Compounded TRT and HRT: Where the FDA Stands Now

For the better part of a decade, the FDA has been quietly building a regulatory weapon that could erase compounded testosterone, estradiol, and progesterone from the US market. The instrument is called the "Demonstrably Difficult to Compound" (DDC) list — a roster of drugs the agency considers too complex for 503A and 503B pharmacies to make safely. Compounded bioidentical hormones have been nominated for that list since 2020.

In May 2026, that fight is at an inflection point. Commissioner Marty Makary's November 2025 press conference removing black-box warnings from menopausal HRT carried a softer tone on compounded hormones than any FDA leadership in twenty years. But the proposed DDC rule has not been withdrawn. Patients on compounded testosterone — men taking custom-concentration cypionate, women on low-dose cream, anyone using pellets outside the single FDA-approved product — are caught between a regulatory threat and a political signal pointing the other direction.

Here's where things actually stand, and what to do about it.

Key Takeaways

• Testosterone, estradiol, progesterone, and seven other bioidentical hormones were nominated for the FDA's DDC list in 2020 — adding them would effectively ban compounding them
• No final rule has been issued. FDA filed a proposed rule on three unrelated dosage forms in March 2024; hormones were not included
• Commissioner Makary signaled support for compounded BHT access at the November 2025 black-box warning press conference, but did not formally withdraw the hormone nomination
• Pellet formulations face the highest separate risk because of bioavailability and peak-level concerns
• Compounded testosterone is still legally available through 503A pharmacies as of May 2026
• Patients should know their backup commercial options and confirm their clinic uses a 503A (not 503B) pharmacy for hormones

What the "Difficult to Compound" List Actually Is

The DDC list isn't new policy. Congress created it in the Drug Quality and Security Act of 2013 (DQSA), which gave the FDA authority to identify drugs that "present demonstrable difficulties for compounding" and prohibit them from being compounded under both Section 503A (traditional patient-specific compounding pharmacies) and Section 503B (outsourcing facilities making bulk batches).

The Six Criteria

The FDA evaluates candidate drugs against six criteria:

1. Complex formulation
2. Complex drug delivery mechanism
3. Complex dosage form
4. Bioavailability issues
5. Compounding process complexity
6. Physicochemical or analytical testing complexity

A drug doesn't need to fail all six — failing on any combination can be enough.

What's On the List So Far

For a regulation in development since 2013, the actual list is thin. In March 2024, the FDA filed a proposed rule covering just three drug categories:

Category	Why
Oral solid modified-release products with coated systems	Manufacturing complexity for extended release
Drugs where the active ingredient is contained in liposomes	Specialized vesicle formation
Products made through hot melt extrusion	Specialized manufacturing equipment

Notably absent: hormones.

The 2020 NASEM Report — The Document Behind the Threat

In July 2020, the National Academies of Science, Engineering, and Medicine (NASEM) released a report the FDA had commissioned in 2018. The headline conclusion: compounded bioidentical hormone therapy (cBHT) poses a "public health concern" because of insufficient evidence of effectiveness and safety, and prescribers should "restrict the use of non-FDA-approved compounded bioidentical hormones, except for specific medical circumstances."

The report's most consequential recommendation came in the appendix: the FDA's Pharmacy Compounding Advisory Committee (PCAC) should review ten cBHTs as candidates for the DDC list.

The Ten Hormones Nominated

Hormone	Used For
Estradiol	Menopausal HRT
Estrone	Menopausal HRT (rare)
Estradiol cypionate	Long-acting estrogen injections
Estriol	Topical menopausal HRT (very popular in cBHT)
Progesterone	Cycle support, perimenopausal HRT
Pregnenolone	Cognitive support, neurosteroid
Dehydroepiandrosterone (DHEA)	Adrenal support, vaginal atrophy
Testosterone	Men's and women's TRT
Testosterone cypionate	Men's TRT injections
Testosterone propionate	Older short-acting TRT (rare in modern practice)

A separate recommendation: all pellet formulations of these hormones should be considered for the list — pellets specifically, regardless of which hormone.

Why NASEM Said What It Said

The report's reasoning was narrow: most compounded BHT formulations haven't been through the FDA approval process, so there's no agency-graded data on bioavailability, dose-uniformity batch-to-batch, or long-term outcomes. NASEM didn't claim compounded BHT was demonstrably harmful — it argued the evidence base was insufficient relative to FDA-approved alternatives.

Critics, including the Alliance for Pharmacy Compounding (APC) and the American Association of Naturopathic Physicians, pushed back hard: dose customization that commercial products simply don't offer, decades of clinical use, and the absence of robust pharmaceutical-industry incentive to do FDA studies on hormones already off-patent.

What Changed in November 2025

For five years after the NASEM report, the FDA's posture stayed cautiously hostile to compounded BHT. That changed at a single press conference.

On November 7, 2025, HHS Secretary Robert F. Kennedy Jr. and FDA Commissioner Marty Makary announced the removal of black-box warnings from menopausal HRT — labels that had governed the market since 2002. In his prepared remarks and Q&A, Makary made several points the compounding industry seized on:

• The 2002 Women's Health Initiative warnings "deterred" women from accessing HRT and represented "an American tragedy"
• The FDA needs to align its regulatory posture with modern evidence on hormone therapy
• Compounded BHT serves patients who can't access or don't respond well to commercial products

What he did not do: formally withdraw the cBHT nomination from the DDC list pathway, set a timeline for action on the proposed rule, or commit the agency to any specific regulatory step on compounded hormones.

The Alliance for Natural Health's Read

In a December 2025 statement titled "A New Tone at the FDA on Compounded Hormones — But We Can't Let Up," the ANH-USA characterized Makary's remarks as encouraging but emphasized: "until we see concrete policy changes, this fight isn't over."

That assessment remains accurate in May 2026. There is no formal regulatory step in either direction since November.

Why Compounded Testosterone Specifically Matters

Commercial testosterone products are available — and growing. The FDA approved oral testosterone undecanoate (Jatenzo, Tlando, Kyzatrex), and a major telehealth platform launched branded oral testosterone in 2026. New generic testosterone cypionate manufacturers are coming online to ease the ongoing cypionate shortage.

So why does compounded testosterone still matter? Five reasons:

1. Custom Concentrations

Commercial testosterone cypionate comes in 200 mg/mL vials almost exclusively. That's fine for a man taking 100-200 mg/week. For a woman on 1.5-4 mg/week, that's a measurement problem — you'd inject 0.0075-0.02 mL, well below the precision threshold of standard 1 mL syringes. Compounding pharmacies routinely dispense 20 mg/mL or even 10 mg/mL T cypionate for women's TRT, where 0.1-0.4 mL is reliably measurable.

2. Alcohol-Free Creams

Commercial testosterone gels (AndroGel, Testim) use ethanol as the solvent for skin absorption. Patients with sensitive skin, eczema, or alcohol intolerance need alcohol-free vehicles — typically poloxamer or pluronic lecithin organogel (PLO) bases that only compounding pharmacies prepare.

3. Women's Microdoses

There is no FDA-approved testosterone product for women in the US. Off-label use of commercial gels means dividing a male daily dose by 10 — a process that creates significant inter-dose variability and contamination risk for partners. Compounded testosterone cream at 1-10 mg/mL strengths is the standard women's HRT formulation in clinical practice.

4. Combination Products

Many menopausal HRT protocols combine multiple hormones: estradiol + estriol (Biest), progesterone + estradiol, testosterone + DHEA. Each component is dosed to individual patient response. Commercial combination products are limited in available ratios; compounded combinations let clinicians titrate each hormone independently.

5. Supply During Shortages

When testosterone cypionate hit a multi-year shortage in 2023-2026, 503A compounding pharmacies were one of the only reliable sources for patients whose commercial product was on backorder. Banning compounding would eliminate this safety valve.

Pellet Therapy: The Highest-Risk Category

Of all compounded hormone formulations, pellets carry the most regulatory risk — and the most physiologic risk.

Testosterone pellets are small (3 mm × 9 mm) solid cylinders inserted subcutaneously, typically in the upper hip or buttock. They dissolve over 3-6 months, releasing testosterone slowly. Brands like Testopel are FDA-approved (200 mg pellets, men only). But the vast majority of pellets used in US practice — especially for women and at non-standard doses — are compounded.

NASEM specifically called out pellets because:

• Bioavailability is unproven. Compounded pellets don't undergo FDA-required bioavailability testing. Hormone delivery varies meaningfully pellet-to-pellet.
• Peak levels can exceed physiologic ranges. Studies of compounded testosterone pellets in women have documented peak total testosterone levels of 200-500+ ng/dL (vs. a target range of 30-60 ng/dL for women). These supraphysiologic peaks may be driving side effects like acne, hair loss, and voice changes.
• You can't titrate down once inserted. If a patient develops side effects two weeks after pellet insertion, the only option is wait it out or surgically remove the pellet — both poor outcomes.

If the FDA acts on the DDC list, pellets are the most likely first target.

How the 503A vs 503B Distinction Matters

Not all compounding pharmacies are regulated the same way. Understanding this distinction is critical if you're on compounded TRT or HRT.

503A Pharmacies (Patient-Specific Compounding)

• Compound on individual patient prescriptions
• Regulated primarily by state boards of pharmacy
• Cannot make bulk batches or stock medications
• Can use bulk drug substances on FDA's 503A bulks list

503B Outsourcing Facilities

• Compound in bulk batches that can be sold to clinics without a patient-specific prescription
• Regulated directly by the FDA, including manufacturing standards similar to commercial drug manufacturers
• Must use bulk drug substances on a separate 503B bulks list
• Subject to more stringent inspection and quality requirements

Which Pathway Is at Higher Risk?

A DDC listing would apply to both pathways. But the practical impact would differ:

• 503B facilities depend on bulk-batch economics. Losing testosterone from the 503B bulks list would shut down testosterone production at most outsourcing facilities almost immediately.
• 503A pharmacies could theoretically continue compounding from individual prescriptions using API obtained through alternative pathways — but the FDA would likely use enforcement to close that loophole.

If you're an existing compounded TRT or HRT patient, ask your clinic which type of pharmacy fills your prescription. 503A patient-specific compounding has historically been more politically protected, partly because shutting it down would obviously eliminate medication for specific named patients.

What Patients Should Do Right Now

1. Don't Panic — No Ban Has Been Issued

As of May 16, 2026, compounded testosterone, estradiol, and progesterone are legally available through both 503A and 503B pathways. No FDA final rule has been published. No comment period is currently open on hormone-specific DDC listing.

2. Know Your FDA-Approved Backup

For men on compounded T cypionate or enanthate, FDA-approved commercial alternatives exist at standard 200 mg/mL concentrations. If your dose is at standard increments (100 mg, 140 mg, 200 mg/week), commercial product would substitute directly. See our comparison of testosterone cypionate vs. enanthate for switching considerations.

For women, there is no clean FDA-approved alternative. Off-label use of AndroGel pump (1 pump = 12.5 mg testosterone, vs. typical female dose of 1-4 mg) at sub-dose increments is the workaround most clinicians use. This is workable but imprecise.

3. Confirm Your Clinic Has a Plan

A well-run telehealth TRT or HRT clinic should already have:

• Relationships with multiple compounding pharmacies (no single-pharmacy dependency)
• Commercial-product prescribing pathways ready as backup
• Internal protocols for the dose-conversion math if patients switch

If your clinic can't answer "what happens if compounded testosterone becomes unavailable" in a couple of sentences, that's a signal to look at other options. Our reviews of online TRT and HRT clinics include their compounding pharmacy relationships and backup strategies.

4. Watch for Comment Periods

If FDA does formally propose adding hormones to the DDC list, there will be a public comment period (typically 60-90 days). Patient comments matter — the 2020 NASEM report itself triggered an FDA call for public input, and patient testimony was cited heavily in subsequent FDA materials. Sign up for alerts from the Alliance for Pharmacy Compounding (a4pc.org) or the Alliance for Natural Health (anh-usa.org) — both groups will mobilize comment campaigns if the rule moves.

5. Don't Stockpile

It might be tempting to ask your prescriber for a 6-month supply "just in case." Don't. Stockpiling controlled substances (testosterone is Schedule III in the US, though FDA panels have recommended descheduling) is illegal and can jeopardize your existing prescription. Even non-controlled compounded hormones have stability and sterility limits — most compounded testosterone is dated 90-180 days from compounding.

What to Watch Next

The most likely scenarios over the next 12 months, in order of probability:

1. Status quo extends (most likely). FDA continues developing DDC rules but doesn't add hormones in 2026. Compounded TRT and HRT remain available. Makary's softer tone holds.
2. Withdrawal of cBHT nomination. FDA formally announces it will not pursue hormone listings. This would be the most patient-friendly outcome and is the explicit ask of compounding-industry advocacy groups.
3. Pellet-only listing. FDA adds compounded hormone pellets to the DDC list while leaving creams, gels, and injections alone. This would be politically defensible given pellet-specific safety concerns.
4. Full hormone DDC listing (least likely under current FDA leadership). All ten NASEM-nominated hormones added to the list, effectively ending compounded BHT.

Bookmark this article — we'll update as the regulatory picture moves.

The Bigger Picture

The hormone compounding fight isn't happening in isolation. Three other regulatory threads are converging in 2026:

• The black-box warning removal (covered here) has driven HRT prescriptions up 184% since 2018, increasing demand for both commercial and compounded products
• The FDA's potential testosterone label expansion for low libido in idiopathic hypogonadism signals broader regulatory liberalization
• The TRAVERSE trial follow-up (European panel position) cementing testosterone's cardiovascular safety profile

If the regulatory winds keep blowing the same direction — toward patient access — the cBHT nomination becomes harder to defend. The case for restricting hormones the FDA itself has just declared substantially safer than previously labeled is weaker than it was five years ago. Compounded BHT advocacy groups know this and are pushing hard for formal withdrawal of the nomination.

For now, compounded testosterone and HRT remain available. The fight to keep them that way is ongoing.

---

References

1. National Academies of Sciences, Engineering, and Medicine. "The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use." July 2020.
2. FDA. "Drug Products or Categories of Drug Products That Present Demonstrable Difficulties for Compounding Under Sections 503A or 503B." Proposed Rule. March 2024.
3. HHS. "HHS Advances Women's Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy." November 7, 2025.
4. Alliance for Natural Health USA. "A New Tone at the FDA on Compounded Hormones — But We Can't Let Up." December 2025.
5. Frier Levitt. "Regulatory Update on Compounded Bioidentical Hormone Therapy (cBHT)." 2024.
6. Pharmacy Times. "Updates on 503A Compounding: The Impact of Drug Shortages." 2026.
7. Davis SR, et al. "Global Consensus Position Statement on the Use of Testosterone Therapy for Women." J Clin Endocrinol Metab. 2019;104(10):4660-4666.

Related Reading

• Testosterone Cypionate Shortage: What to Do Now
• Estrogen Patch Shortage: 5 Alternatives
• HRT Black Box Warning Removed: What Changed
• Bioidentical vs Synthetic HRT for Women
• Compare Online TRT Clinics