Exogenous testosterone is used to inhibit gonadotropin secretion, so inhibiting testicular activity is important for hormone-based male contraceptive methods. In this regard, trestolone acetate, when used on healthy men, can cause gonadotropin suppression and spermatogenesis suppression, making it a potential male contraceptive. In the case of testosterone, the combination with gonadotropin inhibitors (such as progesterone) is more effective in inhibiting sperm production than testosterone alone (Bebb et al. 1996).
More recently, Walton et al. (2007) showed that a combination of trestolone acetate with progesterone, similar to a combined testosterone formulation, leads to rapid inhibition of spermatogenesis, and noted the importance of synthetic progesterone doses relative to androgen doses in improving spermatogenesis inhibition. However, subjects treated with four trestolone acetate plants showed higher and longer inhibition of spermatogenesis than those treated with two trestolone acetate implants plus two ENG implants. During the first and second 6 months of treatment, the four trestolone acetate implants caused azoospermia or severe oligospermia (sperm count <1×106/ml) in 82% and 100% of subjects, respectively. Therefore, in the last 6 months of treatment, trestolone acetate alone was as effective as testosterone undecanoate plus net enantioic acid given at an 8-week interval.
Several synthetic progesterone appear as weak androgens, notably medroxyprogesterone acetate, liquefied natural gas, and NET. In fact, in a previous publication by the lab, these compounds were able to activate AR-dependent reporter gene expression, with LNG being the strongest activator. In males, administration of P4 or synthetic progesterone inhibited gonadotropin secretion and spermatogenesis in addition to its inhibitory effect on Leydig cell steroid production and 5α-reductase activity.
Although the addition of some other anti-gonadotropin compounds ensures effective inhibition of gonadotropin secretion, it remains unclear whether the combination of hormones influences androgen activity at AR levels in an agonist-antagonist manner. This observation is particularly important because androgens are necessary for the maintenance of many physiological parameters in men, including muscle metabolism, red blood cell production, sexual activity, and accessory sex organ function. Therefore, we believe that it is meaningful to evaluate the ability of trestolone acetate alone or in combination with other synthetic progesterone to activate gene transcription through AR.
More recently, Walton et al. (2007) showed that a combination of trestolone acetate with progesterone, similar to a combined testosterone formulation, leads to rapid inhibition of spermatogenesis, and noted the importance of synthetic progesterone doses relative to androgen doses in improving spermatogenesis inhibition. However, subjects treated with four trestolone acetate plants showed higher and longer inhibition of spermatogenesis than those treated with two trestolone acetate implants plus two ENG implants. During the first and second 6 months of treatment, the four trestolone acetate implants caused azoospermia or severe oligospermia (sperm count <1×106/ml) in 82% and 100% of subjects, respectively. Therefore, in the last 6 months of treatment, trestolone acetate alone was as effective as testosterone undecanoate plus net enantioic acid given at an 8-week interval.
Several synthetic progesterone appear as weak androgens, notably medroxyprogesterone acetate, liquefied natural gas, and NET. In fact, in a previous publication by the lab, these compounds were able to activate AR-dependent reporter gene expression, with LNG being the strongest activator. In males, administration of P4 or synthetic progesterone inhibited gonadotropin secretion and spermatogenesis in addition to its inhibitory effect on Leydig cell steroid production and 5α-reductase activity.
Although the addition of some other anti-gonadotropin compounds ensures effective inhibition of gonadotropin secretion, it remains unclear whether the combination of hormones influences androgen activity at AR levels in an agonist-antagonist manner. This observation is particularly important because androgens are necessary for the maintenance of many physiological parameters in men, including muscle metabolism, red blood cell production, sexual activity, and accessory sex organ function. Therefore, we believe that it is meaningful to evaluate the ability of trestolone acetate alone or in combination with other synthetic progesterone to activate gene transcription through AR.