Does CBD impact testosterone levels, and if so, how?

Testosterone is the dominant sex hormone in males. Besides helping maintain a healthy mood, testosterone plays several essential roles. 

These roles include the development of the penis and testes, muscle size, strength, sperm production, and sex drive or libido (1).

Testosterone is also one of several androgens (male sex hormones) in females, and they are produced in the adrenal gland and ovaries. 

Androgens have significant effects on a variety of bodily functions, such as the ovaries, bone strength, and sexual behavior, including healthy libido. 

The proper balance between testosterone (including androgens) and estrogen is vital for the ovaries to work healthily. 

While the specifics are uncertain, it is possible that androgens also play a critical role in normal brain function, including mood, sex drive, and cognitive function.

A testosterone levels test measures the levels of testosterone in the blood. Testosterone levels that are either too high or too low can cause health problems in both men and women.(2)

CBD and Testosterone: The Role of the ECS Explained

The endocannabinoid system (ECS) is a system of the human body which includes the naturally-produced cannabinoids. 

Among its many critical bodily functions is its vital role in reproduction, which is essential to consider when discussing CBD (cannabidiol) and testosterone (3).

The ECS is also one of the primary regulatory feedback mechanisms in the hypothalamic-pituitary-gonadal (HPG) axis. When CB1 and CB2 receptors are triggered, the reproductive hormones are also signaled and activated (4).

However, unlike THC (tetrahydrocannabinol), CBD does not directly bind to the CB1 and CB2 receptors. Instead, it indirectly impacts the ECS through other neurotransmitter systems present. 

The binding of cannabinoids to either receptor can have adverse effects on the male reproductive system.

Evidence suggests that CBD could play a role in balancing testosterone levels. 

In one of the earliest research on CBD and testosterone, researchers found that male sexual and reproductive function in animal models could be affected not only by THC but also by CBD (5). 

In a study published in Molecular and Cellular Endocrinology, the researchers noted that CBD might reduce the generation of testosterone in rats but the effect was worse with THC(6). 

The results also indicated that CBD could stifle the decline or oxidation of testosterone in the liver. 

CBD, however, cannot lower the already-circulating serum testosterone levels in the blood, as shown in a study, published in Drug Metabolism and Disposition, that was conducted in rats (7).

Ultimately, testosterone production reverts to its natural state when CBD is no longer present. 

CBD’s Impact on Testosterone Levels

According to the American Psychological Association, ongoing stress over an extended period can affect testosterone production, resulting in a decline in sex drive or libido. It can even cause erectile dysfunction or impotence (8). 

Meanwhile, studies have shown CBD’s therapeutic benefits that might impact testosterone levels by helping the body produce more of the hormones.

A study published in the Journal of Psychopharmacology demonstrated CBD’s anti-anxiety characteristics (9).

The authors noted that CBD could be a useful addition to treatment plans for both social and general anxiety disorders. 

By limiting the amount of emotional stress individuals feel, they can help their body produce testosterone.

When stress affects the immune system, the body can become vulnerable to infection. In the male anatomy, infections to the urethra, testes, and prostate gland can impact male reproductive functioning (10).

Meanwhile, research has demonstrated that cannabinoids, like cannabidiol, can interfere with the release of cytokines (11). Cytokines are proteins involved in acute and chronic inflammation (12).

 Also, the essential fatty acids found in hemp extracts, like CBD oil, have been shown to help increase testosterone production.

A year-long study published in the Asian Journal of Andrology examined the link between fat intake and reproductive hormone levels among healthy human subjects (13). 

The study found a positive correlation between the ingestion of polyunsaturated fats, like omega-3 and 6, and hormone concentrations. 

Ultimately, results showed that subjects who increased their intake of essential fatty acids experienced improved testicular function, which likely helped improve their levels of production of testosterone.

Conclusion

Most experts recommend that individuals looking to improve their testosterone levels naturally should focus on prioritizing sleep, eating a healthy and balanced diet, maintaining a healthy weight, exercising regularly, and finding ways to reduce stress.

CBD can be utilized in all of these measures, as the potent cannabinoid has been shown to possess several therapeutic benefits that may help manage and improve testosterone levels. 

Still, before embarking on a CBD regimen or including it as an adjunct therapy, consult with a doctor experienced in cannabis use for advice. 


  1. Harvard Health Publishing. (2019, Aug 29). Testosterone — What It Does And Doesn’t Do. Retrieved from https://www.health.harvard.edu/drugs-and-medications/testosterone–what-it-does-and-doesnt-do.
  2. MedlinePlus. (2020, Feb 26). Testosterone Levels Test. Retrieved from https://medlineplus.gov/lab-tests/testosterone-levels-test/.
  3. Habayeb OM, Bell SC, Konje JC. Endogenous cannabinoids: metabolism and their role in reproduction. Life Sci. 2002;70(17):1963–1977. DOI:10.1016/s0024-3205(01)01539-9.
  4. Hillard CJ. Endocannabinoids and the Endocrine System in Health and Disease. Handb Exp Pharmacol. 2015;231:317–339. DOI:10.1007/978-3-319-20825-1_11.
  5. Dalterio S, Bartke A, Burstein S. Cannabinoids inhibit testosterone secretion by mouse testes in vitro. Science. 1977;196(4297):1472–1473. DOI:10.1126/science.867048. 
  6. Jakubovic A, McGeer EG, McGeer PL. Effects of cannabinoids on testosterone and protein synthesis in rat testis Leydig cells in vitro. Mol Cell Endocrinol. 1979;15(1):41–50. DOI:10.1016/0303-7207(79)90069-8.
  7. Narimatsu S, Watanabe K, Yamamoto I, Yoshimura H. Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver. Drug Metab Dispos. 1988;16(6):880–889.
  8. APA. Stress Effects on the Body. Retrieved from https://www.apa.org/helpcenter/stress/effects-male-reproductive.
  9. Crippa JA, Derenusson GN, Ferrari TB, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011;25(1):121–130. DOI:10.1177/0269881110379283.
  10. APA. op. cit.
  11. Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333–1349. DOI:10.4155/fmc.09.93.
  12. Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci. 1997 Jan 1;2:d12-26. DOI: 10.2741/a171.
  13. MInguez-Alarcón L, Chavarro JE, Mendiola J, et al. Fatty acid intake in relation to reproductive hormones and testicular volume among young healthy men. Asian J Androl. 2017;19(2):184–190. DOI:10.4103/1008-682X.190323.

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Summary for UKPID

PROGESTOGENS

Helen Seymour, BPharm (Hons)

National Poisons Information Service (Newcastle Centre)

Regional Drug & Therapeutics Centre

Wolfson Building

Claremont Place

Newcastle upon Tyne

NE1 4LP

UK

This monograph has been produced by staff of a National Poisons

Information Service Centre in the United Kingdom. The work was

commissioned and funded by the UK Departments of Health, and was

designed as a source of detailed information for use by poisons

information centres.

Peer review group: Directors of the UK National Poisons Information

Service.

 

SUMMARY

Type of product

Used for a number of purposes, including treatment of amenorrhea,

abnormal uterine bleeding, contraception, malignant disease and

menopausal symptoms.

 

Ingredients

A progestogen.

Toxicity

Very low.

 

Features

May cause nausea and vomiting.

Rarely, withdrawal bleeding may occur in pre-pubertal girls.

 

Treatment

None required.

 

SUBSTANCE

Progestogen

 

ORIGIN OF SUBSTANCE

Synthetic

 

NAME

Brand Name/Generic Name

Cyclogest/ Progesterone

Depo-Provera/Medroxyprogesterone

Depostat/ Gestronol hexanoate

Duphaston/ Dydrogesterone

Duphaston HRT/Dydrogesterone

Farlutal/ Medroxyprogesterone

Femulen/ Ethynodiol diacetate

Gestone/ Progesterone

Megace/ Megesterol Acetate

Menzol/ Norethisterone

Micronor HRT/ Norethisterone

Micronor/ Norethisterone

Microval/ Levonorgestrel

Mirena/Levonorgestrel

Neogest/ Norgestrel

Norgeston/ Levonorgestrel

Noriday/ Norethisterone

Noristat/ Norethisterone

Norplant/ Levonorgestrel

Primolut N/ Norethisterone

Proluten Depot/ Hydroxyprogesterone Hexanoate

Provera/ Medroxyprogesterone Acetate

Utovlan/ Norethisterone

 

CHEMICAL GROUP

Progestogens

BNF 6.4.1.2

Progestogen-Only contraceptives

BNF 7.3.2

Progestogens

BNF 8.3.2

 

SUBSTANCE IDENTITY

 

REFERENCE NUMBER

 

CAS

 

Product licence number

Cyclogest Pessaries 200mg   2343/0001

Cyclogest Pessaries 400mg   2343/0002

Depo-Provera 150mg/ml     0032/0082

Depostat 200mg in 2ml     0053/0190

Duphaston/Duphaston HRT    0512/5004R

Farlutal 100mg tablets     3433/0056

Farlutal 250mg tablets     3433/0058

Farlutal 500mg tablets     3433/0080

Farlutal 200mg/ml, 2.5ml    3433/0045

Farlutal 200mg/ml, 5ml     3433/0045

Femulen 500mcg         08821/0015

Gestone 25mg          3194/0061

Gestone 50mg          3194/0062

Gestone 100mg         3194/0063

Megace 40mg tablets      0125/0144

Megace 160mg tablets      0125/0173

Menzol 5mg tablets

Micronor Oral Contraceptives  0242/0234

Micronor HRT          0242/0241

Microval            0011/0040

Mirena             0484/0025

Neogest            0053/0062

Norgeston           0053/0068

Noriday            088210036

Noristerat           0053/0095

Norplant            0109/0249

Primolut N           0053/5033R

Provera 2.5mg         0032/0168

Provera 5mg          0032/5035R

Provera 10mg          0032/0151

Provera 100mg         0032/0111

Provera 200mg         0032/0112

Provera 400mg         0032/0131

Proluten Depot 250mg      0053/5031R

Proluten Depot 500mg      0053/5032R

 

MANUFACTURER

 

Bristol-Myers Squibb

Pharmaceuticals Ltd

141-149 Staines Rd

Hounslow

Middlesex

TW3 3JA

0181 5727422

 

Ferring Pharmaceuticals Ltd

Greville House

Hatton Road

Feltham

Middlesex

TW14 9PX

0181 8931543

 

Hoechst Rousell Ltd

Broadwater Park

Denham

Uxbridge

Middlesex

UB9 5HP

01895 834343

 

Janssen-Cilag Ltd

PO Box 79,

Saunderton,

High Wycombe,

Bucks

HP14 4HJ

01494 567567

 

Organon Laboratories Ltd

Cambridge Science Park,

Milton Road,

Cambridge

CB4 4FL

01223 423445

 

Ortho

see Janssen-Cilag

 

P-D

Parke-Davis Medical,

Lambert Court,

Chestnut Avenue,

Eastleigh,

Hants

SO53 3ZQ

01703 620500

 

Pharmacia-Leiras Ltd

Pharmacia & Upjohn

Davy Avenue

Knowlhill

Milton Keynes

MK5 8PH

01908 661101

 

Roussell

see Hoechst-Roussell

 

Schering Health Care Ltd

The Brow,

Burgess Hill,

West Sussex

RH15 9NE

01444 232323

 

Schwarz Pharma Ltd

Schwarz House

East Street

Chesham

Bucks

HP5 1DG

01494 772071

 

Searle Pharmaceuticals

PO Box 53,

Lane End Road,

High Wycombe,

Bucks

HP12 4HL

01494 521124

 

Solvay Healthcare Ltd

Hamilton House

Gaters Hill

West End

Southampton

SO18 3JD

01703 472281

 

Upjohn Ltd

See Pharmacia-Upjohn

 

Wyeth Laboratories

Huntercombe Lane South,

Taplow,

Maidenhead,

Berks

SL6 0PH

01628 604377

 

PRESENTATION

 

Form

 

Cyclogest Pessaries 200mg     pessaries

Cyclogest Pessaries 400mg     pessaries

Depo-Provera 150mg/1ml, 3.3ml   injection

Depostat100mg/ml, 2ml       injection

Duphaston/Duphaston HRT 10mg    tablets

Farlutal 100mg,250mg, 500mg    tablets

Farlutal 200mg/ml, 2.5ml & 5ml   injection

Femulen 5mg            tablets

Gestone 25mg            injection

Gestone 50mg            injection

Gestone 100mg           injection

Megace 40mg, 160mg         tablets

Menzol 5mg             tablets

Micronor Oral Contraceptives    tablets

Micronor HRT            tablets

Microval 30mcg           tablets

Mirena 20mcg/24hours        intra-uterine system

Neogest 75mcg           tablets

Norgeston 30 mcg          tablets

Noriday 350mcg           tablets

Noristerat 200mg/ml        injection

Norplant 38mg           implant capsule

Primolut N 5mg           tablets

Provera 2.5mg           tablets

Provera 5mg            tablets

Provera 10mg            tablets

Provera 100mg           tablets

Provera 200mg           tablets

Provera 400mg           tablets

Proluten Depot 250mg        injection

Proluten Depot 500mg        injection

Utovlan 5mg            tablets

 

Pack sizes

 

Cyclogest Pessaries 200mg     – 15

Cyclogest Pessaries 400mg     – 15

Depostat              – 1

Depo-Provera 150mg, 3.3ml     – 1

Depostat              – 1

Duphaston             – 60

Duphaston HRT           – 42

Farlutal 100mg tablets       – 20; 50

Farlutal 500mg tablets       – 56

Farlutal 200mg/ml, 2.5ml      – 1

Farlutal 200mg/ml, 5ml       – 1

Femulen              – 28

Gestone 25mg            – 1

Gestone 50mg            – 1

Gestone 100mg           – 1

Megace 40mg            – 20

Megace 160mg            – 30

Menzol               – 3 x 24; 3 x60

Micronor Oral Contraceptives    – 3 x 28

Micronor HRT            – 3 x 12

Microval              – 35

Mirena               – 1

Neogest              – 35

Norgeston             – 35

Noriday              – 3 x 28

Noristerat             – 1

Norplant              – 6 implants

Primolut N             – 30

Provera 2.5mg           – 30

Provera 5mg            – 10

Provera 10mg            – 10; 90

Provera 100mg           – 60

Provera 200mg           – 30

Provera 400mg           – 30

Proluten Depot 250mg        – 1

Proluten Depot 500mg        – 1

 

PHYSIOCHEMICAL PROPERTIES

 

Chemical structure

 

Dydrogesterone – 6-Dehydro-9ß,10alpha-progesterone

Ethynodiol acetate – 19-Nor-17alpha-pregn-4-en-20-yne-3ß

Gestronol – NIF

Hydroxyprogesterone hexanoate – 17alpha-Hydroxypregn-4-ene-3,20-

dione hexanoate

Levonorgestrel – 13-Ethyl-17ß-hydroxy-18,19-dinor-17alpha-pregn-

4-en-20-yn-3-one

Medroxyprogesterone acetate – 17alpha-Hydroxy-6alpha-methylpregn-

4-ene-3,20-dione acetate

Megestrol Acetate – 6-Methyl-3,20-dioxopregna-4,6-dien-17alpha-yl

acetate

Norgestrel – (±)-13-Ethyl-17ß-hydroxy-18,19-dinor-17alpha-pregn-

4-en-20-yn-3-one

Norethisterone – 17alpha-Ethinyl-19-nortestosterone, 17ß-hydroxy-

19-nor-17alpha-pregn-4-en-20-yn-3-one, 17alpha-ethinyl-17ß-

hydroxy-19-nor-androst-4-en-3-one

Progesterone – Pregn-4-ene-3,20-dione

Physical structure at room temperature

All are solid

 

Colour

 

Dydrogesterone – white to pale yellow

Ethynodiol acetate – white or almost white

Gestronol – NIF

Hydroxyprogesterone hexanoate – white or creamy white

Levonorgestrel – white or almost white

Megestrol Acetate – white or creamy-white

Medroxyprogesterone acetate – white or off-white

Norgestrel – white or almost white

Norethisterone – white or yellowish-white

Progesterone – white or slightly yellowish-white

 

Odour

 

Dydrogesterone – odourless or almost odourless

Ethynodiol acetate – odourless or almost odourless

Gestronol – NIF

Hydroxyprogesterone hexanoate – odourless or almost odourless

Levonorgestrel – odourless

Megestrol Acetate – odourless or almost odourless

Medroxyprogesterone acetate – odourless

Norgestrel – almost odourless

Norethisterone – odourless

Progesterone – odourless

 

Viscosity

 

NA

pH

NA

 

Solubility

 

Dydrogesterone – Practically insoluble in water; soluble 1 in 40 of

alcohol, 1 in 2 of chloroform, and 1 in 200 of ether; soluble in

acetone; sparingly soluble in methyl alcohol; slightly soluble in

fixed oils

 

Ethynodiol acetate – very slightly soluble to practically insoluble in

water; soluble in alcohol; freely to very soluble in chloroform;

freely soluble in ether; sparingly soluble in fixed oils

 

Gestronol – NIF

 

Hydroxyprogesterone hexanoate – practically insoluble in water; freely

soluble in alcohol and ether; very soluble in chloroform; dissolves in

fixed oils and esters

 

Levonorgestrel – practically insoluble in water; slightly soluble in

alcohol, in acetone and in ether; soluble in chloroform; sparingly

soluble in methylene chloride.

 

Megestrol Acetate – practically insoluble in water; sparingly soluble

in alcohol; very soluble in chloroform; soluble in acetone; slightly

soluble in ether and in fixed oils.

 

Medroxyprogesterone acetate – practically insoluble in water;

sparingly soluble in alcohol and in methylalcohol; slightly soluble in

ether; freely soluble in chloroform; soluble in acetone and dioxan

 

Norgestrel – practically insoluble in water; the BP states that it is

slightly, and the USP that it is sparingly soluble in alcohol;

sparingly soluble in methylene chloride; freely soluble in chloroform

 

Norethisterone – practically insoluble in water; slight to sparingly

soluble in alcohol; soluble in chloroform and in dioxan; slightly

soluble in ether.

 

Progesterone – BP solublities are: practically insoluble in water;

freely soluble in dehydrated alcohol; very soluble in chloroform;

sparingly soluble in acetone, in ether and in fixed oils. USP

solubilities are: practically insoluble in water; soluble in alcohol,

in acetone and in dioxan; sparingly soluble in vegetable oils

 

USES

 

Indications

 

To prevent conception; as part of hormone replacement regimes; as a

hormone antagonist in malignant disease.

 

Therapeutic Dose

 

Contraceptive: 1 tablet (of whichever preparation prescribed) daily at

the same time each day, starting on 1st day of cycle then

continuously.

 

Dydrogesterone – Endometriosis, 10mg 2-3 times daily from 5th to 25th

day of cycle or continuously; Infertility, irregular cycles, 10mg

twice daily from 11th to 25th day for at least 6 cycles (but not

recommended); Habitual abortion, 10mg twice daily from day 11 to day

25 of cycle until conception, then continuously until 20th week of

pregnancy and gradually reduced; Dysfunctional uterine bleeding, 10mg

twice daily (together with an oestrogen) for 5-7 days to arrest

bleeding; 10mg twice daily (together with an oestrogen) from 11th to

25th day of cycle to prevent bleeding; Dysmenorrhoea, 10mg twice daily

from 5th to 25th day of cycle; Amenorrhoea, 10mg twice daily form 11th

to 25th day of cycle with oestrogen therapy from 1st to 25th day of

cycle; Pre-menstrual syndrome, 10mg twice daily from 12th to 26th day

of cycle, increased if necessary (but not recommended); HRT, 10mg

daily on days 15-28 of each 28-day oestrogen HRT cycle, increased to

10mg twice daily if withdrawal bleed is early or endometrial biopsy

shows inadequate progestational response.

 

Hydroxyprogesterone hexanoate – Habitual abortion, 250-500mg weekly by

slow intra-muscular injection during first half of pregnancy.

 

Medroxyprogesterone acetate – Dysfunctional uterine bleeding, 2.5-10mg

daily for 5-10 days beginning on 16th-21st day of cycle, repeated for

2 cycles, for secondary amenorrhoea repeat for 3 cycles; Mild to

moderate endometriosis, 10mg 3 times daily for 90 consecutive days,

beginning on 1st day of cycle; Endometrial, prostate and renal cancer,

100-500mg daily; Breast cancer, various doses in range 0.4-1.5g daily;

 

by deep intramuscular injection for malignant disease, various doses

in range 1g daily down to 250mg weekly.

 

Megestrol Acetate – Breast cancer, 160mg daily in single or divided

doses; endometrial cancer, 40-320mg daily in divided doses.

 

Norethisterone – Endometriosis, 10mg daily starting on 5th day of

cycle (increased if spotting occurs to 20-25mg daily, reduced once

bleeding has stopped); Menorrhagia, 5mg 3 times daily for 10 days to

arrest bleeding; to prevent bleeding 5mg twice daily from 19th to 26th

day; Dysmenorrhoea, 5mg 3 times daily from 5th to 24th day for 3-4

cycles; Pre-menstrual syndrome, 5mg 2-3 times daily from 19th to 26th

day for several cycles (but not recommended); Postponement of

menstruation, 5mg three times daily starting 3 days before anticipated

onset (menstruation occurs 2-3 days after stopping); HRT 1mg daily on

days 15-26 of each 28-day oestrogen HRT cycle; Breast cancer, 40mg

daily, increased to 60mg daily if required.

 

Progesterone – Pre-menstrual syndrome, pessaries – 200mg daily to

400mg twice daily starting on day 12-14 and continued until onset of

menstruation (but not recommended); rectally if barrier methods of

contraception are used, or if vaginal infection; Embryo transfer, deep

intramuscular injection as per data sheet.

 

Contraindications

 

Pregnancy (except where licensed);a history during pregnancy of

idiopathic jaundice or severe pruritis. Acute or severe chronic liver

diseases including liver tumours. Dubin-Johnson or Rotor syndrome.

Undiagnosed abnormal vaginal bleeding. Thrombo-embolic disorders,

thrombophlebitis, cerebrovascular disorders, coronary artery disease,

myocardial infarction, angina, hyperlipidaemia or a history of these

conditions.

 

Abuses

 

NIF

 

HAZARD/RISK CLASSIFICATION

 

NIF

 

PHARMACOKINETICS

 

Absorption

 

Dydrogesterone

NIF

 

Ethynodiol acetate

almost 100%

 

Gestronol

NIF

 

Hydroxyprogesterone hexanoate

90%

 

Megestrol Acetate

about 100%

 

Medroxyprogesterone acetate

<100%

 

Norgestrel

NIF

 

Norethisterone

100%

 

Progesterone – extensive

 

Distribution

 

Dydrogesterone

NIF

 

Ethynodiol acetate

33l – extensively bound to albumin and more specifically to sex

hormone binding globulin

 

Gestronol

NIF

 

Hydroxyprogesterone hexanoate

5l

 

Levonorgestrel

93-95% plasma bound

 

Megestrol Acetate

NIF

 

Medroxyprogesterone acetate

>20l, 94% is protein bound

 

Norethisterone

95% plasma bound

 

Norgestimate

NIF

 

Norgestrel

NIF

 

Progesterone

17-29l, 95-98% plasma protein bound

 

Metabolism

 

Dydrogesterone

Metabolised to glucuronide conjugates

 

Ethynodiol acetate

Metabolised in liver or gut wall to norethisterone and then to

sulphate and glucuronide conjugates.

 

Gestronol

NIF

 

Hydroxyprogesterone hexanoate

metabolised in liver

 

Levonorgestrel

Extensively metabolised by the liver

 

Megestrol Acetate

metabolised by liver to glucuronide conjugates

 

Medroxyprogesterone acetate

extensively metabolised in the liver

 

Norgestimate

NIF

 

Norgestrel

NIF

 

Norethisterone

Metabolised in the intestinal wall and liver

 

Progesterone

About 75% is metabolised presystemically to glucuronide

conjugates by the liver

 

Elimination

 

Dydrogesterone

60% is excreted via the urine within 72 hours. Only small amounts

are excreted via the faeces

 

Ethynodiol acetate

via urine and faeces

 

Gestronol

NIF

 

Hydroxyprogesterone hexanoate

NIF

 

Levonorgestrel

20-30% eliminated via the faeces and the rest via the urine

 

Megestrol Acetate

excreted as metabolites via the urine and faeces

 

Medroxyprogesterone acetate

mainly as conjugated metabolites in the faeces

 

Norethisterone

60% as metabolites in urine and faeces

 

Norgestrel

NIF

 

Progesterone

mainly as conjugates in the urine

 

Half-life

 

Dydrogesterone

about 6h

 

Ethynodiol acetate

about 25h

 

Gestronol

NIF

 

Hydroxyprogesterone hexanoate

2-11h, mean 4h

 

Levonorgestrel

10.26h

 

Megestrol Acetate

15-20h

 

Medroxyprogesterone acetate

about 30h

 

Norgestrel

NIF

 

Norethisterone

5 -12h

 

Progesterone

distribution – 3-6min; elimination – 19-95min

 

Breast Milk

 

Dydrogesterone

small quantities are have been measured in breast milk, but this

is unlikely to present any risk to the infant

 

Ethynodiol acetate

norethisterone concentration appears to reach a peak at about

4-8h after ingestion of ethynodiol acetate, small amounts of

norethisterone are excreted into breast milk, the concentration

being 10-20% of that in plasma

 

Gestronol

NIF, contraindicated in lactation

 

Hydroxyprogesterone hexanoate

contraindicated in lactation

 

Levonorgestrel

Approximately 0.1% of the daily dose passes into breast milk

 

Megestrol Acetate

Disease states being treated would usually contraindicate

breast-feeding

 

Medroxyprogesterone acetate

excreted into breast milk in concentrations similar to those in

plasma. No special precautions are advised.

 

Norgestrel

NIF

 

Norethisterone

daily oral dose of 350micrograms for contraception were reported

in one study to reduce milk volume somewhat but do not usually

affect volume or composition. Intramuscular injections of 200mg

each 8 weeks do not interfere with lactation. The plasma/milk

ratio of the heptanoate is about 10 and only 0.1% of the dose,

estimated as a maximum of 1.5micrograms daily, reaches the baby.

this is unlikely to affect the bay and is undetectable in the

baby’s plasma at the time of the peak maternal plasma level.

There is a theoretical risk of all steroids interfering with

bilirubin conjugation, and maternal use of norethisterone should

probably be avoided whilst a baby has neonatal jaundice.

 

Progesterone

excreted in low concentrations, which are unlikely to have any

effect on the infant

 

TOXICOKINETICS

 

NIF

 

EPIDEMIOLOGY OF POISONING

 

In 1994, 2007 calls were made to UK NPIS centres about hormonal

contraceptive poisoning.

 

ADVERSE EFFECTS

 

General – Headaches/migraine, nausea, vomiting, breast changes, change

in weight, changes in libido, chloasma, breakthrough bleeding and

spotting, rash, depression, irregular cycle length, ocular changes,

increase in size uterine myofibromata and changes in carbohydrate,

lipid or vitamin metabolism. Rarely dizziness, hirsutism, haemorrhagic

eruption and colitis have been reported in users of progestogen-only

oral contraceptives

 

Megesterol – as above, rare reports of dyspnoea, heart failure,

hypertension, hot flushes, mood changes, cushingoid faces, tumour

flare (with or without hypercalcaemia), hyperglycaemia, alopecia and

carpel tunnel syndrome. Prolonged administration may cause urticaria.

Clinical and laboratory evidence of mild adrenal suppression

 

INTERACTIONS

 

Metabolism accelerated by rifamycins; increased plasma-cyclosporin

levels (inhibition of metabolism); aminoglutethimide reduces plasma

concentration of medroxyprogesterone

 

MECHANISM OF ACTION

 

Progestogens are synthetic compounds with actions similar to that of

progesterone. Progesterone is the main hormone secreted by the corpus

luteum. Large quantities are produced by the placenta during

pregnancy. It acts on the endometrium by converting the proliferative

phase induced by oestrogen to a secretory phase and preparing the

uterus to receive the fertilised ovum.

 

FEATURES OF POISONING

 

Acute

 

Ingestion

 

Toxicity is unlikely following an acute overdose. Occasionally there

may be nausea and vomiting. Withdrawal bleding may occur in females

even in pre-pubertal girls.

 

Chronic

 

Ingestion/Injection

 

Chronic or high dose therapy can result in jaundice, headache,

dizziness, oligomenorrhea or amenorrhea, congestion of the breasts and

decreased libido. Chronic toxicity may produce a thromboembolic state.

 

Pregnancy

 

During the pre-embryonic phase, which lasts until 17 days

post-conception, the ‘all or nothing’ concept is thought to apply.

During this period, cells damaged by a toxic insult, such as a drug

exposure, will be replaced by extra divisions of the remaining cells

which will then develop normally. If extensive damage occurs, failure

of implantation and spontaneous abortion may occur. Thus, if the

pregnancy is maintained, the risks to the fetus are likely to be no

greater than those for the general population.

 

The maternal administration of norethisterone to several species of

animals, including non-human primates, caused masculinisation of the

external female genitalia of the offspring but did not increase the

incidence of non-genital adverse fetal effects.1

 

There is no conclusive evidence of an association between progestogen

exposure in early pregnancy and non-genital malformations. Androgenic

hormones in human pregnancy have been associated with a small risk of

genital abnormalities when exposure occurs around about 6-7 weeks of

gestational age when the genitalia are beginning to develop.1-4

Approximately 1% of female fetuses exposed at this critical period of

development develop genital anomalies e.g. enlarged clitoris and

labial folds1,4. Internal genitalia and subsequent pubertal

development are not affected by norethisterone taken during pregnancy.

Male infants have an even smaller risk of genital anomalies, usually

hypospadias which can be treated surgically.

 

However, a recent meta-analysis of 14 studies involving 65,567 women

concluded that there was no association between 1st trimester exposure

to sex hormones generally, or to oral contraceptives specifically, and

external genital malformations.5

 

The use of norethisterone during any stage of pregnancy is

contra-indicated.

 

A number of congenital malformations, including cardiovascular,

central nervous system, multiple organ and limb defects, have been

reported in infants exposed to the drug in utero.1,2,3,4 However, the

role of norethisterone in the development of these anomalies has not

been established due to the influence of other factors such as alcohol

ingestion, cigarette smoking, concomitant drug therapy and maternal

obstetric history.1,3

 

There are three prospective follow-up reports from the European

Network of Teratology Information Services (ENTIS) following exposure

to progestogens during pregnancy. One patient had Norplant removed

after conception (details of timing of exposure not available), a

normal full term infant was born; there were two reports of exposure

to Depo-Provera, one woman had a dose at 1 week and 12 weeks of

gestation, a normal fullterm infant was born, the second woman was

exposed at 5 weeks of gestation and had an elective termination.

 

References

 

  1. Gilstrap III LC, Little BB. Drugs and Pregnancy. Amsterdam:

Elsevier Science Publishing, 1992: 242-244

 

  1. Folb PI, Dukes MNG (Eds). Drug Safety in Pregnancy. Amsterdam:

Elsevier Science Publishing, 1990: 273-281

 

  1. Briggs CG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation.

4th ed. Baltimore: Williams and Wilkins, 1994

 

  1. Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York:

Marcel Dekker, 1993

 

  1. Raman-Wilms L et al. Obs Gyn 1995; 85: 141-9

 

MANAGEMENT

 

Symptomatic treatment only is required.

Parents of prepubertal girls should be warned of the possibility of a

withdrawal bleed several days after ingestion.

 

ANALYSIS

 

NIF

 

PREVENTION OF POISONING

 

NIF

 

OTHER TOXICOLOGICAL DATA

 

Carcinogenicity

 

In a retrospective study of 5000 black women who received depot

medroxyprogesterone for contraception, no increased incidence in

breast, ovarian, or uterine corpus cancer was seen up to 13 years

later. (Liang et al 1993).

There is considerable evidence suggesting that after induction by

chemical carcinogens, sex hormones act as promoters of

heptocarcinogenesis.

 

Teratogenicity

 

There is no conclusive evidence of an association between progestogen

exposure in early pregnancy and non-genital malformations. Exposed

female infant have a small risk (approximately 1%) of clitoral

hypertrophy and fusion of the labioscrotal folds, when exposure occurs

during the critical period of genital development. These anomalies can

be corrected surgically. Male infants have an even smaller risk of

genital anomalies, usually hypospadias which can be treated

surgically.

 

Author

 

Helen Seymour, BPharm (Hons)

 

National Poisons Information Service (Newcastle Centre)

 

This monograph was produced by the staff of the Newcastle Centre of

the National Poisons Information Service in the United Kingdom. The

work was commissioned and funded by the UK Departments of Health, and

was designed as a source of detailed information for use by poisons

information centres.

 

Peer review was undertaken by the Directors of the UK National Poisons

Information Service.

 

Last updated January 1997

 

REFERENCES

 

  1. Martindale: The Extra Pharmacopoeia. 31st Edition. Reynolds JEF

(Ed.). Pharmaceutical Press 1996.

 

  1. Therapeutic Drugs. Dollery C. (Ed.). Churchill Livingstone 1991.

 

  1. ABPI Compendium of Data Sheets and Summaries of Product

Characteristics. Datapharm Publications Ltd. 1996-97.

 

  1. British National Formulary. Number 32 (September 1996). British

Medical Association and Royal Pharmaceutical Society.

 

  1. Poisindex Systemœ, Micromedex, Inc., Denver Colorado, Edition

Expires 31.12.96.

 

  1. National Teratology Information Service.

 

  1. European Commission; Poison centres: Collection of the annual

reports 1994, Analysis and synthesis, Final Report 31.8.96.

 

See Also:

Combined oral contraceptives (UK PID)

 

INTOX Home Page

Stanolone

  1. NAME

1.1 Substance

1.2 Group

1.3 Synonyms

1.4 Identification numbers

1.4.1 CAS number

1.4.2 Other numbers

1.5 Main brand names, main trade names

1.6 Main manufacturers, main importers

  1. SUMMARY

2.1 Main risks and target organs

2.2 Summary of clinical effects

2.3 Diagnosis

2.4 First aid measures and management principles

  1. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

3.2 Chemical structure

3.3 Physical properties

3.3.1 Colour

3.3.2 State/form

3.3.3 Description

3.4 Other characteristics

3.4.1 Shelf-life of the substance

3.4.2 Storage conditions

  1. USES

4.1 Indications

4.1.1 Indications

4.1.2 Description

4.2 Therapeutic dosage

4.2.1 Adults

4.2.2 Children

4.3 Contraindications

  1. ROUTES OF EXPOSURE

5.1 Oral

5.2 Inhalation

5.3 Dermal

5.4 Eye

5.5 Parenteral

5.6 Other

  1. KINETICS

6.1 Absorption by route of exposure

6.2 Distribution by route of exposure

6.3 Biological half-life by route of exposure

6.4 Metabolism

6.5 Elimination by route of exposure

  1. PHARMACOLOGY AND TOXICOLOGY

7.1 Mode of action

7.1.1 Toxicodynamics

7.1.2 Pharmacodynamics

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

7.2.1.2 Children

7.2.2 Relevant animal data

7.2.3 Relevant in vitro data

7.3 Carcinogenicity

7.4 Teratogenicity

7.5 Mutagenicity

7.6 Interactions

7.7 Main adverse effects

  1. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan

8.1.1 Sampling and specimen collection

8.1.1.1 Toxicological analyses

8.1.1.2 Biomedical analyses

8.1.1.3 Arterial blood gas analysis

8.1.1.4 Haematological analyses

8.1.1.5 Other (unspecified) analyses

8.1.2 Storage of laboratory samples and specimens

8.1.2.1 Toxicological analyses

8.1.2.2 Biomedical analyses

8.1.2.3 Arterial blood gas analysis

8.1.2.4 Haematological analyses

8.1.2.5 Other (unspecified) analyses

8.1.3 Transport of laboratory samples and specimens

8.1.3.1 Toxicological analyses

8.1.3.2 Biomedical analyses

8.1.3.3 Arterial blood gas analysis

8.1.3.4 Haematological analyses

8.1.3.5 Other (unspecified) analyses

8.2 Toxicological Analyses and Their Interpretation

8.2.1 Tests on toxic ingredient(s) of material

8.2.1.1 Simple Qualitative Test(s)

8.2.1.2 Advanced Qualitative Confirmation Test(s)

8.2.1.3 Simple Quantitative Method(s)

8.2.1.4 Advanced Quantitative Method(s)

8.2.2 Tests for biological specimens

8.2.2.1 Simple Qualitative Test(s)

8.2.2.2 Advanced Qualitative Confirmation Test(s)

8.2.2.3 Simple Quantitative Method(s)

8.2.2.4 Advanced Quantitative Method(s)

8.2.2.5 Other Dedicated Method(s)

8.2.3 Interpretation of toxicological analyses

8.3 Biomedical investigations and their interpretation

8.3.1 Biochemical analysis

8.3.1.1 Blood, plasma or serum

8.3.1.2 Urine

8.3.1.3 Other fluids

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

8.3.4 Interpretation of biomedical investigations

8.4 Other biomedical (diagnostic) investigations and their interpretation

8.5 Overall Interpretation of all toxicological analyses and toxicological investigations

8.6 References

  1. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

9.1.2 Inhalation

9.1.3 Skin exposure

9.1.4 Eye contact

9.1.5 Parenteral exposure

9.1.6 Other

9.2 Chronic poisoning

9.2.1 Ingestion

9.2.2 Inhalation

9.2.3 Skin exposure

9.2.4 Eye contact

9.2.5 Parenteral exposure

9.2.6 Other

9.3 Course, prognosis, cause of death

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

9.4.2 Respiratory

9.4.3 Neurological

9.4.3.1 Central nervous system

9.4.3.2 Peripheral nervous system

9.4.3.3 Autonomic nervous system

9.4.3.4 Skeletal and smooth muscle

9.4.4 Gastrointestinal

9.4.5 Hepatic

9.4.6 Urinary

9.4.6.1 Renal

9.4.6.2 Other

9.4.7 Endocrine and reproductive systems

9.4.8 Dermatological

9.4.9 Eye, ear, nose, throat: local effects

9.4.10 Haematological

9.4.11 Immunological

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

9.4.12.2 Fluid and electrolyte disturbances

9.4.12.3 Others

9.4.13 Allergic reactions

9.4.12 Other clinical effects

9.4.13 Special risks

9.5 Other

9.6 Summary

  1. MANAGEMENT

10.1 General principles

10.2 Life supportive procedures and symptomatic/specific treatment

10.3 Decontamination

10.4 Enhanced elimination

10.5 Antidote treatment

10.5.1 Adults

10.5.2 Children

10.6 Management discussion

  1. ILLUSTRATIVE CASES

11.1 Case reports from literature

  1. Additional information

12.1 Specific preventive measures

12.2 Other

  1. REFERENCES
  2. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)

Stanolone

 

International Programme on Chemical Safety

Poisons Information Monograph 917

Pharmaceutical

 

This monograph does not contain all of the sections completed. This

mongraph is harmonised with the Group monograph on Anabolic Steroids

(PIM G007).

 

  1. NAME

 

1.1 Substance

 

Stanolone

 

1.2 Group

 

ATC Classification:

A14 (Anabolic Agents for Systemic Use)

A14A (Anabolic steroids)

 

1.3 Synonyms

 

Androstanolone; Dihydrotestosterone.

 

1.4 Identification numbers

 

1.4.1 CAS number

 

521-18-6

 

1.4.2 Other numbers

 

1.5 Main brand names, main trade names

 

Andractim; Gelovit; Ophtovitol (multi-ingredient

preparations)

 

1.6 Main manufacturers, main importers

 

  1. SUMMARY

 

2.1 Main risks and target organs

 

There is no serious risk from acute poisoning, but

chronic use can cause harm. The main risks are those of

excessive androgens: menstrual irregularities and

virilization in women and impotence, premature cardiovascular

disease and prostatic hypertrophy in men. Both men and women

can suffer liver damage with oral anabolic steroids

 

containing a substituted 17-alpha-carbon. Psychiatric changes

can occur during use or after cessation of these

agents.

 

2.2 Summary of clinical effects

 

Acute overdosage can produce nausea and gastrointestinal

upset. Chronic usage is thought to cause an increase in

muscle bulk, and can cause an exageration of male

characteristics and effects related to male hormones.

Anabolic steroids can influence sexual function. They can

also cause cardiovascular and hepatic damage. Acne and male-

pattern baldness occur in both sexes; irregular menses,

atrophy of the breasts, and clitoromegaly in women; and

testicular atrophy and prostatic hypertrophy in men.

 

2.3 Diagnosis

 

The diagnosis depends on a history of use of oral or

injected anabolic steroids, together with signs of increased

muscle bulk, commonly seen in “body-builders”. Biochemical

tests of liver function are often abnormal in patients who

take excessive doses of oral anabolic steroids.

 

Laboratory analyses of urinary anabolic steroids and their

metabolites can be helpful in detecting covert use of these

drugs.

 

2.4 First aid measures and management principles

 

Supportive care is the only treatment necessary or

appropriate for acute intoxication. Chronic (ab)users can be

very reluctant to cease abuse, and may require professional

help as with other drug misuse.

 

  1. PHYSICO-CHEMICAL PROPERTIES

 

3.1 Origin of the substance

 

Naturally-occuring anabolic steroids are synthesised in

the testis, ovary and adrenal gland from cholesterol via

pregnenolone. Synthetic anabolic steroids are based on the

principal male hormone testosterone, modified in one of three

ways:

 

alkylation of the 17-carbon

esterification of the 17-OH group

modification of the steroid nucleus

 

(Murad & Haynes, 1985).

 

3.2 Chemical structure

 

Chemical Name:

17beta-Hydroxy-5alpha-androstan-3-one

 

Molecular Formula: C19H30O2

 

Molecular Weight: 290.4

 

3.3 Physical properties

 

3.3.1 Colour

 

3.3.2 State/form

 

3.3.3 Description

 

3.4 Other characteristics

 

3.4.1 Shelf-life of the substance

 

3.4.2 Storage conditions

 

Protect from light.

 

Vials for parenteral administration should be stored

at room temperature (15 to 30°C). Visual inspection

for particulate and/or discoloration is

advisable.

 

  1. USES

 

4.1 Indications

 

4.1.1 Indications

 

Anabolic agent; systemic

Anabolic steroid

Androstan derivative; anabolic steroid

Estren derivative; anabolic steroid

Other anabolic agent

Anabolic agent for systemic use; veterinary

Anabolic steroid; veterinary

Estren derivative; veterinary

 

4.1.2 Description

 

The only legitimate therapeutic indications for

anabolic steroids are:

 

(a) replacement of male sex steroids in men who have

androgen deficiency, for example as a result of loss

of both testes

 

 

(b) the treatment of certain rare forms of aplastic

anaemia which are or may be responsive to anabolic

androgens.

 

(ABPI Data Sheet Compendium, 1993)

 

(c) the drugs have been used in certain countries to

counteract catabolic states, for example after major

trauma.

 

4.2 Therapeutic dosage

 

4.2.1 Adults

 

4.2.2 Children

 

Not applicable

 

4.3 Contraindications

 

Known or suspected cancer of the prostate or (in men)

breast.

Pregnancy or breast-feeding.

Known cardiovascular disease is a relative contraindication.

 

  1. ROUTES OF EXPOSURE

 

5.1 Oral

 

Anabolic steroids can be absorbed from the

gastrointestinal tract, but many compounds undergo such

extensive first-pass metabolism in the liver that they are

inactive. Those compounds in which substitution of the 17-

carbon protects the compound from the rapid hepatic

metabolism are active orally (Murad and Haynes, 1985).

There are preparations of testosterone that can be taken

sublingually.

 

5.2 Inhalation

 

Not relevant

 

5.3 Dermal

 

No data available

 

5.4 Eye

 

Not relevant

 

5.5 Parenteral

 

Intramuscular or deep subcutaneous injection is the

principal route of administration of all the anabolic

steroids except the 17-alpha-substituted steroids which are

active orally.

 

5.6 Other

 

Not relevant

 

  1. KINETICS

 

6.1 Absorption by route of exposure

 

The absorption after oral dosing is rapid for

testosterone and probably for other anabolic steroids, but

there is extensive first-pass hepatic metabolism for all

anabolic steroids except those that are substituted at the

17-alpha position.

 

The rate of absorption from subcutaneous or intramuscular

depots depends on the product and its formulation. Absorption

is slow for the lipid-soluble esters such as the cypionate or

enanthate, and for oily suspensions.

 

6.2 Distribution by route of exposure

 

The anabolic steroids are highly protein bound, and is

carried in plasma by a specific protein called sex-hormone

binding globulin.

 

6.3 Biological half-life by route of exposure

 

The metabolism of absorbed drug is rapid, and the

elimination half-life from plasma is very short. The duration

of the biological effects is therefore determined almost

entirely by the rate of absorption from subcutaneous or

intramuscular depots, and on the de-esterification which

precedes it (Wilson, 1992).

 

6.4 Metabolism

 

Free (de-esterified) anabolic androgens are metabolized

by hepatic mixed function oxidases (Wilson, 1992).

 

6.5 Elimination by route of exposure

 

After administration of radiolabelled testosterone,

about 90% of the radioactivity appears in the urine, and 6%

in the faeces; there is some enterohepatic recirculation

(Wilson, 1992).

 

  1. PHARMACOLOGY AND TOXICOLOGY

 

7.1 Mode of action

 

7.1.1 Toxicodynamics

 

The toxic effects are an exaggeration of the

normal pharmacological effects.

 

7.1.2 Pharmacodynamics

 

Anabolic steroids bind to specific receptors

present especially in reproductive tissue, muscle and

fat (Mooradian & Morley, 1987). The anabolic steroids

reduce nitrogen excretion from tissue breakdown in

androgen deficient men. They are also responsible for

normal male sexual differentiation. The ratio of

anabolic (“body-building”) effects to androgenic

(virilizing) effects may differ among the members of

the class, but in practice all agents possess both

properties to some degree. There is no clear evidence

that anabolic steroids enhance overall athletic

performance (Elashoff et al, 1991).

 

7.2 Toxicity

 

7.2.1 Human data

 

7.2.1.1 Adults

 

No data available.

 

7.2.1.2 Children

 

No data available.

 

7.2.2 Relevant animal data

 

No data available.

 

7.2.3 Relevant in vitro data

 

No data

 

7.3 Carcinogenicity

 

Anabolic steroids may be carcinogenic. They can

stimulate growth of sex-hormone dependent tissue, primarily

the prostate gland in men. Precocious prostatic cancer has

been described after long-term anabolic steroid abuse(Roberts

& Essenhigh, 1986). Cases where hepatic cancers have been

associated with anabolic steroid abuse have been reported

(Overly et al, 1984).

 

7.4 Teratogenicity

 

Androgen ingestion by a pregnant mother can cause

virilization of a female fetus (Dewhurst & Gordon,

1984).

 

7.5 Mutagenicity

 

No data available.

 

7.6 Interactions

 

No data available.

 

7.7 Main adverse effects

 

The adverse effects of anabolic steroids include weight

gain, fluid retention, and abnormal liver function as

measured by biochemical tests. Administration to children can

cause premature closure of the epiphyses. Men can develop

impotence and azoospermia. Women are at risk of

virilization.

 

  1. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

 

8.1 Material sampling plan

8.1.1 Sampling and specimen collection

8.1.1.1 Toxicological analyses

8.1.1.2 Biomedical analyses

8.1.1.3 Arterial blood gas analysis

8.1.1.4 Haematological analyses

8.1.1.5 Other (unspecified) analyses

8.1.2 Storage of laboratory samples and specimens

8.1.2.1 Toxicological analyses

8.1.2.2 Biomedical analyses

8.1.2.3 Arterial blood gas analysis

8.1.2.4 Haematological analyses

8.1.2.5 Other (unspecified) analyses

8.1.3 Transport of laboratory samples and specimens

8.1.3.1 Toxicological analyses

8.1.3.2 Biomedical analyses

8.1.3.3 Arterial blood gas analysis

8.1.3.4 Haematological analyses

8.1.3.5 Other (unspecified) analyses

8.2 Toxicological Analyses and Their Interpretation

8.2.1 Tests on toxic ingredient(s) of material

8.2.1.1 Simple Qualitative Test(s)

8.2.1.2 Advanced Qualitative Confirmation Test(s)

8.2.1.3 Simple Quantitative Method(s)

8.2.1.4 Advanced Quantitative Method(s)

 

8.2.2 Tests for biological specimens

8.2.2.1 Simple Qualitative Test(s)

8.2.2.2 Advanced Qualitative Confirmation Test(s)

8.2.2.3 Simple Quantitative Method(s)

8.2.2.4 Advanced Quantitative Method(s)

8.2.2.5 Other Dedicated Method(s)

8.2.3 Interpretation of toxicological analyses

8.3 Biomedical investigations and their interpretation

8.3.1 Biochemical analysis

8.3.1.1 Blood, plasma or serum

8.3.1.2 Urine

8.3.1.3 Other fluids

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

8.3.4 Interpretation of biomedical investigations

 

8.4 Other biomedical (diagnostic) investigations and their

interpretation

 

8.5 Overall Interpretation of all toxicological analyses and

toxicological investigations

 

Biomedical analysis

The following tests can be relevant in the investigation of

chronic anabolic steroid abuse:

  1. a) full blood count
  2. b) electrolytes and renal function tests
  3. c) hepatic function tests
  4. d) testosterone
  5. e) Lutenizing hormone
  6. f) prostatic acid phosphatase or prostate related antigen
  7.  g) blood glucose concentration
  8. h) cholesterol concentration

 

Toxicological analysis

-urinary analysis for anabolic steroids and their

metabolites

 

Other investigations

-electrocardiogram

 

8.6 References

 

  1. CLINICAL EFFECTS

 

9.1 Acute poisoning

 

9.1.1 Ingestion

 

Nausea and vomiting can occur.

 

9.1.2 Inhalation

 

Not relevant

 

9.1.3 Skin exposure

 

Not relevant

 

9.1.4 Eye contact

 

Not relevant

 

9.1.5 Parenteral exposure

 

Patients are expected to recover rapidly after

acute overdosage, but there are few data. “Body-

builders” use doses many times the standard

therapeutic doses for these compounds but do not

suffer acute toxic effects.

 

9.1.6 Other

 

Not relevant

 

9.2 Chronic poisoning

 

9.2.1 Ingestion

 

Hepatic damage, manifest as derangement of

biochemical tests of liver function and sometimes

severe enough to cause jaundice; virilization in

women; prostatic hypertrophy, impotence and

azoospermia in men; acne, abnormal lipids, premature

cardiovascular disease (including stroke and

myocardial infarction), abnormal glucose tolerance,

and muscular hypertrophy in both sexes; psychiatric

disturbances can occur during or after prolonged

treatment (Ferner & Rawlins, 1988; Kennedy, 1992; Ross

& Deutch, 1990; Ryan, 1981; Wagner, 1989).

 

9.2.2 Inhalation

 

Not relevant

 

9.2.3 Skin exposure

 

Not relevant

 

9.2.4 Eye contact

 

Not relevant

 

9.2.5 Parenteral exposure

 

Virilization in women; prostatic hypertrophy,

impotence and azoospermia in men; acne, abnormal

lipids, premature cardiovascular disease (including

 

stroke and myocardial infarction), abnormal glucose

tolerance, and muscular hypertrophy in both sexes.

Psychiatric disturbances can occur during or after

prolonged treatment. Hepatic damage is not expected

from parenteral preparations.

 

9.2.6 Other

 

Not relevant

 

9.3 Course, prognosis, cause of death

 

Patients with symptoms of acute poisoning are expected

to recover rapidly. Patients who persistently abuse high

doses of anabolic steroids are at risk of death from

premature heart disease or cancer, especially prostatic

cancer. Non-fatal but long-lasting effects include voice

changes in women and fusion of the epiphyses in children.

Other effects are reversible over weeks or months.

 

9.4 Systematic description of clinical effects

 

9.4.1 Cardiovascular

 

Chronic ingestion of high doses of anabolic

steroids can cause elevations in blood pressure, left

ventricular hypertrophy and premature coronary artery

disease (McKillop et al., 1986; Bowman, 1990; McNutt

et al., 1988).

 

9.4.2 Respiratory

 

Not reported

 

9.4.3 Neurological

 

9.4.3.1 Central nervous system

 

Stroke has been described in a young

anabolic steroid abuser (Frankle et al.,

1988).

 

Pope & Katz (1988) described mania and

psychotic symptoms of hallucination and

delusion in anabolic steroid abusers. They

also described depression after withdrawal

from anabolic steroids. There is also

considerable debate about the effects of

anabolic steroids on aggressive behaviour

(Schulte et al., 1993) and on criminal

behaviour (Dalby, 1992). Mood swings were

 

significantly more common in normal

volunteers during the active phase of a trial

comparing methyltestosterone with placebo (Su

et al., 1993).

 

9.4.3.2 Peripheral nervous system

 

No data available

 

9.4.3.3 Autonomic nervous system

 

No data available

 

9.4.3.4 Skeletal and smooth muscle

 

No data available

 

9.4.4 Gastrointestinal

 

Acute ingestion of large doses can cause nausea

and gastrointestinal upset.

 

9.4.5 Hepatic

 

Orally active (17-alpha substituted) anabolic

steroids can cause abnormalities of hepatic function,

manifest as abnormally elevated hepatic enzyme

activity in biochemical tests of liver function, and

sometimes as overt jaundice.

 

The histological abnormality of peliosis hepatis has

been associated with anabolic steroid use (Soe et al.,

1992).

 

Angiosarcoma (Falk et al, 1979) and a case of

hepatocellular carcinoma in an anabolic steroid user

has been reported (Overly et al., 1984).

 

9.4.6 Urinary

 

9.4.6.1 Renal

 

Not reported

 

9.4.6.2 Other

 

Men who take large doses of anabolic

steroids can develop prostatic hypertrophy.

Prostatic carcinoma has been described in

young men who have abused anabolic steroids

(Roberts & Essenhigh, 1986).

 

9.4.7 Endocrine and reproductive systems

 

Small doses of anabolic steroids are said to

increase libido, but larger doses lead to azoospermia

and impotence. Testicular atrophy is a common clinical

feature of long-term abuse of anabolic steroids, and

gynaecomastia can occur (Martikainen et al., 1986;

Schurmeyer et al., 1984; Spano & Ryan, 1984).

 

Women develop signs of virilism, with increased facial

hair, male pattern baldness, acne, deepening of the

voice, irregular menses and clitoral enlargement

(Malarkey et al., 1991; Strauss et al., 1984).

 

9.4.8 Dermatological

 

Acne occurs in both male and female anabolic

steroids abusers. Women can develop signs of virilism,

with increased facial hair and male pattern

baldness.

 

9.4.9 Eye, ear, nose, throat: local effects

 

Changes in the larynx in women caused by

anabolic steroids can result in a hoarse, deep voice.

The changes are irreversible.

 

9.4.10 Haematological

 

Anabolic androgens stimulate erythropoesis.

 

9.4.11 Immunological

 

No data available

 

9.4.12 Metabolic

 

9.4.12.1 Acid-base disturbances

 

No data available.

 

9.4.12.2 Fluid and electrolyte disturbances

 

Sodium and water retention can

occur, and result in oedema; hypercalcaemia

is also reported (Reynolds, 1992).

 

9.4.12.3 Others

 

Insulin resistance with a fall in

glucose tolerance (Cohen & Hickman, 1987),

and hypercholesterolaemia with a fall in high

 

density lipoprotein cholesterol, have been

reported (Cohen et al., 1988; Glazer, 1991;

Webb et al., 1984).

 

9.4.13 Allergic reactions

 

No data available

 

9.4.12 Other clinical effects

 

No data available

 

9.4.13 Special risks

 

Risk of abuse

 

9.5 Other

 

No data available

 

9.6 Summary

 

  1. MANAGEMENT

 

10.1 General principles

 

The management of acute overdosage consists of

supportive treatment, with fluid replacement if vomiting is

severe. Chronic abuse should be discouraged, and

psychological support may be needed as in the treatment of

other drug abuse. The possibility of clinically important

depression after cessation of usage should be borne in

mind.

 

10.2 Life supportive procedures and symptomatic/specific treatment

 

Not relevant

 

10.3 Decontamination

 

Not usually required.

 

10.4 Enhanced elimination

 

Not indicated

 

10.5 Antidote treatment

 

10.5.1 Adults

 

None available

 

10.5.2 Children

 

None available

 

10.6 Management discussion

 

Not relevant

 

  1. ILLUSTRATIVE CASES

 

11.1 Case reports from literature

 

A 38-year old man presented with acute urinary

retention, and was found to have carcinoma of the prostate.

He had taken anabolic steroids for many years, and worked as

a “strong-man” (Roberts and Essenhigh, 1986).

 

A 22-year old male world-class weight lifter developed severe

chest pain awaking him from sleep, and was shown to have

myocardial infarction. For six weeks before, he had been

taking high doses of oral and injected anabolic steroids.

Total serum cholesterol was 596 mg/dL (HDL 14 mg/dL, LDL 513

mg/dL) (McNutt et al., 1988). Values of total cholesterol

concentration above 200 mg/dL are considered undesirable.

 

A 22-year old body builder took two eight-week courses of

anabolic steroids. He became severely depressed after the

second course, and when the depression gradually receded, he

had prominent paranoid and religious delusions (Pope and

Katz, 1987).

 

A 19-year old American college footballer took intramuscular

testosterone and oral methandrostenolone over 4 months. He

became increasingly aggressive with his wife and child. After

he severely injured the child, he ceased using anabolic

steroids, and his violence and aggression resolved within 2

months (Schulte et al, 1993).

 

  1. Additional information

 

12.1 Specific preventive measures

 

Anabolic steroid abuse amongst athletes, weight

lifters, body builders and others is now apparently common at

all levels of these sports. Not all abusers are competitive

sportsmen.

There is therefore scope for a public health campaign, for

example, based on gymnasia, to emphasize the dangers of

anabolic steroid abuse and to support those who wish to stop

using the drugs.

 

12.2 Other

 

No data available.

 

  1. REFERENCES

 

ABPI Data Sheet Compendium (1993) Datapharm Publications,

London.

 

Bowman S. (1990) Anabolic steroids and infarction. Br Med J;

300:

 

Cohen JC & Hickman R. (1987) Insulin Resistance and diminished

glucose tolerance in powerlifters ingesting anabolic steroids. J

Clin Endocrinol Metab 64: 960.

 

Cohen JC, Noakes TD, & Spinnler Benade AJ. (1988)

Hypercholesterolemia in male power lifters using Anabolic

Androgenic Steroids. The Physician and Sports medicine 16:

49-56.

 

Dalby JT. (1992) Brief anabolic steroid use and sustained

behavioral reaction. Am J Psychiatry 149: 271-272.

 

Dewhurst J. & Gordon RR (1984). Fertility following change of sex:

a follow-up. Lancet: ii: 1461-2.

 

Elashoff JD, Jacknow AD, Shain SG, & Braunstein GD. (1991) Effects

of anabolic-androgenic steroids on muscular strength. Annals Inter

Med 115: 387-393.

 

Falk H, Thomas LB, Popper H, Ishak KG. (1979). Hepatic

angiosacroma associated with androgenic-anabolic steroids. Lancet

2; 1120-1123.

 

Ferner RE & Rawlins MD (1988) Anabolic steroids: the power and the

glory? Br Med J 1988; 297: 877-878.

 

Frankle MA, Eichberg R, & Zacharian SB. (1988) Anabolic Androgenic

steroids and stroke in an athlete: case report. Arch Phys Med

Rehabil 1988; 69: 632-633.

 

Glazer G. (1991) Atherogenic effects of anabolic steroids on serum

lipid levels. Arch Intern Med 151: 1925-1933.

 

Kennedy MC. (1992). Anabolic steroid abuse and toxicology. Aust NZ

J Med 22: 374-381.

 

Malarkey WB, Strauss RH, Leizman DJ, Liggett M, & Demers LM.

(1991). Endocrine effects in femal weight lifters who self-

administer testosterone and anabolic steroids. Am J Obstet Gynecol

165: 1385-1390.

 

Martikainen H, Alen M, Rahkila P, & Vihko R. (1986) Testicular

responsiveness to human chorionic gonadotrophin during transient

hypogonadotrophic hypogondasim induced by androgenic/anabolic

steroids in power athletes. Biochem 25: 109-112.

 

McKillop G, Todd IC, Ballantyne D. (1986) Increased left

ventricular mass in a body builder using anabolic steroids. Brit J

Sports Med 20: 151-152.

 

McNutt RA, Ferenchick GS, Kirlin PC, & Hamlin NJ. (1988) Acute

myocardial infarction in a 22 year old world class weight lifter

using anabolic steroids. Am J Cardiol 62: 164.

 

Mooradian JE, Morley JE, Korenman SG. (1987) Biological actions of

androgens. Endocrine Reviews 8:1-27.

 

Murad F, & Haynes RC. (1985). Androgens. in. Ed: Goodman Gilman A,

Goodman L S, Roll T W, Murad F. The Pharmacological Basis of

Therapeutics, 7th edition, Macmillan, New York: 1440-1458

 

Overly WL et al. (1984). Androgens and hepatocellular carcinoma in

an athlete. Ann Int Med 100: 158-159.

 

Pope GR, & Katz DL. (1988). Affective and psychotic symptoms

associated with anabolic steroid use. Am J Psychiatry 145:

487-490.

 

Reynolds Ed. (1992) Martindale-The Extra Pharmacopeia. The

Pharmaceutical Press. London.

 

Roberts JT, & Essenhigh DM. (1986) Adenocarcinoma of prostate in

40-year old body builder. Lancet 2: 742.

 

Ross RB, & Deutsch S I.(1990) Hooked on hormones. JAMA 263:

2048-2049.

 

Ryan A J. (1981) Anabolic steroids are fool’s gold. Fed Proc 40:

2682-2688.

 

Schurmeyer T, Belkien L, Knuth UA, & Nieschlag E. (1984)

Reversible azoospermia induced by the anabolic steroid

19-nortestosterone. Lancet i: 417-420.

 

Soe KL. Soe M. & Gluud C. (1992). Liver pathology associated with

the use of anabolic-androgenic steroids. Liver 12: 73-9.

 

Schulte HM, Hall MJ, & Boyer M. (1993). Domestic violence

associated with anabolic steroid abuse. Am J Psychiatr 150:

348.

 

Spano F, & Ryan W G. (1989) Tamoxifen for gynecomastia induced by

anabolic steroids? New Engl J Med 311: 861-862.

 

Strauss RH, Liggett MT, & Lanese RR. (1984) Anabolic steroid use

and perceived effects in 10 weight-trained women athletes JAMA

253: 2871-2873.

 

Su T-P, Pagliaro M, Schmidt PJ, Pickar D, Wolkowitz O, & Rubinow

  1. (1993) Neuropsychiatric effects of anabolic steroids in male

normal volunteers. JAMA 269: 2760-2764.

 

Wagner JC (1989). Abuse of drugs used to enhance athletic

performance. Am J Hosp Pharm 46: 2059-2067

 

Webb O L, Laskarzewski P M, & Glueck, CJ. (1984) Severe depression

of high-density lipo protein cholesterol levels in weight lifters

and body builders by self-administered exogenous testerone and

anabolic-andorgenic steroids. Metabolism 33: 971-975.

 

Wilson J D. (1992). Androgens. In: Goodman Gilman A., Rall T W,

Nies A S, & Taylor P. Goodman and Gilman’s Pharmacological Basis

of Therapeutics. McGraw-Hill, Toronto. Pages 1413-1430.

 

  1. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE

ADDRESS(ES)

 

Author:    Dr R. E. Ferner,

Date:     1994

Peer review: INTOX Meeting, Sao Paulo, Brazil, September 1994

(Drs P.Kulling, R.McKuowen, A.Borges, R.Higa,

R.Garnier, Hartigan-Go, E.Wickstrom)

Editor:    Dr M.Ruse, March 1998

 

International Agency for Research on Cancer (IARC) – Summaries & Evaluations

OXYMETHOLONE

VOL.: 13 (1977) (p. 131)

 

  1. Summary of Data Reported and Evaluation

5.1 Animal data

No data were available to the Working Group.

5.2 Human data

Although ten cases of liver-cell tumours have been reported in patients with aplastic anaemia, Fanconi’s anaemia or paroxysmal nocturnal haemoglobinuria treated for long periods with oxymetholone alone or in combination with other androgenic drugs, a causal relationship cannot be established.

The increased risk of developing liver-cell tumours could be related to hepatic damage known to be caused by oxymetholone. On the other hand, patients with congenital anaemias many have an intrinsically higher risk of developing tumours; this risk many become manifest during the extended survival resulting from administration of the drug.

 

Subsequent evaluation: Suppl. 7 (1987) (Androgenic (Anabolic) Steroids)

 

Last updated: 25 March 1998

See Also:

Oxymetholone (PIM 915)

 

INTOX Home Page

Oxymetholone

  1. NAME

1.1 Substance

1.2 Group

1.3 Synonyms

1.4 Identification numbers

1.4.1 CAS number

1.4.2 Other numbers

1.5 Main brand names, main trade names

1.6 Main manufacturers, main importers

  1. SUMMARY

2.1 Main risks and target organs

2.2 Summary of clinical effects

2.3 Diagnosis

2.4 First aid measures and management principles

  1. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

3.2 Chemical structure

3.3 Physical properties

3.3.1 Colour

3.3.2 State/form

3.3.3 Description

3.4 Other characteristics

3.4.1 Shelf-life of the substance

3.4.2 Storage conditions

  1. USES

4.1 Indications

4.1.1 Indications

4.1.2 Description

4.2 Therapeutic dosage

4.2.1 Adults

4.2.2 Children

4.3 Contraindications

  1. ROUTES OF EXPOSURE

5.1 Oral

5.2 Inhalation

5.3 Dermal

5.4 Eye

5.5 Parenteral

5.6 Other

  1. KINETICS

6.1 Absorption by route of exposure

6.2 Distribution by route of exposure

6.3 Biological half-life by route of exposure

6.4 Metabolism

6.5 Elimination by route of exposure

  1. PHARMACOLOGY AND TOXICOLOGY

7.1 Mode of action

7.1.1 Toxicodynamics

7.1.2 Pharmacodynamics

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

7.2.1.2 Children

7.2.2 Relevant animal data

7.2.3 Relevant in vitro data

7.3 Carcinogenicity

7.4 Teratogenicity

7.5 Mutagenicity

7.6 Interactions

7.7 Main adverse effects

  1. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan

8.1.1 Sampling and specimen collection

8.1.1.1 Toxicological analyses

8.1.1.2 Biomedical analyses

8.1.1.3 Arterial blood gas analysis

8.1.1.4 Haematological analyses

8.1.1.5 Other (unspecified) analyses

8.1.2 Storage of laboratory samples and specimens

8.1.2.1 Toxicological analyses

8.1.2.2 Biomedical analyses

8.1.2.3 Arterial blood gas analysis

8.1.2.4 Haematological analyses

8.1.2.5 Other (unspecified) analyses

8.1.3 Transport of laboratory samples and specimens

8.1.3.1 Toxicological analyses

8.1.3.2 Biomedical analyses

8.1.3.3 Arterial blood gas analysis

8.1.3.4 Haematological analyses

8.1.3.5 Other (unspecified) analyses

8.2 Toxicological Analyses and Their Interpretation

8.2.1 Tests on toxic ingredient(s) of material

8.2.1.1 Simple Qualitative Test(s)

8.2.1.2 Advanced Qualitative Confirmation Test(s)

8.2.1.3 Simple Quantitative Method(s)

8.2.1.4 Advanced Quantitative Method(s)

8.2.2 Tests for biological specimens

8.2.2.1 Simple Qualitative Test(s)

8.2.2.2 Advanced Qualitative Confirmation Test(s)

8.2.2.3 Simple Quantitative Method(s)

8.2.2.4 Advanced Quantitative Method(s)

8.2.2.5 Other Dedicated Method(s)

8.2.3 Interpretation of toxicological analyses

8.3 Biomedical investigations and their interpretation

8.3.1 Biochemical analysis

8.3.1.1 Blood, plasma or serum

8.3.1.2 Urine

8.3.1.3 Other fluids

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

8.3.4 Interpretation of biomedical investigations

8.4 Other biomedical (diagnostic) investigations and their interpretation

8.5 Overall Interpretation of all toxicological analyses and toxicological investigations

8.6 References

  1. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

9.1.2 Inhalation

9.1.3 Skin exposure

9.1.4 Eye contact

9.1.5 Parenteral exposure

9.1.6 Other

9.2 Chronic poisoning

9.2.1 Ingestion

9.2.2 Inhalation

9.2.3 Skin exposure

9.2.4 Eye contact

9.2.5 Parenteral exposure

9.2.6 Other

9.3 Course, prognosis, cause of death

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

9.4.2 Respiratory

9.4.3 Neurological

9.4.3.1 Central nervous system

9.4.3.2 Peripheral nervous system

9.4.3.3 Autonomic nervous system

9.4.3.4 Skeletal and smooth muscle

9.4.4 Gastrointestinal

9.4.5 Hepatic

9.4.6 Urinary

9.4.6.1 Renal

9.4.6.2 Other

9.4.7 Endocrine and reproductive systems

9.4.8 Dermatological

9.4.9 Eye, ear, nose, throat: local effects

9.4.10 Haematological

9.4.11 Immunological

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

9.4.12.2 Fluid and electrolyte disturbances

9.4.12.3 Others

9.4.13 Allergic reactions

9.4.14 Other clinical effects

9.4.15 Special risks

9.5 Other

9.6 Summary

  1. MANAGEMENT

10.1 General principles

10.2 Life supportive procedures and symptomatic/specific treatment

10.3 Decontamination

10.4 Enhanced elimination

10.5 Antidote treatment

10.5.1 Adults

10.5.2 Children

10.6 Management discussion

  1. ILLUSTRATIVE CASES

11.1 Case reports from literature

  1. Additional information

12.1 Specific preventive measures

12.2 Other

  1. REFERENCES
  2. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)

 

Oxymetholone

 

International Programme on Chemical Safety

Poisons Information Monograph 915

Pharmaceutical

 

This monograph does not contain all of the sections completed. This

mongraph is harmonised with the Group monograph on Anabolic Steroids

(PIM G007).

 

  1. NAME

 

1.1 Substance

 

Oxymetholone

 

1.2 Group

 

ATC Classification:

A14 (Anabolic Agents for Systemic Use)

A14A (Anabolic steroids)

 

1.3 Synonyms

 

CI-406; HMD

 

1.4 Identification numbers

 

1.4.1 CAS number

 

434-07-1

 

1.4.2 Other numbers

 

1.5 Main brand names, main trade names

 

1.6 Main manufacturers, main importers

 

  1. SUMMARY

 

2.1 Main risks and target organs

 

There is no serious risk from acute poisoning, but

chronic use can cause harm. The main risks are those of

excessive androgens: menstrual irregularities and

virilization in women and impotence, premature cardiovascular

disease and prostatic hypertrophy in men. Both men and women

can suffer liver damage with oral anabolic steroids

containing a substituted 17-alpha-carbon. Psychiatric changes

can occur during use or after cessation of these

agents.

 

2.2 Summary of clinical effects

 

Acute overdosage can produce nausea and gastrointestinal

upset. Chronic usage is thought to cause an increase in

muscle bulk, and can cause an exageration of male

characteristics and effects related to male hormones.

Anabolic steroids can influence sexual function. They can

also cause cardiovascular and hepatic damage. Acne and male-

pattern baldness occur in both sexes; irregular menses,

atrophy of the breasts, and clitoromegaly in women; and

testicular atrophy and prostatic hypertrophy in men.

 

2.3 Diagnosis

 

The diagnosis depends on a history of use of oral or

injected anabolic steroids, together with signs of increased

muscle bulk, commonly seen in “body-builders”. Biochemical

tests of liver function are often abnormal in patients who

take excessive doses of oral anabolic steroids.

 

Laboratory analyses of urinary anabolic steroids and their

metabolites can be helpful in detecting covert use of these

drugs.

 

2.4 First aid measures and management principles

 

Supportive care is the only treatment necessary or

appropriate for acute intoxication. Chronic (ab)users can be

very reluctant to cease abuse, and may require professional

help as with other drug misuse.

 

  1. PHYSICO-CHEMICAL PROPERTIES

 

3.1 Origin of the substance

 

Naturally-occuring anabolic steroids are synthesised in

the testis, ovary and adrenal gland from cholesterol via

pregnenolone. Synthetic anabolic steroids are based on the

principal male hormone testosterone, modified in one of three

ways:

 

alkylation of the 17-carbon

esterification of the 17-OH group

modification of the steroid nucleus

 

(Murad & Haynes, 1985).

 

3.2 Chemical structure

 

Chemical Name:

17beta-Hydroxy-2-hydroxymethylene-17alpha-methyl-

-5alpha-androstan-3-one.

 

 

Molecular Formula: C21H32O3

 

Molecular Weight: 332.5

 

3.3 Physical properties

 

3.3.1 Colour

 

White to creamy-white

 

3.3.2 State/form

 

Solid-crystals

 

3.3.3 Description

 

Odourless or almost odourless.

British Pharmacopoeia solubilities are: practically

insoluble in water; soluble in alcohol and freely

soluble in chloroform; slightly soluble in ether.

US Pharmacopoeia solubilities are: practically

insoluble in water; soluble 1 in 40 of alcohol, 1 in 5

of chloroform, 1 in 82 of ether, and 1 in 14 of

dioxan.

Avoid contact with ferrous metals.

 

3.4 Other characteristics

 

3.4.1 Shelf-life of the substance

 

3.4.2 Storage conditions

 

Protect from light.

 

Vials for parenteral administration should be stored

at room temperature (15 to 30°C). Visual inspection

for particulate and/or discoloration is

advisable.

 

  1. USES

 

4.1 Indications

 

4.1.1 Indications

 

Anabolic agent; systemic

Anabolic steroid

Androstan derivative; anabolic steroid

Estren derivative; anabolic steroid

Other anabolic agent

Anabolic agent for systemic use; veterinary

Anabolic steroid; veterinary

Estren derivative; veterinary

 

4.1.2 Description

 

The only legitimate therapeutic indications for

anabolic steroids are:

 

(a) replacement of male sex steroids in men who have

androgen deficiency, for example as a result of loss

of both testes

 

(b) the treatment of certain rare forms of aplastic

anaemia which are or may be responsive to anabolic

androgens.

 

(ABPI Data Sheet Compendium, 1993)

 

(c) the drugs have been used in certain countries to

counteract catabolic states, for example after major

trauma.

 

4.2 Therapeutic dosage

 

4.2.1 Adults

 

4.2.2 Children

 

Not applicable

 

4.3 Contraindications

 

Known or suspected cancer of the prostate or (in men)

breast.

Pregnancy or breast-feeding.

Known cardiovascular disease is a relative contraindication.

 

  1. ROUTES OF EXPOSURE

 

5.1 Oral

 

Anabolic steroids can be absorbed from the

gastrointestinal tract, but many compounds undergo such

extensive first-pass metabolism in the liver that they are

inactive. Those compounds in which substitution of the 17-

carbon protects the compound from the rapid hepatic

metabolism are active orally (Murad and Haynes, 1985).

There are preparations of testosterone that can be taken

sublingually.

 

5.2 Inhalation

 

Not relevant

 

5.3 Dermal

 

No data available

 

5.4 Eye

 

Not relevant

 

5.5 Parenteral

 

Intramuscular or deep subcutaneous injection is the

principal route of administration of all the anabolic

steroids except the 17-alpha-substituted steroids which are

active orally.

 

5.6 Other

 

Not relevant

 

  1. KINETICS

 

6.1 Absorption by route of exposure

 

The absorption after oral dosing is rapid for

testosterone and probably for other anabolic steroids, but

there is extensive first-pass hepatic metabolism for all

anabolic steroids except those that are substituted at the

17-alpha position.

 

The rate of absorption from subcutaneous or intramuscular

depots depends on the product and its formulation. Absorption

is slow for the lipid-soluble esters such as the cypionate or

enanthate, and for oily suspensions.

 

6.2 Distribution by route of exposure

 

The anabolic steroids are highly protein bound, and is

carried in plasma by a specific protein called sex-hormone

binding globulin.

 

6.3 Biological half-life by route of exposure

 

The metabolism of absorbed drug is rapid, and the

elimination half-life from plasma is very short. The duration

of the biological effects is therefore determined almost

entirely by the rate of absorption from subcutaneous or

intramuscular depots, and on the de-esterification which

precedes it (Wilson, 1992).

 

6.4 Metabolism

 

Free (de-esterified) anabolic androgens are metabolized

by hepatic mixed function oxidases (Wilson, 1992).

 

6.5 Elimination by route of exposure

 

After administration of radiolabelled testosterone,

about 90% of the radioactivity appears in the urine, and 6%

in the faeces; there is some enterohepatic recirculation

(Wilson, 1992).

 

  1. PHARMACOLOGY AND TOXICOLOGY

 

7.1 Mode of action

 

7.1.1 Toxicodynamics

 

The toxic effects are an exaggeration of the

normal pharmacological effects.

 

7.1.2 Pharmacodynamics

 

Anabolic steroids bind to specific receptors

present especially in reproductive tissue, muscle and

fat (Mooradian & Morley, 1987). The anabolic steroids

reduce nitrogen excretion from tissue breakdown in

androgen deficient men. They are also responsible for

normal male sexual differentiation. The ratio of

anabolic (“body-building”) effects to androgenic

(virilizing) effects may differ among the members of

the class, but in practice all agents possess both

properties to some degree. There is no clear evidence

that anabolic steroids enhance overall athletic

performance (Elashoff et al, 1991).

 

7.2 Toxicity

 

7.2.1 Human data

 

7.2.1.1 Adults

 

No data available.

 

7.2.1.2 Children

 

No data available.

 

7.2.2 Relevant animal data

 

No data available.

 

7.2.3 Relevant in vitro data

 

No data

 

7.3 Carcinogenicity

 

Anabolic steroids may be carcinogenic. They can

stimulate growth of sex-hormone dependent tissue, primarily

the prostate gland in men. Precocious prostatic cancer has

been described after long-term anabolic steroid abuse

(Roberts & Essenhigh, 1986). Cases where hepatic cancers have

been associated with anabolic steroid abuse have been

reported (Overly et al, 1984).

 

7.4 Teratogenicity

 

Androgen ingestion by a pregnant mother can cause

virilization of a female fetus (Dewhurst & Gordon,

1984).

 

7.5 Mutagenicity

 

No data available.

 

7.6 Interactions

 

No data available.

 

7.7 Main adverse effects

 

The adverse effects of anabolic steroids include weight

gain, fluid retention, and abnormal liver function as

measured by biochemical tests. Administration to children can

cause premature closure of the epiphyses. Men can develop

impotence and azoospermia. Women are at risk of

virilization.

 

  1. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

 

8.1 Material sampling plan

8.1.1 Sampling and specimen collection

8.1.1.1 Toxicological analyses

8.1.1.2 Biomedical analyses

8.1.1.3 Arterial blood gas analysis

8.1.1.4 Haematological analyses

8.1.1.5 Other (unspecified) analyses

8.1.2 Storage of laboratory samples and specimens

8.1.2.1 Toxicological analyses

8.1.2.2 Biomedical analyses

8.1.2.3 Arterial blood gas analysis

8.1.2.4 Haematological analyses

8.1.2.5 Other (unspecified) analyses

8.1.3 Transport of laboratory samples and specimens

8.1.3.1 Toxicological analyses

8.1.3.2 Biomedical analyses

8.1.3.3 Arterial blood gas analysis

 

8.1.3.4 Haematological analyses

8.1.3.5 Other (unspecified) analyses

8.2 Toxicological Analyses and Their Interpretation

8.2.1 Tests on toxic ingredient(s) of material

8.2.1.1 Simple Qualitative Test(s)

8.2.1.2 Advanced Qualitative Confirmation Test(s)

8.2.1.3 Simple Quantitative Method(s)

8.2.1.4 Advanced Quantitative Method(s)

8.2.2 Tests for biological specimens

8.2.2.1 Simple Qualitative Test(s)

8.2.2.2 Advanced Qualitative Confirmation Test(s)

8.2.2.3 Simple Quantitative Method(s)

8.2.2.4 Advanced Quantitative Method(s)

8.2.2.5 Other Dedicated Method(s)

8.2.3 Interpretation of toxicological analyses

8.3 Biomedical investigations and their interpretation

8.3.1 Biochemical analysis

8.3.1.1 Blood, plasma or serum

8.3.1.2 Urine

8.3.1.3 Other fluids

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

8.3.4 Interpretation of biomedical investigations

 

8.4 Other biomedical (diagnostic) investigations and their

interpretation

 

8.5 Overall Interpretation of all toxicological analyses and

toxicological investigations

 

Biomedical analysis

The following tests can be relevant in the investigation of

chronic anabolic steroid abuse:

  1. a) full blood count
  2. b) electrolytes and renal function tests
  3. c) hepatic function tests
  4. d) testosterone
  5. e) Lutenizing hormone
  6. f) prostatic acid phosphatase or prostate related antigen
  7. g) blood glucose concentration
  8. h) cholesterol concentration

 

Toxicological analysis

-urinary analysis for anabolic steroids and their

metabolites

 

Other investigations

-electrocardiogram

 

8.6 References

 

  1. CLINICAL EFFECTS

 

9.1 Acute poisoning

 

9.1.1 Ingestion

 

Nausea and vomiting can occur.

 

9.1.2 Inhalation

 

Not relevant

 

9.1.3 Skin exposure

 

Not relevant

 

9.1.4 Eye contact

 

Not relevant

 

9.1.5 Parenteral exposure

 

Patients are expected to recover rapidly after

acute overdosage, but there are few data. “Body-

builders” use doses many times the standard

therapeutic doses for these compounds but do not

suffer acute toxic effects.

 

9.1.6 Other

 

Not relevant

 

9.2 Chronic poisoning

 

9.2.1 Ingestion

 

Hepatic damage, manifest as derangement of

biochemical tests of liver function and sometimes

severe enough to cause jaundice; virilization in

women; prostatic hypertrophy, impotence and

azoospermia in men; acne, abnormal lipids, premature

cardiovascular disease (including stroke and

myocardial infarction), abnormal glucose tolerance,

and muscular hypertrophy in both sexes; psychiatric

disturbances can occur during or after prolonged

treatment (Ferner & Rawlins, 1988; Kennedy, 1992; Ross

& Deutch, 1990; Ryan, 1981; Wagner, 1989).

 

9.2.2 Inhalation

 

Not relevant

 

9.2.3 Skin exposure

 

Not relevant

 

9.2.4 Eye contact

 

Not relevant

 

9.2.5 Parenteral exposure

 

Virilization in women; prostatic hypertrophy,

impotence and azoospermia in men; acne, abnormal

lipids, premature cardiovascular disease (including

stroke and myocardial infarction), abnormal glucose

tolerance, and muscular hypertrophy in both sexes.

Psychiatric disturbances can occur during or after

prolonged treatment. Hepatic damage is not expected

from parenteral preparations.

 

9.2.6 Other

 

Not relevant

 

9.3 Course, prognosis, cause of death

 

Patients with symptoms of acute poisoning are expected

to recover rapidly. Patients who persistently abuse high

doses of anabolic steroids are at risk of death from

premature heart disease or cancer, especially prostatic

cancer. Non-fatal but long-lasting effects include voice

changes in women and fusion of the epiphyses in children.

Other effects are reversible over weeks or months.

 

9.4 Systematic description of clinical effects

 

9.4.1 Cardiovascular

 

Chronic ingestion of high doses of anabolic

steroids can cause elevations in blood pressure, left

ventricular hypertrophy and premature coronary artery

disease (McKillop et al., 1986; Bowman, 1990; McNutt

et al., 1988).

 

9.4.2 Respiratory

 

Not reported

 

9.4.3 Neurological

 

9.4.3.1 Central nervous system

 

Stroke has been described in a young

anabolic steroid abuser (Frankle et al.,

1988).

 

 

Pope & Katz (1988) described mania and

psychotic symptoms of hallucination and

delusion in anabolic steroid abusers. They

also described depression after withdrawal

from anabolic steroids. There is also

considerable debate about the effects of

anabolic steroids on aggressive behaviour

(Schulte et al., 1993) and on criminal

behaviour (Dalby, 1992). Mood swings were

significantly more common in normal

volunteers during the active phase of a trial

comparing methyltestosterone with placebo (Su

et al., 1993).

 

9.4.3.2 Peripheral nervous system

 

No data available

 

9.4.3.3 Autonomic nervous system

 

No data available

 

9.4.3.4 Skeletal and smooth muscle

 

No data available

 

9.4.4 Gastrointestinal

 

Acute ingestion of large doses can cause nausea

and gastrointestinal upset.

 

9.4.5 Hepatic

 

Orally active (17-alpha substituted) anabolic

steroids can cause abnormalities of hepatic function,

manifest as abnormally elevated hepatic enzyme

activity in biochemical tests of liver function,and

sometimes as overt jaundice.

 

The histological abnormality of peliosis hepatis has

been associated with anabolic steroid use (Soe et al.,

1992).

 

Angiosarcoma (Falk et al, 1979) and a case of

hepatocellular carcinoma in an anabolic steroid user

has been reported (Overly et al., 1984).

 

9.4.6 Urinary

 

9.4.6.1 Renal

 

Not reported

 

9.4.6.2 Other

 

Men who take large doses of anabolic

steroids can develop prostatic hypertrophy.

Prostatic carcinoma has been described in

young men who have abused anabolic steroids

(Roberts & Essenhigh, 1986).

 

9.4.7 Endocrine and reproductive systems

 

Small doses of anabolic steroids are said to

increase libido, but larger doses lead to azoospermia

and impotence. Testicular atrophy is a common clinical

feature of long-term abuse of anabolic steroids, and

gynaecomastia can occur (Martikainen et al., 1986;

Schurmeyer et al., 1984; Spano & Ryan, 1984).

 

Women develop signs of virilism, with increased facial

hair, male pattern baldness, acne, deepening of the

voice, irregular menses and clitoral enlargement

(Malarkey et al., 1991; Strauss et al., 1984).

 

9.4.8 Dermatological

 

Acne occurs in both male and female anabolic

steroids abusers. Women can develop signs of virilism,

with increased facial hair and male pattern

baldness.

 

9.4.9 Eye, ear, nose, throat: local effects

 

Changes in the larynx in women caused by

anabolic steroids can result in a hoarse, deep voice.

The changes are irreversible.

 

9.4.10 Haematological

 

Anabolic androgens stimulate erythropoesis.

 

9.4.11 Immunological

 

No data available

 

9.4.12 Metabolic

 

9.4.12.1 Acid-base disturbances

 

No data available.

 

9.4.12.2 Fluid and electrolyte disturbances

 

Sodium and water retention can

occur, and result in oedema; hypercalcaemia

is also reported (Reynolds, 1992).

 

9.4.12.3 Others

 

Insulin resistance with a fall in

glucose tolerance (Cohen & Hickman, 1987),

and hypercholesterolaemia with a fall in high

density lipoprotein cholesterol, have been

reported (Cohen et al., 1988; Glazer, 1991;

Webb et al., 1984).

 

9.4.13 Allergic reactions

 

No data available

 

9.4.14 Other clinical effects

 

No data available

 

9.4.15 Special risks

 

Risk of abuse

 

9.5 Other

 

No data available

 

9.6 Summary

 

  1. MANAGEMENT

 

10.1 General principles

 

The management of acute overdosage consists of

supportive treatment, with fluid replacement if vomiting is

severe. Chronic abuse should be discouraged, and

psychological support may be needed as in the treatment of

other drug abuse. The possibility of clinically important

depression after cessation of usage should be borne in

mind.

 

10.2 Life supportive procedures and symptomatic/specific treatment

 

Not relevant

 

10.3 Decontamination

 

Not usually required.

 

10.4 Enhanced elimination

 

Not indicated

 

10.5 Antidote treatment

 

10.5.1 Adults

 

None available

 

10.5.2 Children

 

None available

 

10.6 Management discussion

 

Not relevant

 

  1. ILLUSTRATIVE CASES

 

11.1 Case reports from literature

 

A 38-year old man presented with acute urinary

retention, and was found to have carcinoma of the prostate.

He had taken anabolic steroids for many years, and worked as

a “strong-man” (Roberts and Essenhigh, 1986).

 

A 22-year old male world-class weight lifter developed severe

chest pain awaking him from sleep, and was shown to have

myocardial infarction. For six weeks before, he had been

taking high doses of oral and injected anabolic steroids.

Total serum cholesterol was 596 mg/dL (HDL 14 mg/dL, LDL 513

mg/dL) (McNutt et al., 1988). Values of total cholesterol

concentration above 200 mg/dL are considered undesirable.

 

A 22-year old body builder took two eight-week courses of

anabolic steroids. He became severely depressed after the

second course, and when the depression gradually receded, he

had prominent paranoid and religious delusions (Pope and

Katz, 1987).

 

A 19-year old American college footballer took intramuscular

testosterone and oral methandrostenolone over 4 months. He

became increasingly aggressive with his wife and child. After

he severely injured the child, he ceased using anabolic

steroids, and his violence and aggression resolved within 2

months (Schulte et al, 1993).

 

  1. Additional information

 

12.1 Specific preventive measures

 

Anabolic steroid abuse amongst athletes, weight

lifters, body builders and others is now apparently common at

all levels of these sports. Not all abusers are competitive

sportsmen.

There is therefore scope for a public health campaign, for

example, based on gymnasia, to emphasize the dangers of

anabolic steroid abuse and to support those who wish to stop

using the drugs.

 

12.2 Other

 

No data available.

 

  1. REFERENCES

 

ABPI Data Sheet Compendium (1993) Datapharm Publications,

London.

 

Bowman S. (1990) Anabolic steroids and infarction. Br Med J;

300:

 

Cohen JC & Hickman R. (1987) Insulin Resistance and diminished

glucose tolerance in powerlifters ingesting anabolic steroids. J

Clin Endocrinol Metab 64: 960.

 

Cohen JC, Noakes TD, & Spinnler Benade AJ. (1988)

Hypercholesterolemia in male power lifters using Anabolic

Androgenic Steroids. The Physician and Sports medicine 16:

49-56.

 

Dalby JT. (1992) Brief anabolic steroid use and sustained

behavioral reaction. Am J Psychiatry 149: 271-272.

 

Dewhurst J. & Gordon RR (1984). Fertility following change of sex:

a follow-up. Lancet: ii: 1461-2.

 

Elashoff JD, Jacknow AD, Shain SG, & Braunstein GD. (1991) Effects

of anabolic-androgenic steroids on muscular strength. Annals Inter

Med 115: 387-393.

 

Falk H, Thomas LB, Popper H, Ishak KG. (1979). Hepatic

angiosacroma associated with androgenic-anabolic steroids. Lancet

2; 1120-1123.

 

Ferner RE & Rawlins MD (1988) Anabolic steroids: the power and the

glory? Br Med J 1988; 297: 877-878.

 

 

Frankle MA, Eichberg R, & Zacharian SB. (1988) Anabolic Androgenic

steroids and stroke in an athlete: case report. Arch Phys Med

Rehabil 1988; 69: 632-633.

 

Glazer G. (1991) Atherogenic effects of anabolic steroids on serum

lipid levels. Arch Intern Med 151: 1925-1933.

 

Kennedy MC. (1992). Anabolic steroid abuse and toxicology. Aust NZ

J Med 22: 374-381.

 

Malarkey WB, Strauss RH, Leizman DJ, Liggett M, & Demers LM.

(1991). Endocrine effects in femal weight lifters who self-

administer testosterone and anabolic steroids. Am J Obstet Gynecol

165: 1385-1390.

 

Martikainen H, Alen M, Rahkila P, & Vihko R. (1986) Testicular

responsiveness to human chorionic gonadotrophin during transient

hypogonadotrophic hypogondasim induced by androgenic/anabolic

steroids in power athletes. Biochem 25: 109-112.

 

McKillop G, Todd IC, Ballantyne D. (1986) Increased left

ventricular mass in a body builder using anabolic steroids. Brit J

Sports Med 20: 151-152.

 

McNutt RA, Ferenchick GS, Kirlin PC, & Hamlin NJ. (1988) Acute

myocardial infarction in a 22 year old world class weight lifter

using anabolic steroids. Am J Cardiol 62: 164.

 

Mooradian JE, Morley JE, Korenman SG. (1987) Biological actions

of androgens. Endocrine Reviews 8:1-27.

 

Murad F, & Haynes RC. (1985). Androgens. in. Ed: Goodman Gilman

A, Goodman L S, Roll T W, Murad F. The Pharmacological Basis of

Therapeutics, 7th edition, Macmillan, New York: 1440-1458

 

Overly WL et al. (1984). Androgens and hepatocellular carcinoma in

an athlete. Ann Int Med 100: 158-159.

 

Pope GR,, & Katz DL. (1988). Affective and psychotic symptoms

associated with anabolic steroid use. Am J Psychiatry 145:

487-490.

 

Reynolds Ed. (1992) Martindale-The Extra Pharmacopeia. The

Pharmaceutical Press. London.

 

Roberts JT, & Essenhigh DM. (1986) Adenocarcinoma of prostate in

40-year old body builder. Lancet 2: 742.

 

Ross RB, & Deutsch S I.(1990) Hooked on hormones. JAMA 263:

2048-2049.

 

Ryan A J. (1981) Anabolic steroids are fool’s gold. Fed Proc 40:

2682-2688.

 

 

Schurmeyer T, Belkien L, Knuth UA, & Nieschlag E. (1984)

Reversible azoospermia induced by the anabolic steroid

19-nortestosterone. Lancet i: 417-420.

 

Soe KL. Soe M. & Gluud C. (1992). Liver pathology associated

with the use of anabolic-androgenic steroids. Liver 12:

73-9.

 

Schulte HM, Hall MJ, & Boyer M. (1993). Domestic violence

associated with anabolic steroid abuse. Am J Psychiatr 150:

348.

 

Spano F, & Ryan W G. (1989) Tamoxifen for gynecomastia induced by

anabolic steroids? New Engl J Med 311: 861-862.

 

Strauss RH, Liggett MT, & Lanese RR. (1984) Anabolic steroid use

and perceived effects in 10 weight-trained women athletes JAMA

253: 2871-2873.

 

Su T-P, Pagliaro M, Schmidt PJ, Pickar D, Wolkowitz O, & Rubinow

  1. (1993) Neuropsychiatric effects of anabolic steroids in male

normal volunteers. JAMA 269: 2760-2764.

 

Wagner JC (1989). Abuse of drugs used to enhance athletic

performance. Am J Hosp Pharm 46: 2059-2067

 

Webb O L, Laskarzewski P M, & Glueck, CJ. (1984) Severe depression

of high-density lipo protein cholesterol levels in weight lifters

and body builders by self-administered exogenous testerone and

anabolic-andorgenic steroids. Metabolism 33: 971-975.

 

Wilson J D. (1992). Androgens. In: Goodman Gilman A., Rall T W,

Nies A S, & Taylor P. Goodman and Gilman’s Pharmacological Basis

of Therapeutics. McGraw-Hill, Toronto. Pages 1413-1430.

 

  1. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE

ADDRESS(ES)

 

Author:    Dr R. E. Ferner,

Date:     1994

Peer review: INTOX Meeting, Sao Paulo, Brazil, September 1994

(Drs P.Kulling, R.McKuowen, A.Borges, R.Higa,

R.Garnier, Hartigan-Go, E.Wickstrom)

 

Editor:    Dr M.Ruse, March 1998

 

See Also:

Oxymetholone (IARC Summary & Evaluation, Volume 13, 1977)

 

INTOX Home Page

Stanozolol

  1. NAME

1.1 Substance

1.2 Group

1.3 Synonyms

1.4 Identification numbers

1.4.1 CAS number

1.4.2 Other numbers

1.5 Main brand names, main trade names

1.6 Main manufacturers, main importers

  1. SUMMARY

2.1 Main risks and target organs

2.2 Summary of clinical effects

2.3 Diagnosis

2.4 First aid measures and management principles

  1. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

3.2 Chemical structure

3.3 Physical properties

3.3.1 Colour

3.3.2 State/form

3.3.3 Description

3.4 Other characteristics

3.4.1 Shelf-life of the substance

3.4.2 Storage conditions

  1. USES

4.1 Indications

4.1.1 Indications

4.1.2 Description

4.2 Therapeutic dosage

4.2.1 Adults

4.2.2 Children

4.3 Contraindications

  1. ROUTES OF EXPOSURE

5.1 Oral

5.2 Inhalation

5.3 Dermal

5.4 Eye

5.5 Parenteral

5.6 Other

  1. KINETICS

6.1 Absorption by route of exposure

6.2 Distribution by route of exposure

6.3 Biological half-life by route of exposure

6.4 Metabolism

6.5 Elimination by route of exposure

  1. PHARMACOLOGY AND TOXICOLOGY

7.1 Mode of action

7.1.1 Toxicodynamics

7.1.2 Pharmacodynamics

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

7.2.1.2 Children

7.2.2 Relevant animal data

7.2.3 Relevant in vitro data

7.3 Carcinogenicity

7.4 Teratogenicity

7.5 Mutagenicity

7.6 Interactions

7.7 Main adverse effects

  1. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan

8.1.1 Sampling and specimen collection

8.1.1.1 Toxicological analyses

8.1.1.2 Biomedical analyses

8.1.1.3 Arterial blood gas analysis

8.1.1.4 Haematological analyses

8.1.1.5 Other (unspecified) analyses

8.1.2 Storage of laboratory samples and specimens

8.1.2.1 Toxicological analyses

8.1.2.2 Biomedical analyses

8.1.2.3 Arterial blood gas analysis

8.1.2.4 Haematological analyses

8.1.2.5 Other (unspecified) analyses

8.1.3 Transport of laboratory samples and specimens

8.1.3.1 Toxicological analyses

8.1.3.2 Biomedical analyses

8.1.3.3 Arterial blood gas analysis

8.1.3.4 Haematological analyses

8.1.3.5 Other (unspecified) analyses

8.2 Toxicological Analyses and Their Interpretation

8.2.1 Tests on toxic ingredient(s) of material

8.2.1.1 Simple Qualitative Test(s)

8.2.1.2 Advanced Qualitative Confirmation Test(s)

8.2.1.3 Simple Quantitative Method(s)

8.2.1.4 Advanced Quantitative Method(s)

8.2.2 Tests for biological specimens

8.2.2.1 Simple Qualitative Test(s)

8.2.2.2 Advanced Qualitative Confirmation Test(s)

8.2.2.3 Simple Quantitative Method(s)

8.2.2.4 Advanced Quantitative Method(s)

8.2.2.5 Other Dedicated Method(s)

8.2.3 Interpretation of toxicological analyses

8.3 Biomedical investigations and their interpretation

8.3.1 Biochemical analysis

8.3.1.1 Blood, plasma or serum

8.3.1.2 Urine

8.3.1.3 Other fluids

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

8.3.4 Interpretation of biomedical investigations

8.4 Other biomedical (diagnostic) investigations and their interpretation

8.5 Overall Interpretation of all toxicological analyses and toxicological investigations

8.6 References

  1. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

9.1.2 Inhalation

9.1.3 Skin exposure

9.1.4 Eye contact

9.1.5 Parenteral exposure

9.1.6 Other

9.2 Chronic poisoning

9.2.1 Ingestion

9.2.2 Inhalation

9.2.3 Skin exposure

9.2.4 Eye contact

9.2.5 Parenteral exposure

9.2.6 Other

9.3 Course, prognosis, cause of death

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

9.4.2 Respiratory

9.4.3 Neurological

9.4.3.1 Central nervous system

9.4.3.2 Peripheral nervous system

9.4.3.3 Autonomic nervous system

9.4.3.4 Skeletal and smooth muscle

9.4.4 Gastrointestinal

9.4.5 Hepatic

9.4.6 Urinary

9.4.6.1 Renal

9.4.6.2 Other

9.4.7 Endocrine and reproductive systems

9.4.8 Dermatological

9.4.9 Eye, ear, nose, throat: local effects

9.4.10 Haematological

9.4.11 Immunological

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

9.4.12.2 Fluid and electrolyte disturbances

9.4.12.3 Others

9.4.13 Allergic reactions

9.4.12 Other clinical effects

9.4.13 Special risks

9.5 Other

9.6 Summary

  1. MANAGEMENT

10.1 General principles

10.2 Life supportive procedures and symptomatic/specific treatment

10.3 Decontamination

10.4 Enhanced elimination

10.5 Antidote treatment

10.5.1 Adults

10.5.2 Children

10.6 Management discussion

  1. ILLUSTRATIVE CASES

11.1 Case reports from literature

  1. Additional information

12.1 Specific preventive measures

12.2 Other

  1. REFERENCES
  2. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)

 

Stanozolol

 

International Programme on Chemical Safety

Poisons Information Monograph 918

Pharmaceutical

 

This monograph does not contain all of the sections completed. This

mongraph is harmonised with the Group monograph on Anabolic Steroids

(PIM G007).

 

  1. NAME

 

1.1 Substance

 

Stanozolol

 

1.2 Group

 

ATC Classification:

A14 (Anabolic Agents for Systemic Use)

A14A (Anabolic steroids)

 

1.3 Synonyms

 

Androstanazole; Methylstanazole; NSC-43193; Win-14833

 

1.4 Identification numbers

 

1.4.1 CAS number

 

10418-03-8

 

1.4.2 Other numbers

 

1.5 Main brand names, main trade names

 

1.6 Main manufacturers, main importers

 

  1. SUMMARY

 

2.1 Main risks and target organs

 

There is no serious risk from acute poisoning, but

chronic use can cause harm. The main risks are those of

excessive androgens: menstrual irregularities and

virilization in women and impotence, premature cardiovascular

disease and prostatic hypertrophy in men. Both men and women

can suffer liver damage with oral anabolic steroids

containing a substituted 17-alpha-carbon. Psychiatric changes

can occur during use or after cessation of these

agents.

 

2.2 Summary of clinical effects

 

Acute overdosage can produce nausea and gastrointestinal

upset. Chronic usage is thought to cause an increase in

muscle bulk, and can cause an exageration of male

characteristics and effects related to male hormones.

Anabolic steroids can influence sexual function. They can

also cause cardiovascular and hepatic damage. Acne and male-

pattern baldness occur in both sexes; irregular menses,

atrophy of the breasts, and clitoromegaly in women; and

testicular atrophy and prostatic hypertrophy in men.

 

2.3 Diagnosis

 

The diagnosis depends on a history of use of oral or

injected anabolic steroids, together with signs of increased

muscle bulk, commonly seen in “body-builders”. Biochemical

tests of liver function are often abnormal in patients who

take excessive doses of oral anabolic steroids.

 

Laboratory analyses of urinary anabolic steroids and their

metabolites can be helpful in detecting covert use of these

drugs.

 

2.4 First aid measures and management principles

 

Supportive care is the only treatment necessary or

appropriate for acute intoxication. Chronic (ab)users can be

very reluctant to cease abuse, and may require professional

help as with other drug misuse.

 

  1. PHYSICO-CHEMICAL PROPERTIES

 

3.1 Origin of the substance

 

Naturally-occuring anabolic steroids are synthesised in

the testis, ovary and adrenal gland from cholesterol via

pregnenolone. Synthetic anabolic steroids are based on the

principal male hormone testosterone, modified in one of three

ways:

 

alkylation of the 17-carbon

esterification of the 17-OH group

modification of the steroid nucleus

 

(Murad & Haynes, 1985).

 

3.2 Chemical structure

 

Chemical Name:

17alpha-Methyl-2’H-5alpha-androst-2- -eno(3,2-c)pyrazol-

17beta-ol

 

 

Molecular Formula: C21H32N2O

 

Molecular Weight: 328.5

 

3.3 Physical properties

 

3.3.1 Colour

 

White or almost white

 

3.3.2 State/form

 

Solid-crystals

 

3.3.3 Description

 

Odourless.

There are 2 forms; needles melt at about 155 degrees

and prisms at about 235 degrees. Practically insoluble

in water; soluble 1 in 41 of alcohol, 1 in 74 of

chloroform, and 1 in 370 of ether; soluble in

dimethylformamide; slightly soluble in acetone and

ethyl acetate.

 

3.4 Other characteristics

 

3.4.1 Shelf-life of the substance

 

3.4.2 Storage conditions

 

Protect from light.

 

Vials for parenteral administration should be stored

at room temperature (15 to 30°C). Visual inspection

for particulate and/or discoloration is

advisable.

 

  1. USES

 

4.1 Indications

 

4.1.1 Indications

 

Anabolic agent; systemic

Anabolic steroid

Androstan derivative; anabolic steroid

Estren derivative; anabolic steroid

Other anabolic agent

Anabolic agent for systemic use; veterinary

Anabolic steroid; veterinary

Estren derivative; veterinary

 

4.1.2 Description

 

The only legitimate therapeutic indications for

anabolic steroids are:

 

(a) replacement of male sex steroids in men who have

androgen deficiency, for example as a result of loss

of both testes

 

(b) the treatment of certain rare forms of aplastic

anaemia which are or may be responsive to anabolic

androgens.

 

(ABPI Data Sheet Compendium, 1993)

 

(c) the drugs have been used in certain countries to

counteract catabolic states, for example after major

trauma.

 

4.2 Therapeutic dosage

 

4.2.1 Adults

 

4.2.2 Children

 

Not applicable

 

4.3 Contraindications

 

Known or suspected cancer of the prostate or (in men)

breast.

Pregnancy or breast-feeding.

Known cardiovascular disease is a relative contraindication.

 

  1. ROUTES OF EXPOSURE

 

5.1 Oral

 

Anabolic steroids can be absorbed from the

gastrointestinal tract, but many compounds undergo such

extensive first-pass metabolism in the liver that they are

inactive. Those compounds in which substitution of the 17-

carbon protects the compound from the rapid hepatic

metabolism are active orally (Murad and Haynes, 1985).

There are preparations of testosterone that can be taken

sublingually.

 

5.2 Inhalation

 

Not relevant

 

5.3 Dermal

 

No data available

 

5.4 Eye

 

Not relevant

 

5.5 Parenteral

 

Intramuscular or deep subcutaneous injection is the

principal route of administration of all the anabolic

steroids except the 17-alpha-substituted steroids which are

active orally.

 

5.6 Other

 

Not relevant

 

  1. KINETICS

 

6.1 Absorption by route of exposure

 

The absorption after oral dosing is rapid for

testosterone and probably for other anabolic steroids, but

there is extensive first-pass hepatic metabolism for all

anabolic steroids except those that are substituted at the

17-alpha position.

 

The rate of absorption from subcutaneous or intramuscular

depots depends on the product and its formulation. Absorption

is slow for the lipid-soluble esters such as the cypionate or

enanthate, and for oily suspensions.

 

6.2 Distribution by route of exposure

 

The anabolic steroids are highly protein bound, and is

carried in plasma by a specific protein called sex-hormone

binding globulin.

 

6.3 Biological half-life by route of exposure

 

The metabolism of absorbed drug is rapid, and the

elimination half-life from plasma is very short. The duration

of the biological effects is therefore determined almost

entirely by the rate of absorption from subcutaneous or

intramuscular depots, and on the de-esterification which

precedes it (Wilson, 1992).

 

6.4 Metabolism

 

Free (de-esterified) anabolic androgens are metabolized

by hepatic mixed function oxidases (Wilson, 1992).

 

6.5 Elimination by route of exposure

 

After administration of radiolabelled testosterone,

about 90% of the radioactivity appears in the urine, and 6%

in the faeces; there is some enterohepatic recirculation

(Wilson, 1992).

 

  1. PHARMACOLOGY AND TOXICOLOGY

 

7.1 Mode of action

 

7.1.1 Toxicodynamics

 

The toxic effects are an exaggeration of the

normal pharmacological effects.

 

7.1.2 Pharmacodynamics

 

Anabolic steroids bind to specific receptors

present especially in reproductive tissue, muscle and

fat (Mooradian & Morley, 1987). The anabolic steroids

reduce nitrogen excretion from tissue breakdown in

androgen deficient men. They are also responsible for

normal male sexual differentiation. The ratio of

anabolic (“body-building”) effects to androgenic

(virilizing) effects may differ among the members of

the class, but in practice all agents possess both

properties to some degree. There is no clear evidence

that anabolic steroids enhance overall athletic

performance (Elashoff et al, 1991).

 

7.2 Toxicity

 

7.2.1 Human data

 

7.2.1.1 Adults

 

No data available.

 

7.2.1.2 Children

 

No data available.

 

7.2.2 Relevant animal data

 

No data available.

 

7.2.3 Relevant in vitro data

 

No data

 

7.3 Carcinogenicity

 

Anabolic steroids may be carcinogenic. They can

stimulate growth of sex-hormone dependent tissue, primarily

the prostate gland in men. Precocious prostatic cancer has

been described after long-term anabolic steroid abuse(Roberts

& Essenhigh, 1986). Cases where hepatic cancers have been

associated with anabolic steroid abuse have been reported

(Overly et al, 1984).

 

7.4 Teratogenicity

 

Androgen ingestion by a pregnant mother can cause

virilization of a female fetus (Dewhurst & Gordon,

1984).

 

7.5 Mutagenicity

 

No data available.

 

7.6 Interactions

 

No data available.

 

7.7 Main adverse effects

 

The adverse effects of anabolic steroids include weight

gain, fluid retention, and abnormal liver function as

measured by biochemical tests. Administration to children can

cause premature closure of the epiphyses. Men can develop

impotence and azoospermia. Women are at risk of

virilization.

 

  1. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

 

8.1 Material sampling plan

8.1.1 Sampling and specimen collection

8.1.1.1 Toxicological analyses

8.1.1.2 Biomedical analyses

8.1.1.3 Arterial blood gas analysis

8.1.1.4 Haematological analyses

8.1.1.5 Other (unspecified) analyses

8.1.2 Storage of laboratory samples and specimens

8.1.2.1 Toxicological analyses

8.1.2.2 Biomedical analyses

8.1.2.3 Arterial blood gas analysis

8.1.2.4 Haematological analyses

8.1.2.5 Other (unspecified) analyses

8.1.3 Transport of laboratory samples and specimens

8.1.3.1 Toxicological analyses

8.1.3.2 Biomedical analyses

8.1.3.3 Arterial blood gas analysis

8.1.3.4 Haematological analyses

8.1.3.5 Other (unspecified) analyses

8.2 Toxicological Analyses and Their Interpretation

8.2.1 Tests on toxic ingredient(s) of material

8.2.1.1 Simple Qualitative Test(s)

8.2.1.2 Advanced Qualitative Confirmation Test(s)

8.2.1.3 Simple Quantitative Method(s)

8.2.1.4 Advanced Quantitative Method(s)

8.2.2 Tests for biological specimens

8.2.2.1 Simple Qualitative Test(s)

8.2.2.2 Advanced Qualitative Confirmation Test(s)

8.2.2.3 Simple Quantitative Method(s)

8.2.2.4 Advanced Quantitative Method(s)

8.2.2.5 Other Dedicated Method(s)

8.2.3 Interpretation of toxicological analyses

8.3 Biomedical investigations and their interpretation

8.3.1 Biochemical analysis

8.3.1.1 Blood, plasma or serum

8.3.1.2 Urine

8.3.1.3 Other fluids

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

8.3.4 Interpretation of biomedical investigations

 

8.4 Other biomedical (diagnostic) investigations and their

interpretation

8.5 Overall Interpretation of all toxicological analyses and

toxicological investigations

 

Biomedical analysis

The following tests can be relevant in the investigation of

chronic anabolic steroid abuse:

  1. a) full blood count
  2. b) electrolytes and renal function tests
  3. c) hepatic function tests
  4. d) testosterone
  5. e) Lutenizing hormone
  6. f) prostatic acid phosphatase or prostate related antigen
  7. g) blood glucose concentration
  8. h) cholesterol concentration

 

Toxicological analysis

-urinary analysis for anabolic steroids and their

metabolites

 

Other investigations

-electrocardiogram

 

8.6 References

 

  1. CLINICAL EFFECTS

 

9.1 Acute poisoning

 

9.1.1 Ingestion

 

Nausea and vomiting can occur.

 

9.1.2 Inhalation

 

Not relevant

 

9.1.3 Skin exposure

 

Not relevant

 

9.1.4 Eye contact

 

Not relevant

 

9.1.5 Parenteral exposure

 

Patients are expected to recover rapidly after

acute overdosage, but there are few data. “Body-

builders” use doses many times the standard

therapeutic doses for these compounds but do not

suffer acute toxic effects.

 

9.1.6 Other

 

Not relevant

 

9.2 Chronic poisoning

 

9.2.1 Ingestion

 

Hepatic damage, manifest as derangement of

biochemical tests of liver function and sometimes

severe enough to cause jaundice; virilization in

women; prostatic hypertrophy, impotence and

azoospermia in men; acne, abnormal lipids, premature

cardiovascular disease (including stroke and

myocardial infarction), abnormal glucose tolerance,

and muscular hypertrophy in both sexes; psychiatric

disturbances can occur during or after prolonged

treatment (Ferner & Rawlins, 1988; Kennedy, 1992; Ross

& Deutch, 1990; Ryan, 1981; Wagner, 1989).

 

9.2.2 Inhalation

 

Not relevant

 

9.2.3 Skin exposure

 

Not relevant

 

9.2.4 Eye contact

 

Not relevant

 

9.2.5 Parenteral exposure

 

Virilization in women; prostatic hypertrophy,

impotence and azoospermia in men; acne, abnormal

lipids, premature cardiovascular disease (including

stroke and myocardial infarction), abnormal glucose

tolerance, and muscular hypertrophy in both sexes.

Psychiatric disturbances can occur during or after

prolonged treatment. Hepatic damage is not expected

from parenteral preparations.

 

9.2.6 Other

 

Not relevant

 

9.3 Course, prognosis, cause of death

 

Patients with symptoms of acute poisoning are expected

to recover rapidly. Patients who persistently abuse high

doses of anabolic steroids are at risk of death from

premature heart disease or cancer, especially prostatic

cancer. Non-fatal but long-lasting effects include voice

changes in women and fusion of the epiphyses in children.

Other effects are reversible over weeks or months.

 

9.4 Systematic description of clinical effects

 

9.4.1 Cardiovascular

 

Chronic ingestion of high doses of anabolic

steroids can cause elevations in blood pressure, left

ventricular hypertrophy and premature coronary artery

disease (McKillop et al., 1986; Bowman, 1990; McNutt

et al., 1988).

 

9.4.2 Respiratory

 

Not reported

 

9.4.3 Neurological

 

9.4.3.1 Central nervous system

 

Stroke has been described in a young

anabolic steroid abuser (Frankle et al.,

1988).

 

Pope & Katz (1988) described mania and

psychotic symptoms of hallucination and

delusion in anabolic steroid abusers. They

also described depression after withdrawal

from anabolic steroids. There is also

considerable debate about the effects of

anabolic steroids on aggressive behaviour

(Schulte et al., 1993) and on criminal

behaviour (Dalby, 1992). Mood swings were

significantly more common in normal

volunteers during the active phase of a trial

comparing methyltestosterone with placebo (Su

et al., 1993).

 

9.4.3.2 Peripheral nervous system

 

No data available

 

9.4.3.3 Autonomic nervous system

 

No data available

 

9.4.3.4 Skeletal and smooth muscle

 

No data available

 

9.4.4 Gastrointestinal

 

Acute ingestion of large doses can cause nausea

and gastrointestinal upset.

 

9.4.5 Hepatic

 

Orally active (17-alpha substituted) anabolic

steroids can cause abnormalities of hepatic function,

manifest as abnormally elevated hepatic enzyme

activity in biochemical tests of liver function, and

sometimes as overt jaundice.

 

The histological abnormality of peliosis hepatis has

been associated with anabolic steroid use (Soe et al.,

1992).

 

 

Angiosarcoma (Falk et al, 1979) and a case of

hepatocellular carcinoma in an anabolic steroid user

has been reported (Overly et al., 1984).

 

9.4.6 Urinary

 

9.4.6.1 Renal

 

Not reported

 

9.4.6.2 Other

 

Men who take large doses of anabolic

steroids can develop prostatic hypertrophy.

Prostatic carcinoma has been described in

young men who have abused anabolic steroids

(Roberts & Essenhigh, 1986).

 

9.4.7 Endocrine and reproductive systems

 

Small doses of anabolic steroids are said to

increase libido, but larger doses lead to azoospermia

and impotence. Testicular atrophy is a common clinical

feature of long-term abuse of anabolic steroids, and

gynaecomastia can occur (Martikainen et al., 1986;

Schurmeyer et al., 1984; Spano & Ryan, 1984).

 

Women develop signs of virilism, with increased facial

hair, male pattern baldness, acne, deepening of the

voice, irregular menses and clitoral enlargement

(Malarkey et al., 1991; Strauss et al., 1984).

 

9.4.8 Dermatological

 

Acne occurs in both male and female anabolic

steroids abusers. Women can develop signs of virilism,

with increased facial hair and male pattern

baldness.

 

9.4.9 Eye, ear, nose, throat: local effects

 

Changes in the larynx in women caused by

anabolic steroids can result in a hoarse, deep voice.

The changes are irreversible.

 

9.4.10 Haematological

 

Anabolic androgens stimulate erythropoesis.

 

9.4.11 Immunological

 

No data available

 

9.4.12 Metabolic

 

9.4.12.1 Acid-base disturbances

 

No data available.

 

9.4.12.2 Fluid and electrolyte disturbances

 

Sodium and water retention can

occur, and result in oedema; hypercalcaemia

is also reported (Reynolds, 1992).

 

9.4.12.3 Others

 

Insulin resistance with a fall in

glucose tolerance (Cohen & Hickman, 1987),

and hypercholesterolaemia with a fall in high

density lipoprotein cholesterol, have been

reported (Cohen et al., 1988; Glazer, 1991;

Webb et al., 1984).

 

9.4.13 Allergic reactions

No data available

9.4.12 Other clinical effects

No data available

9.4.13 Special risks

Risk of abuse

9.5 Other

No data available

 

9.6 Summary

 

  1. MANAGEMENT

 

10.1 General principles

 

The management of acute overdosage consists of

supportive treatment, with fluid replacement if vomiting is

severe. Chronic abuse should be discouraged, and

psychological support may be needed as in the treatment of

other drug abuse. The possibility of clinically important

depression after cessation of usage should be borne in

mind.

 

10.2 Life supportive procedures and symptomatic/specific treatment

 

Not relevant

 

10.3 Decontamination

 

Not usually required.

 

10.4 Enhanced elimination

 

Not indicated

 

10.5 Antidote treatment

 

10.5.1 Adults

 

None available

 

10.5.2 Children

 

None available

 

10.6 Management discussion

 

Not relevant

 

  1. ILLUSTRATIVE CASES

 

11.1 Case reports from literature

 

A 38-year old man presented with acute urinary

retention, and was found to have carcinoma of the prostate.

He had taken anabolic steroids for many years, and worked as

a “strong-man” (Roberts and Essenhigh, 1986).

 

A 22-year old male world-class weight lifter developed severe

chest pain awaking him from sleep, and was shown to have

myocardial infarction. For six weeks before, he had been

taking high doses of oral and injected anabolic steroids.

Total serum cholesterol was 596 mg/dL (HDL 14 mg/dL, LDL 513

mg/dL) (McNutt et al., 1988). Values of total cholesterol

concentration above 200 mg/dL are considered undesirable.

 

A 22-year old body builder took two eight-week courses of

anabolic steroids. He became severely depressed after the

second course, and when the depression gradually receded, he

had prominent paranoid and religious delusions (Pope and

Katz, 1987).

 

A 19-year old American college footballer took intramuscular

testosterone and oral methandrostenolone over 4 months. He

became increasingly aggressive with his wife and child. After

 

he severely injured the child, he ceased using anabolic

steroids, and his violence and aggression resolved within 2

months (Schulte et al, 1993).

 

  1. Additional information

 

12.1 Specific preventive measures

 

Anabolic steroid abuse amongst athletes, weight

lifters, body builders and others is now apparently common at

all levels of these sports. Not all abusers are competitive

sportsmen.

There is therefore scope for a public health campaign, for

example, based on gymnasia, to emphasize the dangers of

anabolic steroid abuse and to support those who wish to stop

using the drugs.

 

12.2 Other

 

No data available.

 

  1. REFERENCES

 

ABPI Data Sheet Compendium (1993) Datapharm Publications,

London.

 

Bowman S. (1990) Anabolic steroids and infarction. Br Med J;

300:

 

Cohen JC & Hickman R. (1987) Insulin Resistance and diminished

glucose tolerance in powerlifters ingesting anabolic steroids. J

Clin Endocrinol Metab 64: 960.

 

Cohen JC, Noakes TD, & Spinnler Benade AJ. (1988)

Hypercholesterolemia in male power lifters using Anabolic

Androgenic Steroids. The Physician and Sports medicine 16:

49-56.

 

Dalby JT. (1992) Brief anabolic steroid use and sustained

behavioral reaction. Am J Psychiatry 149: 271-272.

 

Dewhurst J. & Gordon RR (1984). Fertility following change of sex:

a follow-up. Lancet: ii: 1461-2.

 

Elashoff JD, Jacknow AD, Shain SG, & Braunstein GD. (1991) Effects

of anabolic-androgenic steroids on muscular strength. Annals Inter

Med 115: 387-393.

 

Falk H, Thomas LB, Popper H, Ishak KG. (1979). Hepatic

angiosacroma associated with androgenic-anabolic steroids. Lancet

2; 1120-1123.

 

 

Ferner RE & Rawlins MD (1988) Anabolic steroids: the power and the

glory? Br Med J 1988; 297: 877-878.

 

Frankle MA, Eichberg R, & Zacharian SB. (1988) Anabolic Androgenic

steroids and stroke in an athlete: case report. Arch Phys Med

Rehabil 1988; 69: 632-633.

 

Glazer G. (1991) Atherogenic effects of anabolic steroids on serum

lipid levels. Arch Intern Med 151: 1925-1933.

 

Kennedy MC. (1992). Anabolic steroid abuse and toxicology. Aust NZ

J Med 22: 374-381.

 

Malarkey WB, Strauss RH, Leizman DJ, Liggett M, & Demers LM.

(1991). Endocrine effects in femal weight lifters who self-

administer testosterone and anabolic steroids. Am J Obstet Gynecol

165: 1385-1390.

 

Martikainen H, Alen M, Rahkila P, & Vihko R. (1986) Testicular

responsiveness to human chorionic gonadotrophin during transient

hypogonadotrophic hypogondasim induced by androgenic/anabolic

steroids in power athletes. Biochem 25: 109-112.

 

McKillop G, Todd IC, Ballantyne D. (1986) Increased left

ventricular mass in a body builder using anabolic steroids. Brit J

Sports Med 20: 151-152.

 

McNutt RA, Ferenchick GS, Kirlin PC, & Hamlin NJ. (1988) Acute

myocardial infarction in a 22 year old world class weight lifter

using anabolic steroids. Am J Cardiol 62: 164.

 

Mooradian JE, Morley JE, Korenman SG. (1987) Biological actions of

androgens. Endocrine Reviews 8:1-27.

 

Murad F, & Haynes RC. (1985). Androgens. in. Ed: Goodman Gilman A,

Goodman L S, Roll T W, Murad F. The Pharmacological Basis of

Therapeutics, 7th edition, Macmillan, New York: 1440-1458

 

Overly WL et al. (1984). Androgens and hepatocellular carcinoma in

an athlete. Ann Int Med 100: 158-159.

 

Pope GR, & Katz DL. (1988). Affective and psychotic symptoms

associated with anabolic steroid use. Am J Psychiatry 145:

487-490.

 

Reynolds Ed. (1992) Martindale-The Extra Pharmacopeia. The

Pharmaceutical Press. London.

 

Roberts JT, & Essenhigh DM. (1986) Adenocarcinoma of prostate in

40-year old body builder. Lancet 2: 742.

 

Ross RB, & Deutsch S I.(1990) Hooked on hormones. JAMA 263:

2048-2049.

 

 

Ryan A J. (1981) Anabolic steroids are fool’s gold. Fed Proc 40:

2682-2688.

 

Schurmeyer T, Belkien L, Knuth UA, & Nieschlag E. (1984)

Reversible azoospermia induced by the anabolic steroid

19-nortestosterone. Lancet i: 417-420.

 

Soe KL. Soe M. & Gluud C. (1992). Liver pathology associated with

the use of anabolic-androgenic steroids. Liver 12: 73-9.

 

Schulte HM, Hall MJ, & Boyer M. (1993). Domestic violence

associated with anabolic steroid abuse. Am J Psychiatr 150:

348.

 

Spano F, & Ryan W G. (1989) Tamoxifen for gynecomastia induced by

anabolic steroids? New Engl J Med 311: 861-862.

 

Strauss RH, Liggett MT, & Lanese RR. (1984) Anabolic steroid use

and perceived effects in 10 weight-trained women athletes JAMA

253: 2871-2873.

 

Su T-P, Pagliaro M, Schmidt PJ, Pickar D, Wolkowitz O, & Rubinow

  1. (1993) Neuropsychiatric effects of anabolic steroids in male

normal volunteers. JAMA 269: 2760-2764.

 

Wagner JC (1989). Abuse of drugs used to enhance athletic

performance. Am J Hosp Pharm 46: 2059-2067

 

Webb O L, Laskarzewski P M, & Glueck, CJ. (1984) Severe depression

of high-density lipo protein cholesterol levels in weight lifters

and body builders by self-administered exogenous testerone and

anabolic-andorgenic steroids. Metabolism 33: 971-975.

 

Wilson J D. (1992). Androgens. In: Goodman Gilman A., Rall T W,

Nies A S, & Taylor P. Goodman and Gilman’s Pharmacological Basis

of Therapeutics. McGraw-Hill, Toronto. Pages 1413-1430.

 

  1. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE

ADDRESS(ES)

 

Author:    Dr R. E. Ferner,

Date:     1994

Peer review: INTOX Meeting, Sao Paulo, Brazil, September 1994

(Drs P.Kulling, R.McKuowen, A.Borges, R.Higa,

R.Garnier, Hartigan-Go, E.Wickstrom)

Editor:    Dr M.Ruse, March 1998

 

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