Department of Pharmacological and Biomolecular Sciences-Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, Italy.
J Sex Med. 2013 Oct;10(10):2598-603. doi: 10.1111/jsm.12269. Epub 2013 Jul 24.
Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation.
A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology.
The levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in three postfinasteride patients and compared to those of five healthy controls.
Neuroactive steroid levels in plasma and cerebrospinal fluid of postfinasteride patients and healthy controls.
At the examination, the three postfinasteride patients reported muscular stiffness, cramps, tremors, and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Severity and frequency of the anxious/depressive symptoms were quite variable; overall, all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in patients showed some interindividual differences. However, the most important finding was the comparison of their neuroactive steroid levels with those of healthy controls. Indeed, decreased levels of tetrahydroprogesterone, isopregnanolone and dihydrotestosterone and increased levels of testosterone and 17β-estradiol were reported in cerebrospinal fluid of postfinasteride patients. Moreover, decreased levels of dihydroprogesterone and increased levels of 5α-androstane-3α,17β-diol and 17β-estradiol were observed in plasma.
The present observations confirm that an impairment of neuroactive steroid levels, associated with depression symptoms, is still present in androgenic alopecia patients treated with finasteride despite the discontinuation of the treatment.
在接受非那雄胺（5α-还原酶抑制剂）治疗男性型脱发的患者亚组中进行的观察似乎表明，性功能障碍以及焦虑/抑郁症状可能在治疗结束时发生，并在停药后持续存在。
解释非那雄胺治疗后抑郁症状的一个可能假说可能是神经活性甾体水平受损。因此，评估了接受非那雄胺治疗雄激素性脱发的男性患者的配对血浆和脑脊液样本中的神经活性甾体水平，这些患者在停药后仍表现出长期的性功能副作用以及焦虑/抑郁症状。
通过液相色谱-串联质谱法在三名接受非那雄胺治疗的患者和五名健康对照者中评估神经活性甾体水平。
接受非那雄胺治疗的患者和健康对照者的血浆和脑脊液中的神经活性甾体水平。
在检查时，三名接受非那雄胺治疗的患者报告肌肉僵硬、痉挛、震颤和慢性疲劳，而没有任何肌肉疾病或力量减弱的临床证据。焦虑/抑郁症状的严重程度和频率差异较大；总体而言，所有患者都有相当复杂和持续的神经精神模式。对患者神经活性甾体水平的评估显示出一些个体间差异。然而，最重要的发现是将他们的神经活性甾体水平与健康对照者进行比较。事实上，在接受非那雄胺治疗的患者的脑脊液中报告了四氢孕酮、异孕烯醇酮和二氢睾酮水平降低，而睾酮和 17β-雌二醇水平升高。此外，在血浆中观察到了二氢孕酮水平降低和 5α-雄烷-3α，17β-二醇和 17β-雌二醇水平升高。
本观察结果证实，尽管停止治疗，接受非那雄胺治疗的雄激素性脱发患者的神经活性甾体水平仍然存在与抑郁症状相关的损害。
