Predictors In Non-suppression Of Spermatogenesis Of Hormonal Male Contraception

Now, there is no male contraceptive that is available in clinic use. The need for a safe, effective, reversible and more acceptable contraception has been greater. It has been 30 years when testosterone was used for male hormonal contraception. Most clinical trials demonstrated that exogenous high-dosage testosterone combined with or without progestin is a safe, effective and fully reversible method of male contraception.The goal of hormonal male contraception is induction of azoospermia and severe oligozoospermia as the accepted prerequisite for reliable prevention of pregnancy. However, the heterogeneity response of volunteers to suppression of spermatogenesis remained unresolved. The suppression of spermatogenesis was still incomplete although some volunteers' serum gonadotrophin concentrations had been suppressed to a very low degree. This response difference is significant between ethnic and also exists in the same ethnic, and is the key issue influencing the clinical efficacy, general acceptance and wider applicability of hormonal male contraceptives.While seeking an explanation for the variability in response, observations revealed differences in pretreatment hormone values, intratesticular testosterone metabolism and in the sensitivity of the pituitary-hypothalamic feedback system to testosterone. Within recent years an increasing body of evidence has shown that at the molecular level, individual response to drug therapy is in part determined by polymorphism in genes, resulting in subtle difference of protein action or drug metabolism.Based on previous findings, the potential factors which may affect the efficacy of hormonal male contraception including clinical parameters, hormone values and gene polymorphism on androgen receptor (AR) and FSH receptor (FSHR), were measured and assessed in the present study to detect predictors in non-suppression of spermatogenesis of hormonal male contraception.Methods: 43 men, who did not reach azoospermia or severe oligozoospermia within the 6-month suppression phase of a multicenter contraceptive efficacy clinical trial using 500 mg TU monthly IM injections, were enrolled into this study and defined as non-suppressors. This clinical trial consisted of a 2-month baseline period prior to a 30-month treatment period (6-month suppression phase and 24-month efficacy phase) and a 12-month recovery period. During the suppression phase 190 men discontinued, including 43 men who did not reach azoospermia or severe oligozoospermia (≤1 million per mL) and 855 men entered the efficacy phase. The difference in sperm density, serum T, LH and FSH concentrations at the baseline and suppression phase, and number of CAG sequence repeats of AR and SNP of FSHR determined by PCR and DNA sequencing technique was compared between non-suppressors and suppressors. Results: Serum LH level at the baseline was significantly lower in TU suppressors. Serum LH and FSH levels at the suppression phase were statistically less suppressed in TU non-suppressors. Larger testis volume, higher serum FSH concentrations alone, or interaction of serum LH, FSH, T and sperm concentrations could hinder the success rate assessed by analysis of a logistic regression. Men failed to achieve azoospermia or severe oligozoospermia in this study could not be explained by the polymorphisms in AR gene and FSHR gene from the present assay methods. In cases with incomplete gonadotrophin suppression, the chances of becoming azoospermia were 1.5 times higher in men with CAG repeats number more than 22. Conclusion: Non-suppression of spermatogenesis induced by 500mg TU monthly IM injections is partly attributed to the parameters of clinical feature, whereas polymorphism in AR gene and FSHR gene seems not to be direct influence on it.