Peptides and hormones overlap: a peptide is a short chain of amino acids, a hormone is any molecule a gland releases to signal at a distance, and insulin, oxytocin and GLP-1 are both at once. US law draws the line by size, since FDA defines a protein as any amino acid polymer longer than 40 residues, so a 40-residue chain is a drug and a 41-residue chain is a biologic [20]. More than 80 peptide drugs have reached the market since insulin, and most of the compounds a clinic menu calls peptides are analogs of hormones or of the releasing factors that control them [3].
A practitioner comparing a peptide program with a hormone program needs three things in view: the chemistry that separates peptide hormones, steroid hormones and secretagogues, the current US regulatory status of the common examples, and the feedback-axis distinction that matters most in practice, since a secretagogue works upstream of the gland while an exogenous hormone works downstream and suppresses the axis that made it [1, 7]. Each is laid out below for practitioners, and for patients who want the two words defined before a consultation. ExaVeyra writes as a supplier, and the prescriber decides what fits a patient.
Regulatory status
In the United States the two classes travel different routes. Testosterone, estradiol, progesterone, levothyroxine and liothyronine are active ingredients of FDA-approved drugs, and testosterone is also a Schedule III controlled substance [24, 25]. Insulin and growth hormone are licensed biologics that no 503A pharmacy may compound [21]. Most peptides sold as peptides, among them BPC-157, CJC-1295, ipamorelin and kisspeptin-10, are approved for nothing and appear on FDA’s category 2 or withdrawn-nomination tables [23]. On 30 October 2026 HHS published a draft enforcement discretion policy for six peptide bulk substances, BPC-157 among them, interim until rulemaking and stated to be not binding on HHS or the public [29]. Compounded hormone preparations 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.
Peptides and hormones are overlapping chemical categories
The word peptide describes structure. Amino acids joined by amide bonds form a chain, and the conventional usage in the drug discovery literature reserves peptide for short chains and protein for long ones, with the boundary set by convention [4]. Wang and colleagues reviewed the field in 2022 and noted that both chemical synthesis and recombinant production now make peptides at scale [4].
The word hormone describes function. A hormone is secreted by one tissue and acts on another through a receptor, whatever its chemistry, and the endocrine system uses three chemical families for the job: peptides and proteins, steroids built from cholesterol, and small amino acid derivatives such as the thyroid hormones [16]. Insulin is a peptide and a hormone; testosterone is a hormone and no peptide at all [16].
Muttenthaler and colleagues traced the peptide drug field back to insulin and recorded that its early decades focused almost entirely on human hormones, which is why so many approved peptide drugs are hormone analogs [3]. Lau and Dunn counted over 60 approved peptide drugs and over 150 in active clinical development in 2018, a pipeline that has since grown [5].
Chain length determines the regulatory pathway a molecule follows
FDA settled the size question by rule. Its final rule defining the term biological product, effective 23 March 2020, states that a protein is any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size [20]. A chain of 40 or fewer residues is regulated as a drug under the Food, Drug, and Cosmetic Act, and anything longer is a biologic licensed under the Public Health Service Act [20].
That line moved several hormones. Insulin, human growth hormone and the reproductive hormones had historically been approved as drugs, and on 23 March 2020 their approvals became biologics licenses [20]. FDA told compounders in advance that from that date the transitioning products would no longer be eligible for the compounding exemptions in sections 503A and 503B [21].
The practical result is a three-way split. Growth hormone, at 191 residues, and insulin, at 51 residues across two chains, are biologics that only a licensed manufacturer supplies [13, 15, 20]. Sermorelin at 29 residues, kisspeptin-10 at 10 and oxytocin at 9 are drugs by size, and their availability then depends on whether an approved product exists or a 503A route applies [7, 14, 22].
| Molecule | Chemical class and size | US regulatory status (verified 4 November 2026) |
|---|---|---|
| Insulin | Peptide hormone, 51 amino acids in two chains | Licensed biologic since the 23 March 2020 transition; outside the 503A compounding exemptions [20, 21] |
| Human growth hormone (somatropin) | Protein hormone, 191 amino acids | Licensed biologic since 23 March 2020; recombinant products approved since 1985; outside the 503A exemptions [13, 20, 21] |
| GLP-1 receptor agonists (semaglutide, liraglutide) | Peptide hormone analogs of about 30 to 40 residues | FDA-approved drugs acting through a single G protein-coupled receptor [6] |
| Oxytocin | Peptide hormone, 9 amino acids | Active ingredient of an approved injectable; one receptor carries all of its actions [14] |
| Sermorelin | GHRH(1-29) analog, 29 amino acids; a secretagogue | Approved product (Geref) discontinued; compounded under 503A where the pharmacy confirms the route [7, 28] |
| CJC-1295, ipamorelin, BPC-157, kisspeptin-10 | Synthetic peptides of 5 to 30 residues | No approved product; listed on FDA’s category 2 or withdrawn-nomination tables [23] |
| Testosterone | Steroid hormone from cholesterol, 19 carbons | Approved drug; Schedule III controlled substance; labeling updated after TRAVERSE [16, 24, 25] |
| Estradiol and progesterone | Steroid hormones from cholesterol | Approved drugs in several forms; also compounded under 503A against a prescription [10, 22] |
| DHEA | Precursor steroid converted in peripheral tissue | Compounded under 503A; two meta-analyses report a thin outcome record [11, 12, 17] |
| Levothyroxine and liothyronine (T4 and T3) | Iodinated tyrosine derivatives | Approved drugs; combination ratios compounded under 503A against a prescription [22] |
Peptide hormones and steroid hormones signal through different receptors
Peptide hormones are water soluble and cannot cross a cell membrane, so they act at receptors on the cell surface. GLP-1 and oxytocin each work through a single G protein-coupled receptor, and the whole range of their effects, from insulin release to uterine contraction, follows from the signaling cascades that one receptor starts [6, 14].
Steroid hormones are built from cholesterol by a shared set of enzymes, beginning with the rate-limiting conversion of cholesterol to pregnenolone by CYP11A1, and the same pathway runs in the adrenal, the ovary and the testis with tissue-specific variations [16]. Because they are lipid soluble they pass through membranes and bind receptors inside the cell that act as transcription factors.
DHEA shows how loosely a serum value and a tissue effect can be linked. Labrie described the conversion of DHEA into androgens and estrogens inside peripheral cells, with the products inactivated locally, so that two tissues exposed to the same circulating DHEA receive different steroid signals [17]. That chemistry is why DHEA is listed as a precursor steroid [17].
Secretagogues act upstream of the gland while exogenous hormones act downstream
The distinction that matters most in a clinic is where a molecule enters the axis. A growth hormone secretagogue such as sermorelin imitates GHRH, or such as ipamorelin acts at the ghrelin receptor, and either way the pituitary releases its own GH in pulses that the body’s feedback loops still govern [7]. The gland keeps working, and IGF-1 rises only as far as the pituitary allows [7].
An exogenous hormone enters below the gland. The Endocrine Society guideline recommends against starting testosterone in men who plan fertility in the near term because the exogenous steroid suppresses the gonadotropins that drive the testis [1]. Hochu and colleagues reviewed the same physiology in 2025: conventional testosterone restores the serum value while LH and FSH fall, and spermatogenesis falls with them [9].
The two axes also talk to each other. Dias and colleagues randomized 37 older men to transdermal testosterone, an aromatase inhibitor or placebo and found that testosterone increased GH pulse frequency, while the IGF-1 rise at 6 months depended on aromatization to estradiol [8]. A steroid hormone therefore changes the baseline against which a peptide secretagogue is later measured [8].
The guideline and the axis reviews place a secretagogue upstream of the gland and an exogenous hormone downstream. Every monitoring plan in the guidelines follows from which of the two a prescriber has chosen.
The two classes have been studied to very different depths
The question "are peptides safer than hormones" has no single answer, because the two classes have been studied to very different depths. The gaps below are specific, and each is a question a controlled trial could settle.
- No randomized outcome trial of a compounded growth hormone secretagogue exists; the located human data, such as Sigalos 2017, are retrospective, measure IGF-1 as a surrogate and lack a control group [19].
- Dominikowski 2026 reported no long-term safety data for sermorelin or the other compounded secretagogues, and no current approval for body-composition goals [7].
- TRAVERSE answered the cardiovascular question for testosterone gel in men at high cardiovascular risk with a mean follow-up of 33 months, and reported more atrial fibrillation, acute kidney injury and pulmonary embolism in the testosterone group; whether those signals apply to other formulations and lower-risk men is unmeasured [2].
- Two meta-analyses of DHEA, covering 1,188 women and 1,353 men, found no effect on sexual function, lipids, glucose or bone, with low confidence in the estimates, so the precursor steroid has neither a clear benefit nor a clear harm on record [11, 12].
- FDA’s safety-risk entries for BPC-157 and kisspeptin-10 state that the agency has no, or only limited, safety-related information for the proposed routes, an absence of data that supports no safety finding, and the CJC-1295 entry records serious adverse events including increased heart rate and systemic vasodilatory reaction [23].
- The National Academies found the information on compounded hormone preparations came mostly from low quality data such as anecdotal claims and prescriber testimony, so compounded and approved versions of the same steroid cannot be assumed equivalent [26, 27].
Published trials report different safety profiles for each class
For the steroid hormones the record is deep. TRAVERSE enrolled 5,246 men aged 45 to 80 with hypogonadal symptoms and cardiovascular risk and found a primary cardiovascular event in 7.0 percent of the testosterone group and 7.3 percent of the placebo group, meeting its noninferiority margin [2]. FDA then updated every testosterone label, removing the boxed cardiovascular language and adding a blood pressure warning [24].
Erythrocytosis is the adverse effect the testosterone literature documents best, with short-acting injectable formulations carrying the highest incidence [18]. That is why the Endocrine Society’s monitoring plan measures hematocrit alongside serum testosterone and prostate cancer risk during the first year [1].
For menopausal hormone therapy the 2022 position statement describes risks that differ by type, dose, duration, route, timing of initiation and progestogen use, with a favorable benefit-risk ratio for women younger than 60 or within 10 years of menopause onset [10]. For the compounded secretagogues no comparable dataset exists, so "safer" cannot be read from the literature in either direction [7, 19].
Peptides and TRT differ in mechanism, evidence and controlled-substance status
The phrase "peptides vs TRT" usually compares a secretagogue program with exogenous testosterone. Mechanistically one acts on the GH axis upstream of the pituitary and the other replaces a gonadal steroid downstream, so they are not alternatives for the same endpoint; a secretagogue raises IGF-1, and testosterone raises testosterone [7, 8].
Regulatory status separates them further. Testosterone is listed by name among the Schedule III anabolic steroids at 21 CFR 1308.13, FDA-approved testosterone labeling carries the CIII designation, and the DEA telemedicine flexibilities that permit remote prescribing of controlled medications run through 31 December 2026 under the fourth temporary extension [25]. Sermorelin carries no schedule, and its compounding rests on a 503A route the pharmacy confirms in writing [22, 28].
Evidence separates them most of all. Testosterone has guideline-grade diagnostic criteria, repeated fasting morning measurements and a monitoring schedule [1]. The compounded secretagogues have a retrospective series of 14 men and a set of reviews that call for trials [7, 19].
Documenting the supply route for each class
A 503A pharmacy may compound with a bulk substance only when it complies with an applicable USP or NF monograph, is a component of an FDA-approved drug, or appears on FDA’s 503A bulks list [22]. Estradiol, progesterone, DHEA, levothyroxine and liothyronine clear that test through approved products, which is why compounded hormone formulations are the largest group in a 503A formulary [22].
Insulin and growth hormone fall outside the route entirely because they are biologics [21]. Peptides on the category 2 or withdrawn-nomination tables have no qualifying route, and the HHS draft enforcement discretion policy of 30 October 2026 changes enforcement intent for six of them and leaves their approval status unchanged [29]. Non-catalog peptides such as BPC-157, CJC-1295 and ipamorelin are offered for IND-authorized clinical trials through our pharmacy partner, with the sponsor’s IND number, sponsor details and protocol confirmed before any supply [23].
- Hormone optimization formulations (estradiol, progesterone, Bi-Est, DHEA, T4/T3) are compounded by our 503A pharmacy partner against a patient-specific prescription.
- Where a controlled substance such as testosterone is prescribed, our 503A pharmacy partner dispenses it under its own DEA registration.
- Sermorelin is compounded by our 503A pharmacy partner against a patient-specific prescription, with the qualifying 503A route stated in writing.
- Non-catalog peptides are offered for IND-authorized clinical trials through our pharmacy partner, with the sponsor’s IND number, sponsor details and protocol confirmed before any supply.
- A certificate of analysis exists for every lot, and the COA and characterization records are available on request.
Building a program on verified supply and clear documentation
Practices that keep the two classes distinct in their charts, their consent forms and their marketing are on firm ground, because the chemistry, the evidence and the regulatory route differ at every step. 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 peptide and hormone literature is growing quickly, and a practice that reads it with the axis diagram in mind is well placed to offer both classes responsibly.
Aviso Educativo: 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.
Referencias
- 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 task force of 10 content experts and a methodologist, developed with the GRADE approach and two commissioned systematic reviews. Carries in this article: the recommendation to diagnose only on symptoms plus repeated fasting morning total testosterone, the recommendation against starting testosterone in men planning fertility in the near term (exogenous androgen suppresses the gonadal axis), and the standardized monitoring plan of symptoms, serum testosterone, hematocrit and prostate cancer risk in the first year. The Endocrine Society funded the guideline; author disclosures are listed in the publication.
- 2.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, followed for a mean of 33 months. Carries in this article: a primary cardiovascular event in 7.0 percent of the testosterone group and 7.3 percent of the placebo group (hazard ratio 0.96), with a higher incidence of atrial fibrillation, acute kidney injury and pulmonary embolism in the testosterone group. Funded by a consortium of testosterone manufacturers led by AbbVie, as the publication states.
- 3.Muttenthaler M, King GF, Adams DJ, Alewood PF. Trends in peptide drug discovery. Nat Rev Drug Discov. 2021;20(4):309-325. PMID 33536635. doi:10.1038/s41573-020-00135-8Perspective review from academic peptide chemistry groups. Carries in this article: more than 80 peptide drugs have reached the market since insulin, the early focus of the field on human hormones, and the medicinal chemistry strategies that extend a peptide’s half-life. The authors declared no competing interests.
- 4.Wang L, Wang N, Zhang W, Cheng X, Yan Z, Shao G, et al. Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther. 2022;7(1):48. PMID 35165272. PMC8844085. doi:10.1038/s41392-022-00904-4Narrative review of peptide drug discovery, production and modification. Carries in this article: the conventional working definition of a peptide drug as a short chain of amino acids, the chemical and recombinant routes by which peptides are made, and the stability and delivery limits that modification addresses. One author is an editorial board member of the journal; the others declared no competing interests.
- 5.Lau JL, Dunn MK. Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg Med Chem. 2018;26(10):2700-2707. PMID 28720325. doi:10.1016/j.bmc.2017.06.052Landscape review built on a proprietary dataset of peptides that entered human clinical studies. Carries in this article: over 60 peptide drugs approved in the United States and other major markets at the time of writing, over 150 in active clinical development, and the field’s origin in insulin in the 1920s. Both authors were employed by Ferring Research Institute.
- 6.Drucker DJ. GLP-1 physiology informs the pharmacotherapy of obesity. Mol Metab. 2022;57:101351. PMID 34626851. PMC8859548. doi:10.1016/j.molmet.2021.101351Narrative review by a GLP-1 physiologist. Carries in this article: GLP-1 receptor agonists as peptide drugs that act through a single G protein-coupled receptor to augment glucose-dependent insulin release, reduce glucagon, slow gastric emptying and reduce food intake, which is the example of a peptide hormone analog with FDA-approved products. The author disclosed consulting and research support from several GLP-1 developers, listed in the publication.
- 7.Dominikowski A, Rękoś Z, Olejarz M, Szczepanek-Parulska E, Domin R, Ruchała M. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration. Front Endocrinol (Lausanne). 2026;17:1822475. PMID 42395176. PMC13322892. doi:10.3389/fendo.2026.1822475Narrative review from an academic endocrinology department, read in full text. Carries in this article: the secretagogue mechanism (a GHRH analog or a ghrelin receptor agonist raises the pituitary’s own pulsatile GH output), sermorelin as the GHRH(1-29) analog whose approved product was withdrawn, and the absence of long-term safety data for the compounded secretagogues. The authors declared no commercial conflicts.
- 8.Dias JP, Veldhuis JD, Carlson O, Shardell M, Chia CW, Melvin D, et al. Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone. Metabolism. 2017;69:143-147. PMID 28285644. PMC5950718. doi:10.1016/j.metabol.2017.01.025Randomized controlled proof-of-concept trial at the National Institute on Aging; 37 men aged 65 or older with total testosterone below 350 ng/dL, randomized to transdermal testosterone, an aromatase inhibitor or placebo for 12 months. Carries in this article: testosterone increased GH pulse frequency, and the IGF-1 rise at 6 months depended on aromatization to estradiol, which is the evidence that a steroid hormone changes the output of a peptide hormone axis. The authors declared no conflicts.
- 9.Hochu G, Geyer-Kim I, Kim E. Preserving spermatogenesis in testosterone deficiency: innovations in replacement and stimulatory therapies. Transl Androl Urol. 2025;14(12):3975-3987. PMID 41522318. PMC12779434. doi:10.21037/tau-2025-480Narrative review from an academic urology group updating the authors’ 2013 publication. Carries in this article: conventional exogenous testosterone restores serum testosterone but suppresses LH and FSH, which impairs spermatogenesis, while gonadotropin support (hCG) and enclomiphene act at other nodes of the same axis. The note on disclosures in the publication records none.
- 10.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 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 call for periodic reevaluation. Panel disclosures are listed in the publication.
- 11.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 controlled trials enrolling 1,188 postmenopausal women, judged 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. Commissioned to inform an Endocrine Society guideline.
- 12.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 with a mean follow-up of 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, which places DHEA as a precursor steroid with a thin outcome record.
- 13.Ranke MB, Wit JM. Growth hormone - past, present and future. Nat Rev Endocrinol. 2018;14(5):285-300. PMID 29546874. doi:10.1038/nrendo.2018.22Historical and clinical review. Carries in this article: pituitary-derived human GH was used from 1958 to 1985 and recombinant human GH since, GH acts in conjunction with the insulin-like growth factors, and safety concerns still accompany GH treatment in the authors’ words, which supports the article’s placement of GH as a protein hormone with licensed products and a monitored axis.
- 14.Jurek B, Neumann ID. The Oxytocin Receptor: From Intracellular Signaling to Behavior. Physiol Rev. 2018;98(3):1805-1908. PMID 29897293. doi:10.1152/physrev.00031.2017Comprehensive physiology review. Carries in this article: oxytocin as a short peptide hormone whose many actions, from milk let-down and uterine contraction to social behavior, run through a single G protein-coupled receptor, the example of a nine-residue peptide hormone with an approved injectable product.
- 15.Sims EK, Carr ALJ, Oram RA, DiMeglio LA, Evans-Molina C. 100 years of insulin: celebrating the past, present and future of diabetes therapy. Nat Med. 2021;27(7):1154-1164. PMID 34267380. PMC8802620. doi:10.1038/s41591-021-01418-2Centenary review. Carries in this article: insulin as the first peptide hormone brought into medicine, in the 1920s, and the century of analog development that followed, which is the example the article uses for a peptide hormone that is also a protein biologic under current US law.
- 16.Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32(1):81-151. PMID 21051590. PMC3365799. doi:10.1210/er.2010-0013Comprehensive review. Carries in this article: every steroid hormone is made from cholesterol through a shared set of cytochrome P450 enzymes and hydroxysteroid dehydrogenases, beginning with the rate-limiting conversion of cholesterol to pregnenolone by CYP11A1, which is the chemical definition the article uses to separate steroid hormones from peptides.
- 17.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 as a precursor steroid converted inside peripheral tissues into androgens and estrogens, so that serum values and tissue exposure are loosely coupled. The author founded EndoCeutics, which developed a DHEA product.
- 18.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 a monitoring endpoint for the steroid hormone class and has no counterpart in the secretagogue literature.
- 19.Sigalos JT, Pastuszak AW, Allison A, Ohlander SJ, Herati A, Lindgren MC, et al. Growth Hormone Secretagogue Treatment in Hypogonadal Men Raises Serum Insulin-Like Growth Factor-1 Levels. Am J Mens Health. 2017;11(6):1752-1757. PMID 28830317. PMC5675260. doi:10.1177/1557988317718662Retrospective chart review at an academic center; 105 records reviewed, 14 men met inclusion. Carries in this article: the located human data on compounded secretagogues measure IGF-1, a surrogate marker, without a control group, which is the evidence base the article contrasts with the randomized record for testosterone. The authors declared no conflicts.
- 20.U.S. Food and Drug Administration. Definition of the Term “Biological Product”; final rule. 85 FR 10057 (21 February 2020), effective 23 March 2020. https://www.federalregister.gov/documents/2020/02/21/2020-03505/definition-of-the-term-biological-product. Agency summary of the transition: https://www.fda.gov/drugs/guidance-compliance-regulatory-information/deemed-be-license-provision-bpci-act (content current as of 9 February 2024). Both verified 4 November 2026.Final rule and the agency’s transition page, read 4 November 2026. Carries in this article: the term protein means any alpha amino acid polymer with a specific, defined sequence greater than 40 amino acids in size, so a chain of 40 or fewer is regulated as a drug and a longer chain as a biologic, and the statement that insulin, human growth hormone and reproductive hormones historically approved as drugs transitioned to biologics licenses on 23 March 2020.
- 21.U.S. Food and Drug Administration. Notice to Compounders: Changes that affect compounding as of March 23, 2020. Content current as of 5 March 2020. https://www.fda.gov/drugs/human-drug-compounding/notice-compounders-changes-affect-compounding-march-23-2020. Verified 4 November 2026.Agency notice, read 4 November 2026. Carries in this article: from 23 March 2020 the transitioning biological products are not eligible for the exemptions for compounded drugs under sections 503A and 503B, which is why insulin and growth hormone sit outside the 503A route that compounded peptides and steroid hormones use.
- 22.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), which is the test that separates estradiol, progesterone, DHEA and thyroid hormone from the peptides that have no qualifying route.
- 23.U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. Content current as of 22 April 2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. Verified 4 November 2026.Agency web page with the category 2 table and the nominated-but-withdrawn table, read 4 November 2026. Carries in this article: kisspeptin-10 and ipamorelin acetate appear in the category 2 table (added 29 September 2023), BPC-157 and CJC-1295 appear in the nominated-but-withdrawn table, and FDA’s stated concern for each is immunogenicity, peptide-related impurities and limited safety information.
- 24.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, the TRAVERSE results are being added to all testosterone labels, the boxed warning language on cardiovascular outcomes is being removed, the limitation-of-use language for age-related hypogonadism is retained, and a blood pressure warning is being added.
- 25.Controlled substance status 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, FDA-approved testosterone labeling carries the CIII designation, and the telemedicine flexibilities for prescribing controlled medications run through 31 December 2026 under the fourth temporary extension, after which a prescriber relies on whatever rule DEA has published.
- 26.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, NASEM delivered its analysis of compounded estradiol, estrone, DHEA and testosterone on 1 July 2020, and NASEM found the safety and effectiveness information came mostly from low quality data and concluded that widespread use poses a public health concern.
- 27.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 report’s charge to describe the physical and chemical characteristics of compounded hormone preparations and assess the evidence for their safety and effectiveness, and its framing of their widespread use as a public health concern. Funded by FDA.
- 28.U.S. Food and Drug Administration. Drugs@FDA record for NDA 019863, GEREF (sermorelin acetate), EMD Serono: marketing status Discontinued, with the Federal Register determination that the product was not withdrawn for safety or effectiveness reasons. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019863. Verified 4 November 2026.Agency database record, read 4 November 2026. Carries in this article: sermorelin was once the active ingredient of an approved product and that product is discontinued, which is the regulatory position of the one GHRH analog the 503A route still reaches, as distinct from an approved and marketed hormone.
- 29.U.S. Department of Health and Human Services. Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances; notice of availability. 91 FR 68526-68527 (30 October 2026). Docket HHS-OASH-2026-0496. https://www.federalregister.gov/documents/2026/10/30/2026-22192/enforcement-discretion-policy-regarding-503a-compounding-using-certain-peptide-bulk-drug-substances. Verified 4 November 2026.Federal Register notice, full text read through the Federal Register API on 4 November 2026. Carries in this article: HHS announced a draft policy under which it does not intend to take enforcement action against a state-licensed pharmacy, federal facility or licensed physician compounding with a peptide bulk substance listed in the policy’s Appendix A while the 503A bulks list is developed through rulemaking; the notice states that compounded drugs are not FDA-approved, that HHS may revisit the interim policy if a safety signal or quality issue arises, and that the draft establishes no rights and is not binding on HHS or the public. The policy document itself covers six peptides (BPC-157, epitalon, KPV, MOTS-c, semax and TB-500) with conditions and route limits; CJC-1295, ipamorelin and sermorelin are outside it.