Meriggiola M C, Marcovina S, Paulsen C A, Bremner W J
Population Center for Research in Reproduction, Department of Veterans Affairs Medical Center, Seattle, WA, USA.
Int J Androl. 1995 Oct;18(5):237-42.
The concept that androgen alone can provide an effective male contraceptive has been tested in a multicentre, multiphase trial by the World Health Organization. Results from this trial showed that an ester of testosterone, testosterone enanthate (TE), administered at a dose of 200 mg/week, has a very high contraceptive efficacy, and suggested that, at least in some populations, androgen alone might provide a viable option for the control of male fertility. It has been claimed that testosterone represents one of the gender-related risk factors for coronary artery disease (CAD) in men. Epidemiological and interventional studies have failed to establish a convincing relationship between testosterone and high density lipoprotein cholesterol (HDL-C). Therefore, there is concern about possible negative effects on lipoprotein asset of an androgen-alone male contraceptive. In this study we analysed the effects of long-term (12 months) administration of TE (200 mg/week) in normal healthy men. Blood samples (six men > 10 h fast = Group 1; 30 men > 4 h fast = Group 2) were drawn from 36 men, monthly before the beginning of the injections (control), every 3 months throughout the study period (treatment), and 1 month after stopping TE injections (recovery). Total cholesterol (chol), triglycerides, HDL-C and LDL-C levels were measured in these samples. Biochemical parameters were also monitored. TE administration induced a significant decrease (15-20%) in HDL-C levels that was of comparable magnitude in men from both groups (fasting and non-fasting) and occurred regardless of basal HDL-C levels. No statistically significant effect on other lipoproteins was detected. Considering all men together, HDL-C levels were decreased in 78% of the men by month 3, 83% by month 6, 94% by month 9 and 97% by month 12 of treatment. In all men the HDL-C decrease was reversible within 1 month of stopping TE administration. It is concluded that: (1) injection of 200 mg TE/week causes a 15-20% decrease in HDL-C in normal men with no effect on other lipoproteins, (2) the suppressive effect of TE is maintained throughout the 1-year-injection period, and a direct relationship between the duration of TE administration and the proportion of men showing decreased HDL-C levels, was observed. (3) The HDL-C decrease was reversible within 1 month of stopping TE administration. These data will be important in designing further studies on male contraception, and in interpreting the relationship between testosterone levels, HDL-C levels and potential cardiovascular risk.
世界卫生组织在一项多中心、多阶段试验中对仅使用雄激素就能成为一种有效的男性避孕药这一概念进行了测试。该试验结果表明，以每周200毫克的剂量注射睾酮的一种酯——庚酸睾酮（TE），具有非常高的避孕效果，并表明至少在某些人群中，仅使用雄激素可能为控制男性生育能力提供一个可行的选择。有人声称睾酮是男性冠状动脉疾病（CAD）的性别相关风险因素之一。流行病学和干预性研究未能证实睾酮与高密度脂蛋白胆固醇（HDL-C）之间存在令人信服的关系。因此，人们担心仅使用雄激素的男性避孕药可能会对脂蛋白水平产生负面影响。在本研究中，我们分析了对正常健康男性长期（12个月）注射TE（每周200毫克）的影响。从36名男性中采集血样（6名男性禁食超过10小时 = 第1组；30名男性禁食超过4小时 = 第2组），在开始注射前每月采集一次（对照），在整个研究期间每3个月采集一次（治疗），并在停止注射TE后1个月采集一次（恢复）。测量这些样本中的总胆固醇（chol）、甘油三酯、HDL-C和低密度脂蛋白胆固醇（LDL-C）水平。还监测了生化参数。注射TE导致HDL-C水平显著降低（15 - 20%），两组男性（禁食和非禁食）的降低幅度相当，且与基础HDL-C水平无关。未检测到对其他脂蛋白有统计学显著影响。综合所有男性来看，在治疗的第3个月，78%的男性HDL-C水平降低；第6个月，83%；第9个月，94%；第12个月，97%。在所有男性中，停止注射TE后1个月内HDL-C的降低是可逆的。得出以下结论：（1）每周注射200毫克TE会使正常男性的HDL-C降低15 - 20%，对其他脂蛋白无影响；（2）TE的抑制作用在整个1年的注射期内持续存在，且观察到TE给药时间与HDL-C水平降低的男性比例之间存在直接关系；（3）停止注射TE后1个月内HDL-C的降低是可逆的。这些数据对于设计进一步的男性避孕研究以及解释睾酮水平、HDL-C水平与潜在心血管风险之间的关系将具有重要意义。
