TESTOSTERONE

First marketed in 1937

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H28O2
Molecular Weight	288.4244
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@]34C)[C@@H]1CC[C@@H]2O

InChI

InChIKey=MUMGGOZAMZWBJJ-DYKIIFRCSA-N

InChI=1S/C19H28O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h11,14-17,21H,3-10H2,1-2H3/t14-,15-,16-,17-,18-,19-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00624
Curator's Comment: Description was created based on several sources, including

Testosterone is a steroid sex hormone found in both men and women. In men, testosterone is produced primarily by the Leydig (interstitial) cells of the testes when stimulated by luteinizing hormone (LH). It functions to stimulate spermatogenesis, promote physical and functional maturation of spermatozoa, maintain accessory organs of the male reproductive tract, support development of secondary sexual characteristics, stimulate growth and metabolism throughout the body and influence brain development by stimulating sexual behaviors and sexual drive. In women, testosterone is produced by the ovaries (25%), adrenals (25%) and via peripheral conversion from androstenedione (50%). Testerone in women functions to maintain libido and general wellbeing. Testosterone exerts a negative feedback mechanism on pituitary release of LH and follicle-stimulating hormone (FSH). Testosterone may be further converted to dihydrotestosterone or estradiol depending on the tissue. The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 2.5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects. Testosterone is used as hormone replacement or substitution of diminished or absent endogenous testosterone. Use in males: For management of congenital or acquired hypogonadism, hypogonadism associated with HIV infection, and male climacteric (andopause). Use in females: For palliative treatment of androgen-responsive, advanced, inoperable, metastatis (skeletal) carcinoma of the breast in women who are 1-5 years postmenopausal; testosterone esters may be used in combination with estrogens in the management of moderate to severe vasomotor symptoms associated with menopause in women who do not respond to adequately to estrogen therapy alone.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen receptor 42 Target ID: P10275 Gene ID: 367.0 Gene Symbol: AR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17635942	Agonist 2752
Androgen Receptor 169 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19856921	Agonist 2752		3.16 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypogonadism 29 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203098s006lbl.pdf	Primary		Approved 8583	TESTOSTERONE Approved Use Testosterone is an androgen indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: • Primary Hypogonadism (Congenital or Acquired) (1) • Hypogonadotropic Hypogonadism (Congenital or Acquired) Launch Date 2013

C_max

Value	Dose	Analyte	Population
930.1 ng/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01386606	5 g 1 times / day multiple, topical dose: 5 g route of administration: topical experiment type: multiple co-administered:	TESTOSTERONE plasma	Homo sapiens
231 ng/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01725451	30 mg single, topical dose: 30 mg route of administration: topical experiment type: single co-administered:	TESTOSTERONE serum	Homo sapiens population: healthy age: sex: food status:
214 ng/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01725451	30 mg single, topical dose: 30 mg route of administration: topical experiment type: single co-administered:	TESTOSTERONE serum	Homo sapiens population: healthy age: sex: food status:
13.1 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10902784/	8.2 mg single, topical dose: 8.2 mg route of administration: Topical experiment type: SINGLE co-administered:	TESTOSTERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
3110 ng*h/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01725451	30 mg single, topical dose: 30 mg route of administration: topical experiment type: single co-administered:	TESTOSTERONE serum	Homo sapiens population: healthy age: sex: food status:
2120 ng*h/dL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01725451	30 mg single, topical dose: 30 mg route of administration: topical experiment type: single co-administered:	TESTOSTERONE serum	Homo sapiens population: healthy age: sex: food status:
948 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10902784/	8.2 mg single, topical dose: 8.2 mg route of administration: Topical experiment type: SINGLE co-administered:	TESTOSTERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10902784/	8.2 mg single, topical dose: 8.2 mg route of administration: Topical experiment type: SINGLE co-administered:		TESTOSTERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
13% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10902784/	8.2 mg single, topical dose: 8.2 mg route of administration: Topical experiment type: SINGLE co-administered:		TESTOSTERONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 P-gp 1741 MRP2 499	UGT1A1 479 UGT1A3 470 UGT1A4 399 UGT1A5 56 UGT1A6 343 UGT1A7 249 UGT1A8 323 UGT1A9 423 UGT1A10 331 UGT2A1 39 UGT2A2 49 UGT2A3 49 UGT2B4 278 UGT2B7 456 UGT2B10 131 UGT2B15 236 UGT2B17 237 UGT2B28 65 CYP3A5 446 CYP3A7 109 P-gp 2052	MCT4 19 P-gp 301

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0 Page: -	no
MRP2 625	inhibitor 4027 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0 Page: -	no
P-gp 1932	inhibitor 4027 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0 Page: -	no
MCT4 31	inducer 1966 Sources: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/jphysiol.2006.115436 Page: -	yes
P-gp 1932	inducer 1966 Sources: https://www.sciencedirect.com/science/article/pii/S0024320506000786 Page: -	yes

Drug as victim

Target	Modality	Activity
UGT2B17 237	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	major [Km 10 uM]
UGT2A1 39	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	major [Km 38.7 uM]
UGT1A10 331	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A3 470	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A4 399	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A8 323	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A9 423	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT2A2 49	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT2B15 236	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT2B7 456	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	minor
UGT1A1 479	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT1A5 56	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT1A6 343	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT1A7 249	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT2A3 49	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT2B10 131	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT2B28 65	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
UGT2B4 278	substrate 4014 Sources: https://dmd.aspetjournals.org/content/37/2/417.short Page: -	no
CYP3A4 1946	substrate 4014 Sources: https://jpet.aspetjournals.org/content/299/3/825.short Page: -	yes
CYP3A5 446	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697443/ Page: -	yes
CYP3A7 109	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697443/ Page: -	yes
P-gp 2052	substrate 4014 Sources: https://www.sciencedirect.com/science/article/pii/S0006291X19317887 Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:17347	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:17347
ChemicalBook	CB5380541	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5380541
eMolecules	511977	https://www.emolecules.com/cgi-bin/more?vid=511977
ZINC	ZINC000118912393	http://zinc15.docking.org/substances/ZINC000118912393

PubMed

Title	Date	PubMed
Leydig cells.	1975 May	1095296
Elevation of steroid 5 alpha-reductase mRNA levels in rat cerebellum by toluene inhalation: possible relation to GFAP expression.	2000 Aug	10987130
Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity.	2000 Aug	10975606
Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene.	2000 Nov	11075820
Changes in serum and tissue zinc levels in sex hormone-induced prostatic carcinogenesis in the noble rat.	2000 Nov-Dec	11006573
Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study.	2000 Oct 17	11034937
Ornithine metabolism along the female mouse nephron: localization of ornithine decarboxylase and ornithine aminotransferase.	2000 Sep	11007319
Effects of estrogenic (o,p'-DDT; octylphenol) and anti-androgenic (p,p'-DDE) chemicals on indicators of endocrine status in juvenile male summer flounder (Paralichthys dentatus).	2001 Apr	11164537
Psychophysiological responses to the Stroop Task after a maximal cycle ergometry in elite sportsmen and physically active subjects.	2001 Feb	11166107
Spz1, a novel bHLH-Zip protein, is specifically expressed in testis.	2001 Feb	11165476
Effects of the anti-androgen finasteride on the modulatory actions of oestradiol on androgen metabolism by human gingival fibroblasts.	2001 Feb	11163318
Androgens and the role of female "hyperaggressiveness" in spotted hyenas (Crocuta crocuta).	2001 Feb	11161886
Interactions among paternal behavior, steroid hormones, and parental experience in male marmosets (Callithrix kuhlii).	2001 Feb	11161885
Castration in Gambel's and Scaled Quail: ornate plumage and dominance persist, but courtship and threat behaviors do not.	2001 Feb	11161878
Substitution mutation C268Y causes 17 beta-hydroxysteroid dehydrogenase 3 deficiency.	2001 Feb	11158067
Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance.	2001 Feb	11158002
Disparate response of wild-type and variant forms of LH to GnRH stimulation in individuals heterozygous for the LHbeta variant allele.	2001 Feb	11157812
Use of salivary biomarkers in biobehavioral research: cotton-based sample collection methods can interfere with salivary immunoassay results.	2001 Feb	11087962
Testosterone concentrations in women aged 25-50 years: associations with lifestyle, body composition, and ovarian status.	2001 Feb 1	11157413
Neuronal size in the spinal nucleus of the bulbocavernosus: direct modulation by androgen in rats with mosaic androgen insensitivity.	2001 Feb 1	11157092
Luteinizing hormone-dependent activity and luteinizing hormone-independent differentiation of rat fetal Leydig cells.	2001 Feb 14	11165053
Porcine gonadal and placental isozymes of aromatase cytochrome P450: sub-cellular distribution and support by NADPH-cytochrome P450 reductase.	2001 Feb 14	11165045
Self-augmentation effect of male-specific products on sexually differentiated progesterone metabolism in adult male rat liver microsomes.	2001 Feb 16	10995741
Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer.	2001 Jan	11164157
Long-term remission of ovarian hyperandrogenism after short-term treatment with a gonadotropin-releasing hormone agonist.	2001 Jan	11163817
Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS.	2001 Jan	11163816
Concentrations of steroid hormones in layers and biopsies of chelonian egg yolks.	2001 Jan	11161774
Insulin action and insulin secretion in polycystic ovary syndrome treated with ethinyl oestradiol/cyproterone acetate.	2001 Jan	11161134
Androgenic anabolic steroids and arterial structure and function in male bodybuilders.	2001 Jan	11153743
Glucocorticoids regulate plasma membrane potential during rat thymocyte apoptosis in vivo and in vitro.	2001 Jan	11145606
Differential effects of dexamethasone treatment on lipopolysaccharide-induced testicular inflammation and reproductive hormone inhibition in adult rats.	2001 Jan	11139783
Testosterone-induced inhibition of spermatogenesis is more closely related to suppression of FSH than to testicular androgen levels in the cynomolgus monkey model (Macaca fascicularis).	2001 Jan	11139767
Side of ovulation, hormones and sex ratios.	2001 Jan	11139565
Short-term 17beta-estradiol decreases glucose R(a) but not whole body metabolism during endurance exercise.	2001 Jan	11133904
Effects of testosterone on production of perivitelline membrane glycoprotein ZPC by granulosa cells of Japanese quail (Coturnix japonica).	2001 Jan	11133688
Chlorinated hydrocarbons and biomarkers of exposure in wading birds and fish of the lower Rio Grande Valley, Texas.	2001 Jan	11116345
Novel approaches to female sexual dysfunction.	2001 Jan	11116282
Androgen receptors in cranial nerve motor nuclei of male and female rats.	2001 Jan	11108611
Signs of sexual behaviour are not increased after subchronic treatment with LHRH in young men.	2001 Jan	11070330
Induction of nuclear transcription factors, cytochrome P450 monooxygenases, and glutathione S-transferase alpha gene expression in Aroclor 1254-treated rat hepatocyte cultures.	2001 Jan 15	11163329
Expression of the 17beta-hydroxysteroid dehydrogenase type 5 mRNA in the human brain.	2001 Jan 22	11165025
Distribution of 17beta-hydroxysteroid dehydrogenases in human osteoblast-like cells.	2001 Jan 22	11165024
Phytoestrogens inhibit human 17beta-hydroxysteroid dehydrogenase type 5.	2001 Jan 22	11165023
Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3).	2001 Jan 22	11165022
Inhibitors of type II 17beta-hydroxysteroid dehydrogenase.	2001 Jan 22	11165020
Pan1b (17betaHSD11)-enzymatic activity and distribution in the lung.	2001 Jan 22	11165019
17beta-Hydroxysteroid dehydrogenase type 9 and other short-chain dehydrogenases/reductases that catalyze retinoid, 17beta- and 3alpha-hydroxysteroid metabolism.	2001 Jan 22	11165018
Type 5 17beta-hydroxysteroid dehydrogenase: its role in the formation of androgens in women.	2001 Jan 22	11165014
Sex difference in the phosphorylation of cAMP response element binding protein (CREB) in neonatal rat brain.	2001 Jan 26	11164773
Testosterone modulates the dendritic architecture of arcuate neuroendocrine neurons in adult male rats.	2001 Jan 26	11164770

Patents

Sample Use Guides

In Vivo Use Guide

Starting dose of testosterone gel is 50 mg of testosterone (4 pump actuations, two 25 mg packets, or one 50 mg packet), applied once daily in the morning.

Route of Administration: Topical

In Vitro Use Guide

10 nM Testosterone significantly reduced secretion of BDNF in in human airway smooth muscle

Name

Type

Language

TESTOSTERONE

Official Name

English

TESTOSTERONE CIII

Preferred Name

English

TESTOSTERONE [JAN]

Common Name

English

TESTOSTERONE [EP MONOGRAPH]

Common Name

English

TESTOSTERONE [MART.]

Common Name

English

ANDROST-4-EN-3-ONE, 17-HYDROXY-, (17.BETA.)-

Systematic Name

English

TESTOSTERONE PROPIONATE IMPURITY C [EP IMPURITY]

Common Name

English

INTRINSA

Brand Name

English

ANDROGEL

Brand Name

English

TESTOSTERONE [GREEN BOOK]

Common Name

English

TESTOSTERONE [EP IMPURITY]

Common Name

English

ANDROID-T

Brand Name

English

TESTOSTERONE ENANTATE IMPURITY D [EP IMPURITY]

Common Name

English

LIVENSA

Brand Name

English

TESTOSTERONE [ORANGE BOOK]

Common Name

English

TESTOSTERONE [HSDB]

Common Name

English

TESTOSTERONE [EMA EPAR]

Common Name

English

NSC-9700

Code

English

TESTIM

Code

English

VOGELXO

Brand Name

English

ANDROLAN

Brand Name

English

17?-Hydroxyandrost-4-en-3-one

Systematic Name

English

NATESTO

Brand Name

English

Testosterone [WHO-DD]

Common Name

English

TESTICULOSTERONE

Common Name

English

MERTESTATE

Common Name

English

TESTOSTERONE [USP MONOGRAPH]

Common Name

English

VIROSTERONE

Common Name

English

testosterone [INN]

Common Name

English

TESTOSTERONE [VANDF]

Common Name

English

TESTOSTERONE [MI]

Common Name

English

HOMOSTERONE

Common Name

English

ANDRODERM

Brand Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

52590