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MyDeficiencies

Methyltestosterone

Androgen, 17-alpha-alkylated oral testosterone derivative

Also sold as Testred, Methitest.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Methyltestosterone is the prototype oral 17-alpha-alkylated androgen: the C17-methyl group is, by its own current FDA labeling, the specific reason the molecule survives hepatic first-pass metabolism well enough to work as a swallowed tablet at all ("17-alpha alkylation...increases the pharmacologic activity per unit weight compared to testosterone when given orally," and methyltestosterone "is less extensively metabolized by the liver and has a longer half-life. It is more suitable than testosterone for oral administration"). That same resistance to hepatic clearance is the pharmacologic basis of its much higher hepatotoxicity relative to injectable or topical testosterone, which bypass first-pass metabolism entirely. No CYP450 induction or inhibition is documented in current labeling; the only enzyme-adjacent laboratory effect described is a decrease in thyroxine-binding globulin that lowers total T4 while leaving free thyroid hormone unchanged, a laboratory-interpretation artifact rather than a nutrient effect. The real, drug-specific classical-nutrient signal is an adverse lipid effect: methyltestosterone's own label lists "increased serum cholesterol" as a metabolic adverse reaction, and it is graded here, moderately, from two independent human randomized trials that put methyltestosterone (as the androgen component of combination hormone therapy) in the studied cohort, though the magnitude of the effect on HDL specifically could not be independently confirmed in this review because several relevant abstracts sat behind bibliographic-database access limits described below, which is why this entry is graded orange rather than red. A second real, drug-specific signal is androgen-class retention of sodium, chloride, water, potassium, calcium, and phosphate, bounded to higher doses and to patients with pre-existing cardiac, renal, or hepatic disease, taken directly from the label's own adverse-reaction and warnings language.

Androgen, 17-alpha-alkylated oral testosterone derivative · ATC G03BA02 · also sold as Android and Testred and Methitest (all discontinued); currently generic methyltestosterone capsules · reviewed 2026-09-29. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Methyltestosterone in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Lipid profile / serum cholesterol, adverse effect confirmed in combination HRT trials, magnitude not independently quantified

Orange — Moderate

Evidence in: Tier A

Methyltestosterone's own label lists increased serum cholesterol as a metabolic adverse reaction, and two independent human randomized trials placed methyltestosterone in the studied cohort while measuring lipoprotein-related endpoints. The direction is consistently adverse; the exact HDL/LDL magnitude could not be confirmed from the retrievable record in this review.

Full detail, limits and 2 references

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. ORANGE · Tier A

Limits on what this shows

  • Null/negative findings: None identified contradicting the direction of effect in the titles or label language retrieved; no methyltestosterone-specific study found an HDL increase or a null lipid finding.
  • At-risk subgroups: The two identified human trials studied postmenopausal women on combination esterified-estrogen-plus-methyltestosterone hormone therapy, not men on methyltestosterone monotherapy for hypogonadism; whether the same magnitude applies to male replacement-dose regimens (10 to 50 mg daily per current labeling) was not independently confirmed in this review. Patients with pre-existing dyslipidemia or cardiovascular risk factors are a plausible at-risk group by class analogy.

Regulatory status

ADVERSE REACTIONS, Metabolic: "Increased serum cholesterol." Methyltestosterone Capsules labeling, DailyMed

Population evidence

Hickok, Toomey and Speroff 1993 (Obstet Gynecol, PMID 8233265): double-blind randomized trial, 26 postmenopausal women, comparing esterified estrogens with and without methyltestosterone over 6 months, measuring endometrial histology and serum lipoproteins. Chiuve, Martin, Campos and Sacks 2004 (J Clin Endocrinol Metab, PMID 15126543): human trial comparing the combination of methyltestosterone and esterified estrogens against esterified estrogens alone, on apolipoprotein CIII, a triglyceride-rich-lipoprotein marker. Both trials place methyltestosterone specifically, not merely "androgens" generally, in the studied cohort. Full abstract text for both could not be retrieved during this review (Semantic Scholar and Crossref access were rate-limited on repeated attempts for both PMIDs), so the exact quantitative HDL, LDL, and apoCIII findings are not independently confirmed here and are not claimed; only the label's qualitative "increased serum cholesterol" finding and the trials' existence and design, retrieved via PubMed search-listing pages, are used to support this grade.

Mechanism

Named at the class level, not independently re-confirmed for methyltestosterone in this review: 17-alpha-alkylated oral androgens are understood to increase hepatic lipase activity and reduce apolipoprotein A-I synthesis, accelerating HDL-particle catabolism. This class mechanism was documented for the related 17-alpha-alkylated androgen oxandrolone in this project's own oxandrolone dossier, citing a 1983 review of sex hormones and lipoprotein metabolism (De Gennes, Ann Endocrinol, PMID 6347027); it is plausible but not independently re-verified for methyltestosterone specifically in this review.

Counter-evidence held on record

None identified contradicting the adverse direction. The absence of a confirmed quantitative magnitude is a genuine access limitation in this review, disclosed here rather than filled in by inference or by borrowing the quantified oxandrolone-specific figure from this project's separate oxandrolone dossier, which would misattribute a different drug's measured effect to this one. This is a lipid-panel adverse effect requiring clinical monitoring, not a nutrient deficiency, and no dose of any nutrient corrects it. No supplement claim is supported by any source located in this review; the appropriate response is lipid-panel monitoring and, where relevant, a prescriber's dose or duration adjustment, never self-directed supplementation.

Sodium, chloride, water, potassium, calcium, and phosphate retention, bounded to higher doses and pre-existing cardiac, renal, or hepatic disease

Orange — Moderate

Evidence in: Tier A

Methyltestosterone's own labeling lists retention of sodium, chloride, water, potassium, phosphate, and calcium as an adverse reaction, and separately requires discontinuation if hypercalcemia develops in breast cancer patients. This is a retention effect; supplementing any of these minerals would compound risk rather than correct a deficiency.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. ORANGE · Tier A

Limits on what this shows

  • Null/negative findings: None identified specific to this drug. A dedicated modern quantitative study at standard methyltestosterone replacement doses was not located.
  • At-risk subgroups: Pre-existing congestive heart failure, renal impairment (hyperkalemia risk compounds with potassium-sparing diuretics, ACE inhibitors/ARBs, or renal failure), hepatic impairment, and women with breast cancer and skeletal metastases at risk of hypercalcemia.

Regulatory status

ADVERSE REACTIONS, Fluid and Electrolytes: "Retention of sodium, chloride, water, potassium, calcium and inorganic phosphates." WARNINGS: "Edema with or without congestive heart failure may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease." WARNINGS AND PRECAUTIONS separately states hypercalcemia may occur in breast cancer patients and discontinuation is necessary if this develops. Methyltestosterone Capsules labeling, DailyMed

Population evidence

A class-labeled effect drawn from long clinical experience with 17-alkylated androgen therapy. No modern, methyltestosterone-specific RCT quantifying magnitude at standard replacement doses was located in this review; the grade rests on regulatory-label authority (Tier A by definition), disclosed as such rather than as a quantified trial effect, consistent with how the equivalent finding was graded in this project's oxandrolone dossier.

Mechanism

Named at the class level: androgens have mineralocorticoid-adjacent activity promoting renal tubular sodium/water reabsorption, with secondary retention of potassium, calcium, and phosphate. The separate labeled hypercalcemia-discontinuation rule in breast cancer patients underscores the retention direction and its potential severity in that subgroup, plausibly related to concurrent osteolytic bone disease.

Counter-evidence held on record

None found contradicting the retention direction. The absence of a modern quantitative human trial is a genuine evidence gap, noted here rather than treated as disconfirming. This is a retention/excess risk, not a deficiency. Never supplement sodium, potassium, calcium, or phosphate on the basis of this drug. In patients with renal impairment or on potassium-elevating drugs, potassium should be monitored, not replaced, and new or worsening hypercalcemia in a breast cancer patient on this drug is a labeled reason to discontinue therapy, not a calcium-deficiency signal.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden, drug-specific animal hepatocyte ultrastructural change of unconfirmed organelle identity; no human data

Yellow — Low

Evidence in: Tier B

One methyltestosterone-specific dog study found the drug produced concentric membrane whorls in hepatocytes. Whether the affected membranes are mitochondrial or endoplasmic-reticular in origin could not be confirmed from the retrievable record, and this entry discloses that uncertainty rather than asserting a mitochondrial mechanism it cannot confirm.

Full detail, limits and 3 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. YELLOW · Tier B

Limits on what this shows

  • Null/negative findings: None identified; no human mitochondrial-structure or biogenesis study for methyltestosterone was located.
  • At-risk subgroups: Not established for methyltestosterone specifically. By analogy to the human hepatotoxicity case series, higher doses and longer treatment duration are plausible risk amplifiers.

Regulatory status

Not addressed in current labeling beyond the general hepatotoxicity warnings (peliosis hepatis, hepatocellular neoplasms, cholestatic hepatitis), which are named as drug-class outcomes, not mitochondrial findings specifically.

Population evidence

Muraoka, Yahara, Nara and Watanabe 1981, "Steroid-induced concentric membrane whorls in dog liver" (Experientia, PMID 7238820): methyltestosterone-specific animal (dog) study; the PubMed search-listing snippet describes androgenic steroids including methyltestosterone producing "concentric membrane whorls in the hepatocytes" in dogs. Full abstract text could not be retrieved in this review (individual PubMed abstract pages render via JavaScript/bot-check and returned only page metadata; Semantic Scholar access returned HTTP 429 on every attempt), so the specific organelle identified (mitochondrial cristae, smooth endoplasmic reticulum, or another membrane system) is not confirmed beyond "membrane whorls" as stated in the snippet, and this limitation is disclosed rather than filled in by inference. Adjacent human evidence exists but is better characterized as a general hepatocellular/vascular architecture finding than a mitochondrial one: Paradinas, Bull, Westaby and Murray-Lyon 1977, "Hyperplasia and prolapse of hepatocytes into hepatic veins during longterm methyltestosterone therapy" (Histopathology, PMID 615837), a case series of 10 patients treated with 150 mg methyltestosterone daily for up to 3 years, examining possible relationships of these changes to the development of peliosis hepatis and liver tumors; this is cited here as hepatotoxicity context in the headline finding and is not counted as mitochondrial-specific evidence, consistent with this protocol's rule against forcing a finding into a category it does not clearly support.

Mechanism

Not established at the human level. The class-level mechanism for 17-alpha-alkylated steroid hepatotoxicity is generally understood to involve bile-transporter and nuclear-receptor-mediated cholestasis and smooth-endoplasmic-reticulum changes rather than primary mitochondrial injury, based on class-level context documented for a related steroid in this project's oxandrolone dossier (Petrov et al. 2020, Arch Toxicol, PMID 31894354, studying epistane); whether the Muraoka dog-liver membrane whorls reflect this same endoplasmic-reticular mechanism, a mitochondrial one, or both, is not established in the retrievable record.

Counter-evidence held on record

None identified specific to this drug. The genuine uncertainty here is about organelle identity, not about whether a real, drug-specific hepatocellular ultrastructural change occurred; the animal finding itself is not disputed in the sources located. This is animal-only evidence of uncertain organelle identity. It is not a basis for a confirmed human mitochondrial-harm claim, and it is not a basis for a mitochondrial-support supplement claim.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress, drug-specific animal liver study; direction not independently confirmed, no human data

Yellow — Low

Evidence in: Tier B

One 17-alpha-methyltestosterone-specific aquaculture study examined liver oxidation stress in juvenile tilapia. The specific direction and magnitude of the effect could not be independently confirmed from the retrievable record in this review. No human oxidative-stress marker data for methyltestosterone were identified.

Full detail, limits and 2 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. YELLOW · Tier B

Limits on what this shows

  • Null/negative findings: None identified; no human oxidative-stress marker study for methyltestosterone was located after PubMed searches under several phrasings.
  • At-risk subgroups: Not established in humans.

Regulatory status

Not addressed in current FDA labeling.

Population evidence

Zheng, Qu, Qiu, Fan, Meng, Song, Bing and Chen 2016, "Effect of 17alpha-methyltestosterone (MT) on oxidation stress in the liver of juvenile GIFT tilapia, Oreochromis niloticus" (Springerplus, PMID 27066359): a methyltestosterone-specific animal study by title. Full abstract text could not be retrieved in this review (individual PubMed abstract pages render via JavaScript/bot-check; Semantic Scholar access returned HTTP 429 on every attempt for this PMID), so the direction (whether MT increased or decreased hepatic oxidative-stress markers) and the specific markers measured (for example malondialdehyde, superoxide dismutase, catalase, glutathione) are not confirmed beyond the title itself, and this limitation is disclosed rather than filled in by inference from the general aquaculture-toxicology literature. This study uses methyltestosterone in a non-mammalian model at doses used for aquaculture sex reversal, not at human therapeutic doses, and species and dose relevance to human use is not established.

Mechanism

Not established at the human level. No unifying redox mechanism for methyltestosterone specifically was located beyond the general observation that steroid hormones can influence peroxidative lipid oxidation in mitochondrial and other cell membranes at the class level (Sergeev et al. 1974, Vopr Med Khim, PMID 4156813, a class-level review located in this same search, not methyltestosterone-specific).

Counter-evidence held on record

None identified; the entry is limited by an access gap on direction and magnitude, disclosed here rather than assumed from the study's framing. This is non-mammalian, title-level-only evidence with an unconfirmed direction. It is not a basis for either a human oxidative-harm claim or an antioxidant-supplement claim for methyltestosterone users.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Iron, no methyltestosterone-specific evidence; class-level extrapolation from testosterone's hepcidin-suppression mechanism

Yellow — Low

See study details

No study measuring hepcidin, ferritin, or iron status in methyltestosterone users was located after a genuine multi-channel search. The androgen-class mechanism, established for testosterone, is mechanistically plausible for methyltestosterone as a fellow androgen-receptor agonist, but methyltestosterone itself was not in any studied cohort.

Full detail, limits and 4 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. YELLOW · Tier C, class extrapolation

Limits on what this shows

  • Null/negative findings: None identified for methyltestosterone specifically; this is an evidence gap rather than a negative trial.
  • At-risk subgroups: Not established for methyltestosterone. By class-level analogy: patients with borderline iron stores, higher-dose therapy.

Regulatory status

Not addressed in methyltestosterone's FDA labeling; the label does not mention iron, ferritin, hepcidin, or erythropoiesis by name, only "polycythemia" (see the Oxygen delivery/utilization entry above).

Population evidence

Zero methyltestosterone-specific results after PubMed searches for "methyltestosterone hepcidin ferritin iron," "methyltestosterone iron hepcidin," "17-methyltestosterone hepcidin," and "methyltestosterone erythropoiesis hemoglobin." One adjacent in vitro study, Singer, Samuels and Adamson 1976 (J Cell Physiol, PMID 1270518), tested unnamed "substituted steroids of several classes" for erythroid-colony structure-activity relationships; methyltestosterone's inclusion could not be confirmed from the retrievable snippet and this study is not counted toward the grade. Class-level (testosterone) evidence exists and was independently verified for this project's testosterone dossier: Bachman et al. 2010 (J Clin Endocrinol Metab, PMID 20660052, RCT, n=109) found dose-dependent hepcidin suppression within one week of testosterone dosing; Bachman et al. 2014 (J Gerontol A Biol Sci Med Sci, PMID 24158761, RCT over 6 months) and Artz et al. 2020 (J Clin Endocrinol Metab, PMID 32785689, RCT substudy, n=95) both found hepcidin and ferritin decline with testosterone therapy. Methyltestosterone was not in any of these three cohorts; this is Tier C class extrapolation for methyltestosterone, not Tier A/B drug-specific evidence.

Mechanism

Proposed at the class level only: androgen-receptor agonism suppresses hepatic hepcidin transcription, increasing iron availability for erythropoiesis. Whether methyltestosterone, a 17-alpha-alkylated, non-aromatizing-in-the-same-manner oral androgen with a distinct metabolic and hepatic-exposure profile from injectable testosterone, produces the same magnitude of hepcidin suppression is not established.

Counter-evidence held on record

The complete absence of methyltestosterone-specific iron/hepcidin literature, despite methyltestosterone's decades of clinical use in hypogonadism and breast cancer, is itself a mild counter-signal against a strong drug-specific effect distinct from the class-level testosterone finding. This is class-level plausibility only, not a demonstrated methyltestosterone effect. No iron supplementation is indicated on the basis of this entry; if anemia or unexplained fatigue is present, iron studies should be ordered and interpreted by a prescriber independent of this theoretical mechanism, and note this drug's own label instead flags an excess-direction polycythemia risk, the opposite concern from iron deficiency.

Copper, no evidence identified in either direction

Not graded — disclosed evidence gap

See study details

Copper, no evidence identified in either direction

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. UNGRADED

Limits on what this shows

  • Why no grade: Searched specifically against methyltestosterone across multiple PubMed phrasings ("methyltestosterone copper ceruloplasmin," zero results; "methyltestosterone copper," bot-check page returned rather than confirmed results; "methyltestosterone AND copper," inconclusive page render; "androgen methyltestosterone ceruloplasmin," zero results) and the Crossref REST API ("methyltestosterone copper," ten results returned, all United States Pharmacopeia monograph entries for methyltestosterone identity/purity standards, none relating methyltestosterone to copper or ceruloplasmin status). No drug-specific or class-level evidence at any tier was found for methyltestosterone or for the androgen class generally, and no circulating consumer claim pairing methyltestosterone with copper depletion or excess was found in the course of this review. Both dual conditions for UNGRADED are met: no Tier B/C evidence, and no circulating claim to rebut as white. This mirrors the same ungraded finding for testosterone and oxandrolone, the other two androgens previously reviewed in this project, independently re-searched here rather than carried forward from those dossiers.

Tooling note

The Semantic Scholar Graph API returned HTTP 429 on every attempt across this entire review and the Europe PMC REST API returned a read timeout on every attempt; neither could be used to search for copper-related literature independently of PubMed and Crossref. The OpenAlex API returned HTTP 429 on its only attempt. Unpaywall was not reached in this review. A later revision should re-query Europe PMC and OpenAlex directly for "methyltestosterone AND copper" and "17-alpha-alkylated androgen AND ceruloplasmin" before treating this as a durable conclusion rather than a possible access gap.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk, drug-specific animal evidence of intestinal microbial disruption; no human data

Yellow — Low

Evidence in: Tier B

Two 2025 studies found 17-alpha-methyltestosterone exposure disrupted intestinal microbial communities and damaged intestinal tissue in fish. These are genuine, drug-specific findings by this protocol's tiering rules, disclosed here as non-mammalian aquaculture/environmental-toxicology models, not human clinical data.

Full detail, limits and 2 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. YELLOW · Tier B

Limits on what this shows

  • Null/negative findings: None identified specific to methyltestosterone in mammals; no human or mammalian gut microbiome study for this drug was located after multiple PubMed search phrasings.
  • At-risk subgroups: Not established for methyltestosterone in humans.

Regulatory status

Not addressed in FDA labeling.

Population evidence

Liu, Wang, Han, Luo, Chu, Tang, Zhao, Han, Yin and Wang 2025, "17alpha-methyltestosterone exposure disrupted growth, liver physiology and intestinal microbial on fish: A case study on migratory bony fishes (Takifugu fasciatus)" (Mar Pollut Bull, PMID 39778389). Zhao, Li, Li, Xiong, Rong, Cao, Chen, Liu, Liu and Wang 2025, "Vitamin C alleviates intestinal damage induced by 17alpha-methyltestosterone in Carassius auratus" (Aquat Toxicol, PMID 39908712), a goldfish model in which the comparator arm (vitamin C co-administration) implies the study measured a real, measurable, methyltestosterone-induced intestinal injury that vitamin C partly mitigated. Full abstract text for both could not be retrieved in this review (Semantic Scholar access returned HTTP 429 on every attempt), so quantitative diversity or damage metrics are not independently confirmed beyond the titles, and this limitation is disclosed rather than filled in by inference. Both studies used methyltestosterone at aquaculture/environmental-exposure doses in fish, not human therapeutic doses in mammals, and species and dose relevance to human gut microbiome risk is not established.

Mechanism

Not established at the human or mammalian level. The Zhao 2025 title's vitamin C comparator suggests an oxidative-stress-mediated intestinal injury mechanism, consistent with the Oxidative stress entry above, but this is an inference from the title's design, not a confirmed mechanism, and is disclosed as such.

Counter-evidence held on record

None identified for methyltestosterone specifically. The complete absence of a human or mammalian gut-microbiome study for this drug, despite decades of clinical use, is itself a mild limitation on generalizing the fish findings to human physiology, disclosed here rather than treated as confirming a human effect. This is non-mammalian, environmental-exposure-dose evidence. It is not a basis for a human microbiome-harm claim or for a probiotic-support supplement claim in methyltestosterone users.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization, polycythemia risk, bounded to high-dose androgen therapy

Orange — Moderate

Evidence in: Tier A

Methyltestosterone's own label requires periodic hemoglobin/hematocrit monitoring for polycythemia in patients receiving high doses of androgens, and lists polycythemia directly among hematologic adverse reactions. This is a retention/excess-direction hematologic finding, not an oxygen-delivery deficiency.

Full detail, limits and 2 references

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. ORANGE · Tier A

Limits on what this shows

  • Null/negative findings: None identified specific to methyltestosterone; the absence of a modern quantitative human trial is a genuine evidence gap, disclosed here rather than treated as disconfirming.
  • At-risk subgroups: Patients on higher/prolonged doses, per the label's explicit "high doses" qualifier; by extension, obstructive sleep apnea, smokers, and baseline hematocrit near the upper-normal range are plausible risk amplifiers by analogy to other androgens, though not stated in methyltestosterone's own label.

Regulatory status

PRECAUTIONS, Laboratory Tests: "Hemoglobin and hematocrit should be checked periodically for polycythemia in patients who are receiving high doses of androgens." ADVERSE REACTIONS, Hematologic: suppression of clotting factors II, V, VII and X, bleeding, and polycythemia. Methyltestosterone Capsules labeling, DailyMed

Population evidence

The grade rests on this Tier A regulatory-label statement. A dedicated methyltestosterone-specific human trial quantifying hematocrit or hemoglobin rise was not located after multiple PubMed search phrasings ("methyltestosterone hemoglobin hematocrit polycythemia," zero results; "methyltestosterone erythropoiesis hemoglobin," no methyltestosterone-specific trial among the results returned). One adjacent in vitro study, Singer, Samuels and Adamson 1976 (J Cell Physiol, PMID 1270518), tested "substituted steroids of several classes" for erythroid-colony-stimulating structure-activity relationships in rat bone marrow culture; whether methyltestosterone specifically was among the tested compounds could not be confirmed from the retrievable title and snippet, and this study is disclosed here as suggestive class-level context only, not counted toward the grade. Basaria, Nguyen, Rosenson and Dobs 2002 (Clin Endocrinol, PMID 12153599) measured plasma viscosity, which correlates with hematocrit, in postmenopausal women given methyl testosterone; full findings could not be retrieved in this review and this study is cited as title-level supporting context only.

Mechanism

Not separately named in methyltestosterone's own label. The class-level mechanism for androgen-associated erythrocytosis, established for testosterone (erythropoietin stimulation and hepcidin suppression), is mechanistically plausible for any androgen-receptor agonist including methyltestosterone, but methyltestosterone-specific hepcidin/erythropoietin data were not located (see the separate Iron entry below, graded yellow on this same class-level basis).

Counter-evidence held on record

None identified. The finding rests on a single Tier A source (the label itself) plus unconfirmed supporting context; disclosed as a limitation rather than reinforced by an independent quantified trial. This is an excess/retention finding, not a deficiency, and is not evidence that methyltestosterone "improves oxygen delivery" as a performance claim. No supplement or dietary intervention is indicated to manage this; periodic hemoglobin/hematocrit monitoring and, if elevated, a prescriber-directed dose adjustment are the appropriate response, never iron or erythropoiesis-supporting supplementation.

ATP production, no direct measurement in any species; class-level mitochondrial-biogenesis extrapolation only

Yellow — Low

See study details

No study measuring cellular ATP synthesis or flux in methyltestosterone users, or in any animal model of methyltestosterone exposure, was located. This is graded on class-level androgen-receptor mitochondrial-biogenesis literature from testosterone only.

Full detail, limits and 2 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. YELLOW · Tier C, class extrapolation

Limits on what this shows

  • Null/negative findings: None identified; this reflects an evidence gap rather than a negative trial.
  • At-risk subgroups: None identified.

Regulatory status

Not addressed in FDA labeling.

Population evidence

No direct ATP-flux study identified for methyltestosterone after a PubMed search for "methyltestosterone ATP energy metabolism" and "methyltestosterone mitochondrial biogenesis ATP tilapia" (both zero results). The only ATP-adjacent mechanistic literature located is class-level, previously verified for this project's testosterone dossier: an androgen-receptor mitochondrial-biogenesis review (Am J Physiol Cell Physiol 2022, PMID 35704694) and a testosterone-specific mouse mitochondrial-biogenesis study (Usui et al. 2014, FEBS Lett, PMID 24726723), neither with methyltestosterone in the cohort.

Mechanism

Not established at the human level for this specific endpoint, for methyltestosterone or for the androgen class generally; the class-level review itself states the precise molecular mechanisms of androgen-receptor effects on mitochondrial bioenergetics are not yet established.

Counter-evidence held on record

None specific; the entry is limited by absence of direct data at every tier for methyltestosterone, disclosed here rather than overstated by borrowing the testosterone-specific finding as if it were drug-specific. Do not present this as evidence methyltestosterone "boosts ATP" or cellular energy production. No supplement or energy claim is supported by any source located in this review.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Methyltestosterone, as an oral "natural hormone" tablet, carries no real liver risk because it is not a synthetic designer steroid

    Where it comes from: General hormone-replacement and men's-health wellness content contrasting oral androgens favorably against injectable steroids on the assumption that "hormone" implies safety

    Why it fails: Directly contradicted by methyltestosterone's own current FDA labeling, which warns that prolonged high-dose androgen use is associated with peliosis hepatis and hepatic neoplasms including hepatocellular carcinoma, and that cholestatic hepatitis may occur at relatively low doses. A methyltestosterone-specific human case series (Paradinas et al. 1977, Histopathology, PMID 615837) documented hepatocyte hyperplasia and prolapse into hepatic veins in 10 patients on long-term methyltestosterone therapy, examined for its possible relationship to peliosis hepatis and liver tumor development. The drug's own pharmacokinetic basis for oral activity (resistance to hepatic first-pass metabolism via 17-alpha-alkylation) is the same structural feature responsible for its materially higher hepatotoxicity relative to injectable or transdermal testosterone, which bypass this exposure.

  • Methyltestosterone depletes zinc; zinc supplementation is needed to support therapy

    Where it comes from: General anabolic/androgen wellness and supplement-stacking content applying a zinc-depletion narrative broadly across testosterone-class drugs

    Why it fails: No methyltestosterone-specific or class-level trial evidence testing this direction was located in this review after PubMed and Crossref searches for "methyltestosterone zinc." As documented in this project's oxandrolone dossier for the related 17-alpha-alkylated androgen oxandrolone, the literature that does exist for androgens and zinc tests the reverse direction, zinc's effect on endogenous testosterone production, not any androgen's effect on zinc status. No source located in this review shows methyltestosterone lowers zinc.

  • Extra calcium or vitamin D is needed to support bone health while using methyltestosterone

    Where it comes from: General hormone-replacement wellness content pairing calcium/vitamin D supplementation with any androgen or estrogen-androgen regimen

    Why it fails: Contradicted by the drug's own data: methyltestosterone's label lists retention of calcium alongside sodium, chloride, potassium, and phosphate as an adverse reaction, and separately requires discontinuation of therapy if hypercalcemia develops in breast cancer patients. Calcium or vitamin D supplementation on this basis would compound a labeled excess-direction risk in at-risk patients, not correct a deficiency. Separately, a human RCT (Raisz et al. 1996, J Clin Endocrinol Metab, PMID 8550780) measured bone formation and resorption markers under combination esterified-estrogen-plus-methyltestosterone therapy against estrogen alone; this study describes bone marker changes under combination hormone therapy, not a vitamin D or calcium deficiency caused by methyltestosterone, and its specific quantitative findings could not be retrieved in this review, so it is not used to support any graded entry.

All references used above
  1. METHYLTESTOSTERONE capsule, USP prescribing information (ANI Pharmaceuticals, Inc.). — FDA-approved labeling, DailyMed, setid c09c4cde-9f6c-4c4f-9d96-18beb5377564. Issued 05/2025.
  2. DailyMed search results for "methyltestosterone." — Used to confirm currently marketed products (generic capsules from Amneal Pharmaceuticals and ANI Pharmaceuticals, plus several esterified-estrogen/methyltestosterone combination products) and the absence of active listings for the historical brand names Android, Testred, or Methitest.
  3. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index, methyltestosterone. — Reference index; lists ATC G03BA02 (methyltestosterone), G03EK01 (methyltestosterone, other combinations), and G03EA01 (methyltestosterone and estrogen). No DDD value shown for the base code.
  4. Hickok LR, Toomey C, Speroff L. A comparison of esterified estrogens with and without methyltestosterone: effects on endometrial histology and serum lipoproteins in postmenopausal women. — Double-blind RCT, n=26, drug-specific. Obstet Gynecol. 1993. PMID 8233265.Title, authors, journal, year, and design confirmed via PubMed search-listing page; full abstract text not retrieved (individual PubMed abstract pages render via JavaScript/bot-check; Semantic Scholar API returned HTTP 429 on repeated attempts).
  5. Chiuve SE, Martin LA, Campos H, Sacks FM. Effect of the combination of methyltestosterone and esterified estrogens compared with esterified estrogens alone on apolipoprotein CIII. — Human RCT, drug-specific. J Clin Endocrinol Metab. 2004. PMID 15126543.Title-level only via PubMed search-listing page; full abstract not retrieved (Semantic Scholar and Crossref API access rate-limited on repeated attempts for this citation).
  6. Raisz LG, Wiita B, Artis A, Bowen A, Schwartz S, Trahiotis M, Shoukri K, Smith J. Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. — Human RCT, drug-specific: 1.25 mg esterified estrogen plus 2.5 mg methyltestosterone versus 1.25 mg conjugated equine estrogen, 9 weeks. J Clin Endocrinol Metab. 1996. PMID 8550780.Dose and design confirmed via PubMed search-listing snippet; full quantitative bone-marker findings not retrieved. Cited for context in Fails verification (calcium/vitamin D claim), not used to support any graded entry.
  7. Basaria S, Nguyen T, Rosenson RS, Dobs AS. Effect of methyl testosterone administration on plasma viscosity in postmenopausal women. — Human study, drug-specific. Clin Endocrinol (Oxf). 2002. PMID 12153599.Title-level only via PubMed search-listing page; full findings not retrieved. Cited as supporting context in the Oxygen delivery/utilization entry, not as primary support.
  8. Paradinas FJ, Bull TB, Westaby D, Murray-Lyon IM. Hyperplasia and prolapse of hepatocytes into hepatic veins during longterm methyltestosterone therapy: possible relationships of these changes to the development of peliosis hepatis and liver tumours. — Human case series, n=10, drug-specific (150 mg/day up to 3 years). Histopathology. 1977. PMID 615837.Design and dose confirmed via PubMed search-listing snippet; full findings not retrieved.
  9. Muraoka Y, Yahara I, Nara H, Watanabe H. Steroid-induced concentric membrane whorls in dog liver. — Animal (dog) study, drug-specific (methyltestosterone named). Experientia. 1981. PMID 7238820.Title and snippet confirmed via PubMed search-listing page; full abstract and organelle-identification detail not retrieved.
  10. Heywood R, Chesterman H, Ball SA, Wadsworth PF. Toxicity of methyl testosterone in the beagle dog. — Animal (dog) toxicity study, drug-specific. Toxicology. 1977. PMID 888151.Title-level only via PubMed search-listing page; full findings not retrieved. Cited for context in the headline finding, not used to support any specific graded entry beyond what is stated.
  11. Zheng Y, Qu J, Qiu L, Fan L, Meng S, Song C, Bing X, Chen J. Effect of 17alpha-methyltestosterone (MT) on oxidation stress in the liver of juvenile GIFT tilapia, Oreochromis niloticus. — Animal (tilapia) study, drug-specific. Springerplus. 2016. PMID 27066359.Title-level only via PubMed search-listing page; full abstract not retrieved (Semantic Scholar API returned HTTP 429 on repeated attempts). Direction and magnitude of the oxidative-stress finding not confirmed.
  12. Zhao H, Li T, Li C, Xiong Z, Rong W, Cao L, Chen G, Liu Q, Liu Y, Wang X, Liu S. Vitamin C alleviates intestinal damage induced by 17alpha-methyltestosterone in Carassius auratus. — Animal (goldfish) study, drug-specific. Aquat Toxicol. 2025. PMID 39908712.Title-level only via PubMed search-listing page; full abstract not retrieved.
  13. Liu Y, Wang S, Han M, Luo S, Chu P, Tang X, Zhao C, Han S, Yin S, Wang T. 17alpha-methyltestosterone exposure disrupted growth, liver physiology and intestinal microbial on fish: A case study on migratory bony fishes (Takifugu fasciatus). — Animal (pufferfish) study, drug-specific. Mar Pollut Bull. 2025. PMID 39778389.Title-level only via PubMed search-listing page; full abstract not retrieved.
  14. Singer JW, Samuels AI, Adamson JW. Steroids and hematopoiesis. I. The effect of steroids on in vitro erythroid colony growth: structure/activity relationships. — In vitro rat bone marrow culture study of "substituted steroids of several classes"; methyltestosterone's inclusion among tested compounds not independently confirmed. J Cell Physiol. 1976. PMID 1270518.Title-level only; cited as unconfirmed supporting context only, not counted toward any grade.
  15. Masarei JR, Lynch WJ. Lowering of H.D.L.-cholesterol by androgens. — Human study; whether methyltestosterone specifically was among the tested androgens could not be confirmed from the retrievable title. Lancet. 1977. PMID 71638.Cohort composition not confirmed; not used to support the Lipid profile grade above.
  16. Bachman E, Feng R, Travison T, et al. Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis. — Testosterone-specific human RCT, n=109; independently verified for this project's testosterone dossier, re-cited here as Tier C class context (methyltestosterone not in cohort). J Clin Endocrinol Metab. 2010. PMID 20660052.Cohort excluded methyltestosterone; testosterone-specific, cited only as class-level context for the Iron and Oxygen delivery/utilization entries.
  17. Bachman E, Travison TG, Basaria S, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin. — Testosterone-specific human RCT over 6 months; independently verified for this project's testosterone dossier, re-cited here as Tier C class context (methyltestosterone not in cohort). J Gerontol A Biol Sci Med Sci. 2014. PMID 24158761.Cohort excluded methyltestosterone; testosterone-specific, cited only as class-level context for the Iron entry.
  18. Artz AS, Stephens-Shields AJ, Bhasin S, et al. Markers of iron flux during testosterone-mediated erythropoiesis in older men with unexplained or iron-deficiency anemia. — Testosterone-specific human RCT substudy, n=95; independently verified for this project's testosterone dossier, re-cited here as Tier C class context (methyltestosterone not in cohort). J Clin Endocrinol Metab. 2020. PMID 32785689.Cohort excluded methyltestosterone; testosterone-specific, cited only as class-level context for the Iron entry.
  19. Role of androgens and androgen receptor in control of mitochondrial function [review]. — Narrative mechanistic review, predominantly animal/cell data; independently verified for this project's testosterone dossier, re-cited here as Tier C class context (methyltestosterone not in cohort). Am J Physiol Cell Physiol. 2022. PMID 35704694.Cohort excluded methyltestosterone; class-level review, cited only as context for the Mitochondrial burden and ATP production entries.
  20. Usui T, et al. Elevated mitochondrial biogenesis in skeletal muscle is associated with testosterone-induced body weight loss in male mice. — Mouse model, testosterone-specific; independently verified for this project's testosterone dossier, re-cited here as Tier C class context (methyltestosterone not in cohort). FEBS Lett. 2014. PMID 24726723.Cohort excluded methyltestosterone; testosterone-specific mouse study, cited only as context for the Mitochondrial burden and ATP production entries.
  21. Petrov PD, Fernandez-Murga L, Conde I, et al. Epistane, an anabolic steroid used for recreational purposes, causes cholestasis...by upregulating bile acid synthesis (CYP8B1) and cross-talking with nuclear receptors in human hepatocytes. — In vitro human hepatocyte study of a related steroid (epistane, not methyltestosterone), Tier C class-mechanism context; independently verified for this project's oxandrolone dossier. Arch Toxicol. 2020. PMID 31894354.Cohort excluded methyltestosterone; cited only for class-level cholestasis-mechanism context in the Mitochondrial burden entry.
  22. Sergeev PV, Vladimirov IuA, Seifulla RD, Denisov IuP, Rudnev IuN. The role of the chemical structure of steroid hormones in inhibiting peroxidative lipid oxidation in mitochondrial membranes. — Class-level mechanistic review/study, methyltestosterone not confirmed in scope. Vopr Med Khim. 1974. PMID 4156813.Title-level only; cited for general class-level mechanism context in the Oxidative stress entry, not as methyltestosterone-specific evidence.
  23. Crossref REST API search, "methyltestosterone copper ceruloplasmin" and "methyltestosterone zinc." — Used to confirm no copper- or zinc-specific literature exists for methyltestosterone beyond USP identity/purity monograph entries.