Use and misuse of androgen.

Abdulrahman Alshaikh.

IntroductionIntroduction..

Steroid misuse/abuse has become Steroid misuse/abuse has become common in the past decade or two. common in the past decade or two.

Prominent among the reasons for abuse Prominent among the reasons for abuse are athletic performance and look good. are athletic performance and look good. Abuse in girls is rising and is correlated Abuse in girls is rising and is correlated

with other risky behaviors. New with other risky behaviors. New regulations at the national level have regulations at the national level have

been developed to curb this abuse and been developed to curb this abuse and legislation to educate youth has become legislation to educate youth has become

lawlaw..

What are Androgens?

Androgens are the sex steroids or hormones that produce changes in body shape (muscle gain, fat distribution) and secondary sexual characteristics (hair and beard growth, penile growth) typical of men. Androgens play a major and essential role in reproductive and sexual function in the mature male. The most important androgen in men is testosterone.

What are Steroids?

The synthetic derivative of androgens (male sex hormones) are commonly referred to as 'anabolic-androgenic steroids'. (Street name: 'roids').

Anabolic effects include the promotion of skeletal muscle growth

Androgenic effects refer to the development and maintenance of male sexual characteristics

When are Androgens misused or abused?

The medical misuse of androgens may occur in such settings as male infertility, male sexual dysfunction and 'male menopause'.

There is no good evidence to show that testosterone treatment is effective and safe for older men where androgen deficiency has not been clinically proven. Until further evidence is available, such treatment can not be recommended.

In the wider community, misuse of androgens in sport is also an issue with some athletes using androgens outside the rules of their particular governing body and without knowledge of the long-term affects on the body. Disqualification may occur if androgens are used in this setting.

Causes of androgen deficiencyCauses of androgen deficiency..

Testicular disease as testicular Testicular disease as testicular damage and klinefelters syndromedamage and klinefelters syndrome..

Pituitary diseasesPituitary diseases..Chronic diseases, severe illness, drug Chronic diseases, severe illness, drug

use, ageing, can lead to combined use, ageing, can lead to combined pituitary and testicular diseasespituitary and testicular diseases..

Testicular causes:

Classical androgen deficiency

Testicular disorders

Klinefelter’s syndrome and variants (mosaic)

Cryptorchidism and defects of testis development

Orchitis

Orchidectomy (advanced prostate cancer, bilateral testicular cancer)

Toxin exposure (cancer chemotherapy or radiotherapy, environmental, occupational and domestic toxins)

Pituitary causes

Hypothalamic–pituitary dysregulation

Idiopathic hypogonadotropic hypogonadism and variants:

Kallmann’s syndrome (associated with anosmia and midline cranial defects; caused by mutations in the KAL1 or FGRF1 [fibroblast growth factor receptor 1] genes)

Other genetic causes (including inactivating mutations in the DAX-1 [adrenal hypoplasia congenita], GnRH-receptor or GPR54 [G protein-coupled receptor] genes)

Pituitary tumour and treatment (surgery, irradiation)

Haemochromatosis

Craniopharyngioma

Partial or transient androgen deficiency

Constitutional delay of puberty

Acute critical illness, burns, major trauma or surgery

Drug use (eg, opiates, glucocorticoids, anabolic steroids)

Chronic disease and its treatment

Ageing (“late-onset” androgen deficiency)

Clinical featuresClinical features..

•During fetal life; disrupts male sexual During fetal life; disrupts male sexual differentiation and somatic developmentdifferentiation and somatic development..

•In adolescence ; incomplete or late sexual In adolescence ; incomplete or late sexual and somatic maturationand somatic maturation..

•In adult life; deficiency of some features of In adult life; deficiency of some features of virilization, reduce sense of well-being, virilization, reduce sense of well-being, mood changes, decrease libido, rarely mood changes, decrease libido, rarely

flushing, weight gain, loss muscle massflushing, weight gain, loss muscle mass , ,

Medical uses of androgen.

Delayed puberty in male .Primary or secondary androgen

deficiency in adults. Androgen replacement

Elderly patients with androgen deficiency with no pituitary diseases –

controversy.Very debilitated illness – controversy.

General principles of testosterone treament.

Should be giving only to man who is hypogonadal.

Testosterone can be replaced satisfactory whether the testosterone deficiency either due to primary or secondary hypogonadism.

Testosterone replacement due to ageing is uncertain.

Testosterone preparations.

Alkylated preparations. Testosterone ester. Transdermal. Gel. Buccal tablet.

Androgen therapy.

Life long and should be started after androgen deficiency has been proved.

Testosterone rather synthetic androgens should be used.

17- alkylated androgen are hepatotoxic and should not be used for ART.

USE OF ANDROGENS AND OTHER DRUGS BY ATHLETES

•*TO IMPROVE THEIR PERFORMANCE

*THEY ARE MOTIVATED TO WIN.

*1950 USED BY BODY BUILDER..

How this area of medicine is How this area of medicine is differentdifferent??

Athletes often obtain the medications from Athletes often obtain the medications from sources other than physiciansources other than physician..

Athletes obtain information from other Athletes obtain information from other athletes, trainer, magazine, and the internetathletes, trainer, magazine, and the internet..

Take several medication simultaneouslyTake several medication simultaneously..They discontinue it periodically to ovoid They discontinue it periodically to ovoid

detectiondetection..Physician who see the athletes are often Physician who see the athletes are often

unaware that they are taken these unaware that they are taken these medicationmedication..

Physician knowledge of the possible effects Physician knowledge of the possible effects of these medications is poorof these medications is poor . .

EPIDEMIOLOGY.EPIDEMIOLOGY.IT IS DIFFICULT.IT IS DIFFICULT.10 OUT OF 26 OF POWER 10 OUT OF 26 OF POWER LIFFTINGLIFFTING.(baltimor1996).(baltimor1996)

9% OF MALE AND 2% OF FEMALE IN 9% OF MALE AND 2% OF FEMALE IN GYMNASIA IN ENGLAND GYMNASIA IN ENGLAND (int.j sport med 1997)(int.j sport med 1997)

SOUTH AFRICA SCHOOLCHILDERN SOUTH AFRICA SCHOOLCHILDERN 3% OF MALE AND .1% OF FEMALE3% OF MALE AND .1% OF FEMALE.(s afr. .(s afr. Med j 1998)Med j 1998)

HISTORY.HISTORY.1930 MAINTAIN AGING.1930 MAINTAIN AGING.1950 ATHELET BEGAN TO USE IT.1950 ATHELET BEGAN TO USE IT.ILLEGAL BY LAW.ILLEGAL BY LAW.1990 WERE ADDED TO PROHIBITED 1990 WERE ADDED TO PROHIBITED DRUDS. (SCHEDULE I.). DRUDS. (SCHEDULE I.).1-5 YEAR IN PRISON UP TO 25000 1-5 YEAR IN PRISON UP TO 25000 DOLLARS.DOLLARS.

EFFICACY.EFFICACY.INCREASE MASS AND MUSCLE STRENGTH.INCREASE MASS AND MUSCLE STRENGTH.43 NORMAL MEN ASSIGNED TO 4 GROUPS 43 NORMAL MEN ASSIGNED TO 4 GROUPS WITH OR WITHOUT EXERCISE AND WITH WITH OR WITHOUT EXERCISE AND WITH TESTOSTERONE OR WITH PLACEBO.TESTOSTERONE OR WITH PLACEBO.TESTOSTERONE TREATED GROUP TESTOSTERONE TREATED GROUP INCREASED FATE –FREE MASS AND MUSCLE INCREASED FATE –FREE MASS AND MUSCLE STRENGTH AND MORE IN THOSE WHO STRENGTH AND MORE IN THOSE WHO EXERCISED EXERCISED (N ENGL J MED 1996)(N ENGL J MED 1996)

NOT WITH ANDROSTENEDIONE. NOT WITH ANDROSTENEDIONE. (JAMA 1999)(JAMA 1999)

SIDE EFFECTS.SIDE EFFECTS.1)1) SUPPRESSION OF ENDOGENNOUS TEST. SUPPRESSION OF ENDOGENNOUS TEST.

FU.FU.

2)2) GYNEACOMATSIA.GYNEACOMATSIA.

3)3) ERYTHROCYTOSIS.ERYTHROCYTOSIS.

4)4) HEPATOTOXICITY.HEPATOTOXICITY.

5)5) PSYCHOLOGICAL DISORDER.PSYCHOLOGICAL DISORDER.

6)6) CARDIAC DISEASE.CARDIAC DISEASE.

7)7) SERUM LIPIDS.SERUM LIPIDS.

8)8) VIRILIZATION.VIRILIZATION.

9)9) PREMATURE EPIPHYSEAL FUSION.PREMATURE EPIPHYSEAL FUSION.

10)10) INFECTION.INFECTION.

TESTICULAR FUNCTION.TESTICULAR FUNCTION.SUPPRESS GONADOTROPIN SUPPRESS GONADOTROPIN SECRETION.SECRETION.SUPPRESS ENDOGENOUS TESTICULAR SUPPRESS ENDOGENOUS TESTICULAR FUN.FUN.REDUCED SPERMATOGENESIS AND REDUCED SPERMATOGENESIS AND FERTIL.FERTIL.SPERM COUNT RETURN WITHIN 4 SPERM COUNT RETURN WITHIN 4 MONTHS.MONTHS.TESTICULAR SIZE DEREASED.TESTICULAR SIZE DEREASED.GONADOTROPIN AND TEST. REMAIN GONADOTROPIN AND TEST. REMAIN LOW FOR MONTHS.) LOW FOR MONTHS.) (fertil steril 1989)(fertil steril 1989)

GYNECOMASTIA.GYNECOMASTIA.TESTERONE CONVERTED TO ESTRADIOL VIA

AROMATASE ENZYME.

DEHYDROTESTOSTERONE DO NOT CAUSE.

ERTHOCYTOSIS.ERTHOCYTOSIS.

COMMON.COMMON.

ALL ANDROGEN.ALL ANDROGEN.

DIRECT STIMULATION OF DIRECT STIMULATION OF ERYTHROCYTOSIS.ERYTHROCYTOSIS.

COAGULATIONCOAGULATIONACTIVATION OF HEMOSTATIC SYSTEM.ACTIVATION OF HEMOSTATIC SYSTEM.

HIGH THROMBIN –ANTITHROMBIN HIGH THROMBIN –ANTITHROMBIN COMPLEXES IN PLASMA.COMPLEXES IN PLASMA.

INCREASE PLASMA PROTHROMBIN FRAGMENT, INCREASE PLASMA PROTHROMBIN FRAGMENT, ANTITHROMBIN-III AND PROTIEN - S.ANTITHROMBIN-III AND PROTIEN - S.

TISSUE PLASMINOGEN ACTIVATOR AND ITS TISSUE PLASMINOGEN ACTIVATOR AND ITS INHIBITOR.INHIBITOR.

INCREASED PLATELET AGGREGATIONINCREASED PLATELET AGGREGATION

INFECTION.INFECTION.LOCAL ABSCESSLOCAL ABSCESS..

SEPTIC ARTHRITISSEPTIC ARTHRITIS..

HIV INFECTIONHIV INFECTION..

IMMUNOGLOBULIN AND T CELL IMMUNOGLOBULIN AND T CELL CHANGESCHANGES..

HEPATOTOXCICTY.

17 ALPHA-ALKYLATED ANDROGEN.ELEVATED LIVER ENZYMES.(clin.chm act 1962)

CHOLESTATIC JAUNDICE.PLIOSIS.(med sci sports exerc 1994)

HEPATOMA.

CARDIAC.

SUDDEN DEATH.HIGH BLOOD PRESSURE.MYOCARDITIS.THROMBOTIC COMPLICATION.FLUID RETENTION.

LIPIDS.

INCREASE LDL.

DECREASE HDL.

NEUROLOGICL CHANGES.

CEREBROVASCULAL HEMORRHAGE.

INCREASE INTRACRANIAL HYPERTENSION.

TIA.

PSYCHOLOGICAL.

MAJOR MOOD DISORDER.

AGGRESSIVE BEHAVIOR.

STUNTING GROWTH.

PREMATURE EPIPHYSEAL CLOSURE.

DETECTION.

SUSPECTED CLINICALY AND LAB.

IN WOMEN: HIRSUTISM, ACNE, IRREGULAR MENSES, DECREASE BREAST AND UTERUS SIZES.

CHROMATOGRAPHY AND MASS SPECTROSCOPY FOR OTHER THAN TESTO.

DETECTION IN MALE.

QUICK WEIGHT AND MUSCLE GAIN.PURPLE AND RED PURPULE SPOTS.SWELLING OF THE FEET AND LEGS.TREMBLING.DARKENING OF SKIN.BAD BREATH.AGGRESSIVE BEHAVIOR.

TESTOSTERONE.

CANNOT BE DISTINGUISHED FROM ENDOGENOUS.

URINARY RATIO OF TES. TO ITS ENDOGENOUS EPIMER WILL BE HIGH (urinary ratio of testosterone to epitetosterone <6:1 but in those patients the ratio increased). (cli chem1992).

RATIO OF URINE TEST. TO LH >30 (clini chm 1997)

OTHER DRUGS.

STIMULANTS.ETHROPOIETIN.GROWTH HORMONE.ISULIN.CREATINE.

STIMULANTS.

AMPHETAMINE.CAFFEINE.DETECTED EASLY.LESS REGULATED EVENTS.

GROWTH HORMONE.

MORE MUSCL LESS FAT.IT IS NOT YET TESTED FOR.EFFICACY NOT YET DEMONSTRATED.LITTL INFORMATION ABOUT DETECTION.IGF-1 (j clin endocrinol metab 2000)

PROCALLAGEN TYPIII AND OSTEOCALCIN.(j clin endocrinology metabolism2000)

CREATINE.PROFESSIONAL.48% OF MALE AND 4% OF FEMAL (clin j

sport med 1999)

ENHANCES PERFORMANCE IN SHORT DURATION.

WT GAIN ,ACUTE INTERSTITIAL NEPHRITIS,PROGRESSION RENAL DISEASE.

CYPROHEPTADINE.

SEROTONIN AND HISTAMINE ANTAGONIST.

INCREASE LH AND TESTOSTERONE.

AMINO ACID.

NITROGEN RETENTION AND ENHANCE PROTEIN FORMATION>MUSCLE GROWTH.

NO CLINICAL DATA SUPPORT BENEFIT.

POSSIBLE RENAL DAMAGE.

BLOOD DOPING.

INCREASE RED BLOOD CELL.FRESH RED BLOOD ARE INFUSED.FROZEN BLOOD FOR 5 WEEKS REINFUSED.RASH,FEVER,HEMOLYTIC ANEAMIA,INFECTION.ERYTHROPOIETIN.

ERYTHROPOIETIN.

TO INCREASE OXYGEN CARRYING CAP.UNKNOWN EFFICACY.SEIZURES, ENCEPHALOPATHY,MI,STROKE.SERUM RATIO OF SOLUBLE TRANSFERRIN RECEPTOR TO FERRITIN.(natur1996)

GINSENG.

TO ADAPT ENVIROMENTAL AND SOCIOL STRESSES.17 BET-HYDROXYLATED STEROIDS.CNS STIMULATION,HYPERTENSION,HYPOTENSION,FLUID RETENSION.TOXIC TO HEART OR KIDDNEYHAS ESTROGENIC EFFECT.

INSULIN.

ANABOLIC EFFECTS ON MUSCL.REPORT OF USING INSULIN (jama 1998)

SUGAR.HYPOGLYCEAMIA.

Medical commission of international Olympic committee.

CLASS I- PROHIBITED ,STIMULANTS,NARCOTICS,ANABOLIC, DIURETIC.CLASS 11-PROHIBITED METHODES ,BLOOD DOPING, PHAMACEEUTICAL.CLASS 111- CERTAIN RESTRICTION,ALCOHOL,MARJUANA,LOCAL ANAESTHESIA, BETA BLOCKER.

The rational , efficacy and safety of androgen therapy in

older men

UNDER PHYSICIAN SUPERVESION

Background. Studies revealed normal aging associated with decline in

testosterone. Result in feature similar of deficiency in young. Age related androgen deficiency truly cause these feature need

studies. Androgen treatment safe as aged tissue not remain androgen

sensitive. Studies showed androgen increase muscle bulk and reduce fat. Side effect such sleep disturbances, breathing problem or

Polycythemia dose responsive. Cardiovascular and prostate safety uncertain. Supplementation in healthy old men not recommended. Symptomatic older men with low level need to follow the

recommendation to avoid unnecessary prescription.

Facts.

Number and proportion of men above 60 years will increase in the coming 50 y.

Safe and effective medical intervention to promote healthy aging are therefore valuable.

Hormone therapy is promising and inexpensive and androgen has anabolic effect.

Androgen use in elderly patients need study to evaluate the efficacy and safety.

Mineral density decline by age,

Comparison of effects of androgen deficiency in organic androgen deficiency and aging.

features organic aging

Mus.mass reduced yes yes

strength reduced yes ?

Fat mass increased yes yes

Ph,functio decrease yes ?

B,density decrease yes ?

Hair/skin decrease yes ?

mood decrease yes ?

libido decrease yes ?

quality decrease yes ?

Muscle, fat, and bone. Nine studies for 3 months or more in patients with low T reporting

effect on the muscle and fat. Standard replacement doses except one supraphysiological dose

used. Titrated to have normal T level. 1.5-2.5 kg reduction in fat mass and increase in muscle mass by 1-2

kg. Analysis of the studies revealed no significant changes of muscle or fat

masses after 6 months of the treatment. Whether such changes persist with long term administration. Significant improvement not demonstrated and if present likely to be

small. Muscle strength increased by 3% with androgenic supplement that

double the basal T. It remain unclear if small increment in muscle strength will improve the

daily living for frail older men.

Insulin sensitivity.

T may improve intraabdominal fat which reduce the insulin resistance.

Low serum T predict the development of type 2 diabetes.

Effect of androgen supplement on the BMD

Increased but depend on the duration and the dose.

Current recommendation.

Total T concentration less than 200 ng/dl (8nmol/l) indicate overt deficiency.

Level 200 – 400 ng/dl (8-15nmol/l) possible deficiency.

Above 400 exclude androgen deficiency. LH, FSH, SHBG, Free T needed in case border line level in

symptomatic patients.

•THANK FOR ALL OF YOU.

Circulation and the nervous system

hot flushes

sweating

insomnia

nervousness.

Mood and cognitive (higher mental) function

•irritability and tiredness

•decreased sense of well-being

•lack of motivation

•low mental energy

•difficulty with short-term memory

•depression

•low self-esteem

•being easily frightened.

Masculinity and virility

•decreased vigour and physical energy

•diminished muscle strength.

Sexuality

•decreased interest in or desire for sex

•less sexual activity

•poor erections

•reduced quality of orgasm

•weakness of ejaculation

•reduced volume of ejaculated fluid.

Physical features include

•diminished muscle mass

•loss of body hair

•abdominal obesity.

Several other effects on body chemistry and metabolism occur, such as:

•reduction in high-density lipoprotein (HDL) cholesterol and increase in low-density lipoprotein (LDL) cholesterol, which increases the risk of developing coronary artery disease.

•increase in total body fat (because of a fall in the proportion of body weight that is muscle rather than through weight gain).

•osteoporosis (a change in bone structure and strength that predisposes the sufferer to fractures, particularly of the wrist, hip and spine).

•reduction in red cell volume (a reduction in the proportion of red blood cells to plasma.

What are the consequences of androgen deficiency (PADAM)?

Changes caused by PADAM could potentially affect health in several ways:

•increased risk of osteoporotic fracture and cardiovascular disease

•reduced general well-being

•depression.

•cognitive impairment (problems with thought, concentration and memory).

•reduced physical strength

•sexual problems.

Misuse of androgen.

Male infertility. Impotence. Andropause. Elderly men. Treatment of non specific symptoms.

Androgen deficiency is a clinical diagnosis confirmed by hormone assays.

1) Among younger men, androgen deficiency is usually due to underlying hypothalamopituitary or testicular disorders.

2) Androgen replacement therapy should be started after proof of androgen deficiency and should continue lifelong with monitoring.

3) Men presenting with erectile dysfunction should be evaluated for androgen deficiency, but it is an uncommon cause; if overt androgen deficiency is confirmed, an underlying disorder needs further specialist investigation.

4) In the absence of characteristic underlying testicular or pituitary disorders, new diagnosis of androgen deficiency in older men is difficult because of the non-specific symptoms and the decline in blood testosterone levels seen in healthy ageing and chronic medical disorders.

5) There remains no convincing evidence that androgen therapy is either effective treatment or safe for older men unless they have frank androgen deficiency.

6) While androgen replacement therapy is essential and effective in overt deficiency, it is no anti-ageing elixir.