Giagulli Vito A, Silvestrini Andrea, Bruno Carmine, Triggiani Vincenzo, Mordente Alvaro, Mancini Antonio
Internal Medicine, Geriatrics, Endocrinology and Rare Disease, Interdisciplinary Department of Medicine, University of Bari, School of Medicine, Policlinico, Bari, Italy.
Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.
Int J Endocrinol. 2020 Jan 21;2020:9649838. doi: 10.1155/2020/9649838. eCollection 2020.
Hypogonadotropic hypogonadism (HH) can be sustained by organic or functional alterations of the hypothalamic-pituitary-testicular axis. Functional HH is related to systemic alterations, such as obesity or chronic inflammatory diseases, but could contribute to a negative course of the illness. For such situation, according to results obtained in infertile women, the administration of selective estrogen receptor modulators (SERMs) has been proposed in males too, with positive results on both metabolic and sexual function. This class of medications increases gonadotropin levels via antagonism to the estrogenic receptor; similar biological effects are also exerted by aromatase inhibitors (AIs), despite different mechanism of action. After a brief review of trials regarding SERMs and AIs use in male HH, we describe the structure and function of the androgen receptor (AR) as a basis for clinical research about compounds able to bind to AR, in order to obtain specific effects (SARMs). The tissue selectivity and different metabolic fate in comparison to testosterone can potentiate anabolic versus androgenic effects; therefore, they might be a valid alternative to testosterone replacement therapy avoiding the negative effects of testosterone (i.e., on prostate, liver, and hematopoiesis). Trials are still at an early phase of investigation and, at the moment, the application seems to be more useful for chronic disease with catabolic status while the validation as replacement for hypogonadism requires further studies.
低促性腺激素性性腺功能减退（HH）可由下丘脑 - 垂体 - 睾丸轴的器质性或功能性改变所致。功能性HH与全身性改变有关，如肥胖或慢性炎症性疾病，但其可能导致疾病的不良进程。针对这种情况，根据在不孕女性中获得的结果，也有人提议在男性中使用选择性雌激素受体调节剂（SERM），其对代谢和性功能均有积极效果。这类药物通过拮抗雌激素受体来提高促性腺激素水平；芳香化酶抑制剂（AI）尽管作用机制不同，但也能产生类似的生物学效应。在简要回顾关于SERM和AI用于男性HH的试验后，我们描述雄激素受体（AR）的结构和功能，作为能够与AR结合以获得特定效应的化合物（选择性雄激素受体调节剂，SARM）临床研究的基础。与睾酮相比，其组织选择性和不同的代谢命运可增强合成代谢而非雄激素效应；因此，它们可能是睾酮替代疗法的有效替代方案，可避免睾酮的负面影响（即对前列腺、肝脏和造血功能的影响）。试验仍处于早期研究阶段，目前，其应用似乎对具有分解代谢状态的慢性疾病更有用，而作为性腺功能减退替代疗法的验证还需要进一步研究。
