Context. Male hormonal contraception via gonadotropin and intratesticular androgen withdrawal disrupts spermatogenesis at two principal sites; (i) spermatogonial maturation and (ii) spermiation.

Objective. To explore the relative dependence of each stage of germ cell development on FSH and LH/intratesticular androgen action.

Design, setting, and participants. Eighteen men enrolled in this prospective, randomized, fourteen-week study at Prince Henrys Institute.

Intervention(s). Subjects (n = 6/group) were assigned to 6 weeks of (i) Testosterone (T) implant (4x 200 mg sc once) + depot medroxy progesterone acetate (DMPA, 150 mg IM once), (ii) T implant + DMPA + FSH (300IU sc twice weekly) and (iii) T implant + DMPA + human chorionic gonadotropin (hCG, 1000IU sc twice weekly as an LH substitute). Men then underwent a vasectomy and testicular biopsy with previously reported control data used for comparison.

Main Outcome Measure(s). Germ cell number (assessed by the optical disector stereological approach) and intratesticular androgen levels were determined.

Results. T+DMPA alone significantly suppressed type B spermatogonia, preleptotene through to pachytene spermatocytes and round spermatids from control (P < 0.05). All germ cell subtypes were maintained at control levels by either FSH or LH activity, except pachytene spermatocytes which were found to be lower in the hCG vs. FSH (P < 0.01) and control groups (P < 0.05).

Conclusions. FSH and LH maintained spermatogenesis independently in this gonadotropin suppressed model. Compared with LH, FSH showed better maintenance of pachytene spermatocyte number while improved conversion to round spermatids was suggested with hCG treatment. Future contraceptive treatment strategies must consider independent regulation of spermatogenesis by both FSH and LH/intratesticular androgens for maximum efficacy.