Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical & Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
Interdisciplinary Department of Medicine, Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari, Bari, Italy.
Clin Endocrinol (Oxf). 2020 Jan;92(1):38-45. doi: 10.1111/cen.14122. Epub 2019 Nov 18.
Clomiphene citrate (CC) has been shown to restore the hypothalamic-pituitary-gonadal (HPG) axis by increasing testosterone (T) levels to physiological levels in patients with dysmetabolic conditions such as obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). However, the data are unclear regarding the effects on Sertoli cell (SC) function.
To study SC function by assessing Inhibin B (IB) and anti-Mullerian hormone (AMH) levels at baseline and after 3 months of CC treatment.
This is an ancillary study of a cross-over, randomised, double-blind, placebo-controlled trial performed to evaluate androgen response to CC treatment in dysmetabolic obese subjects with low T levels treated with metformin. We evaluated SC function by assessing IB and AMH levels at baseline and after 3 months of each treatment in ten dysmetabolic obese subjects with low T levels. In all subjects, the influence of the clinical characteristics, metabolic and hormonal baseline parameters on SC and Leydig (LC) function, evaluated respectively with AMH, IB, follicle-stimulating hormone (FSH) and T levels, was tested.
No significant changes were observed for IB and AMH concentrations after each treatment period. Whereas T and oestradiol (E2) levels were shown to be significantly higher in the CC plus metformin phase (CC/Met) only. No clinical, metabolic or hormonal parameters showed significant effects on serum AMH at baseline or after treatments. However, baseline T, dihydrotestosterone (DHT) and E2 positively affected IB levels during CC/Met therapy (P = .003, P = .038 and P = .049, respectively). Baseline leptin and FSH had a negative (P = 031) and positive (P = .048) respectively role on T levels during CC/Met, as they were statistically significant compared to the placebo period (Plac/Met).
Unlike the LC activity, CC was unable to influence SC function, as shown by the lack of IB and AMH serum modifications, thus suggesting an intrinsic nonreversible defect of SC cells in patients with dysmetabolic conditions.
枸橼酸氯米酚（CC）已被证明通过增加患有代谢紊乱的患者的睾丸激素（T）水平至生理水平来恢复下丘脑-垂体-性腺（HPG）轴，例如肥胖，代谢综合征和 2 型糖尿病（T2DM）。然而，关于其对支持细胞（SC）功能的影响的数据尚不清楚。
通过评估基础和 CC 治疗 3 个月后抑制素 B（IB）和抗缪勒管激素（AMH）的水平来研究 SC 功能。
这是一项交叉，随机，双盲，安慰剂对照试验的辅助研究，旨在评估二甲双胍治疗的低 T 水平代谢紊乱肥胖患者对 CC 治疗的雄激素反应。我们通过评估基础和 3 个月后每个治疗期的 IB 和 AMH 水平来评估十例低 T 水平代谢紊乱肥胖患者的 SC 功能。在所有受试者中，均测试了临床特征，代谢和激素基线参数对 SC 和莱迪希（LC）功能的影响，分别用 AMH，IB，卵泡刺激素（FSH）和 T 水平评估。
在每个治疗期后，IB 和 AMH 浓度均未发生明显变化。只有 CC 加二甲双胍阶段（CC/Met）中 T 和雌二醇（E2）水平显示明显升高。在基础或治疗后，没有任何临床，代谢或激素参数显示对血清 AMH 有明显影响。然而，基础 T，二氢睾酮（DHT）和 E2 在 CC/Met 治疗期间对 IB 水平有积极影响（P=.003，P=.038 和 P=.049）。基础瘦素和 FSH 在 CC/Met 期间对 T 水平具有负作用（P=.031）和正作用（P=.048），与安慰剂期（Plac/Met）相比，它们具有统计学意义。
与 LC 活性不同，CC 无法影响 SC 功能，因为缺乏 IB 和 AMH 血清改变，因此表明代谢紊乱患者的 SC 细胞存在内在的不可逆转缺陷。
