The U.S. Food and Drug Administration (FDA) has approved dozens of hormone therapy products for men and women, including estrogen, progesterone, testosterone, and related compounds. These products have been reviewed for safety and efficacy and are indicated for treatment of symptoms resulting from hormonal changes associated with menopause or other endocrine-based disorders. In recent decades, an increasing number of health care providers and patients have turned to custom-formulated, or compounded, drug preparations as an alternative to FDA-approved drug products for hormone-related health concerns. These compounded hormone preparations are often marketed as “bioidentical” or “natural” and are commonly referred to as compounded bioidentical hormone therapy (cBHT). In light of the fast-growing popularity of cBHT preparations, the clinical utility of these compounded preparations is a substantial public health concern for various stakeholders, including medical practitioners, patients, health advocacy organizations, and federal and state public health agencies. This report examines the clinical utility and uses of cBHT drug preparations and reviews the available evidence that would support marketing claims of the safety and effectiveness of cBHT preparations. It also assesses whether the available evidence suggests that these preparations have clinical utility and safety profiles warranting their clinical use and identifies patient populations that might benefit from cBHT preparations in lieu of FDA-approved BHT.

Contents

• The National Academies of SCIENCES • ENGINEERING • MEDICINE
• COMMITTEE ON THE CLINICAL UTILITY OF TREATING PATIENTS WITH COMPOUNDED BIOIDENTICAL HORMONE REPLACEMENT THERAPY
• Reviewers
• Preface
• Acknowledgments
• Acronyms and Abbreviations
• Summary
  • OVERVIEW OF COMPOUNDING
  • CLINICAL UTILITY OF CBHT
  • CLINICAL UTILITY: SAFETY, EFFECTIVENESS, THERAPEUTIC NEED, AND USE OF CBHT
  • THE CLINICAL UTILITY OF CBHT AND RELATED CONSIDERATIONS FOR PRESCRIBERS
  • RECOMMENDATIONS
• 1. Introduction
  • STUDY CHARGE
  • STUDY SCOPE
  • KEY DEFINITIONS
  • STUDY APPROACH
  • REPORT ORGANIZATION
  • REFERENCES
• 2. An Overview of Compounding
  • COMPOUNDING: TYPES AND SETTINGS
  • THE COMPLEXITY OF COMPOUNDING
  • THE COMPOUNDING MARKET: SUPPLY AND DEMAND
  • REFERENCES
• 3. Regulatory Framework for Compounded Preparations
  • FDA-APPROVED DRUG PRODUCTS
  • FEDERAL REGULATION OF DRUG COMPOUNDING
  • CURRENT CONCERNS WITH FEDERAL REGULATIONS FOR COMPOUNDED DRUGS
  • PROFESSIONAL STANDARDS OF DRUG COMPOUNDING
  • STATE REGULATION OF DRUG COMPOUNDING
  • FINANCIAL ISSUES AND CONFLICTS OF INTEREST
  • REFERENCES
• 4. Reproductive Steroid Hormones: Synthesis, Structure, and Biochemistry
  • REPRODUCTIVE STEROID HORMONES
  • STRUCTURE AND BIOCHEMISTRY OF HORMONES COMMONLY FOUND IN COMPOUNDED BIOIDENTICAL HORMONE PREPARATIONS
  • STEROID HORMONE SIGNALING
  • REFERENCES
• 5. Compounded Bioidentical Hormone Preparations
  • CBHT PREPARATIONS
  • TYPES OF CBHT PREPARATIONS
  • CBHT ACTIVE INGREDIENTS
  • INACTIVE INGREDIENTS
  • REFERENCES
• 6. Bioavailability of Compounded Bioidentical Hormone Therapy Preparations
  • MEASURING CONCENTRATIONS OF STEROID HORMONES
  • BIOANALYTICAL METHODS TO MEASURE THE BIOAVAILABILITY OF STEROID HORMONES
  • BIOAVAILABILITY OF COMPOUNDED BIOIDENTICAL HORMONE THERAPY PREPARATIONS
  • BIOAVAILABILITY OF TRADITIONALLY MANUFACTURED BIOIDENTICAL HORMONE THERAPY PRODUCTS
  • CONCLUDING STATEMENTS
  • REFERENCES
• 7. The Safety and Effectiveness of Compounded Bioidentical Hormone Therapy
  • RESEARCH STRATEGY
  • ESTROGENS AND PROGESTERONE COMPOUNDED PREPARATIONS
  • TESTOSTERONE THERAPY IN MEN
  • TESTOSTERONE THERAPY IN WOMEN
  • DHEA THERAPY
  • CBHT RESEARCH CHALLENGES
  • SUMMARY OF RESEARCH FINDINGS
  • ADVERSE EVENT REPORTING FOR CBHT
  • REFERENCES
• 8. The Use of Compounded Bioidentical Hormone Therapy
  • THE WOMEN'S HEALTH INITIATIVE: IMPACT ON THE CURRENT USE OF HORMONE THERAPY
  • BIOIDENTICAL HORMONE THERAPY: INDICATIONS FOR USE
  • PROFESSIONAL GUIDANCE AND CLINICAL PRACTICE GUIDELINES FOR THE USE OF CBHT
  • THE USE OF CBHT: PATTERNS AND TRENDS
  • FACTORS DRIVING THE USE OF CBHT
  • CONCLUDING STATEMENTS
  • REFERENCES
• 9. Clinical Utility and Recommendations
  • WHAT DOES “CLINICAL UTILITY” MEAN?
  • THE CLINICAL UTILITY OF CBHT AND RELATED CONSIDERATIONS
  • RECOMMENDATIONS
• Appendix A. Study Approach
• Appendix B. Study Methods
• Appendix C. Glossary
• Appendix D. Biosketches
• Appendix E. 503A and 503B Distribution Supplement
• Appendix F. Compounded Bioidentical Hormone Therapy Formulations with a Single Active Ingredient
• Appendix G. Compounded Bioidentical Hormone Therapy Formulations with Two or More Active Ingredients
• Appendix H. Boxed Warnings on U.S. Food and Drug Administration–Approved Estrogen and Testosterone Products

Suggested citation:

National Academies of Sciences, Engineering, and Medicine. 2020. The clinical utility of compounded bioidentical hormone therapy: A review of safety, effectiveness, and use. Washington, DC: The National Academies Press. https://doi.org/10.17226/25791.

Digital Object Identifier: https://doi.org/10.17226/25791

Library of Congress Control Number: 2020941544

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