Matthiesson Kati L, McLachlan Robert I, O'Donnell Liza, Frydenberg Mark, Robertson David M, Stanton Peter G, Meachem Sarah J
Prince Henry's Institute, and Departments of Obstetrics and Gynaecology, Monash University, P.O. Box 5152, Monash Medical Center, Clayton, Victoria 3168, Australia.
J Clin Endocrinol Metab. 2006 Oct;91(10):3962-9. doi: 10.1210/jc.2006-1145. Epub 2006 Aug 8.
Male hormonal contraception via gonadotropin and intratesticular androgen withdrawal disrupts spermatogenesis at two principal sites: 1) spermatogonial maturation, and 2) spermiation.
The objective of this study was 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 14-wk study at Prince Henry's Institute.
Subjects (n = 6/group) were assigned to 6 wk of 1) testosterone (T) implant (4 x 200 mg sc once)+depot medroxy progesterone acetate (DMPA; 150 mg im once); 2) T implant+DMPA+FSH (300 IU sc twice weekly); and 3) T implant+DMPA+human chorionic gonadotropin (hCG; 1000 IU sc twice weekly as an LH substitute). Men then underwent a vasectomy and testicular biopsy with previously reported control data used for comparison.
Germ cell number (assessed by the optical disector stereological approach) and intratesticular androgen levels were determined.
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).
FSH and LH maintained spermatogenesis independently in this gonadotropin-suppressed model. Compared with LH, FSH showed better maintenance of pachytene spermatocyte number, whereas 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.
通过促性腺激素和睾丸内雄激素撤退实现的男性激素避孕在两个主要部位破坏精子发生:1)精原细胞成熟,以及2)精子释放。
本研究的目的是探讨生殖细胞发育各阶段对促卵泡激素(FSH)和促黄体生成素/睾丸内雄激素作用的相对依赖性。
设计、地点和参与者:18名男性参加了在亨利王子研究所进行的这项前瞻性、随机、为期14周的研究。
受试者(每组n = 6)被分配接受为期6周的以下处理:1)睾酮(T)植入(4×200mg,皮下注射一次)+醋酸甲羟孕酮长效注射液(DMPA;150mg,肌肉注射一次);2)T植入+DMPA+FSH(300IU,皮下注射,每周两次);以及3)T植入+DMPA+人绒毛膜促性腺激素(hCG;1000IU,皮下注射,每周两次作为促黄体生成素替代物)。然后男性接受输精管结扎术和睾丸活检,并将先前报道的对照数据用于比较。
测定生殖细胞数量(通过光学分割体视学方法评估)和睾丸内雄激素水平。
单独使用T+DMPA可显著抑制B型精原细胞、细线前期至粗线期精母细胞以及对照中的圆形精子细胞(P < 0.05)。除粗线期精母细胞外,所有生殖细胞亚型通过FSH或促黄体生成素活性维持在对照水平,粗线期精母细胞在hCG组与FSH组相比(P < 0.01)以及与对照组相比(P < 0.05)均较低。
在这个促性腺激素抑制模型中,FSH和促黄体生成素独立维持精子发生。与促黄体生成素相比,FSH对粗线期精母细胞数量的维持效果更好,而hCG治疗提示向圆形精子细胞的转化率有所提高。未来的避孕治疗策略必须考虑FSH和促黄体生成素/睾丸内雄激素对精子发生的独立调节,以实现最大疗效。