CLINICAL TRIALS PROFILE FOR ESTROGENS, CONJUGATED; MEDROXYPROGESTERONE ACETATE

All Clinical Trials for Estrogens, Conjugated; Medroxyprogesterone Acetate

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000466 ↗	Postmenopausal Estrogen/Progestin Interventions (PEPI)	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 3	1987-09-01	To assess the effects of various postmenopausal estrogen replacement therapies on selected cardiovascular risk factors, including high density lipoprotein cholesterol, systolic blood pressure, fibrinogen, and insulin and on osteoporosis risk factors. Conducted in collaboration with the National Institute of Child Health and Human Development, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, The National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute on Aging. The extended follow-up is for 3 years focusing on endometrium and breast evaluation.
NCT00000466 ↗	Postmenopausal Estrogen/Progestin Interventions (PEPI)	Completed	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)	Phase 3	1987-09-01	To assess the effects of various postmenopausal estrogen replacement therapies on selected cardiovascular risk factors, including high density lipoprotein cholesterol, systolic blood pressure, fibrinogen, and insulin and on osteoporosis risk factors. Conducted in collaboration with the National Institute of Child Health and Human Development, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, The National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute on Aging. The extended follow-up is for 3 years focusing on endometrium and breast evaluation.
NCT00000466 ↗	Postmenopausal Estrogen/Progestin Interventions (PEPI)	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 3	1987-09-01	To assess the effects of various postmenopausal estrogen replacement therapies on selected cardiovascular risk factors, including high density lipoprotein cholesterol, systolic blood pressure, fibrinogen, and insulin and on osteoporosis risk factors. Conducted in collaboration with the National Institute of Child Health and Human Development, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, The National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute on Aging. The extended follow-up is for 3 years focusing on endometrium and breast evaluation.
NCT00000466 ↗	Postmenopausal Estrogen/Progestin Interventions (PEPI)	Completed	National Institute on Aging (NIA)	Phase 3	1987-09-01	To assess the effects of various postmenopausal estrogen replacement therapies on selected cardiovascular risk factors, including high density lipoprotein cholesterol, systolic blood pressure, fibrinogen, and insulin and on osteoporosis risk factors. Conducted in collaboration with the National Institute of Child Health and Human Development, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, The National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute on Aging. The extended follow-up is for 3 years focusing on endometrium and breast evaluation.
NCT00000466 ↗	Postmenopausal Estrogen/Progestin Interventions (PEPI)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1987-09-01	To assess the effects of various postmenopausal estrogen replacement therapies on selected cardiovascular risk factors, including high density lipoprotein cholesterol, systolic blood pressure, fibrinogen, and insulin and on osteoporosis risk factors. Conducted in collaboration with the National Institute of Child Health and Human Development, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, The National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute on Aging. The extended follow-up is for 3 years focusing on endometrium and breast evaluation.

Clinical Trial Conditions for Estrogens, Conjugated; Medroxyprogesterone Acetate

Condition Name

Condition Name for Estrogens, Conjugated; Medroxyprogesterone Acetate
Intervention	Trials
Osteoporosis	2
Postmenopause	2
Myocardial Ischemia	1
Bone Diseases	1

Condition MeSH

Condition MeSH for Estrogens, Conjugated; Medroxyprogesterone Acetate
Intervention	Trials
Osteoporosis	2
Heart Diseases	1
Lupus Erythematosus, Systemic	1
Diabetes Mellitus	1

Clinical Trial Locations for Estrogens, Conjugated; Medroxyprogesterone Acetate

Trials by Country

Trials by Country for Estrogens, Conjugated; Medroxyprogesterone Acetate
Location	Trials
Taiwan	2
Brazil	1
Mexico	1
Netherlands	1
Italy	1

Clinical Trial Progress for Estrogens, Conjugated; Medroxyprogesterone Acetate

Clinical Trial Phase

Clinical Trial Phase for Estrogens, Conjugated; Medroxyprogesterone Acetate
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	2
N/A	1

Clinical Trial Status

Clinical Trial Status for Estrogens, Conjugated; Medroxyprogesterone Acetate
Clinical Trial Phase	Trials
Completed	4
Active, not recruiting	1
Recruiting	1

Clinical Trial Sponsors for Estrogens, Conjugated; Medroxyprogesterone Acetate

Sponsor Name

Sponsor Name for Estrogens, Conjugated; Medroxyprogesterone Acetate
Sponsor	Trials
National Institute on Aging (NIA)	1
National Heart, Lung, and Blood Institute (NHLBI)	1
Organon	1

Sponsor Type

Sponsor Type for Estrogens, Conjugated; Medroxyprogesterone Acetate
Sponsor	Trials
Other	5
NIH	5
Industry	1

Estrogens, Conjugated; Medroxyprogesterone Acetate: Clinical Trials, Market Analysis, and Projections

Introduction

Conjugated estrogens combined with medroxyprogesterone acetate (MPA) are widely used in the treatment of menopausal symptoms and the prevention of postmenopausal osteoporosis. This combination, often marketed as Prempro, has been the subject of extensive clinical trials and market analysis. Here, we delve into the key findings from clinical trials, the current market landscape, and future projections for this drug combination.

Clinical Trials Overview

Women's Health Initiative (WHI) Trial

One of the most significant clinical trials involving conjugated estrogens and MPA is the Women's Health Initiative (WHI) trial. This randomized, double-blind, placebo-controlled trial involved 16,608 postmenopausal women with a uterus, who were assigned to either daily conjugated equine estrogens (CEE) 0.625 mg plus MPA 2.5 mg or a placebo[3].

• Cardiovascular Outcomes: The trial found that the combination did not reduce the overall rate of coronary heart disease (CHD) events and actually increased the risk of thromboembolic events and gallbladder disease[1][2].
• Cancer Risks: The WHI trial also reported increased risks of invasive breast cancer, stroke, and deep vein thrombosis (DVT) in postmenopausal women taking the combination therapy[2].
• Colorectal Cancer: Although there was a significant reduction in the incidence of colorectal cancer during the intervention period, the cancers that did occur were more likely to be lymph node-positive, which may indicate a more aggressive form of the disease[4].

Heart and Estrogen/progestin Replacement Study (HERS)

The HERS trial, another significant study, focused on postmenopausal women with established coronary disease. This trial found that the combination of CEE and MPA did not reduce the combined rate of nonfatal myocardial infarction and CHD death. Instead, it showed an early increase in the risk of CHD events, although this risk seemed to stabilize after several years of therapy[1].

Market Analysis

Indications and Usage

Conjugated estrogens and MPA are approved for several indications, including:

• Treatment of moderate to severe vasomotor symptoms due to menopause.
• Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.
• Prevention of postmenopausal osteoporosis[2].

Market Presence

Prempro, the brand name for this combination, has been a dominant player in the menopausal treatment market since its approval in 1994. The drug is marketed by Wyeth Pharmaceuticals Inc. (now part of Pfizer) and remains one of the leading hormone replacement therapies (HRT) available[5].

Competitive Landscape

The market for HRT is competitive, with various other estrogen and progestin combinations available. However, Prempro's long history and established brand recognition have helped it maintain a significant market share. Generic versions of conjugated estrogens and MPA are also available, which has increased accessibility and reduced costs for patients[5].

Adverse Effects and Safety Concerns

Cardiovascular Risks

The combination of conjugated estrogens and MPA is associated with increased risks of myocardial infarction, stroke, and DVT. These risks are particularly concerning for postmenopausal women with existing cardiovascular disease[1][2].

Cancer Risks

There is an increased risk of invasive breast cancer and possibly other cancers such as colorectal cancer, although the latter may have a complex risk profile[2][4].

Other Adverse Effects

Common adverse effects include changes in vaginal bleeding patterns, cervical disorders, dysmenorrhea, leukorrhea, vaginal candidiasis, and vaginitis. Gastrointestinal symptoms like dyspepsia, diarrhea, flatulence, and nausea are also reported[3].

Pharmacokinetics and Drug Interactions

Absorption and Metabolism

Conjugated estrogens are well-absorbed from the gastrointestinal tract, while MPA is immediately released and absorbed. The pharmacokinetic parameters indicate that both components are effectively absorbed and metabolized in postmenopausal women[2].

Drug Interactions

Conjugated estrogens and MPA can interact with other drugs, affecting their efficacy and safety. For example, they can impair carbohydrate metabolism and glucose tolerance, leading to hyperglycemia in some women[3].

Market Projections

Future Demand

Despite the safety concerns and adverse effects, the demand for HRT is expected to remain steady due to the growing population of postmenopausal women. Advances in formulation and delivery systems, such as transdermal patches and vaginal rings, may also influence market trends.

Regulatory Environment

The FDA continues to monitor and update guidelines for HRT, emphasizing the importance of individualized treatment plans and careful risk-benefit assessments. This regulatory scrutiny may impact market dynamics and influence prescribing practices.

Competitive Innovations

The development of new HRT products with improved safety profiles and targeted delivery systems is likely to shape the future market. Bioidentical hormones and selective estrogen receptor modulators (SERMs) are areas of ongoing research and may offer alternatives to traditional conjugated estrogens and MPA combinations.

Key Takeaways

• Clinical Trials: The WHI and HERS trials have highlighted significant cardiovascular and cancer risks associated with conjugated estrogens and MPA.
• Market Presence: Prempro remains a leading HRT product despite safety concerns and the availability of generic alternatives.
• Adverse Effects: The combination is associated with various adverse effects, including cardiovascular risks, cancer risks, and gastrointestinal symptoms.
• Pharmacokinetics: Both components are well-absorbed and metabolized, but can interact with other drugs.
• Market Projections: The demand for HRT is expected to remain steady, with future market trends influenced by regulatory updates, new product developments, and individualized treatment approaches.

FAQs

Q: What are the primary indications for conjugated estrogens and medroxyprogesterone acetate?

A: The primary indications include treatment of moderate to severe vasomotor symptoms, treatment of moderate to severe symptoms of vulvar and vaginal atrophy, and prevention of postmenopausal osteoporosis.

Q: What are the major risks associated with this combination therapy?

A: The major risks include increased cardiovascular events, invasive breast cancer, stroke, and deep vein thrombosis.

Q: How do conjugated estrogens and medroxyprogesterone acetate interact with other drugs?

A: They can impair carbohydrate metabolism and glucose tolerance, leading to hyperglycemia, and may interact with other drugs affecting their efficacy and safety.

Q: What are the common adverse effects of this combination therapy?

A: Common adverse effects include changes in vaginal bleeding patterns, cervical disorders, dysmenorrhea, leukorrhea, vaginal candidiasis, and gastrointestinal symptoms.

Q: Are there any ongoing research or developments in HRT that could impact the market for conjugated estrogens and medroxyprogesterone acetate?

A: Yes, research into bioidentical hormones and selective estrogen receptor modulators (SERMs) may offer safer and more targeted alternatives in the future.

Sources

1. JAMA Network: Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women with Established Coronary Disease.
2. FDA: Approval Package for Prempro and Premphase.
3. Elsevier Health: Conjugated Estrogens; Medroxyprogesterone.
4. PubMed: Estrogen Plus Progestin and Colorectal Cancer.
5. OIG.HHS: Review of the Food and Drug Administration's Handling of Issues Related to Conjugated Estrogens.