Currently, the most popular form of therapy for androgen deficiency is testosterone replacement therapy.
The first reports on the successful treatment of androgen deficiency were dated to the 40s of the last century. However, drugs of that time had many side effects and did not have the full spectrum of natural testosterone.
The first popular synthetic testosterone drugs were sold in the form of tablets (methyltestosterone, fluoxymesterone, etc.). Oral intake testosterone metabolized in the liver, as a result of which most of it was destroyed, while having a strong toxic and carcinogenic effect on the liver. In this regard, in most countries, preparations based on these testosterone derivatives are prohibited to use, giving way to modern analogues.
A great influence on the development of synthetic forms of testosterone plays its role in sport. Despite the fact that the use of anabolic steroids is prohibited, doping control incidents continue to thunder at the Olympic Games and other major competitions.
Forms of administration of testosterone drugs
Methods for introducing androgens are divided into the following:
- oral (tablets, capsules);
- injection (injections);
- transdermal (patches, gels, creams);
- subcutaneous (implant).
Table 1 - Exogenous testosterone preparations (S. Yu. Kalinchenko, I. A. Tyuzikov, 2009)
|PREPARATION GROUP||CHEMICAL NAME||TRADENAME||DOSAGE|
|Injection forms||Testosterone Cypionate||Depot Testosterone Cypionate||200-400 mg every 3-4 weeks|
|Testosterone Enanthate|| Delasteril |
|200-400 mg every 2-4 weeks|
|Testosterone Ester Blend|| Sustanol-250 |
|250 mg every 2-3 weeks|
|Testosterone Undecanoate||Nebido||1000 mg 1 time in 3 months|
|Oral form||Fluoxymesterone *||Halotestin||5-20 mg daily|
|Methyltestosterone *||Methadren||10-30 mg daily|
|Testosterone Undecanoate||Andriol||120-200 mg daily|
|Mesterolon ***|| Proviron |
|25-75 mg daily|
|Buccal tablets||Striant||30 mg 3 times a day|
|Subcutaneous form||Implants||Testosterone implants||1200 mg every 6 months|
|Transdermal forms||Testosterone gel||Androgel||25-75-100 mg daily|
|Testosterone plasters (scrotal and cutaneous) **|| Androderm |
|2.5-7.5 mg daily|
|Testosterone cream||Andromene||10-15 mg daily|
Notes: * - hepatoxic and in some countries prohibited; ** - not registered in Russia; *** - discontinued.
Fig. 1 - The share of various forms of androgenic drugs in the pharmaceutical market of Russia (2007) (source: “Practical Andrology”, S. Yu. Kalinchenko, I. A. Tyuzikov, 2009)
Intramuscular injections of testosterone are the most used method of replacement therapy. The most well-known testosterone esters - testosterone cypionate and testosterone enanthate have their own characteristics: when they enter the bloodstream, testosterone levels reach their maximum value 2-3 days after injection, then gradually decrease over 2 weeks and reach their minimum. This causes the so-called. “Roller coaster effect”, when mood, well-being and libido increases with the level of androgens in the blood, and also dramatically decreases, when testosterone levels are at their lowest level. The same properties are possessed by preparations containing a mixture of testosterone esters (Sustanol, Omnadren).
Nevertheless, both individual testosterone esters and their mixture are still being successfully used due to their low cost, availability, and effectiveness. In particular, testosterone esters are loved by strength sports athletes and bodybuilders for their anabolic properties and the ability to create a high concentration of testosterone in the blood.
The injection drug of choice for hormone replacement therapy (HRT) today is testosterone undecanoate (Nebido). Its difference from other testosterone esters is a prolonged action (1 injection in 10-12 weeks) and the absence of pathological jumps in the level of androgens. The drug Nebido has the full spectrum of testosterone and does not cause hepatotoxic and hepatogenic effects.
Oral preparations have a less pronounced effect compared with injectable forms, even with the use of high doses. Therefore, it is advisable to use oral forms of testosterone in cases where there is a slight decrease in androgens. The drug of choice for HRT is Andriol. Compared with the old analogues (methyltestosterone, fluoxymesterolone), when Andriol is used, most of the testosterone passes metabolism in the liver and enters directly into the systemic circulation, which contributes to the rapid achievement of the required hormone concentration. However, this also causes a rapid half-life of the drug (3-4 hours), which forces the patient to re-take (3-4 times a day).
Transdermal forms of testosterone preparations (gels, patches) are gaining increasing popularity. They quickly create the necessary level of androgens in the blood, but they do not undergo hepatic metabolism as oral medications, and at the same time do not create supraphysiological level of testosterone, as is the case when using testosterone esters (cypionate, enanthate) and mixtures of esters (Sustanol, Omnadren) . The advantage of transdermal forms is their non-invasiveness, the possibility of self-administration, and the absence of pronounced side effects.
In some countries, implants are a common method of treating androgen deficiency. With the help of surgical intervention, the implant is placed subcutaneously to the patient, evenly releasing the hormone for 6 months. In Russia, testosterone implants are not registered.
Fig. 2 - Pharmacokinetics of various testosterone preparations.
Table 2 - Characteristics of various forms of testosterone drugs
|The effectiveness of therapy|| +
Highly effective. Ability to create high concentrations of hormone in the blood
Effective only with mild androgen deficiency
Effective enough to overcome various degrees of androgen deficiency.
The presence in the sale of a wide selection of different testosterone esters
Available on prescription
Availability of only testosterone gel (AndroGel). Testosterone plasters are not registered in Russia
Testosterone implants are not registered in Russia
|Duration of action|| +
Nebido has the longest duration of action among all testosterone drugs (1 injection every 3 months.)
Daily from 2-4 times a day (Andriol)
Daily, once a day
The duration of one implant is 6 months.
|The possibility of an emergency stop of therapy||-||+||+||-|
|Sharp fluctuations in hormone levels|| +
Not detected when using Nebido-Marks when using testosterone propionate, testosterone enanthate and mixtures of esters
Have a fast half-life
Evenly absorbed throughout the day, keeping hormone levels in the normal range.
Uniform testosterone release over the life of the implant
The procedure is performed by a specialist, however, the possibility of independent use is not excluded.
|Side effects||Depending on the dosage||They have some toxicity to the liver, especially old drugs.||May cause skin reactions at skin contact points.||Complications caused by surgery|
- Prostate cancer. Androgen therapy can stimulate the growth of an existing tumor;
- Breast cancer (rare). Androgen therapy can lead to an increase in estrogen levels, which can trigger further tumor growth.
- Sleep apnea;
- Gynecomastia ;
- Fluid retention;
- Enlarged prostate;
- Violation of spermatogenesis.
Relative contraindications mean that with android hormone may worsen the course of the condition.
Possible indications for replacement therapy
- Primary and secondary hypogonadism .
- Decreased libido and erectile dysfunction on the background of androgen deficiency.
- Age androgen deficiency .
- Obesity , difficult to treat.
Side effects of testosterone occur only with the use of large doses of the drug, exceeding normal physiological parameters. The use of androgens in physiological doses does not lead to side effects.
Possible side effects caused by large doses of androgens:
- suppression of production of own testosterone;
- swelling, water retention;
- acne, seborrhea;
- spermatogenesis inhibition;
- testicular atrophy.
Read more on "Side effects of testosterone during replacement therapy . "