Wikipedia

Pharmacokinetics of testosterone

The pharmacology of testosterone, an androgen and anabolic steroid (AAS) medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.

Testosterone
Clinical data
Routes of
administration		Oral, buccal, sublingual, intranasal, transdermal (gel, cream, patch, solution), vaginal (cream, gel, suppository), rectal (suppository), intramuscular or subcutaneous injection (oil solution, aqueous suspension), subcutaneous implant (pellet)
Drug classAndrogen, anabolic steroid
Pharmacokinetic data
BioavailabilityOral: very low (due to extensive first pass metabolism)
Protein binding97.0–99.5% (to SHBGTooltip sex hormone-binding globulin and albumin)[1]
MetabolismLiver (mainly reduction and conjugation)
Elimination half-life2–4 hours[citation needed]
ExcretionUrine (90%), feces (6%)

Testosterone is a naturally occurring and bioidentical AAS, or an agonist of the androgen receptor, the biological target of androgens like endogenous testosterone and dihydrotestosterone (DHT).

Testosterone is used by both men and women and can be taken by a variety of different routes of administration.[2]

Routes of administration

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See also: Testosterone (medication) § Available forms

Testosterone can be taken by a variety of different routes of administration.[2][3] These include oral, buccal, sublingual, intranasal, transdermal (gels, creams, patches, solutions), vaginal (creams, gels, suppositories), rectal (suppositories), by intramuscular or subcutaneous injection (in oil solutions or aqueous suspensions), and as a subcutaneous implant.[2][3] The pharmacokinetics of testosterone, including its bioavailability, metabolism, biological half-life, and other parameters, differ by route of administration.[2] Likewise, the potency of testosterone, and its local effects in certain tissues, for instance the liver, differ by route of administration as well.[2] In particular, the oral route is subject to a high first-pass effect, which results in high levels of testosterone in the liver and consequent hepatic androgenic effects, as well as low potency due to first-pass metabolism in the intestines and liver into metabolites like dihydrotestosterone and androgen conjugates.[2] Conversely, this is not the case for non-oral routes, which bypass the first pass.[2]

Different testosterone routes and dosages can achieve widely varying circulating testosterone levels.[2] For purposes of comparison with normal physiological circumstances, circulating levels of total testosterone in men range from about 250 to 1,100 ng/dL (mean 630 ng/dL) and in women range from about 2 to 50 ng/dL (mean 32 ng/dL).[4][5][6][7] Testosterone levels decline with age in men.[8] In women with polycystic ovary syndrome (PCOS), a condition of androgen excess, testosterone levels are typically around 50 to 80 ng/dL, with a range of about 30 to 140 ng/dL.[9][10][7] Total testosterone levels are about 20-fold and free testosterone levels about 40-fold higher in men than in women on average.[11] Similarly, testosterone production is approximately 30 times higher in men than in women.[12]

Available forms of testosterone[a]
Route Ingredient Form Dose[b] Brand names[c]
Oral Test. undecanoate Capsule 40 mg Andriol, Jatenzo
Sublingual Testosterone Tablet 10 mg Testoral
Buccal Testosterone Tablet 30 mg Striant
Intranasal Testosterone Nasal gel 5.5 mg/spray, 120 sprays Natesto
Transdermal Testosterone Non-scrotal patch 2.5, 4, 5, 6 mg/day Androderm
Non-scrotal patch 150, 300 μg/day Intrinsa
Scrotal patch[d] 4, 6 mg/day Testoderm
Topical gel 25, 50, 75, 100, 125 mg/pump AndroGel, Testim
Axillary solution 30 mg/pump Axiron
Rectal Testosterone Suppository 40 mg Rektandron
Injection[e] Test. enanthate Oil solution 50, 100, 180, 200, 250 mg/mL Delatestryl
Test. cypionate Oil solution 50, 100, 200, 250 mg/mL Depo-Testosterone
Mixed test. esters[f] Oil solution 100, 250 mg/mL Sustanon
Test. undecanoate Oil solution 750, 1000 mg Aveed, Nebido
Implant Testosterone Pellet 50, 75, 100, 200 mg Testopel
Footnotes and sources:
  1. ^ This table does not include combination products with other medications/hormones. The availability of specific products may vary by country - see Testosterone (medication) § Availability.
  2. ^ These dosages may be given at varying frequencies - dosages listed are "each" (ex: per tablet, per spray, etc) and not indicative of total daily dose or equivalent.
  3. ^ Other brand names may be currently or historically marketed.
  4. ^ Potentially discontinued.
  5. ^ May be by intramuscular injection or subcutaneous injection.
  6. ^ Combination of testosterone propionate, testosterone phenylpropionate, testosterone isocaproate, and testosterone decanoate.
Sources: [13][14][15][16][17][18][19][20][21][22][23][24][25][26]
Androgen replacement therapy formulations and dosages used in men
Route Medication Major brand names Form Dosage
Oral Testosteronea – Tablet 400–800 mg/day (in divided doses)
Testosterone undecanoate Andriol, Jatenzo Capsule 40–80 mg/2–4× day (with meals)
Methyltestosteroneb Android, Metandren, Testred Tablet 10–50 mg/day
Fluoxymesteroneb Halotestin, Ora-Testryl, Ultandren Tablet 5–20 mg/day
Metandienoneb Dianabol Tablet 5–15 mg/day
Mesteroloneb Proviron Tablet 25–150 mg/day
Sublingual Testosteroneb Testoral Tablet 5–10 mg 1–4×/day
Methyltestosteroneb Metandren, Oreton Methyl Tablet 10–30 mg/day
Buccal Testosterone Striant Tablet 30 mg 2×/day
Methyltestosteroneb Metandren, Oreton Methyl Tablet 5–25 mg/day
Transdermal Testosterone AndroGel, Testim, TestoGel Gel 25–125 mg/day
Androderm, AndroPatch, TestoPatch Non-scrotal patch 2.5–15 mg/day
Testoderm Scrotal patch 4–6 mg/day
Axiron Axillary solution 30–120 mg/day
Androstanolone (DHT) Andractim Gel 100–250 mg/day
Rectal Testosterone Rektandron, Testosteronb Suppository 40 mg 2–3×/day
Injection (IMTooltip intramuscular injection or SCTooltip subcutaneous injection) Testosterone Andronaq, Sterotate, Virosterone Aqueous suspension 10–50 mg 2–3×/week
Testosterone propionateb Testoviron Oil solution 10–50 mg 2–3×/week
Testosterone enanthate Delatestryl Oil solution 50–250 mg 1x/1–4 weeks
Xyosted Auto-injector 50–100 mg 1×/week
Testosterone cypionate Depo-Testosterone Oil solution 50–250 mg 1x/1–4 weeks
Testosterone isobutyrate Agovirin Depot Aqueous suspension 50–100 mg 1x/1–2 weeks
Testosterone phenylacetateb Perandren, Androject Oil solution 50–200 mg 1×/3–5 weeks
Mixed testosterone esters Sustanon 100, Sustanon 250 Oil solution 50–250 mg 1×/2–4 weeks
Testosterone undecanoate Aveed, Nebido Oil solution 750–1,000 mg 1×/10–14 weeks
Testosterone buciclatea – Aqueous suspension 600–1,000 mg 1×/12–20 weeks
Implant Testosterone Testopel Pellet 150–1,200 mg/3–6 months
Notes: Men produce about 3 to 11 mg of testosterone per day (mean 7 mg/day in young men). Footnotes: a = Never marketed. b = No longer used and/or no longer marketed. Sources: See template.
Androgen replacement therapy formulations and dosages used in women
Route Medication Major brand names Form Dosage
Oral Testosterone undecanoate Andriol, Jatenzo Capsule 40–80 mg 1x/1–2 days
Methyltestosterone Metandren, Estratest Tablet 0.5–10 mg/day
Fluoxymesterone Halotestin Tablet 1–2.5 mg 1x/1–2 days
Normethandronea Ginecoside Tablet 5 mg/day
Tibolone Livial Tablet 1.25–2.5 mg/day
Prasterone (DHEA)b – Tablet 10–100 mg/day
Sublingual Methyltestosterone Metandren Tablet 0.25 mg/day
Transdermal Testosterone Intrinsa Patch 150–300 μg/day
AndroGel Gel, cream 1–10 mg/day
Vaginal Prasterone (DHEA) Intrarosa Insert 6.5 mg/day
Injection Testosterone propionatea Testoviron Oil solution 25 mg 1x/1–2 weeks
Testosterone enanthate Delatestryl, Primodian Depot Oil solution 25–100 mg 1x/4–6 weeks
Testosterone cypionate Depo-Testosterone, Depo-Testadiol Oil solution 25–100 mg 1x/4–6 weeks
Testosterone isobutyratea Femandren M, Folivirin Aqueous suspension 25–50 mg 1x/4–6 weeks
Mixed testosterone esters Climacterona Oil solution 150 mg 1x/4–8 weeks
Omnadren, Sustanon Oil solution 50–100 mg 1x/4–6 weeks
Nandrolone decanoate Deca-Durabolin Oil solution 25–50 mg 1x/6–12 weeks
Prasterone enanthatea Gynodian Depot Oil solution 200 mg 1x/4–6 weeks
Implant Testosterone Testopel Pellet 50–100 mg 1x/3–6 months
Notes: Premenopausal women produce about 230 ± 70 μg testosterone per day (6.4 ± 2.0 mg testosterone per 4 weeks), with a range of 130 to 330 μg per day (3.6–9.2 mg per 4 weeks). Footnotes: a = Mostly discontinued or unavailable. b = Over-the-counter. Sources: See template.
Testosterone levels in males and females
Total testosterone
Stage Age range Male Female
Values SI units Values SI units
Infant Premature (26–28 weeks) 59–125 ng/dL 2.047–4.337 nmol/L 5–16 ng/dL 0.173–0.555 nmol/L
Premature (31–35 weeks) 37–198 ng/dL 1.284–6.871 nmol/L 5–22 ng/dL 0.173–0.763 nmol/L
Newborn 75–400 ng/dL 2.602–13.877 nmol/L 20–64 ng/dL 0.694–2.220 nmol/L
Child 1–6 years ND ND ND ND
7–9 years 0–8 ng/dL 0–0.277 nmol/L 1–12 ng/dL 0.035–0.416 nmol/L
Just before puberty 3–10 ng/dL* 0.104–0.347 nmol/L* <10 ng/dL* <0.347 nmol/L*
Puberty 10–11 years 1–48 ng/dL 0.035–1.666 nmol/L 2–35 ng/dL 0.069–1.214 nmol/L
12–13 years 5–619 ng/dL 0.173–21.480 nmol/L 5–53 ng/dL 0.173–1.839 nmol/L
14–15 years 100–320 ng/dL 3.47–11.10 nmol/L 8–41 ng/dL 0.278–1.423 nmol/L
16–17 years 200–970 ng/dL* 6.94–33.66 nmol/L* 8–53 ng/dL 0.278–1.839 nmol/L
Adult ≥18 years 350–1080 ng/dL* 12.15–37.48 nmol/L* – –
20–39 years 400–1080 ng/dL 13.88–37.48 nmol/L – –
40–59 years 350–890 ng/dL 12.15–30.88 nmol/L – –
≥60 years 350–720 ng/dL 12.15–24.98 nmol/L – –
Premenopausal – – 10–54 ng/dL 0.347–1.873 nmol/L
Postmenopausal – – 7–40 ng/dL 0.243–1.388 nmol/L
Bioavailable testosterone
Stage Age range Male Female
Values SI units Values SI units
Child 1–6 years 0.2–1.3 ng/dL 0.007–0.045 nmol/L 0.2–1.3 ng/dL 0.007–0.045 nmol/L
7–9 years 0.2–2.3 ng/dL 0.007–0.079 nmol/L 0.2–4.2 ng/dL 0.007–0.146 nmol/L
Puberty 10–11 years 0.2–14.8 ng/dL 0.007–0.513 nmol/L 0.4–19.3 ng/dL 0.014–0.670 nmol/L
12–13 years 0.3–232.8 ng/dL 0.010–8.082 nmol/L 1.1–15.6 ng/dL 0.038–0.541 nmol/L
14–15 years 7.9–274.5 ng/dL 0.274–9.525 nmol/L 2.5–18.8 ng/dL 0.087–0.652 nmol/L
16–17 years 24.1–416.5 ng/dL 0.836–14.452 nmol/L 2.7–23.8 ng/dL 0.094–0.826 nmol/L
Adult ≥18 years ND ND – –
Premenopausal – – 1.9–22.8 ng/dL 0.066–0.791 nmol/L
Postmenopausal – – 1.6–19.1 ng/dL 0.055–0.662 nmol/L
Free testosterone
Stage Age range Male Female
Values SI units Values SI units
Child 1–6 years 0.1–0.6 pg/mL 0.3–2.1 pmol/L 0.1–0.6 pg/mL 0.3–2.1 pmol/L
7–9 years 0.1–0.8 pg/mL 0.3–2.8 pmol/L 0.1–1.6 pg/mL 0.3–5.6 pmol/L
Puberty 10–11 years 0.1–5.2 pg/mL 0.3–18.0 pmol/L 0.1–2.9 pg/mL 0.3–10.1 pmol/L
12–13 years 0.4–79.6 pg/mL 1.4–276.2 pmol/L 0.6–5.6 pg/mL 2.1–19.4 pmol/L
14–15 years 2.7–112.3 pg/mL 9.4–389.7 pmol/L 1.0–6.2 pg/mL 3.5–21.5 pmol/L
16–17 years 31.5–159 pg/mL 109.3–551.7 pmol/L 1.0–8.3 pg/mL 3.5–28.8 pmol/L
Adult ≥18 years 44–244 pg/mL 153–847 pmol/L – –
Premenopausal – – 0.8–9.2 pg/mL 2.8–31.9 pmol/L
Postmenopausal – – 0.6–6.7 pg/mL 2.1–23.2 pmol/L
Sources: See template.

Oral administration

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Oral testosterone

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Testosterone is well-absorbed but extensively metabolized with oral administration due to the first pass through the intestines and liver.[2][27][28][3] It is rapidly and completely inactivated in men at doses of less than 200 mg.[2][27] In large doses, such as 200 mg however, significant increases in circulating testosterone levels become apparent.[2][27] In addition, while a 60 mg dose has no effect on testosterone levels in men, this dose does measurably increase testosterone levels in prepubertal boys and women.[27] The oral bioavailability of testosterone in young women after a single 25 mg dose was found to be 3.6 ± 2.5%.[29] High levels of testosterone are also achieved with a 60 mg dose of oral testosterone in men with liver cirrhosis.[2] These findings are attributed to induction of liver enzymes by testosterone and consequent activation of its own metabolism.[2][27] Substitution dosages of oral testosterone in men are in the range of 400 to 800 mg/day.[27][28] Such doses exceed the amount of testosterone produced by the body, which is approximately 7 mg/day, by approximately 100-fold.[2][27][28] The elimination half-life of oral testosterone is rapid at about 5 to 7 hours.[28][30] As a result, it requires administration several times per day in divided doses.[28] Due to its limitations, such as the high doses required and necessity of multiple daily doses, oral testosterone is not used clinically in its unmodified form.[28][3]

Oral testosterone has been studied in combination with a 5α-reductase inhibitor to reduce its first-pass metabolism and improve its bioavailability.[2][31]

Oral testosterone undecanoate

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Instead of in its free unesterified form, testosterone is used by oral administration in the form of testosterone undecanoate.[2] Due to the unique chemical properties afforded by its long fatty acid ester chain, this testosterone ester is partially absorbed from the gastrointestinal tract into the lymphatic system, thereby bypassing a portion of first-pass metabolism in the liver and producing measurable increases in testosterone levels at much lower doses than free testosterone.[2][3] Of oral testosterone undecanoate that reaches circulation, 90 to 100% is transported lymphatically.[32] However, its duration remains short, with an elimination half-life of 1.6 hours and a mean residence time of 3.7 hours.[33][34][35] Oral testosterone undecanoate is provided as 40 mg oil-filled capsules and requires administration 2 to 4 times per day (i.e., 80 to 160 mg/day) for substitution in men.[2][33][3] It must be taken with food containing at least a moderate or "normal" amount of fat in order to achieve adequate absorption.[2][36][37][38] In addition, there is very high interindividual variability in levels of testosterone with oral testosterone undecanoate.[39] The bioavailability of oral testosterone undecanoate taken with food is 3 to 7%.[32][40] Inappropriately high levels of testosterone have been observed with 10 to 40 mg/day oral testosterone undecanoate in women.[41][42] The oral bioavailability of testosterone undecanoate in young women after a single 40 mg dose was found to be 6.8 ± 3.3%.[29]

A novel self-emulsifying formulation of oral testosterone undecanoate in 300-mg capsules for use once per day is under development.[39]

First-pass effect and differences

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Oral testosterone and oral testosterone undecanoate are not hepatotoxic, unlike orally administered 17α-alkylated anabolic steroids such as methyltestosterone and fluoxymesterone but similarly to parenteral routes and forms of bioidentical testosterone like injections.[43][2][39]

Buccal administration

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Testosterone can be used by buccal administration (e.g., brand name Striant).[2]

Sublingual administration

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Testosterone can be used by sublingual administration.[2][44][45] A 10 mg sublingual tablet with the brand name Testoral was previously marketed for use one to four times per day in men.[46]

Inhalational administration

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Testosterone has been studied by inhalation.[47]

Intranasal administration

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Testosterone can be used by intranasal administration (e.g., brand name Natesto).[2]

Transdermal administration

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See also: Testosterone (patch)

Testosterone is available for transdermal administration in the form of gels, creams, scrotal and non-scrotal patches, and axillary solutions.[2]

Transdermal testosterone gel has a bioavailability of about 8 to 14% when administered to recommended skin sites including the abdomen, arms, shoulders, and thighs.[48][49] Scrotal skin is the thinnest skin of the body[50] and has enhanced absorption characteristics relative to other skin areas.[51][52][53][54] Application of testosterone gels and creams to the scrotum has been studied and achieves much higher levels of testosterone than conventional skin sites.[55][56][57][58] Scrotal application of testosterone requires approximately 5-fold lower doses relative to non-scrotal application.[59][50]

The development of transdermal preparations of testosterone (and of progesterone)[60] has been more difficult than the case of estradiol.[50] This is because testosterone levels in men are about 100 to 1,000 times higher than estradiol levels in women (300 to 1,000 ng/dL vs. 50 to 150 pg/mL, respectively).[50] Non-scrotal testosterone patches were assessed and were found to be ineffective in raising testosterone levels in men.[50] As a result, scrotal testosterone patches were initially marketed.[50] Subsequently, however, non-scrotal testosterone patches with special permeation enhancers that could successfully increase testosterone levels were developed and marketed.[50] However, non-scrotal testosterone patches nonetheless require a large skin area for application (up to 60 cm2) and must be replaced daily.[50]

Supraphysiological levels of dihydrotestosterone (DHT) occur with scrotal application of testosterone, whereas this does not occur with non-scrotal transdermal application.[50] This is due to the high expression of 5α-reductase in scrotal skin.[50] Estradiol levels are similar with scrotal versus non-scrotal application of transdermal testosterone.[50]

Low-dose transdermal testosterone patches in women have been found to result in testosterone levels of 64 ng/dL with 150 μg/day and 102 ng/dL with 300 μg/day.[41] When testosterone is used transdermally in women or trans men, hair growth at the application sites can happen.[61]

Vaginal administration

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Testosterone can be used by vaginal administration of creams, suppositories, and vaginal rings available from compounding pharmacies.[62][63][64][65][66][67]

Rectal administration

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Testosterone levels with single-dose rectal administration of a 40 mg testosterone suppository in hypogonadal men.[27]

Testosterone was marketed as a suppository for rectal administration by Ferring Pharmaceuticals from the early 1960s under brand names such as Rektandron and Testosteron.[43][25][26] Rectal administration of testosterone avoids the first-pass effect with oral administration similarly to other non-oral routes.[2] A single 40 mg dose of rectal testosterone has been found to result in maximal testosterone levels of almost 1,200 ng/dL within 30 minutes.[27] Subsequently, testosterone levels steadily decline, reaching levels of about 700 ng/dL after 4 hours and levels of about 400 ng/dL after 8 hours.[27] Other studies have also assessed the use of rectal testosterone, with similar findings.[2][68][69][70][71][72] Rectal use of testosterone requires administration two or three times per day to maintain adequate testosterone levels.[27][2] The route is poorly accepted, owing to its inconvenience.[2] Rectal testosterone has been used in transmasculine hormone therapy.[69]

Intramuscular injection

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See also: Androgen ester
 
Testosterone levels over 16 weeks with intramuscular injection of different testosterone esters in hypogonadal men.[33]

Testosterone can be administered by intramuscular injection either as an aqueous suspension of testosterone or as an oil solution or aqueous suspension of testosterone esters such as testosterone propionate, testosterone enanthate, testosterone cypionate, testosterone undecanoate, and testosterone isobutyrate.[2][35][3] An even longer-acting testosterone ester that was developed but ultimately never marketed is testosterone buciclate.[3] These preparations are prodrugs of progesterone that have a long-lasting depot effect when injected into muscle or fat, ranging from days to months in duration.[2]

The bioavailability of drugs that are administered intramuscularly is generally almost 95%.[73]

As oil solutions by intramuscular injection, the elimination half-lives of testosterone esters are 0.8 days for testosterone propionate, 4.5 days for testosterone enanthate, 20.9 days (in tea seed oil) and 33.9 days (in caster oil) for testosterone undecanoate, and 29.5 days for testosterone buciclate.[8][33] The pharmacokinetics of testosterone cypionate are said to be the same as those of testosterone enanthate, with "extremely comparable" patterns of testosterone release.[35][33] Due to their varying and different elimination half-lives, the different intramuscular testosterone esters are administered with differing frequencies.[74] Testosterone propionate is injected two to three times per week, testosterone enanthate and testosterone cypionate are injected once every two to four weeks, and testosterone undecanoate and testosterone buciclate are injected once every 10 to 14 weeks.[74] Due to its relatively short duration, testosterone propionate is now relatively little used and testosterone undecanoate is the preferred testosterone ester for intramuscular use.[8][33] Testosterone undecanoate and testosterone buciclate can be injected intramuscularly as infrequently as four times per year.[8][33]

High doses of testosterone esters by intramuscular injection have been studied in healthy young men.[75] Levels of testosterone with intramuscular injections of testosterone cypionate were about 700 ng/dL for 100 mg/week, 1100 ng/dL for 250 mg/week, and 2000 ng/dL for 500 mg/week.[75][76] In another study, testosterone levels with 600 mg/week testosterone enanthate by intramuscular injection were 2,800–3,200 ng/dL.[75][77]

Intramuscular injection of testosterone propionate as an oil solution, aqueous suspension, and emulsion has been compared.[78]

Intramuscular injection of testosterone-containing biodegradable microspheres has been studied.[2]

Structural properties of major testosterone esters
Androgen Structure Ester Relative
mol. weight		 Relative
T contentb		 logPc
Position(s) Moiet(ies) Type Lengtha
Testosterone   – – – – 1.00 1.00 3.0–3.4
Testosterone propionate   C17β Propanoic acid Straight-chain fatty acid 3 1.19 0.84 3.7–4.9
Testosterone isobutyrate   C17β Isobutyric acid Branched-chain fatty acid – (~3) 1.24 0.80 4.9–5.3
Testosterone isocaproate   C17β Isohexanoic acid Branched-chain fatty acid – (~5) 1.34 0.75 4.4–6.3
Testosterone caproate   C17β Hexanoic acid Straight-chain fatty acid 6 1.35 0.75 5.8–6.5
Testosterone phenylpropionate   C17β Phenylpropanoic acid Aromatic fatty acid – (~6) 1.46 0.69 5.8–6.5
Testosterone cypionate   C17β Cyclopentylpropanoic acid Cyclic carboxylic acid – (~6) 1.43 0.70 5.1–7.0
Testosterone enanthate   C17β Heptanoic acid Straight-chain fatty acid 7 1.39 0.72 3.6–7.0
Testosterone decanoate   C17β Decanoic acid Straight-chain fatty acid 10 1.53 0.65 6.3–8.6
Testosterone undecanoate   C17β Undecanoic acid Straight-chain fatty acid 11 1.58 0.63 6.7–9.2
Testosterone buciclated   C17β Bucyclic acide Cyclic carboxylic acid – (~9) 1.58 0.63 7.9–8.5
Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic or cyclic fatty acids. b = Relative testosterone content by weight (i.e., relative androgenic/anabolic potency). c = Experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). Retrieved from PubChem, ChemSpider, and DrugBank. d = Never marketed. e = Bucyclic acid = trans-4-Butylcyclohexane-1-carboxylic acid. Sources: See individual articles.
Pharmacokinetics of testosterone esters
Testosterone ester Form Route TmaxTooltip Time to peak levels t1/2Tooltip Elimination half-life MRTTooltip Mean residence time
Testosterone undecanoate Oil-filled capsules Oral ? 1.6 hours 3.7 hours
Testosterone propionate Oil solution Intramuscular injection ? 0.8 days 1.5 days
Testosterone enanthate Castor oil solution Intramuscular injection 10 days 4.5 days 8.5 days
Testosterone undecanoate Tea seed oil solution Intramuscular injection 13.0 days 20.9 days 34.9 days
Testosterone undecanoate Castor oil solution Intramuscular injection 11.4 days 33.9 days 36.0 days
Testosterone buciclatea Aqueous suspension Intramuscular injection 25.8 days 29.5 days 60.0 days
Notes: Testosterone cypionate has similar pharmacokinetics to Testosterone enanthate. Footnotes: a = Never marketed. Sources: See template.
Parenteral durations of androgens/anabolic steroids
Medication Form Major brand names Duration
Testosterone Aqueous suspension Andronaq, Sterotate, Virosterone 2–3 days
Testosterone propionate Oil solution Androteston, Perandren, Testoviron 3–4 days
Testosterone phenylpropionate Oil solution Testolent 8 days
Testosterone isobutyrate Aqueous suspension Agovirin Depot, Perandren M 14 days
Mixed testosterone estersa Oil solution Triolandren 10–20 days
Mixed testosterone estersb Oil solution Testosid Depot 14–20 days
Testosterone enanthate Oil solution Delatestryl 14–28 days
Testosterone cypionate Oil solution Depovirin 14–28 days
Mixed testosterone estersc Oil solution Sustanon 250 28 days
Testosterone undecanoate Oil solution Aveed, Nebido 100 days
Testosterone buciclated Aqueous suspension 20 Aet-1, CDB-1781e 90–120 days
Nandrolone phenylpropionate Oil solution Durabolin 10 days
Nandrolone decanoate Oil solution Deca Durabolin 21–28 days
Methandriol Aqueous suspension Notandron, Protandren 8 days
Methandriol bisenanthoyl acetate Oil solution Notandron Depot 16 days
Metenolone acetate Oil solution Primobolan 3 days
Metenolone enanthate Oil solution Primobolan Depot 14 days
Note: All are via i.m. injection. Footnotes: a = TP, TV, and TUe. b = TP and TKL. c = TP, TPP, TiCa, and TD. d = Studied but never marketed. e = Developmental code names. Sources: See template.

Subcutaneous injection

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See also: Androgen ester

Testosterone esters like testosterone enanthate and testosterone cypionate can be given by subcutaneous injection instead of intramuscular injection. Studies have shown that subcutaneous injection of testosterone and closely related esters in oil like testosterone cypionate, testosterone enantate, and nandrolone decanoate is effective and has similar pharmacokinetics to intramuscular injection.[79][80][81][82][83][84][85]

Subcutaneous implant

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Testosterone can be administered in the form of a subcutaneous pellet implant.[2]

The bioavailability of testosterone when administered as a subcutaneous pellet implant is virtually 100%.[86] Levels of testosterone vary considerably between individuals, but are fairly constant within individuals.[41] The absorption half-life of subdermal testosterone implants is 2.5 months.[8] The replacement interval is once every four to six months.[41][87] A single 50 mg testosterone pellet implanted every 4 to 6 months has been found to result in testosterone levels of 70 to 90 ng/dL in women.[41]

Intravenous injection

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Testosterone esters like testosterone enanthate are hydrolyzed into testosterone so rapidly in the blood that testosterone and testosterone enanthate have nearly identical pharmacokinetics when administered via intravenous injection.[2]

General

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Absorption

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The oral bioavailability of testosterone is very low.[8][88] The bioavailability of oral testosterone undecanoate is 3 to 7%.[32][40] Topical testosterone gels have a bioavailability of about 8 to 14% when administered to recommended skin sites including the abdomen, arms, shoulders, and thighs.[48][49] The bioavailability of testosterone by subcutaneous implant is virtually 100%.[86] The bioavailability of drugs that are administered intramuscularly is generally almost 95%.[73]

Distribution

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In the circulation, 97.0 to 99.5% of testosterone is bound to plasma proteins, with 0.5 to 3.0% unbound.[1] It is tightly bound to SHBG and weakly to albumin.[1] Of circulating testosterone, 30 to 44% is bound to SHBG while 54 to 68% is bound to albumin.[1] Testosterone that is unbound is referred to as free testosterone and testosterone that is bound to albumin is referred to as bioavailable testosterone.[1] Unlike testosterone that is bound to SHBG, bioavailable testosterone is bound to plasma proteins weakly enough such that, similarly to free testosterone, it may be biologically active, at least to a certain extent.[1] When referenced collectively (i.e., free, bioavailable, and SHBG-bound), circulating testosterone is referred to as total testosterone.[1]

Metabolism

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See also: Testosterone § Metabolism
 
 
This diagram illustrates the metabolic pathways involved in the metabolism of testosterone in humans. In addition to the transformations shown in the diagram, conjugation via sulfation and glucuronidation occurs with testosterone and metabolites that have one or more available hydroxyl (–OH) groups.

Testosterone is metabolized primarily in the liver mainly (90%) by reduction via 5α- and 5β-reductase and conjugation via glucuronidation and sulfation.[1][89][90] The major urinary metabolites of testosterone are androsterone glucuronide and etiocholanolone glucuronide.[1][89][90][91]

The elimination half-life of testosterone varies depending on the route of administration and formulation and on whether or not it is esterified.[8] The elimination half-life of testosterone in the blood or by intravenous injection is only about 10 minutes.[8][33] Conversely, testosterone and testosterone esters in oil solution or crystalline aqueous suspension administered by intramuscular or subcutaneous injection have much longer half-lives, in the range of days to months, due to slow release from the injection site.[8][33]

Elimination

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Testosterone and its metabolites are eliminated in urine.[92] It is excreted mainly as androsterone glucuronide and etiocholanolone glucuronide.[91] It is also excreted to a small extent as other conjugates such as testosterone glucuronide (1%), testosterone sulfate (0.03%), and androstanediol glucuronides.[91][93] Only a very small amount of testosterone (less than 0.01%) is found unchanged in the urine.[92][93]

See also

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References

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Further reading

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