EFFECTS OF ENDOGENOUS TESTOSTERONE AND ESTRADIOL ON SEXUAL-BEHAVIOR IN NORMAL YOUNG MEN
EFFECTS OF ENDOGENOUS TESTOSTERONE AND ESTRADIOL ON SEXUAL-BEHAVIOR IN NORMAL YOUNG MEN
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DOI：
10.1210/jc.78.3.711
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发表时间：
1994-03-01
影响因子：
5.8
通讯作者：
BREMNER, WJ
中科院分区：
文献类型：
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作者：
BAGATELL, CJ;HEIMAN, JR;BREMNER, WJ
雄激素在大多数物种雄性中建立和维持性功能的重要性是公认的。在一些物种中，雌激素也能刺激雄性的性功能。在男性中，大多数关于雄激素对行为影响的研究都使用性腺功能低下的男性作为实验模型；对于内源性睾酮(T)或雌二醇（E(2)）在调节健康、性腺功能正常的男性行为中的作用，我们知之甚少。在一项随机、双盲研究中，我们使用GnRH拮抗剂Nal-Glu，不使用T替代，诱导9名正常男性急性、深度、可逆的性腺类固醇缺乏，持续6周（单独使用Nal-Glu）。我们还研究了部分雄激素替代的效果，通过给予Nal-Glu和T - entanthate，每周50毫克，给另外10名男性。第三组10名男性接受Nal-Glu加T，每周100毫克。我们研究了内源性E(2)的作用，通过给另外10名男性（Nal-Glu+T+Teslac）每周100 mg的Nal-Glu+T，加上芳香化酶抑制剂睾丸内酯（Teslac），每天250 mg。九名男性接受了安慰剂注射和药片治疗。所有受试者在治疗前、治疗第2、4、6周和治疗后3周完成一份行为问卷。单独接受Nal-Glu治疗的男性在治疗开始后1周内出现严重的性腺功能减退。血清T水平在对照组和接受完全T替代的男性中没有显著变化，但在接受部分T替代的男性中下降到大约基线水平的一半。单独接受Nal-Glu或Nal-Glu+T+Teslac治疗的患者E(2)水平明显下降，接受部分T替代治疗的患者E(2)水平下降程度较轻。在单独接受Nal-Glu治疗的男性中，在4-6周时，性欲、性幻想和性交的频率在临床上和统计学上都有显著降低。这些男性在治疗4周和6周后自发性勃起也有明显的下降趋势（P = 0.55）。6周后，自慰频率明显下降。治疗后第3周，各项指标恢复正常。性腺功能低下的男性有攻击性增加的趋势，但没有达到统计学意义。他们对伴侣的满意度和幸福感没有变化。在研究期间，接受任何其他方案的男性在任何行为参数上都没有明显的变化。我们的数据证实了生理水平的T对维持正常男性性行为的重要性。他们还表明，急性性腺功能减退的影响不会立即表现出来，但在雄激素缺乏4-6周后，这些影响在临床上和统计上都是显著的。大约在血清T恢复到正常水平的同时，性功能也恢复了。我们的数据还表明，在实验性性腺功能低下的男性中，每周50毫克的雄激素替代剂量足以维持正常的性功能和行为，并且循环中的E(2)水平在正常男性的性行为调节中作用有限。由GnRH拮抗剂加不同剂量的雄激素替代引起的急性、可逆性性腺功能减退模型为评估男性雄激素的作用提供了一种极好的体内生物测定方法。
The importance of androgens in establishing and maintaining sexual function in males of most species is well recognized. Estrogens also stimulate male sexual function in some species. In men, most studies of androgen effects on behavior have used hypogonadal men as an experimental model; much less is known about the role of endogenous testosterone (T) or estradiol (E(2)) in the regulation of behavior in healthy, eugonadal men. In a randomized, double-blind study, we used a GnRH antagonist, Nal-Glu, without T replacement, to induce acute, profound, reversible gonadal steroid deficiency in 9 normal men for 6 weeks (Nal-Glu alone). We also studied the effects of partial androgen replacement by administering Nal-Glu together with T enanthate, 50 mg im weekly, to 10 other men. A third group of 10 men received Nal-Glu plus T, 100 mg im weekly. We studied the role of endogenous E(2) by administering Nal-Glu plus T, 100 mg im weekly, plus an aromatase inhibitor, testolactone (Teslac), 250 mg po qid, to 10 additional men (Nal-Glu+T+Teslac). Nine men received placebo injections and tablets. All subjects completed a behavioral questionnaire during the pretreatment period, at weeks 2, 4, and 6 of treatment, and at 3 weeks posttreatment.Men who received Nal-Glu alone became profoundly hypogonadal within 1 week after treatment began. Serum T levels did not change significantly in the controls and in the men who received full T replacement but decreased to approximately half the baseline level in men who received partial T replacement. E(2) levels decreased profoundly in men who received Nal-Glu alone or Nal-Glu+T+Teslac and to a lesser degree in men who received partial T replacement. In men who received Nal-Glu alone, there were clinically and statistically significant decreases in the frequency of sexual desire, sexual fantasies, and intercourse at 4-6 weeks. These men also showed a strong trend (P = 0.55) towards decreased spontaneous erections after 4 and 6 weeks of treatment. A significant decrease in the frequency of masturbation was evident after 6 weeks. All measures returned to normal by posttreatment week 3. There was a trend toward increased aggression in the hypogonadal men, but this did not reach statistical significance. No changes in satisfaction or happiness with their partners were observed. There were no significant changes in any behavioral parameter during the study in men who received any of the other regimens.Our data confirm the importance of physiological levels of T in maintaining sexual behavior in normal men. They also demonstrate that the effects of acute hypogonadism are not manifested immediately, but they become clinically and statistically significant after 4-6 weeks of androgen deficiency. Sexual function is restored at approximately the same time that serum T returns to normal levels. Our data also show that in experimentally hypogonadal men, replacement of androgens at a dose of 50 mg/week is adequate to maintain normal sexual function and behavior, and that circulating levels of E(2) have a limited role in the regulation of sexual behavior in normal men. The model of acute, reversible hypogonadism induced by GnRH antagonists plus varying amounts of androgen replacement offers an excellent in vivo bioassay for assessing androgen effects in men.