Are bioidentical hormones safe?

Are Bioidentical Hormones Safe?

Custom-compounded bioidentical hormones are not recommended because data supporting claims that they are safer and more effective than standard hormones are lacking. 1, 2 The FDA has not approved any type or class of bioidentical hormone therapy for prevention of chronic diseases, and these products have not been evaluated through the FDA's drug approval process. 1, 2

Understanding the Term "Bioidentical"

• The FDA defines "bioidentical hormone replacement therapy" as a marketing term rather than a formally defined drug classification. 1, 2
• Many FDA-approved conventional hormone therapies actually contain bioidentical hormones (such as 17β-estradiol and micronized progesterone), which are chemically identical to human hormones. 3, 4
• The critical distinction is between FDA-approved bioidentical formulations versus custom-compounded preparations that lack standardization and quality control. 3, 4

Safety Evidence and Risks

Lack of Safety Data for Compounded Products

• No randomized controlled trials have studied the potential benefits or harms of compounded bioidentical hormones for prevention of chronic conditions in postmenopausal women. 1, 2
• Compounded bioidentical hormones lack well-controlled studies examining route of administration, pharmacokinetics, and safety. 3
• There is insufficient scientific evidence to support claims that compounded bioidentical hormones are safer than FDA-approved hormone therapies. 1, 2, 3

Known Risks from Hormone Therapy Studies

All estrogen-based hormone therapies, regardless of source, carry similar risks demonstrated in the Women's Health Initiative (WHI) trial: 1, 5

• Cardiovascular risks: Increased risk of coronary heart disease events, stroke, and venous thromboembolism (blood clots). 1, 5
• Cancer risks: Increased risk of breast cancer with estrogen plus progestin therapy (relative risk 1.24), with larger and more advanced tumors at diagnosis. 5
• Endometrial cancer: 2 to 12 times greater risk with unopposed estrogen in women with a uterus. 5
• Ovarian cancer: Increased risk with prolonged use (5+ years). 5
• Dementia: Two-fold increased risk of probable dementia in women 65 years and older. 5, 6

Specific Safety Concerns with Compounded Products

• Custom-compounded preparations lack standardization in dosing, purity, and quality control. 3, 4
• Salivary hormone testing used by many compounding advocates contradicts evidence-based guidelines and is unreliable for dose adjustment. 3, 7, 4
• Compounded products may contain estriol, which lacks FDA approval and has insufficient long-term safety data. 3, 4

Clinical Recommendations

What NOT to Use

• Avoid custom-compounded bioidentical hormones due to lack of safety and efficacy data, lack of standardization, and unsubstantiated marketing claims. 1, 2
• Do not use salivary hormone testing to guide therapy; adjust doses based on symptom improvement instead. 3, 7, 4
• Do not prescribe hormone therapy for prevention of chronic diseases such as cardiovascular disease, osteoporosis, or dementia. 1, 2

FDA-Approved Options (If Hormone Therapy Is Indicated for Symptoms)

If treating moderate to severe menopausal symptoms after non-hormonal alternatives have failed: 1

• Use FDA-approved formulations of bioidentical hormones (17β-estradiol, micronized progesterone) at the lowest effective dose for the shortest duration. 1, 4
• Transdermal estradiol formulations may be preferred over oral due to lower rates of venous thromboembolism and stroke. 1
• Micronized progesterone may be preferred over medroxyprogesterone acetate due to lower rates of venous thromboembolism and breast cancer risk. 1
• Always use progestogen therapy in women with an intact uterus to prevent endometrial hyperplasia. 5, 8

Absolute Contraindications

Hormone therapy of any type is contraindicated in: 1

• History of hormone-dependent cancers (breast, endometrial, ovarian)
• History of venous thromboembolism
• Active or recent stroke or coronary heart disease
• Unexplained vaginal bleeding
• Active liver disease
• Pregnancy

Use With Caution In

• Current smokers
• Women with hypertension or coronary heart disease
• Women with increased genetic cancer risk
• Women 65 years and older (increased dementia risk) 5, 6

Key Clinical Pitfalls to Avoid

• Do not assume "natural" or "bioidentical" means safer: All estrogen-based therapies carry similar risks regardless of source. 1, 2, 3
• Do not prescribe compounded formulations: They offer no proven advantages and lack quality control. 1, 2, 3
• Do not use hormone therapy for disease prevention: It increases rather than decreases risks of cardiovascular disease and cancer. 1, 2
• Do not fail to discuss risks: Patients must understand that hormone therapy increases risks of blood clots, stroke, heart disease, and breast cancer. 2, 5