A Clinical Trial of Injectable Testosterone Undecanoate as a Potential Male Contraceptive in Normal Chinese Men

Abstract

This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n ϭ 13) received 500 mg TU, group II (n ϭ 12) received 1000 mg TU, and group III (n ϭ 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men. (J Clin Endocrinol Metab 84: [3642][3643][3644][3645][3646][3647] 1999) T ESTOSTERONE undecanoate (TU; 17-hydroxy-4-androsten-3-one 17-undecanoate) is an unsaturated, aliphatic, fatty acid ester of testosterone (T) that is partially absorbed via the gut lymphatic system after oral administration. Oral TU has been used for androgen substitution therapy and other purposes in clinical treatment for more than 2 decades (1-6). Oral TU has also been tested as a possible contraceptive alone or in combination with cyproterone acetate (CPA) for male fertility control (7,8). The frequency of administration, fluctuation of serum T levels, and insufficient suppression of gonadotropins and spermatogenesis render an oral TU regimen impractical for male hormonal contraception. These previous studies indicated that an oral TU regimen alone or in combination with CPA was not sufficiently effective in spermatogenic suppression.A number of clinical approaches to male hormonal contraception with T esters given alone or in combination with additional gonadotropin-suppressive agents have been investigated (9 -12). In these studies weekly im injections of T enanthate (TE) were required for consistent suppression of gonadotropins and androgen replacement. Moreover, to attain physiological mean T levels, it is necessary to accept fluctuations in circulating T levels between injections, sometimes causing unwanted side-effects. These disadvantages hindered the acceptability of these regimens and highlighted the need for long acting preparations of T with more stable delivery kinetics. Crystalline T pellet implants that produce sustained elevation of serum T for 6 months and suppress gonadotropin levels were evaluated in clinical trials. When six 200-mg T pellet implants were administered to normal Caucasian men,...

Late - Onset Hypogonadism - New Point of View

“…Furthermore, many peer reviewed papers, including the report from World Health Organization, confirmed that after up to three months of HRT with testosterone, from 40% to 90% male patients developed azoo-spermy or significant oligo-spermy -clearly a contraceptive situation -leading to a permanent pharmacological sterilization of men! (WHO, 1990, Wallace, et al, 1993, Anderson & Wu, 1996, Zhang et al, 1999, Baird, 2002, Anderson & Waites, 2003, Si-Tian, et al, 2004. These facts have been known for over 20 years, but are still suppressed from information available to the general public.…”

“…The information that taking synthetic testosterone not only inhibits spermatogenesis, but also inhibits male's own testosterone endo-synthesis, is now almost labeled as "classified". In fact, after three months of taking synthetic testosterone, a man becomes totally infertile (WHO, 1990, Wallace, et al, 1993, Anderson & Wu, 1996, Zhang et al, 1999, Baird, 2002, Anderson & Waites, 2003, Si-Tian, et al, 2004. Furthermore, long-time testosterone therapy may result in irreversible testicular atrophy.…”

Advances in Male Contraception

“…In the first study, conducted in China, volunteers received monthly doses of 500 or 1000 mg TU. Eleven of the 12 men in the 500-mg group and all 12 in the 1000-mg group became azoospermic, with the 1000-mg group achieving azoospermia more quickly (229). In the two other pilot studies, conducted in Germany, TU was used alone or in combination with a progestin (see Section V.C) (230,231).…”

Regulation of testicular function in men: implications for male hormonal contraceptive development

“…Testosterone undecanoate (TU) is a very long-chain ester that results in normal serum T levels for at least 6 weeks in hypogonadal men [25][26][27]. Recently, contraceptive trials using TU have been conducted in China and Germany [28][29][30]. In the Chinese study, subjects received monthly injections of 500 or 1000 mg TU alone.…”

“…In the Chinese study, subjects received monthly injections of 500 or 1000 mg TU alone. Eleven of 12 in the 500 mg group and 12/12 in the 1000 mg group became azoospermic, with the 1000 mg group achieving azoospermia more quickly [28]. Based on these results, TU is currently being tested in a large-scale efficacy trial in China.…”