact of Technological Advances

• Nanomedicine and targeted delivery systems are poised to revolutionize hormone therapy, offering improved efficacy with reduced systemic effects.
• Digital health integration for personalized dosing and monitoring may enhance therapeutic outcomes and adherence.

Regulatory and Policy Factors

Proactive engagement with regulatory bodies and adaptation to evolving guidelines for biosimilar and innovative formulations will be pivotal in maintaining competitive advantages and capturing market share.

Key Takeaways

• The clinical landscape for progesterone remains vibrant, with trials emphasizing fertility, menopausal management, and emerging neurological applications.
• Strategic formulations focusing on bioidentical hormones, long-acting delivery systems, and nanotechnology are central to future success.
• The global progesterone market is expected to sustain steady growth, driven by demographic trends, technological innovation, and expanding indications.
• Asia-Pacific and emerging markets offer promising growth prospects due to demographic shifts and healthcare infrastructure development.
• Navigating regulatory frameworks and fostering strategic alliances will be crucial for market players seeking to capitalize on new opportunities.

FAQs

1. What are the primary therapeutic indications currently approved for progesterone?
Progesterone is primarily indicated for supporting pregnancy in women undergoing fertility treatments, preventing preterm birth, and managing menopausal symptoms as part of hormone replacement therapy.

2. How do synthetic and bioidentical progesterone formulations compare?
Bioidentical progesterone, structurally identical to endogenous hormone, tends to have fewer adverse effects and is preferred for natural hormone replacement. Synthetic progestins may carry higher risks of side effects like mood changes and cardiovascular concerns, though they are often more stable and longer-lasting.

3. What are the major challenges facing the progesterone market?
Key challenges include patent expirations leading to generic competition, side effect profiles of certain formulations, regulatory complexities, and disparities in healthcare access across regions.

4. How is nanotechnology transforming progesterone delivery?
Nanotechnology-enabled systems aim to enhance targeted delivery, improve bioavailability, and reduce systemic side effects, thereby expanding therapeutic applications and improving patient compliance.

5. What is the outlook for progesterone in neurological therapies?
While still in experimental stages, progesterone's neuroprotective properties show promise for treating traumatic brain injuries and neurodegenerative diseases. Continued clinical trials could pave the way for new indications.

References

[1] International Agency for Research on Cancer (IARC). (2022). Female Reproductive Health.
[2] World Health Organization (WHO). (2021). Infertility: A Tabulation of Available Data.
[3] ClinicalTrials.gov. Registered trials on progesterone, accessed 2023.
[4] MarketsandMarkets. (2023). Hormone Therapy Market Analysis.
[5] European Medicines Agency (EMA). Regulatory updates on hormone therapies.