Oral tibolone combined with testosterone as a potential male contraceptive: pharmacodynamic study examining additive effects in suppression of pituitary-testicular axis
C Oxynos1 & FCW Wu2
BACKGROUND: Hormonal male contraception is based on the reversible suppression of LH and FSH resulting in intratesticular testosterone depletion with subsequent spermatogenic arrest and infertility. Tibolone, a unique synthetic steroid with mixed progestational, androgenic and oestrogenic activities, has been shown to suppress gonadotrophins, inhibit ovulation and postmenopausal hot flushes in women. HYPOTHESIS: We hypothesise that the hybrid anti-gonadotrophic action of Tibolone can reversibly suppress FSH and LH in men with greater or similar efficacy than conventional receptor-specific sex steroids. METHODS: Two groups of healthy Caucasian males received Tibolone 2.5 (n=6) or 5mg (n=6) PO daily for 28 days with the addition of TE 100mg i.m. on day 22. Blood samples were taken on days 1, 3, 5 and then weekly for 7 weeks. RESULTS: Tibolone 5mg caused significant LH suppression from a baseline of 4.83 plus/minus 0.64 to a nadir of 3.32 plus/minus 0.56 IU/l (Day 15, P less than 0.05). Addition of TE induced a further decrease in LH from 3.47 plus/minus 0.30 to 0.52 plus/minus 0.09 IU/l (day 29, p less than 0.0001). Tibolone 2.5mg and 5mg caused significant FSH suppression to nadirs of 2.88 plus/minus 0.56 IU/l (day 15, p less than 0.005) and 2.08 plus/minus 0.26 IU/l (day 22, p equals 0.001) respectively. Combined effects of Tibolone and TE treatment resulted in statistically significant differences in FSH levels between the two groups (Day 29; 2.5mg vs 5mg groups; 1.07 plus/minus 0.16 vs 0.51 plus/minus 0.11 IU/l, P less than 0.05). CONCLUSIONS: The combination of Tibolone 5mg PO with TE 100mg i.m., significantly suppressed FSH and LH in males (to 23% and 10% of baseline values, respectively). Further studies are indicated to investigate the effects of Tibolone and T on spermatogenesis.