Why are guidelines against the use of bioidentical hormones in hormone replacement therapy (HRT)?

Why Guidelines Are Against Bioidentical Hormones

Guidelines oppose custom-compounded bioidentical hormones because they lack FDA approval, have not undergone rigorous safety and efficacy testing, and carry the same risks as conventional hormone therapy while introducing additional uncertainties related to compounding quality and consistency. 1, 2

The Core Problem: Marketing Term vs. Medical Classification

The FDA explicitly states that "bioidentical hormone replacement therapy" is a marketing term rather than a formally defined drug classification. 1 This is a critical distinction that patients and clinicians must understand—the term itself has no regulatory or scientific meaning. 2

Many FDA-approved conventional hormone therapies actually contain bioidentical hormones (chemically identical to human hormones), so the distinction being marketed is false. 2 The real issue is not whether hormones are "bioidentical," but whether they are FDA-approved and have undergone proper safety testing.

Lack of Evidence for Safety and Efficacy

No randomized controlled trials have studied the potential benefits or harms of custom-compounded bioidentical hormones for the prevention of chronic conditions or symptom management in postmenopausal women. 1 This represents a fundamental gap in evidence that makes their use problematic from a medical standpoint.

The safety and effectiveness of these compounded products have not been evaluated through the FDA's drug approval process. 1, 2 Without this rigorous evaluation:

• Actual hormone content is uncertain and may vary between batches 3
• Pharmacokinetics are not well-characterized 4
• Long-term safety profiles are unknown 5
• Quality control standards are inconsistent 2

Same Risks as Conventional Hormone Therapy

All estrogen-based hormone therapies, regardless of source or whether they are labeled "bioidentical," carry similar risks demonstrated in the Women's Health Initiative (WHI) trial. 2 These risks include:

• Increased coronary heart disease events (7 additional per 10,000 women-years) 1
• Increased stroke (8 additional per 10,000 women-years) 1
• Increased venous thromboembolism (8 additional per 10,000 women-years) 1
• Increased invasive breast cancer with estrogen-plus-progestin (8 additional per 10,000 women-years) 1

The American College of Obstetricians and Gynecologists emphasizes that bioidentical or natural hormones are expected to have similar efficacy and safety profiles as commercially available hormonal therapies that have been studied in clinical trials, regardless of whether they are compounded or manufactured. 6

Additional Risks Specific to Compounding

Custom-compounded preparations introduce risks beyond those of conventional hormone therapy:

• Lack of standardization: Hormone content may vary significantly between batches and pharmacies 2, 3
• No FDA oversight: These products bypass the rigorous testing and quality control required for FDA approval 1, 2
• Unproven formulations: Many compounded preparations include estriol or hormone combinations in ratios that have never been studied in clinical trials 4
• Inappropriate dosing guidance: Many advocates customize prescriptions based on saliva testing, which contradicts evidence-based guidelines 4

Consensus Position of Major Medical Organizations

The U.S. Preventive Services Task Force, American Heart Association, American Congress of Obstetricians and Gynecologists, and National Comprehensive Cancer Network all recommend against the use of custom-compounded bioidentical hormones. 1, 2

The ACOG specifically states that compounded bioidentical menopausal hormone therapy should not be prescribed routinely when FDA-approved formulations exist. 5 The National Comprehensive Cancer Network explicitly notes there is no data supporting claims that custom-compounded bioidentical hormones are safer and more effective than standard hormone therapies. 1, 2

When Hormone Therapy Is Appropriate

Guidelines do support hormone therapy for specific indications, but recommend FDA-approved formulations:

• For moderate to severe vasomotor symptoms in women under 60 or within 10 years of menopause 2
• Transdermal estradiol is preferred over oral formulations due to lower thrombotic risk 2
• Micronized progesterone is preferred over medroxyprogesterone acetate for endometrial protection 2
• Lowest effective dose for shortest duration necessary to control symptoms 1, 2

Critical Contraindications Apply to All Hormone Therapy

Whether bioidentical or conventional, hormone therapy is contraindicated in:

• History of hormone-dependent cancers 1, 2
• History of venous thromboembolism 1, 2
• Active or recent stroke or coronary heart disease 1, 2
• Active liver disease 1, 2

The Bottom Line for Clinical Practice

Clinicians should counsel patients that FDA-approved menopausal hormone therapies are recommended for the management of menopausal symptoms over compounded bioidentical menopausal hormone therapy. 5 If a patient requests compounded bioidentical hormones, educate them on:

• The lack of FDA approval and safety testing 5
• The absence of evidence supporting superior safety or efficacy 5, 6
• The risks specific to compounding (variable content, lack of quality control) 2, 3
• The availability of FDA-approved bioidentical hormone formulations that have been properly studied 2

The widespread use of compounded bioidentical hormone therapy despite the lack of evidence to support its safety and efficacy is concerning and represents a departure from evidence-based medicine. 3