+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate



Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate



Journal of Clinical Endocrinology and Metabolism 81(3): 896-901



Hormonal suppression of spermatogenesis is currently being investigated as a method of reversible male contraception. However, administration of exogenous testosterone (T) induces azoospermia in only 40-70% of Caucasian men, whereas the remainder suppresses to severe oligozoospermia (< 5 x 10(5)/mL). The reason(s) for the heterogeneity in the spermatogenic response is not clear. We have prospectively investigated the possibilities that higher plasma concentrations of T and/or differences in the extent and rate of gonadotropin suppression could maintain a low level of spermatogenesis in subjects taking part in a clinical efficacy trial of hormonal male contraception. Thirty-three healthy adult men, aged 21-41 yr, were given 200 mg T enanthate (TE), im, weekly for up to 18 months. Azoospermia was achieved in 18 men (55%) after 20 weeks of treatment, at which time the remaining 15 (45%) stabilized at a mean sperm density of 2.0 +/- 0.8 (+/- SD) x 10(6)/mL. These 15 subjects remained oligozoospermic for the rest of the efficacy study. To compare the pharmacokinetics and pharmacodynamics of TE between the azoospermic and oligozoospermic responders, plasma samples were obtained immediately before and 1, 2, 4, and 7 days after the 1st and 16th TE injections. Further samples were taken after 2, 4, 8, and 12 weeks of treatment. Plasma concentrations of total, free, and non-sex hormone-binding globulin (non-SHBG)-bound T, estradiol, LH, and FSH were measured. Compared to baseline, preinjection levels of total T increased 2.5-fold, reaching a steady state around 12 weeks of treatment. Peak concentrations of total T increased by 5-fold, but free and non-SHBG-bound T levels were increased by 10-fold after 16 weeks. The plasma levels of estradiol showed similar changes as T. However, neither T (bound or free) nor estradiol was significantly different between azoospermic and oligozoospermic responders. Plasma SHBG was reduced to a similar degree in both groups of men after 16 weeks of TE treatment. Plasma concentrations of both LH and FSH decreased rapidly after the first TE injection; a significant decline in LH was detectable after 24 h. Mean levels of both gonadotropins decreased to less than 0.5 U/L by the end of 4 weeks and to below the limit of sensitivity of the assays (0.05 IU/L) by 12 weeks. There were no significant differences in plasma concentrations of LH or FSH or in the rates of suppression between azoospermic and oligozoospermic responders. We conclude that the polymorphism of spermatogenic suppression in response to exogenous T is unlikely to be due to differences in the pharmacokinetics or pharmacodynamics of TE or in the sensitivity of the hypothalamo-pituitary-testicular axis to sex steroid inhibition. Measurements of total plasma T considerably underestimate the increase in bioavailable T during the weekly TE regimen.

(PDF emailed within 0-6 h: $19.90)

Accession: 008354219

Download citation: RISBibTeXText

PMID: 8772547

DOI: 10.1210/jcem.81.3.8772547


Related references

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. III. Higher 5 alpha-reductase activity in oligozoospermic men administered supraphysiological doses of testosterone. Journal of Clinical Endocrinology and Metabolism 81(3): 902-908, 1996

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. V. Localization of higher 5 alpha-reductase activity to the reproductive tract in oligozoospermic men administered supraphysiological doses of testosterone. Journal of Andrology 18(4): 366-371, 1997

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. I: Plasma luteinizing hormone, follicle stimulating hormone, testosterone, estradiol, and inhibin concentrations. Journal of Clinical Endocrinology and Metabolism 77(1): 290-293, 1993

Residual sperm function in oligozoospermia induced by testosterone enanthate administered as a potential steroid male contraceptive. International Journal of Andrology 15(5): 416-424, 1992

Pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone enanthate in non-human primates. Acta Endocrinologica 122(4): 432-442, 1990

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. Journal of Clinical Endocrinology and Metabolism 84(10): 3469-3478, 1999

Serum lipid and sex hormone binding globulin shbg changes in men after administration of 17a methyltestosterone met testosterone enanthate te and testosterone enanthate with testolactone tl. Clinical Research 36(1): 122A, 1988

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens. Human Reproduction 12(8): 1657-1662, 1997

Injectable testosterone undecanoate has more favourable pharmacokinetics and pharmacodynamics than testosterone enanthate. European Journal Of Endocrinology. 132(4): 514-519, 1995

Fertility of male rabbits during oligozoospermia induced by injections of medroxyprogesterone acetate and testosterone enanthate. Andrologia 15 Spec No: 578-583, 1983

Comparison of pharmacokinetics of testosterone after sublingual testosterone cyclodextrin or testosterone enanthate injections. Clinical Research 42(1): 74A, 1994

Effect of chronic administration of testosterone enanthate on sperm production and plasma testosterone follicle stimulating hormone and luteinizing hormone levels a preliminary evaluation of a possible male contraceptive. Fertility and Sterility 28(12): 1320-1328, 1977

Pharmacokinetics and pharmacodynamics of oral testosterone enanthate plus dutasteride for four weeks in normal men: Implications for male hormonal contraception. 2008

Pharmacokinetics and pharmacodynamics of oral testosterone enanthate plus dutasteride for 4 weeks in normal men: implications for male hormonal contraception. Journal of Andrology 29(3): 260-271, 2007

Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate--a clinical research center study. Journal of Clinical Endocrinology and Metabolism 80(12): 3567-3575, 1995