Are gel or versa base formulations of compounded hormones more stable or effective?

Compounded Hormones: Gel vs. Versa Base Formulations

Neither gel nor versa base formulations of compounded hormones should be routinely prescribed, as FDA-approved transdermal estradiol patches and gels provide superior standardization, safety data, and regulatory oversight compared to custom-compounded preparations. 1, 2

Primary Recommendation: FDA-Approved Transdermal Formulations

The evidence strongly supports using FDA-approved transdermal estradiol products rather than compounded preparations, regardless of base formulation. 3, 4

• Standard FDA-approved transdermal estradiol patches (50-100 mcg/24-hour applied twice weekly) represent the gold standard for hormone replacement therapy due to their proven cardiovascular safety profile and consistent dosing 3, 4
• Transdermal estradiol has a neutral effect on venous thromboembolism risk (OR 0.9) compared to oral formulations (OR 4.2), making route of administration more critical than compounding base 4
• FDA-approved transdermal gels (such as AndroGel for testosterone) provide standardized dosing with established pharmacokinetic profiles, though absorption can be variable between patients 1

Critical Problems with Compounded Formulations

Custom-compounded bioidentical hormones lack the scientific evidence, quality control, and safety data that support FDA-approved products. 1, 2, 5

Lack of Evidence for Safety or Superiority

• The NCCN explicitly states that "custom compounded bioidentical hormones are not recommended because data supporting claims that they are safer and more effective than standard hormones are lacking" 1
• The American College of Obstetricians and Gynecologists (ACOG) issued a clinical consensus stating that "compounded bioidentical menopausal hormone therapy should not be prescribed routinely when FDA-approved formulations exist" 2
• The Endocrine Society's scientific statement concludes "there is no rationale for routine prescribing of unregulated, untested, and potentially harmful custom compounded bioidentical hormone therapies" 5

Quality Control and Dosing Inconsistencies

• Compounded preparations lack standardized manufacturing processes, leading to potential dosing inconsistencies that could result in under- or over-treatment 6, 7
• There is no FDA oversight of compounded hormone formulations, meaning batch-to-batch variability in potency and purity cannot be assured 2, 7
• Saliva testing commonly used to guide compounded hormone dosing contradicts evidence-based guidelines, which support tailoring therapy according to symptoms rather than hormone levels 7

Addressing the Gel vs. Versa Base Question Directly

The question of gel versus versa base stability is clinically irrelevant because neither compounded formulation should be used when FDA-approved alternatives exist. 1, 2

• No high-quality comparative studies exist examining stability differences between compounded gel and versa base formulations 8, 7
• The absence of FDA approval means neither formulation has undergone rigorous stability testing required for pharmaceutical products 2, 5
• Any theoretical stability advantages of one compounding base over another are overshadowed by the fundamental lack of quality control and safety data for all compounded preparations 6, 7

When Patients Request Compounded Hormones

If a patient specifically requests compounded bioidentical hormones, clinicians must educate them on the lack of FDA approval and potential risks before prescribing. 2

• Counsel patients that FDA-approved menopausal hormone therapies are recommended over compounded preparations 2
• Explain that marketing claims of "natural" and "safer" for compounded hormones lack scientific evidence 1, 8, 6
• Discuss the risks specific to compounding, including dosing inconsistencies and lack of regulatory oversight 2, 7
• Document this informed consent discussion thoroughly in the medical record 2

Preferred FDA-Approved Alternatives

For patients seeking transdermal hormone delivery, prescribe FDA-approved patches or gels with established safety profiles. 3, 4

First-Line: Transdermal Estradiol Patches

• Start with 50 mcg/24-hour patches applied twice weekly, titrating to 100 mcg if symptoms persist after 2-3 months 3
• Patches provide more consistent serum estradiol levels than gels and eliminate concerns about transferability to others 1, 3
• Combined estradiol/levonorgestrel patches are available for women with intact uteri who prefer continuous combined therapy 3

Second-Line: FDA-Approved Transdermal Gels

• FDA-approved estradiol gels provide standardized dosing (typically 0.75-1.5 mg daily) with established pharmacokinetics 3
• Patients must be counseled about proper application technique and avoiding skin-to-skin contact with others for several hours after application 1
• Absorption variability with gels is a known limitation but occurs within a predictable range for FDA-approved products 1

Required Progestogen Opposition

• Women with intact uteri must receive micronized progesterone 200 mg orally for 12-14 days every 28 days to prevent endometrial hyperplasia 1, 3
• Micronized progesterone is preferred over medroxyprogesterone acetate due to lower cardiovascular and breast cancer risk 1

Common Pitfalls to Avoid

• Never prescribe compounded hormones based solely on patient preference without thorough counseling about lack of FDA approval and safety data 2
• Avoid using saliva testing to guide hormone dosing, as this contradicts evidence-based practice and is commonly promoted by compounding pharmacies 7
• Do not assume "bioidentical" means safer—many FDA-approved products contain bioidentical hormones with proven safety profiles 8, 7
• Never use ethinyl estradiol in hormone replacement therapy, as it carries significantly higher thrombotic risk than 17β-estradiol 3