Meta Information
ID:testosterone
Name:Testosterone
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants (e.g., Warfarin)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone can enhance the blood-thinning effect of oral anticoagulants like warfarin, significantly increasing the risk of serious bleeding.
Actionable advice:
Concurrent use should be avoided, or bleeding parameters (INR) should be monitored very closely under strict medical supervision, as dose adjustments will be necessary.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
• Hemorrhagic tendencies or blood dyscrasias • Recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [see Warnings and Precautions (5.8)] • Bleeding tendencies associated with: − Active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract − Central nervous system hemorrhage − Cerebral aneurysm
Label source:
FDA label: Warfarin (target-side evidence)
Action type:
avoid
Target id:
/condition/prostate-cancer
Target name:
Active Prostate Cancer
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone is an absolute contraindication as it can act as a fuel for hormone-sensitive prostate cancer cells, potentially accelerating tumor growth.
Actionable advice:
Absolutely avoid testosterone therapy if you have a current or suspected diagnosis of prostate cancer.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Males with known or suspected carcinoma of the prostate gland
Label source:
FDA label: Testosterone cypionate (Depo-Testosterone)
Action type:
avoid
Target id:
/condition/breast-cancer
Target name:
Breast Cancer (Male)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone is contraindicated in men with breast cancer as it may promote the growth of hormone-sensitive tumor cells.
Actionable advice:
Absolutely avoid testosterone therapy if you have a history of or active breast cancer.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Patients should be informed of the following information: 17.1 Use in Men with Known or Suspected Prostate or Breast Cancer Men with known or suspected prostate or breast cancer should not use testosterone topical solution [see CONTRAINDICATIONS ( 4 ) and WARNINGS AND PRECAUTION ( 5.1 )] . 17.2 Potential for Secondary Exposure to Testosterone and Steps to Prevent Seconda
Label source:
FDA label: Testosterone
Action type:
avoid
Target id:
/condition/polycythemia
Target name:
Polycythemia / High Hematocrit
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone stimulates red blood cell production (erythropoiesis), which can lead to an unsafe increase in blood viscosity (thickening), raising the risk of stroke or heart attack.
Actionable advice:
Testosterone should not be started with an untreated high hematocrit (>50%); if it develops during therapy, it must be managed with dose reduction or blood donation.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
e therapy should be promptly discontinued at least until the cause of virilization has been identified. [see DOSAGE AND ADMINISTRATION ( 2.2 )] . 5.3 Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone.
Label source:
FDA label: Testosterone
Action type:
avoid
Target id:
/intervention/resistance-training
Target name:
Resistance Training
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Resistance exercise provides the essential mechanical stimulus for testosterone to exert its powerful anabolic effects on muscle protein synthesis, leading to gains in muscle mass and strength.
Actionable advice:
Incorporate a consistent resistance training program to realize the full musculoskeletal benefits of testosterone therapy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
testosterone combined with strength training increases muscle size and strength
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/8637535/
Action type:
informational_none
Target id:
/intervention/protein
Target name:
Adequate Protein Intake
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sufficient dietary protein provides the essential amino acid building blocks that are required for testosterone to effectively build and repair muscle tissue.
Actionable advice:
Adequate daily protein intake (e.g., 1.2-1.6 g/kg of body weight) should be maintained to support muscle anabolism.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
adequate protein intake supports anabolic response to testosterone
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/8637535/
Action type:
informational_none
Target id:
/biomarker/complete-blood-count
Target name:
Complete Blood Count (CBC)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Monitoring hemoglobin and hematocrit is a critical safety requirement, as testosterone can cause erythrocytosis (high red blood cell count), increasing thrombotic risk.
Actionable advice:
Obtain a CBC at baseline, 3-6 months after starting, and at least annually thereafter to monitor for erythrocytosis.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Polycythemia: Monitor hematocrit periodically
Label source:
FDA label: Testosterone Cypionate Injection (NDA 216318)
Action type:
monitor
Target id:
/biomarker/comprehensive-sex-hormone-panel
Target name:
Comprehensive Sex Hormone Panel
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Regularly measuring total and free testosterone, estradiol, and SHBG is essential to confirm therapeutic dosing, optimize benefits, and prevent side effects from hormonal imbalances.
Actionable advice:
A full hormone panel should be monitored as directed by a physician to guide therapy and ensure safety.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Circulating testosterone is primarily bound in serum to sex hormone-binding globulin (SHBG) and
Label source:
FDA label: Testosterone Cypionate Injection (NDA 216318)
Action type:
monitor
Target id:
/biomarker/prostate-specific-antigen
Target name:
Prostate Specific Antigen (PSA)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Monitoring PSA is a key safety measure for prostate health, as testosterone can stimulate both benign and malignant prostate tissue.
Actionable advice:
PSA level should be checked and a digital rectal exam performed at baseline and periodically as recommended by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sleep apnea may occur in those with risk factors ( 5.13 ) Monitor serum testosterone, prostate specific antigen (PSA), liver function, lipid concentrations, hematocrit and hemoglobin periodically ( 5.1 , 5.3 , 5.10 , 5.14 ) Testosterone topical solution is flammable until dry ( 5.17 ) 5.1 Worsening of Benign Prostatic Hyperplasia and Potential Risk of Prostate Canc
Label source:
FDA label: Testosterone
Action type:
monitor
Target id:
/condition/heart-failure
Target name:
Severe Heart Failure
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone can cause sodium and water retention (edema), which can exacerbate fluid overload and worsen symptoms in patients with severe, unstable congestive heart failure.
Actionable advice:
Testosterone therapy should be avoided in cases of severe or decompensated heart failure.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Edema, with or without congestive heart failure (CHF)
Label source:
FDA label: Testosterone Cypionate Injection (NDA 216318)
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone is strictly contraindicated in pregnancy due to the high risk of causing virilization (development of male characteristics) in a female fetus.
Actionable advice:
Absolutely avoid all forms of testosterone during pregnancy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
ta in geriatric patients using testosterone topical solution to assess the potential risks of cardiovascular disease and prostate cancer ( 8.5 ). 8.1 Pregnancy Pregnancy Category X [see CONTRAINDICATIONS ( 4 )] Testosterone topical solution is contraindicated during pregnancy or in women who may become pregnant.
Label source:
FDA label: Testosterone
Action type:
avoid
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone can improve insulin sensitivity and lower blood glucose, which may increase the risk of hypoglycemia when combined with insulin or other diabetes drugs.
Actionable advice:
Blood glucose is best monitored closely when starting therapy, as doses of diabetes medications may need to be reduced by a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
DRUG INTERACTIONS Androgens may decrease blood glucose and insulin requirement in diabetic patients ( 7.1 ).
Label source:
FDA label: Testosterone
Action type:
monitor
Target id:
/class/corticosteroids
Target name:
Corticosteroids
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concurrent use of androgens and corticosteroids can increase the risk and severity of fluid retention (edema), especially in patients with underlying cardiac or renal disease.
Actionable advice:
This combination is best used with caution, and it is worth monitoring for signs of fluid retention like swelling in the legs and ankles.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Use of testosterone with Adrenocorticotropic Hormone (ACTH) or corticosteroids may result in increased fluid retention.
Label source:
FDA label: Testosterone
Action type:
monitor
Target id:
/condition/obstructive-sleep-apnea
Target name:
Untreated Severe Obstructive Sleep Apnea
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone therapy may worsen the frequency and severity of breathing interruptions in individuals with pre-existing, untreated severe sleep apnea.
Actionable advice:
It is a good idea for sleep apnea to be diagnosed and effectively treated (e.g., with CPAP) before initiating testosterone therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Sleep Apnea: Testosterone Cypionate Injection may potentiate sleep apnea
Label source:
FDA label: Testosterone Cypionate Injection (NDA 216318)
Action type:
informational_none
Target id:
/condition/urinary-retention
Target name:
Severe BPH / Urinary Symptoms
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By stimulating prostate tissue, testosterone can potentially worsen lower urinary tract symptoms (e.g., weak stream, frequency) in men with severe benign prostatic hyperplasia (BPH).
Actionable advice:
This is best used with caution in men with severe BPH, and it is a good idea to monitor for any worsening of urinary symptoms.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
worsening of signs and symptoms of BPH. Evaluate patients for prostate cancer
Label source:
FDA label: Testosterone Cypionate Injection (NDA 216318)
Action type:
monitor
Target id:
/biomarker/lipid-panel
Target name:
Lipid Panel
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Testosterone therapy can alter cholesterol levels, most commonly by decreasing HDL ('good' cholesterol) and sometimes increasing LDL ('bad' cholesterol).
Actionable advice:
A lipid panel should be monitored at baseline and periodically during therapy to manage any adverse changes to the cardiovascular risk profile.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Lipid Changes: Testosterone may affect serum lipid profile
Label source:
FDA label: Testosterone Cypionate Injection (NDA 216318)
Action type:
monitor
Target id:
/intervention/blood-donation
Target name:
Blood Donation (Therapeutic Phlebotomy)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
For men who develop a high red blood cell count (erythrocytosis) on testosterone, regular blood donation is an effective medical strategy to lower hematocrit and mitigate associated risks.
Actionable advice:
If your hematocrit rises above the safe range, your doctor may prescribe therapeutic phlebotomy (blood donation).
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
therapeutic phlebotomy or blood donation reduces hematocrit in testosterone-treated men
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/24378408/
Action type:
informational_none
Target id:
/class/aromatase-inhibitors
Target name:
Aromatase Inhibitors
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Aromatase inhibitors (e.g., anastrozole) are often prescribed with testosterone to block its conversion to estradiol, helping to manage estrogen-related side effects.
Actionable advice:
An aromatase inhibitor is best used only if prescribed by a physician to manage documented high estradiol levels.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
aromatase inhibitors reduce conversion of testosterone to estradiol
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/24816147/
Action type:
informational_none
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong inhibitors of the CYP3A4 enzyme (e.g., ketoconazole, ritonavir) can slow the breakdown of testosterone, potentially increasing its concentration and the risk of side effects.
Actionable advice:
This is best used with caution, and it is a good idea to monitor for androgenic side effects; a testosterone dose reduction may be needed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Titrate • Sensitive CYP3A4 or CYP3A4 and P-gp Substrates: Concomitant use of dosage by 150 mg daily, no more frequently than every 2-3 weeks (2.2) RECORLEV with these substrates is contraindicated or not recommended • Maximum recommended dosage is 1200 mg daily, administered as 600 mg (7.1) twice daily (2.2) • Atorvastatin: Use lowest atorvastatin dose possible and monitor for adverse • For additi
Label source:
FDA label: Ketoconazole (target-side evidence)
Action type:
adjust_with_prescriber
Target id:
/class/broad-spectrum-inducers
Target name:
Strong CYP3A4 Inducers
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong inducers of the CYP3A4 enzyme (e.g., rifampin, carbamazepine, St. John's Wort) can speed up the breakdown of testosterone, potentially lowering its levels and reducing its effectiveness.
Actionable advice:
Concurrent use is best avoided, or it is worth being aware that a higher dose of testosterone may be required to achieve therapeutic levels.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Concomitant use of lurasidone with strong CYP3A4 inducers (e.g., rifampin) decreased the exposure of lurasidone compared to the use of lurasidone alone (see PRECAUTIONS, Drug Interactions).
Label source:
FDA label: Rifampin (target-side evidence)
Action type:
avoid
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic heavy alcohol intake is toxic to the testes and liver, which can suppress natural testosterone production and impair the metabolism of exogenous testosterone.
Actionable advice:
Alcohol consumption is best limited to support liver health and optimize the effects of hormone therapy.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
When alcohol is consumed in excess, particularly chronically, it negatively affects testosterone production in men.
Label source:
PubMed: Expert review of endocrinology & metabolism (2023)
Source url:
Exact phrase from label:
In the testes, alcohol can adversely affect the Leydig cells, which produce and secrete the hormone testosterone. Studies found that heavy alcohol consumption results in reduced testosterone levels in the blood.
Label source:
PubMed: Alcohol health and research world (1998)
Source url:
Exact phrase from label:
Male alcoholics often suffer from features of hypogonadism related to abnormal metabolism of sex steroids. Since the activity of testosterone reductases is rate limiting for testosterone metabolism in the liver, the effect of prolonged ethanol consumption by rats and human volunteers on the activities of these microsomal and cytosolic enzymes was studied. In rats, long-term ethanol ingestion doubled microsomal 5alpha-testosterone reductase activity, a major pathway for testosterone metabolism, while in human volunteers the activity was increased two- to fivefold.
Label source:
PubMed: Science (New York, N.Y.) (1976)
Action type:
informational_none
Target id:
/biomarker/comprehensive-liver-function-panel
Target name:
Comprehensive Liver Function Panel
Severity:
minor
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While modern injectable and transdermal testosterone have very low liver toxicity, establishing a baseline and performing periodic checks is a prudent safety measure.
Actionable advice:
Obtain a baseline liver function test and consider periodic monitoring as part of routine health screening.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and
Label source:
FDA label: Testosterone cypionate (Depo-Testosterone)
Action type:
monitor
Target id:
/class/hepatotoxic-agents
Target name:
Hepatotoxic Agents
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Although non-oral testosterone is not considered hepatotoxic, combining it with other substances known to stress the liver could theoretically add to the cumulative burden.
Actionable advice:
Minimize use of other potentially liver-toxic drugs or supplements and monitor liver function if concurrent use is necessary.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Sleep apnea may occur in those with risk factors ( 5.13 ) Monitor serum testosterone, prostate specific antigen (PSA), liver function, lipid concentrations, hematocrit and hemoglobin periodically ( 5.1 , 5.3 , 5.10 , 5.14 ) Testosterone topical solution is flammable until dry ( 5.17 ) 5.1 Worsening of Benign Prostatic Hyperplasia and Potential Risk of Prostate Cancer Moni
Label source:
FDA label: Testosterone
Action type:
monitor
Target id:
/intervention/dhea
Target name:
DHEA
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Supplementing with DHEA, a precursor hormone, while on testosterone therapy is generally unnecessary and can lead to excessive levels of androgens and estrogens, increasing side effect risk.
Actionable advice:
DHEA or other prohormone supplements are generally best avoided while on prescribed testosterone therapy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
DHEA is a precursor that contributes minimally to testosterone in hypogonadal men receiving exogenous testosterone
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/29371440/
Action type:
avoid
Derived From
testosterone_systemic_healthspan
Provenance Note
Interactions duplicated from 'testosterone_systemic_healthspan'. Scope-suffix reconciliation.