2014年5月29日,加拿大生物技术公司Trimel宣布,FDA批准首个鼻用睾酮凝胶Natesto用于成年男性与内源性睾酮缺失相关疾病的替代治疗。
Natesto（testosterone gel，睾酮凝胶）是一种雄激素，主要用来治疗先天或后天的原发性或低促性腺素性功能减退症，可通过鼻部涂药器自我给药，给药过程只需几秒，可最大限度地减少妇女或儿童二次接触睾丸激素的风险。
据保守估计，近1300万美国男性睾丸激素水平低下。目前的治疗办法是通过使用外源性睾酮制剂恢复生理学睾酮水平，包括（涂抹）外用凝胶剂、皮下小球、透皮贴剂、肌内注射剂、口服片剂，以及一个颊贴剂。
Natesto是首个、也是目前唯一的睾酮鼻用凝胶制剂，它采用计量泵的形式，每个泵内含有5.5mg睾酮。推荐每次使用的睾酮剂量是11mg，因此每次使用2个泵（一个鼻孔一个），一日三次，每日的睾酮使用剂量是33mg。
Natesto在年龄＜18岁男性中的安全性和疗效尚未得到验证。该药禁用于男性乳腺癌，以及已有或疑似前列腺癌。此外，伴有慢性鼻炎的患者也不宜使用。
FDA批准Natesto基于一项多中心、开放标签、为期90天的3期临床试验结果。该研究在美国各地临床研究中心观察Natesto对男性性腺功能减退患者的治疗效果。统计学分析显示，Natesto对73例患者具有明显疗效，能使其中90%的患者睾酮水平恢复至正常范围。
Natesto(testosterone) nasal gel
Company: Trimel Pharmaceuticals
Approval Status: Approved May 2014
Treatment for: deficiency or absence of endogenous testosterone
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General Information

Natesto is a nasal gel formulation of testosterone). Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics.
Natesto is specifically indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired) and Hypogonadotropic hypogonadism (congenital or acquired).
Natesto is supplied as a gel for intranasal administration. The recommended dose of Natesto is 11 mg of testosterone (2 pump actuations; 1 actuation per nostril) administered intranasally three times daily for a total daily dose of 33 mg. Natesto should be administered once in the morning, once in the afternoon and once in the evening (6 to 8 hours apart), preferably at the same time each day. Serum total testosterone concentrations should be checked periodically, starting as soon as one month after initiating treatment with Natesto. When the total testosterone concentration consistently exceeds 1050 ng/dL, therapy with Natesto should be discontinued.
Clinical Results
FDA ApprovalThe FDA approval of Natesto was based on in a 90-day, open-label, multicenter study of 306 hypogonadal men. Eligible patients were 18 years of age and older (mean age 54 years) and had morning serum total testosterone concentrations less than 300 ng/dL. Subjects were instructed to self-administer Natesto (11 mg of testosterone) intranasally either two or three times daily. The primary endpoint was the percentage of patients with an average serum total testosterone concentration (Cavg) within the normal range (300 to 1050 ng/dL) on Day 90. A total of 78 hypogonadal men received Natesto (11 mg of testosterone) three times daily (33 mg of testosterone daily). Of these, a total of 73 hypogonadal men were included in the statistical evaluation of efficacy (total testosterone pharmacokinetics) on Day 90 based on the intent-to­treat (ITT) population with last observation carried forward (LOCF). Ninety percent (90%) of these 73 patients had a Cavg within the normal range (300 to 1050 ng/dL) on Day 90. The percentages of patients with Cavg below the normal range (less than 300 ng/dL) and above the normal range (greater than 1050 ng/dL) on Day 90 were 10% and 0%, respectively.
Side Effects
Adverse effects associated with the use of Natesto may include, but are not limited to, the following:
PSA increased
headache
rhinorrhea
epistaxis
nasal discomfort
nasopharyngitis
bronchitis
upper respiratory tract infection
sinusitis
nasal scab
Mechanism of Action
Natesto is a nasal gel formulation of testosterone). Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature, and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone.
Additional Information
For additional information regarding Natesto or testosterone deficiency, please visit the Trimel Pharmaceuticals web page.