Testosterone Esters and Injection Protocol's...What you and your Doctor need to know

Written by gdevine.


The following extracts explains the PK/PD of testosterone esters and describes the marked fluctuations with injection and transdermal administration. It strongly supports the weekly injections administration schedule, NOT biweekly or longer. If you have a Doctor who has you on any injection protocol longer then days you must have him/her read this study. Also note the LH/FSH suppression all studies noted.

Testosterone enanthate and testosterone cypionate are long-acting testosterone esters suspended in oil to prolong absorption. Peak levels occur about 24-72 hours after intramuscular injection and are followed by a slow decline during the subsequent 1 to 2 weeks. [url]http://www.testosteroneupdate.org/misc/AUA-highlights.pdf[/url]

Nakazawa R, Baba K, Nakano M, et al. Hormone profiles after intramuscular injection of testosterone enanthate in patients with hypogonadism. Endocr J 2006;53(3):305-10. [url]http://www.jstage.jst.go.jp/article/endocrj/53/3/305/_pdf[/url]

To examine hormone levels after androgen replacement therapy (ART) in Japanese male patients with hypogonadism, nine Japanese male patients with hypogonadism (serum total testosterone (tT) or free testosterone (fT) levels of < or = 2.7 ng/mL or < or = 10 pg/mL, respectively; average age, 59 years) were enrolled. They were treated with 125 mg of testosterone enanthate by single intramuscular injection. Blood samples were collected on the morning of the day of treatment, pre-ART, as well as on days 1 to 7 and day 14 after administration.

Serum levels of tT, fT, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were determined. On day 1 after administration, the mean serum levels of tT and fT were 7.62 ng/mL and 23.22 pg/mL, respectively. Serum levels of tT and fT on day 14 after administration were lower than their pre-ART values. One patient exhibited abnormally high serum tT and fT levels of 19.6 ng/mL and 44.4 pg/mL, respectively. Serum levels of LH and FSH began to decrease gradually on day 5 after administration. Serum levels of SHBG did not change throughout the observation period. Serum levels of E2 increased 1.7 times on day 1 after administration but returned to its pre-ART value by day 14 after administration.

The dose of testosterone enanthate for male patients with hypogonadism requiring ART should be determined carefully because some patients exhibited high serum levels of androgen beyond the physiological range and gonadotropin was suppressed in all treated patients (GD: Noted here at HPTA suppression and why HCG is needed to keep the testes functioning).

Weinbauer GF, Partsch C-J, Zitzmann M, Schlatt S, Nieschlag E. Pharmacokinetics and Degree of Aromatization Rather Than Total Dose of Different Preparations Determine the Effects of Testosterone: A Nonhuman Primate Study in Macaca fascicularis. J Androl 2003;24(5):765-74. [url]http://www.andrologyjournal.org/cgi/content/full/24/5/765[/url]

Currently available testosterone (T) preparations differ substantially in their pharmacokinetic profile that might influence their androgenic properties in terms of suppression of the gonadal axis, effects on anabolic parameters, lipid metabolism, and erythropoiesis. The present work was undertaken to determine the physiological effects of three T preparations with different serum kinetics. Twenty adult male cynomolgus monkeys (Macaca fascicularis) were randomly assigned to receive treatment for 28 weeks with either T enanthate (TE) every 4 weeks, T buciclate (TB) every 7 weeks, or T undecanoate (TU) every 10 weeks orremaining untreated (controls). Each injection delivered 20 mg pure T per kilogram body weight. Pharmacokinetic profiles demonstrated higher peak levels of T for TE-treated animals; serum half-lives were longer for TU or TB. Estradiol levels (area under the curve) were significantly higher in TB vs TU or TE. All T regimens suppressed serum luteinizing hormone bioactivity and testicular volumes declined (all P < .001 vs controls). Sperm counts were markedly lowered in all animals but least in TE (P < .01 vs TB or TU). During recovery phase, return to normal for all three parameters occurred significantly earlier in TE-treated animals, followed by those given TU,compared with TB (all P < .001 between groups). Body weight increased significantly during T exposure. This effect was stronger and more sustained in TB vs TU or TE (both P < .001). Serum creatinine and hemoglobin increased with highsignificance in all T-treated animals (all P < .001 vs controls). The lowering impact of T on serum lipids was markedly stronger in the longer-acting T preparations in comparison with TE, as were effects on purine metabolism (all P < .001). The pattern of exposure and degree of aromatization rather than overall exposure to T determine its effects in the preclinical primate model. Both fluctuations of androgen concentrations and the conversion rate to estradiol influence gonadal suppression as well as metabolism. These results have to be considered in men receiving treatment for hypogonadism or regimens for hormonal contraception.

Dobs AS, Meikle AW, Arver S, Sanders SW, Caramelli KE, Mazer NA. Pharmacokinetics, Efficacy, and Safety of a Permeation-Enhanced Testosterone Transdermal System in Comparison with Bi-Weekly Injections of Testosterone Enanthate for the Treatment of Hypogonadal Men. J Clin Endocrinol Metab 1999;84(10):3469-78. [url]http://jcem.endojournals.org/content/84/10/3469.full[/url]

The pharmacokinetics, efficacy, and safety of the Androderm testosterone (T) transdermal system (TTD) and intramuscular T enanthate injections (IM) for the treatment of male hypogonadism were compared in a 24-week multicenter, randomized, parallel-group study. Sixty-six adult hypogonadal men (22–65 years of age) were withdrawn from prior IM treatment for 4–6 weeks and then randomly assigned to treatment with TTD (two 2.5-mg systems applied nightly) or IM (200 mg injected every 2 weeks); there were 33 patients per group. Twenty-six patients in the TTD group and 32 in the IM group completed the study.

TTD treatment produced circadian variations in the levels of total T, bioavailable T, dihydrotestosterone, and estradiol within the normal physiological ranges. IM treatment produced supraphysiological levels of T, bioavailable T, and estradiol (but not dihydrotestosterone) for several days after each injection. Mean morning sex hormone levels were within the normal range in greater proportions of TTD patients (range, 77–100%) than IM patients (range, 19–84%). Both treatments normalized LH levels in approximately 50% of patients with primary hypogonadism; however, LH levels were suppressed to the subnormal range in 31% of IM patients vs. 0% of TTD patients. Both treatments maintained sexual function (assessed by questionnaire and Rigiscan) and mood (Beck Depression Inventory) at the prior treatment levels.

Prostate-specific antigen levels, prostate volumes, and lipid and serum chemistry parameters were comparable in both treatment groups. Transient skin irritation from the patches was reported by 60% of the TTD patients, but caused only three patients (9%) to discontinue treatment. IM treatment produced local reactions in 33% of patients and was associated with significantly more abnormal hematocrit elevations (43.8% of patients) compared with TTD treatment (15.4% of patients). Gynecomastia resolved more frequently during TTD treatment (4 of 10 patients) than with IM treatment (1 of 9 patients).

Although both treatments seem to be efficacious for replacing T in hypogonadal men, the more physiological sex hormone levels and profiles associated with TTD may offer possible advantages over IM in minimizing excessive stimulation of erythropoiesis, preventing/ameliorating gynecomastia, and not over-suppressing gonadotropins.gynecomastia, and not over-suppressing gonadotropins.

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