Endocrinology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
J Sex Med. 2011 Dec;8(12):3471-8. doi: 10.1111/j.1743-6109.2011.02497.x. Epub 2011 Oct 13.
Androgens are able to induce the development of secondary sexual characteristics in male patients suffering from hypogonadism. So far, the most common method of administering testosterone to induce puberty in these patients has been via the injection of testosterone ester formulations. Moreover, some evidence has showed that the length of polymorphism Cytosine-Adenine-Guanine (CAG) trinucleotide repeats present in androgen receptor (AR) gene might co-regulate the effectiveness of testosterone therapy.
The aim of this study is to evaluate the effectiveness of a long-acting injectable testosterone undecanoate (TU) formulation for the induction of secondary sexual characteristics in young males with hypogonadotropic hypogonadism (HH).
We studied the different stages of puberty development that occur progressively according to the continuous increase in serum testosterone levels and, secondly, whether these changes might be modulated by the length of CAG repeats.
Nine male subjects over the age of 17 that had not undergone pubertal development because of HH were enrolled in this study and compared with 15 control males. Of these patients, 6/9 suffered from idiopathic HH and 3/9 experienced hypogonadism related to β-thalassemia (BT). All patients underwent a clinical examination and a determination of follicle-stimulating hormone, luteinizing hormone, sex hormone binding globulin (SHBG), and total testosterone (T) serum levels; the free fraction (FT) and biologically active fraction of testosterone were also determined. The number of CAG triplets present in the AR gene was obtained for each patient. For treatment, HH patients received an oral TU (Andriol, 120 mg/day) for 3 months, followed by intramuscular injection of parenteral TU (Nebid, 1,000 mg) every 14 weeks for 1 year, then every 12 weeks for a second year. Serum T and SHBG levels were assayed 3 months after the start of oral TU treatment and also in the 10th week following the start of the second round of intramuscular TU injections (e.g., the eighth month). Levels were also determined 12, 18, and 24 months after the start of the parenteral TU treatments.
Serum levels of T, SHBG, FT, and BT increased in all of the patients receiving oral TU and parental TU treatments, and this was accompanied by a development of secondary sexual characteristics. For treated patients with >24 CAG triples vs. the HH subjects with ≤24 CAG triplets, a slight delay in the appearance of the most advanced phases of puberty and a slightly reduced final penis length were observed, suggesting that AR CAG polymorphism might co-regulate the effectiveness of T treatment.
Long-acting parental TU was able to induce the puberty in our group of HH patients, even though additional studies are needed to elucidate the possible role of CAG repeats' length for the development of secondary sexual characteristics in young men with HH.
雄激素能够诱导患有性腺功能减退症的男性患者的第二性征发育。到目前为止，向这些患者给予睾酮以诱导青春期最常见的方法是通过注射睾酮酯制剂。此外，有证据表明雄激素受体（AR）基因中存在的胞嘧啶-腺嘌呤-鸟嘌呤（CAG）三核苷酸重复的长度可能共同调节睾酮治疗的有效性。
本研究旨在评估长效注射用十一酸睾酮（TU）制剂在诱导患有促性腺激素分泌不足性性腺功能减退症（HH）的年轻男性的第二性征方面的有效性。
我们研究了根据血清睾酮水平持续升高而逐渐发生的不同青春期发育阶段，其次是这些变化是否可能受 CAG 重复长度的调节。
我们招募了 9 名年龄在 17 岁以上的男性患者，他们因 HH 而未经历青春期发育，并与 15 名对照男性进行了比较。其中 6/9 例为特发性 HH，3/9 例为β-地中海贫血（BT）相关的性腺功能减退症。所有患者均接受了临床检查和促卵泡激素、促黄体生成素、性激素结合球蛋白（SHBG）和总睾酮（T）血清水平的测定；还测定了游离分数（FT）和睾酮的生物活性分数。获得了每位患者 AR 基因中存在的 CAG 三联体的数量。对于治疗，HH 患者每天口服 TU（安特尔，120mg）3 个月，然后每隔 14 周肌内注射 TU（Nebid，1000mg）1 年，然后每隔 12 周 2 年。在口服 TU 治疗开始后 3 个月和第二轮肌内 TU 注射开始后第 10 周（例如第 8 个月）测定血清 T 和 SHBG 水平。在接受 TU 治疗后 12、18 和 24 个月也测定了这些水平。
接受口服 TU 和 TU 治疗的所有患者的血清 T、SHBG、FT 和 BT 水平均升高，同时第二性征也得到了发育。对于 CAG 三联体数量大于 24 的接受治疗的患者与 CAG 三联体数量小于或等于 24 的 HH 患者相比，青春期最晚期的出现出现轻微延迟，最终阴茎长度略低，提示 AR CAG 多态性可能共同调节 T 治疗的有效性。
长效 TU 可以诱导我们组的 HH 患者的青春期，尽管还需要进一步的研究来阐明 CAG 重复长度在年轻男性 HH 患者的第二性征发育中的可能作用。
