Pharmacokinetics of Testosterone Undecanoate Injected Alone or in Combination With Norethisterone Enanthate in Healthy Men

Abstract

Long-acting injectable testosterone undecanoate (TU) is a promising androgen for male hormonal contraception. As a prerequisite for a planned multicenter male contraceptive efficacy study, we studied the pharmacokinetics of 2 doses of TU alone or in combination with norethisterone enanthate (NETE) in a prospective 2-center study, randomized for TU dose in each center. Twenty healthy male volunteers in each center were administered intramuscular injections of 750 or 1000 mg TU alone or in combination with 200 mg of NETE IM every 8 weeks for 3 injections. There were no significant differences in maximum concentration and area under the curve (AUC) for serum total and free testosterone (T) between the TU 750 and 1000 mg groups, irrespective of whether TU was administered with 200 mg of NETE. TU 1000 mg IM alone or with NETE at 8-weekly intervals resulted in linear increases in average concentration and AUC of serum total and free T with each injection. Accumulation ratios of serum total and free T levels (calculated as 8 weeks post-to preinjection levels) for each period showed significant increases in the TU+ NETE groups. Serum gonadotropins levels and sperm concentration were more consistently suppressed in the TU 1000 mg + NETE group. We conclude that despite some accumulation of T, TU 1000 mg + NETE 200 mg administered every 8 weeks may be preferable for the future contraceptive efficacy study because of more complete suppression of gonadotropins and spermatogenesis.

Simultaneous Measurement of Serum Testosterone and Dihydrotestosterone by Liquid Chromatography–Tandem Mass Spectrometry

“…The data showed that the interference was negligible and not clinically significant. The only exception was at a DHT concentration of 0.0067 nmol/L, for which the addition of 34 nmol/L T (i.e., 5000-fold more T than DHT) caused a 33.4% increase in the measured DHT concentration, which could be due to the imprecision of measurement at such a low DHT concentration or to interference by the very high relative T concentration. We evaluated the potential for chemical interference by over-the-counter drugs and by additives used in blood-collection tubes.…”

“…T analysis by RIA was performed with a Coat-A-Count kit from Diagnostic Products Corporation (12,34 ). The DHT RIA was performed with a kit from Diagnostic Systems Laboratories as previously described (21 ).…”

Early Prenatal Phthalate Exposure, Sex Steroid Hormones, and Birth Outcomes

“…The lower limit of quantification for testosterone was 2 ng/dL (0.069 nmol/L). FT represents the unbound, biologically available testosterone and was measured by equilibrium dialysis using labeled testosterone as described previously (44). Serum E1 and E2 concentrations for all mothers were measured with a validated LC-MS/MS method.…”

Pregnancy rates with intrauterine insemination: comparing 1999 and 2010 World Health Organization semen analysis norms

“…In fact, the new reference values may not be reflective of the 'global' population, as they fail to include representatives of three continents inhabited by millions of fertile men: Asia, South America and Africa. Moreover, in evaluating morphology, the reference studies included in the WHO 2010 guideline resorted to various methods, including both Tygerberg 'strict' criteria and the David classification system (Meriggiola et al, 1996(Meriggiola et al, , 2003(Meriggiola et al, , 2005Bonde et al, 1998;Buchter et al, 1999;McLachlan et al, 2000;Auger et al, 2001;Guzick et al, 2001;Jensen et al, 2001Slama et al, 2002;Gonzalo et al, 2002;Swan et al, 2003;Turner et al, 2003;von Eckardstein et al, 2003;Brady et al, 2004;Brady et al, 2006;Haugen et al, 2006;Qoubaitary et al, 2006;Wang et al, 2006). Another issue with this new edition relates to the fact that the reference studies used only one single ejaculate to characterize each man, despite the significant biological In no cases was the P-value statistically significant when any of the three groups were compared for each parameter.…”