Hormone optimization is the name clinics give to a program that measures a patient’s hormone values, prescribes approved or compounded hormones against those values, and remeasures on a schedule. The schedule and the values come from clinical guidelines: the Endocrine Society recommends two fasting morning testosterone measurements before a diagnosis and a first-year plan that tracks symptoms, serum testosterone, hematocrit and prostate cancer risk [1], and the 2022 Menopause Society statement asks for periodic reevaluation of benefit and risk for every woman on hormone therapy [2].
A patient deciding whether to enroll, or a practice building the service line, can read a program through five parts: what it includes, which guideline defines each laboratory endpoint and follow-up interval, how a compounded hormone differs from an FDA-approved one, what the controlled-substance and telehealth rules add for testosterone, and who prescribes. ExaVeyra writes as a supplier: it states what a product is and how access works, and the prescriber decides what fits a patient.
Regulatory status
In the United States estradiol, progesterone, testosterone, levothyroxine and liothyronine are active ingredients of FDA-approved drugs, and the same molecules are also compounded under section 503A against a patient-specific prescription [21]. A compounded preparation is not FDA-approved, and FDA states that it does not verify its safety, effectiveness or quality before it is marketed [22]. Testosterone is a Schedule III controlled substance [20]. Hormone optimization formulations are compounded by our 503A pharmacy partner against a patient-specific prescription, and where a controlled substance such as testosterone is prescribed, our 503A pharmacy partner dispenses it under its own DEA registration. The practitioner decides use.
Hormone optimization is a measured, guideline-anchored program
The word optimization has no definition in any guideline, so the useful way to read it is as a program with three documented parts: a baseline laboratory panel, a prescription written against that panel, and a follow-up panel at an interval a guideline specifies. Each hormone has a society document that sets the measured endpoint [1, 2, 3].
For men, the Endocrine Society guideline recommends a diagnosis of hypogonadism only in men with symptoms and unequivocally, consistently low serum testosterone, confirmed by repeating a fasting morning measurement, with free testosterone added when the total is borderline or SHBG is altered [1]. For women, the Menopause Society statement sets out risks that differ by type, dose, duration, route, timing and progestogen use, with the most favorable balance in women younger than 60 or within 10 years of menopause onset [2].
For thyroid, the American Thyroid Association guideline makes TSH the endpoint of dose adequacy and levothyroxine the standard of care, and its 2021 consensus with the British and European associations records that 14 trials of combined T4 and T3 had not shown a consistent benefit while patient selection remains the open question [3, 4]. A program that prescribes a compounded ratio documents that position [4].
Clinical guidelines define the endpoints a program measures
The table below places each component of a program beside the document that defines its laboratory endpoint and follow-up. Reading a clinic’s protocol against this table shows quickly whether the program is measuring what the guidelines measure.
| Program component | Guideline or evidence source | Measured endpoint and follow-up the source specifies |
|---|---|---|
| Testosterone in men | Endocrine Society 2018 [1]; TRAVERSE 2023 [6]; Testosterone Trials 2016 [7] | Two fasting morning total testosterone values for diagnosis; symptoms, serum testosterone, hematocrit and prostate cancer risk in the first year; mid-normal target |
| Estradiol and progesterone in women | Menopause Society 2022 [2]; ACOG 2023 on compounded preparations [5] | Individualized choice by type, dose, duration and route; periodic reevaluation of benefit and risk; FDA-approved products preferred when they exist |
| Levothyroxine and liothyronine | ATA 2014 [3]; ATA, BTA and ETA consensus 2021 [4]; Biondi 2019 [12] | TSH as the endpoint of dose adequacy; repeat measurement before a decision; combination therapy evidence recorded as inconsistent |
| DHEA | Elraiyah 2014 [10]; Corona 2013 [11]; Vaidya 2025 [13] | DHEA-S measured in adrenal evaluation; two meta-analyses report no effect on sexual function, lipids, glucose or bone |
| Hematocrit on testosterone | Ohlander 2018 [8]; Endocrine Society 2018 [1] | Erythrocytosis is the best documented adverse effect; hematocrit is tracked through the first year |
| Reference range for the baseline value | Travison 2017 [9] | Harmonized 264 to 916 ng/dL for total testosterone in healthy nonobese men aged 19 to 39 |
Baseline laboratory work establishes the diagnosis before any prescription
The question "what labs are needed for hormone optimization" has a guideline answer for each hormone. Travison and colleagues harmonized testosterone assays across 9,054 men in four cohorts against a CDC reference method and derived a range of 264 to 916 ng/dL for healthy nonobese men aged 19 to 39, which is the range a baseline value is read against [9].
- Total testosterone, fasting and in the morning, repeated on a second day; free testosterone by equilibrium dialysis or a validated formula when the total is borderline or SHBG is altered [1].
- Hematocrit, because an elevated value is a reason not to start testosterone and the first value tracked afterward [1, 8].
- PSA, with the guideline listing a value above 4 ng/mL, or above 3 ng/mL in men at increased prostate cancer risk, among the reasons not to start without urological evaluation [1].
- TSH, with free thyroxine when TSH is abnormal; Biondi and colleagues define subclinical hypothyroidism as an elevated TSH with a normal free thyroxine and stress repeat measurement before any decision [12].
- DHEA-S where DHEA is under consideration, read in the adrenal context Vaidya and colleagues describe, and with Labrie’s point in mind that serum values and tissue exposure are loosely coupled [13, 14].
- For women, a documented menopausal status and the risk factors the Menopause Society statement names, since the benefit-risk balance depends on age and time since menopause onset [2].
Harman and colleagues showed in the Baltimore Longitudinal Study of Aging that total and free testosterone decline with age in healthy men [24]. FDA retains a limitation-of-use statement for age-related hypogonadism on every testosterone label, which is why the guideline’s distinction between an age-related decline and a confirmed symptomatic deficiency is the first thing a program documents [1, 19].
Follow-up intervals and endpoints are specified in the guidelines
The Endocrine Society plan monitors men on testosterone with a standardized schedule that evaluates symptoms, adverse effects and adherence, measures serum testosterone and hematocrit, and evaluates prostate cancer risk during the first year, aiming at mid-normal concentrations [1]. The guideline body schedules the first reassessment 3 to 12 months after starting and annually thereafter, with hematocrit at baseline, at 3 to 6 months, at 12 months and annually thereafter, and therapy withheld when hematocrit rises above 54 percent [1].
The Menopause Society asks for periodic reevaluation of the benefits and risks of continuing therapy, individualized to the woman, and ACOG adds that a patient who requests a compounded preparation should be counseled on the lack of FDA approval and the compounding-specific risks [2, 5]. For thyroid, TSH is remeasured after any change before the next adjustment [3].
The outcome trials show why the intervals matter. TRAVERSE randomized 5,246 men, with a mean follow-up of 33 months, and found a primary cardiovascular event in 7.0 percent on testosterone and 7.3 percent on placebo, with more atrial fibrillation, acute kidney injury and pulmonary embolism on testosterone [6]. The Testosterone Trials followed 790 men for one year and reported a moderate benefit in sexual function with similar adverse event rates in the two groups [7].
Several parts of a typical program rest on thinner evidence
The question "is hormone optimization safe" is answered hormone by hormone and route by route, and several parts of a typical program rest on thinner evidence than the testosterone and menopause literature. The gaps below are specific.
- No randomized trial compares a compounded hormone preparation with its FDA-approved counterpart; NASEM found the information on compounded preparations came mostly from low quality data such as anecdotal claims and prescriber testimony [15, 16].
- ACOG states that evidence to support marketing claims of safety and effectiveness for compounded menopausal hormones is lacking and calls for placebo-controlled trials with long-term follow-up against FDA-approved therapy [5].
- Fourteen trials of combined T4 and T3 had not shown a consistent benefit by 2021, and the consensus names patient selection as the unanswered question [4].
- Two meta-analyses of DHEA, in 1,188 women and 1,353 men, found no effect on sexual function, lipids, glucose or bone, with low confidence in the estimates [10, 11].
- TRAVERSE tested testosterone gel in men at cardiovascular risk; whether its event rates apply to injectable formulations or to younger men was not measured [6].
- The Testosterone Trials lasted one year and found no benefit in vitality, so the long-term endpoints many programs advertise were outside what was measured [7].
FDA-approved and compounded hormones travel different regulatory routes
The phrase "hormone optimization vs HRT" usually contrasts a compounded program with FDA-approved menopausal hormone therapy, and the difference lies in regulation, since the molecule can be identical. An approved product carries FDA-approved labeling, which FDA revised in November 2025 and February 2026 to remove the cardiovascular, breast cancer and probable dementia statements from the boxed warning while keeping the endometrial cancer warning for systemic estrogen-alone products [17, 18].
A compounded preparation has no FDA-approved labeling. A 503A pharmacy may compound with a bulk substance that complies with a USP or NF monograph, is a component of an approved drug, or appears on the 503A bulks list, which is how estradiol, progesterone, DHEA, levothyroxine and liothyronine qualify [21]. FDA states that compounded drugs are not FDA-approved and should only be used in patients whose medical needs cannot be met by an approved drug [22].
FDA asked the National Academies in September 2018 for an independent assessment of compounded bioidentical hormone preparations, and the 2020 report concluded that their widespread use poses a public health concern given the lack of high-quality clinical evidence and minimal oversight [15, 16]. ACOG’s 2023 consensus follows the same line: FDA-approved formulations are recommended, and a compounded preparation is prescribed with documented counseling when a patient requests it [5].
A compounded estradiol capsule and an approved one contain the same molecule. What differs is the label, the premarket review and the record a prescriber keeps to explain the choice.
Controlled substance and telemedicine rules apply to testosterone
Testosterone is approved solely for men who lack or have low testosterone in conjunction with an associated medical condition, and FDA’s February 2025 class-wide labeling change added the TRAVERSE results, removed the boxed cardiovascular language, retained the limitation of use for age-related hypogonadism and added a blood pressure warning [19].
Testosterone is also listed by name among the Schedule III anabolic steroids at 21 CFR 1308.13, and approved labeling carries the CIII designation [20]. A program that prescribes it by telehealth relies on the DEA and HHS fourth temporary extension of the telemedicine flexibilities for controlled medications, in force through 31 December 2026, and on state rules that are frequently stricter [20].
Who prescribes follows from the same rules. A licensed physician, nurse practitioner or physician assistant with prescriptive authority in the patient’s state writes the prescription, and for testosterone that prescriber also holds a DEA registration [20]. The pharmacy that fills a compounded prescription must be licensed for the patient’s state, and a 503A pharmacy compounds for an identified patient rather than for office stock [23].
Program components and the cost structure behind them
No official source publishes a price for hormone optimization, and the question "how much does hormone optimization cost" is best answered by listing the components a practice bills. Each line below is set by the practice, the laboratory or the pharmacy, and the compounded-preparation line is released to verified practices after NPI verification.
| Program component | Who sets it | What the guidelines attach to it |
|---|---|---|
| Initial consultation and history | The prescribing practice | Symptoms and signs consistent with deficiency are a precondition for diagnosis [1] |
| Baseline laboratory panel | The laboratory, ordered by the prescriber | Repeated fasting morning testosterone, hematocrit, PSA, TSH, DHEA-S as indicated [1, 12, 13] |
| Prescription: approved product | The prescriber; dispensed by a pharmacy | FDA-approved labeling, revised in 2025 and 2026 for menopausal products and testosterone [17, 18, 19] |
| Prescription: compounded preparation | The prescriber; compounded by a 503A pharmacy against the prescription | No FDA approval; chart note explaining why an approved product was unsuitable [5, 22] |
| Controlled-substance handling | The prescriber’s DEA registration; the dispensing pharmacy’s DEA registration | Schedule III recordkeeping; telemedicine flexibilities through 31 December 2026 [20] |
| Follow-up panel and visit | The practice and the laboratory | First reassessment 3 to 12 months after starting testosterone and annually thereafter; periodic reevaluation for menopausal therapy [1, 2] |
| Documentation of a lot and its COA | The compounding pharmacy; available on request through the supplier | A certificate of analysis exists for every lot of a compounded preparation [21] |
Building a program on verified supply and guideline-grade records
Practices that measure what the guidelines measure, document why a compounded preparation was chosen, and keep the controlled-substance records testosterone requires are building a program that holds up to any reviewer. A verified ExaVeyra account connects a practice with a 503A pharmacy partner that holds nonresident licenses in 33 jurisdictions including Puerto Rico, confirms formulary availability for the practice’s state, and supplies the COA and characterization records on request.
Anyone may ask the scientific team a question or apply without an NPI, and NPI verification, which takes 1 to 3 business days, gives access to the practitioner portal, product documentation and pricing. The hormone literature has rarely been as active as it is now, with labeling revised in 2025 and 2026 on the strength of new trials, and a program anchored to the guidelines is well placed to grow with it.
Educational Disclaimer: This article is for educational purposes only and does not constitute medical or legal advice. It does not identify any material, compound, device setting or protocol as safe, effective or appropriate for any patient, and it is not intended to diagnose, treat, cure, or prevent any disease. Questions about a treatment belong with the reader’s own licensed provider. Exosome material is supplied for topical aesthetic use by licensed practitioners. No exosome product is FDA-approved for any use, and ExaVeyra Sciences makes no statement about administration, route, or outcome. Compounded medications are not FDA-approved. They are prepared by a 503A compounding pharmacy licensed by the Texas State Board of Pharmacy for an individual patient against that patient’s prescription, and are available to NPI-verified licensed practitioners only, in the states where the pharmacy is licensed. Product, device and brand names mentioned are trademarks of their respective owners and are used only to identify the products discussed. Their mention is not an endorsement, and those owners have not reviewed or endorsed this article. ExaVeyra Sciences is a supplier and takes no part in any diagnosis, treatment decision, or plan of care. Findings described are attributed to the peer-reviewed literature, trial registries and agencies cited. The content of these guides is provided for general informational purposes only. It does not constitute legal, medical, or regulatory advice, and does not establish that any particular product or practice is compliant. Regulatory requirements vary by state and depend on the circumstances of each practice. Each practitioner should consult their own legal counsel and the applicable state licensing boards before acting on anything stated here.
References
- 1.Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. PMID 29562364. doi:10.1210/jc.2018-00229Clinical practice guideline from a 10-member task force using the GRADE approach and two commissioned systematic reviews. Carries in this article: diagnosis only in men with symptoms and unequivocally low testosterone on repeated fasting morning measurements, free testosterone by equilibrium dialysis or a validated formula when total testosterone is borderline or SHBG is altered, the contraindications (including elevated hematocrit, a PSA above 4 ng/mL, and planned fertility), the aim of mid-normal concentrations, and the standardized monitoring plan of symptoms, serum testosterone, hematocrit and prostate cancer risk during the first year. Funded by the Endocrine Society.
- 2.The 2022 Hormone Therapy Position Statement of The North American Menopause Society Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767-794. PMID 35797481. doi:10.1097/GME.0000000000002028Society position statement by an advisory panel of clinicians and researchers using level-of-evidence grading, approved by the NAMS Board of Trustees. Carries in this article: hormone therapy risks differ by type, dose, duration, route, timing of initiation and progestogen use; the favorable benefit-risk ratio for women younger than 60 or within 10 years of menopause onset; and the instruction to individualize and to reevaluate benefits and risks periodically, which is the follow-up principle a program documents.
- 3.Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-1751. PMID 25266247. doi:10.1089/thy.2014.0028Clinical practice guideline answering 24 questions, graded with the American College of Physicians system, with consensus on every recommendation. Carries in this article: levothyroxine as the standard of care, TSH as the laboratory endpoint for dose adequacy, and the task force’s review of levothyroxine-plus-liothyronine combinations and thyroid extracts as alternatives whose evidence it found insufficient to change the standard of care.
- 4.Jonklaas J, Bianco AC, Cappola AR, Celi FS, Fliers E, Heuer H, et al. Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document. Thyroid. 2021;31(2):156-182. PMID 33276704. doi:10.1089/thy.2020.0720Joint consensus document of the American, British and European Thyroid Associations from a November 2019 conference. Carries in this article: fourteen clinical trials have not shown a consistent benefit of combination T4 and T3 therapy, combination therapy is nonetheless widely used, and patient selection is the open research question, which is the position a program documents when it prescribes a compounded ratio.
- 5.American College of Obstetricians and Gynecologists’ Committee on Clinical Consensus-Gynecology. Compounded Bioidentical Menopausal Hormone Therapy: ACOG Clinical Consensus No. 6. Obstet Gynecol. 2023;142(5):1266-1273. PMID 37856860. doi:10.1097/AOG.0000000000005395Clinical consensus of a specialty society committee. Carries in this article: compounded menopausal hormone preparations should not be prescribed routinely when FDA-approved formulations exist, clinicians should counsel that FDA-approved therapies are recommended over compounded ones, and a patient who requests a compounded preparation should be told of the lack of FDA approval and the compounding-specific risks, which is the counseling note a program records.
- 6.Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107-117. PMID 37326322. doi:10.1056/NEJMoa2215025Multicenter randomized, double-blind, placebo-controlled noninferiority trial (TRAVERSE); 5,246 men aged 45 to 80 with hypogonadal symptoms, two fasting testosterone values below 300 ng/dL and existing or high cardiovascular risk; mean follow-up 33 months. Carries in this article: a primary cardiovascular event in 7.0 percent on testosterone and 7.3 percent on placebo (hazard ratio 0.96), with more atrial fibrillation, acute kidney injury and pulmonary embolism on testosterone. Funded by a manufacturer consortium led by AbbVie.
- 7.Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016;374(7):611-624. PMID 26886521. PMC5209754. doi:10.1056/NEJMoa1506119Seven coordinated placebo-controlled trials (the Testosterone Trials); 790 men aged 65 or older with serum testosterone below 275 ng/dL and symptoms, on testosterone or placebo gel for one year. Carries in this article: raising testosterone to the mid-normal range for young men produced a moderate benefit in sexual function, a smaller benefit in walking distance and mood, no benefit in vitality, and similar adverse event rates in the two groups, which is the measured-endpoint record a program is built on. NIH funded with manufacturer-supplied gel.
- 8.Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis Following Testosterone Therapy. Sex Med Rev. 2018;6(1):77-85. PMID 28526632. PMC5690890. doi:10.1016/j.sxmr.2017.04.001Literature review. Carries in this article: erythrocytosis is the best established adverse effect of exogenous testosterone, with short-acting injectable formulations carrying the highest incidence, which is why hematocrit is the first follow-up laboratory value a testosterone program records.
- 9.Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, et al. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe. J Clin Endocrinol Metab. 2017;102(4):1161-1173. PMID 28324103. PMC5460736. doi:10.1210/jc.2016-2935Cross-calibration study of 9,054 community-dwelling men in four cohorts against a CDC reference method. Carries in this article: the harmonized 2.5th to 97.5th percentile range of 264 to 916 ng/dL for total testosterone in healthy nonobese men aged 19 to 39, the reference range a program’s baseline laboratory value is read against.
- 10.Elraiyah T, Sonbol MB, Wang Z, Khairalseed T, Asi N, Undavalli C, et al. Clinical review: The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(10):3536-3542. PMID 25279571. PMC5393492. doi:10.1210/jc.2014-2261Systematic review and meta-analysis of 23 randomized trials enrolling 1,188 postmenopausal women at moderate to high risk of bias. Carries in this article: no significant effect of systemic DHEA on sexual function, serious adverse effects, lipids, glucose, weight or bone density, with low confidence in the estimates.
- 11.Corona G, Rastrelli G, Giagulli VA, Sila A, Sforza A, Forti G, et al. Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials. J Clin Endocrinol Metab. 2013;98(9):3615-3626. PMID 23824417. doi:10.1210/jc.2013-1358Meta-analysis of 25 double-blind placebo-controlled trials enrolling 1,353 older men, mean follow-up 36 weeks. Carries in this article: a small reduction in fat mass that disappeared after adjustment for the rise in testosterone and estradiol, and no effect on lipids, glucose, bone, sexual function or quality of life.
- 12.Biondi B, Cappola AR, Cooper DS. Subclinical Hypothyroidism: A Review. JAMA. 2019;322(2):153-160. PMID 31287527. doi:10.1001/jama.2019.9052Clinical review in a general medical journal. Carries in this article: subclinical hypothyroidism is defined biochemically by an elevated TSH with a normal free thyroxine, which is the laboratory definition a program uses when it records thyroid status, and the review’s emphasis on repeat measurement before any decision.
- 13.Vaidya A, Findling J, Bancos I. Adrenal Insufficiency in Adults: A Review. JAMA. 2025;334(8):714-725. PMID 40522647. doi:10.1001/jama.2025.5485Clinical review in a general medical journal. Carries in this article: DHEA and its sulfate as adrenal products measured in the evaluation of adrenal function, which is the context in which a DHEA-S value on a baseline panel is interpreted.
- 14.Labrie F. Intracrinology and menopause: the science describing the cell-specific intracellular formation of estrogens and androgens from DHEA and their strictly local action and inactivation in peripheral tissues. Menopause. 2019;26(2):220-224. PMID 30130283. doi:10.1097/GME.0000000000001177Narrative review by the author who coined the term intracrinology. Carries in this article: DHEA is converted inside peripheral tissues into androgens and estrogens that act and are inactivated locally, so a serum DHEA-S value and tissue exposure are loosely coupled. The author founded EndoCeutics, which developed a DHEA product.
- 15.U.S. Food and Drug Administration. National Academies of Science, Engineering, and Medicine (NASEM) Study on the Clinical Utility of Treating Patients with Compounded “Bioidentical” Hormone Therapy. Content current as of 2 July 2019. https://www.fda.gov/drugs/human-drug-compounding/national-academies-science-engineering-and-medicine-nasem-study-clinical-utility-treating-patients. Verified 4 November 2026.Agency web page, read 4 November 2026. Carries in this article: FDA asked NASEM in September 2018 for an independent assessment of compounded bioidentical hormone preparations such as estradiol, estrone, DHEA and testosterone; NASEM delivered its analysis on 1 July 2020, found the safety and effectiveness information came mostly from low quality data such as anecdotal claims, patient reports and prescriber testimonies, noted limited federal and state oversight, and concluded that widespread use poses a public health concern.
- 16.National Academies of Sciences, Engineering, and Medicine. The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use. Washington, DC: National Academies Press; 2020. PMID 33048485. doi:10.17226/25791Consensus report of an ad hoc committee convened at FDA’s request, 336 pages, released 1 July 2020. Carries in this article: the committee’s charge to describe the active and inactive ingredients, dosage forms, routes and strengths of compounded hormone preparations and to assess the evidence for their safety and effectiveness, and its conclusion that their widespread use is a public health concern. Funded by FDA.
- 17.U.S. Food and Drug Administration. HHS Advances Women’s Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy. Press announcement, 10 November 2025. https://www.fda.gov/news-events/press-announcements/hhs-advances-womens-health-removes-misleading-fda-warnings-hormone-replacement-therapy. Verified 4 November 2026.Agency press announcement, read 4 November 2026. Carries in this article: FDA initiated removal of the boxed warning language on cardiovascular disease, breast cancer and probable dementia from menopausal hormone therapy products after a literature review, a July 2025 expert panel and a public comment period, and did not seek to remove the boxed warning for endometrial cancer on systemic estrogen-alone products.
- 18.U.S. Food and Drug Administration. FDA Approves Labeling Changes to Menopausal Hormone Therapy Products. Press announcement, 12 February 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-labeling-changes-menopausal-hormone-therapy-products. Verified 4 November 2026.Agency press announcement, read 4 November 2026. Carries in this article: FDA approved labeling changes to six menopausal hormone therapy products removing the cardiovascular, breast cancer and probable dementia statements from the boxed warning, with 29 companies having submitted proposed changes, and the fact that these changes apply to FDA-approved labeling, labeling that a compounded preparation lacks.
- 19.U.S. Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products. Drug Alerts and Statements, 28 February 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-issues-class-wide-labeling-changes-testosterone-products. Verified 4 November 2026.Agency statement, read 4 November 2026. Carries in this article: testosterone is approved solely for men who lack or have low testosterone in conjunction with an associated medical condition; FDA is adding TRAVERSE to all testosterone labels, removing the boxed cardiovascular language, retaining the limitation-of-use language for age-related hypogonadism and adding a blood pressure warning.
- 20.Controlled substance status and telemedicine prescribing of testosterone, verified 4 November 2026: 21 CFR 1308.13(f)(84), Schedule III anabolic steroids, https://www.ecfr.gov/current/title-21/chapter-II/part-1308/section-1308.13; FDA-approved labeling for testosterone cypionate injection, USP CIII, https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/085635s040lbl.pdf; Drug Enforcement Administration and Department of Health and Human Services, Fourth Temporary Extension of COVID-19 Telemedicine Flexibilities for Prescription of Controlled Medications, 90 FR 61301 (31 December 2025), effective 1 January 2026 through 31 December 2026, https://www.federalregister.gov/documents/2025/12/31/2025-24123/fourth-temporary-extension-of-covid-19-telemedicine-flexibilities-for-prescription-of-controlledThree federal records read together on 4 November 2026. Carries in this article: testosterone is listed by name among the Schedule III anabolic steroids, approved testosterone labeling carries the CIII designation, and the DEA and HHS fourth temporary extension keeps the telemedicine flexibilities for prescribing controlled medications in force through 31 December 2026, after which a prescriber relies on whatever rule DEA has published.
- 21.U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. Content current as of 14 May 2026. https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act. Verified 4 November 2026.Agency web page, read 4 November 2026. Carries in this article: the three routes by which a bulk substance qualifies for 503A compounding (an applicable USP or NF monograph, a component of an FDA-approved drug, or the 503A bulks list), the certificate of analysis and FDA-registered manufacturer requirements, and the reason estradiol, progesterone, DHEA, levothyroxine and liothyronine qualify.
- 22.U.S. Food and Drug Administration. Compounding and the FDA: Questions and Answers. Content current as of 16 September 2025. https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers. Verified 4 November 2026.Agency questions and answers page, read 4 November 2026. Carries in this article: compounded drugs are not FDA-approved, FDA does not verify their safety, effectiveness or quality before they are marketed, and they should only be used in patients whose medical needs cannot be met by an FDA-approved drug.
- 23.U.S. Food and Drug Administration. Compounding Laws and Policies. Content current as of 17 December 2024. https://www.fda.gov/drugs/human-drug-compounding/compounding-laws-and-policies. Verified 4 November 2026.Agency web page, read 4 November 2026. Carries in this article: the conditions of section 503A, including the valid patient-specific prescription, and the description of 503B outsourcing facilities, which follow current good manufacturing practice and may fill orders that are not patient-specific, the distinction that decides whether a program can hold stock.
- 24.Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR; Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86(2):724-731. PMID 11158037. doi:10.1210/jcem.86.2.7219Longitudinal cohort analysis of healthy men in the Baltimore Longitudinal Study of Aging. Carries in this article: total and free testosterone decline with age in healthy men, the observation behind the age-related hypogonadism category for which FDA retains a limitation of use on testosterone labels, and the reason a program distinguishes age-related decline from the symptomatic, repeatedly confirmed deficiency the guideline defines.