Hypogonadal symptoms, such as fatigue, mood, and sexual function, as determined from questionnaires and nocturnal penile tumescence, improved with Androderm therapy.3 Management of Skin Irritation

Chronic contact dermatitis (mainly from the alcohol component) occurs in about 10% of males following several weeks of use of Androderm. Two drops of 0.1% triamcinolone acetonide cream applied to the skin under the central drug reservoir greatly reduces contact dermatitis and itching without significantly affecting testosterone delivery or pituitary adrenal function.3 Comparison with intramuscular testosterone

Sixty-six patients were randomized to receive either Androderm or IM testosterone enanthate (200 mg every 2 weeks) treatment for 6 months.3 In the Androderm-treated group the percentage of normal-range serum concentrations of testosterone, bioavailable testosterone, DHT, and estradiol was 82, 87, 76, and 81%, respectively, compared with 72, 39, 70, and 35%, respectively, for IM testosterone injections. Sexual function assessment and lipid profiles were similar between groups. AndroGel

AndroGel 5, 7.5, or 10 g contain packets of 50, 75, or 100 mg testosterone, respectively; a pump dispenser is also available for dosing. On average approximately 10% of the applied testosterone dose is absorbed across skin of average permeability during a 24-h period, producing circulating concentrations of testosterone observed in normal males.26 The 24-h pharmacokinetic profiles of testosterone for patients (Figure 3) maintained on 5 or 10 g AndroGel (to deliver 50 or 100 mg of testosterone, respectively) for 30 days show testosterone values in the normal range. The mean ( + SD) daily testosterone concentration produced by AndroGel 10g on day 30 was 792 ( + 294) ngdL_ 1 and by AndroGel 5g 566 ( + 262) ngdL"1.3

After skin application, AndroGel dries quickly, and release of testosterone into the systemic circulation26 is sustained. After the first 10 g dose testosterone increases in serum testosterone within 30 min, and by 4 h of application most patients have a serum testosterone concentration within the normal range for the 24-h dosing interval. Steady-state levels are achieved by the second or third day of dosing.

Serum testosterone levels decrease after stopping application of the gel, but serum testosterone concentrations remain in the normal range for 24-48 h after the last application and take 5 days to return to baseline. By 180 days of treatment, 87% achieved an average serum testosterone level within the normal range.

Following AndroGel doses of 5 and 10gday_ 1, DHT and estradiol concentrations increased in parallel with testosterone concentrations, and the DHT-to-testosterone ratio and estradiol levels remained within the normal range. SHBG concentrations decreased modestly (1-11%) and serum levels of LH and FSH in males with

Figure 3 The mean steady-state serum testosterone concentrations in patients applying 5 g or 10 g Androgel once daily. (Data on file, Unimed Pharmaceuticals.)

Time (h) after application

Figure 3 The mean steady-state serum testosterone concentrations in patients applying 5 g or 10 g Androgel once daily. (Data on file, Unimed Pharmaceuticals.)

hypergonadotropic hypogonadism fell in a dose- and time-dependent way during treatment with AndroGel. Although skin reactions were reported in 3-5% of patients using AndroGel for up to 6 months, none necessitated discontinuation of drug. Potential partner testosterone transfer

Dermal testosterone transfer between males dosed with AndroGel and their untreated female partners following AndroGel use indicated that unprotected female partners had a serum testosterone concentration more than twice the baseline value at some time during the study. Using a barrier, such as a shirt, to cover the application site(s) abolished this transfer.3

A 5 g tube of Testim applied each morning to the upper arm or shoulder delivers physiologic amounts of testosterone. Following skin application, testosterone concentrations peak at 2-4 h, and average normal concentrations of testosterone are achieved in the 24-h period. In clinical trials, 74% of patients on Testim treatment had serum testosterone concentrations within the normal range at 90 days.27,28 If the testosterone concentrations do not reach the normal range, the dose should be increased to 10 g. Precautions to avoid skin transfer to another person should be followed. Testim is easy to apply and dries quickly and is then invisible.

A new testosterone (T) gel (Cellegy Pharmacueticals, Inc.) has undergone clinical testing in about 200 hypogonadal males. The initial dose applied to the skin daily raises the serum concentrations of testosterone, and steady state is reached by 14 days. A metered canister allows the dose to be adjusted in 10 mg increments. After adjustment of the dose based on the testosterone concentrations on day 14, over 90% of males achieved a 24-h concentration average within the normal physiologic range; the ratio of estradiol to testosterone and DHT to testosterone was also normal. Its safety profile in terms of chemistries, lipid profiles, polycythemia, and prostate-specific antigen (PSA) were comparable to other transdermal testosterone preparations. Six months of therapy also resulted in improvement of hip and spine bone mineral density (BMD) of about 4%.29

Striant is a buccal tablet preparation that is applied to the depression between the gum above the upper incisors and releases testosterone across the buccal mucosa into the peripheral circulation. Twice-daily application may be needed to sustain testosterone concentrations in the therapeutic range.30'31 Oral testosterone

The first orally active, synthesized derivative of testosterone was 17a-methyltestosterone (Table 5). After oral ingestion, peak blood levels occurred between 1.5 and 2h, and its serum half-life was about 150 min, indicating several daily doses would be required to maintain a therapeutic level of the steroid. Hepatic toxicity, characterized as cholestasis, peliosis, and elevation of liver enzymes and reduction of HDL cholesterol has limited its use.3

Fluoxymesterone is a 17a-methyltestosterone steroid with fluorine in the 9 position and has a longer half-life in serum than the parent steroid, but risk of hepatoxicity also limits its clinical use. Mesterolone

Mesterolone is derived from 5-a-dihydrotestosterone with a methyl group in the 1 position, is not hepatoxic, and is not metabolized to estrogen. Dosing is difficult to monitor.3 Testosterone undecanoate

When given with a meal, a 17-p long aliphatic side-chain ester to testosterone produces good absorption from the gut via the lymphatics rather than delivery to the hepatic portal system. Testosterone enters the systemic circulation (63%) without substantial hepatic transformation, and testosterone levels within the normal range are achieved over the first few hours of administration.3 This preparation is not currently available in the US; an improved formulation being tested in the US may overcome some of these deficiencies, making it more suitable for androgen replacement therapy. Human chorionic gonadotropin hCG produced by the human placenta has a specific b subunit that binds to the LH receptors on Leydig cells and stimulates endogenous testosterone production from the testes.3,32 In prepubertal boys between the ages of 4 and 9 years with cryptorchidism not caused by anatomical obstruction, hCG treatment is given to produce testicular descent. The following regimen is given: 4000 United States Pharmacoepia (USP) units of hCG three times weekly for

Table 5 Pharmacokinetics and safety of androgens




Testosterone monitoring

Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook

Post a comment