甲狀腺亢進男性睪丸功能變化

Abstract

睪丸是男人最重要的生殖器官，它的主要功能可以分為兩大類：製造男性賀爾蒙與精子。在過去的研究中，我們發現甲狀腺亢進男性病人體內的賀爾蒙與生化會產生一系列改變，性賀爾蒙比例的改變容易造成甲亢男性病人產生性賀爾蒙低下的相關症狀 (如：勃起功能障礙、性慾下降與男性女乳症)。另一方面，過去許多研究也發現甲亢男病人的精子有著程度不一的缺陷，並且在一些研究中，在治療過後這些缺陷可以得到大幅度地改善。以上的資料表示甲狀腺亢進會影響睪丸功能並造成傷害。因此，本研究的目的是藉由測量甲狀腺亢進男性病人體內賀爾蒙與生化的改變，來評估男性及生殖功能與各項賀爾蒙的代償狀況。 我們以前瞻性式收案內分泌科門診中，新診斷 (或復發) 之甲狀腺亢進之男病人，在病人起始治療時，留取血液檢體。並在病人呈現甲狀腺功能正常至少三個月後，留取第二次血液檢體。以年齡及BMI 配對收案健康控制組，並在收案時留取血液檢體。甲狀腺亢進男病人，共26 人，致病機轉均為Graves’ disease，並且都接受methimazole 作為藥物控制，年齡 (mean ± SD) 為46.15±12.73年，BMI (mean ± SD) 為24.09±3.80 體重(kg)/身高2(m2)。健康控制組26 人，年齡為46.13±12.02年，BMI為23.96±3.68 體重(kg)/身高2 (m2)。研究結果顯示Luteinizing hormone (LH)、total testosterone、Estradiol (E2) 與Sex hormone binding globulin (SHBG) 的平均值 (mean ± SD)，在甲狀腺亢進組，顯著高於對照組 (分別為LH：8.60±2.93 與5.84±2.74 mIU/ml，p < 0.01；total testosterone：810±364與446.08±179.08 ng/dL，p < 0.01；E2：36.97±11.94 與28.45±7.86 pg/mL，p < 0.01；SHBG：132.93±75 與48.92±35.2 nmol/L，p < 0.01)。Albumin 的平均值 (mean ± SD)，在甲狀腺亢進組 (4.42±0.31 g/dL) 顯著低於對照組 (4.76±0.27 g/dL，p <0.01)。在治療過後，以上數值可以回復，並且治療後的結果，與對照組之間沒有顯著差異 (LH：6.59±2.92 mIU/ml；total testosterone：446.92±128.68 ng/dL；E2：28.2± 7.50 pg/mL；SHBG：51.91±29.26 nmol/L； Albumin：4.62 ±0.21 g/dl)。Bioavailable testosterone (BioT)、free testosterone (FT)、follicle stimulating hormone (FSH) 與inhibin B的平均值 (mean ± SD)，在甲狀腺亢進組、治療後與對照組，三組之間無顯著差異 (分別為Bio T：158.09±53.89、171.3±46.44 與181±41.28 ng/dL；FT：6.57±2.13、6.83±1.95 與6.99±1.57 ng/dL；FSH：7.76±3.47、6.88 ±3.82與6.33±2.91 mIU/ml；Inhibin B：123.32±61.47、143.78±71.47與140.22±67.6 pg/ml)。 本項研究顯示甲狀腺亢進會使得體內一系列賀爾蒙與相關的生化數值產生改變，而對於生殖賀爾蒙的改變，我們的資料顯示在甲狀腺亢進病人身上，是有辦法完成代償並達到新的平衡點。研究中FSH 與Inhibin B 數值在三組之間並無差異，有可能暗示Sertoli cell 能力並無缺陷，且精細胞的存量沒有受到影響 (指pachytene spermatocytes 與round spermatids)。因此，對於在之前其他研究中所見的甲亢病人精液問題，其造成的原因可能來自於過量甲狀腺賀爾蒙對精子的直接效應。所以在臨床上，若需要處理男性甲狀腺亢進所造成的不孕問題，應以矯正甲狀腺賀爾蒙為優先。

Testis is the most important reproductive organ in men, including two main functions: steroidgenesis (testosterone) and spermatogenesis. In the past years, certain studies showed reproductive hormone defects in hyperthyroid males, with symptoms of hypogonadism, such as erectile dysfunction, decreased libido and gynecomastia. The past studies also showed sperm parameter defects in hyperthyroid males, which might recover well after treatment. The aim of this prospective controlled study tried to evaluate the effect of hyperthyroidism on human testis, and the compensation of reproductive hormone. Twenty six male patients with Graves’ hyperthyroidism, demographic data revealed 46.15±12.73 year-old (mean ± SD) with body mass index (BMI) as 24.09±3.80 kg/m2. They were matched with 26 healthy male controls (46.13±12.02 year-old and BMI as 23.96±3.68 kg/m2). The blood samples were obtained before treatment and at least 3 months in euthyroid status after treatment with methimazole. The results reveal that the levels of Luteinizing hormone (LH), total testosterone, Estradiol (E2) and Sex hormone binding globulin (SHBG) were higher in hyperthyroidism patients in comparison with controls. (LH, Mean± SD, 8.60±2.93 vs 5.84±2.74 mIU/ml, p <0.01; total testosterone: 810±364 vs 446.08±179.08 ng/dL, p <0.01; E2: 36.97±11.94 vs 28.45±7.86 pg/mL, p <0.01; SHBG: 132.93±75 vs 48.92±35.2 nmol/L, p <0.01). In addition, the level of albumin (4.42±0.31 g/dL) was lower in patients than that of control (4.76±0.27 g/dL, p <0.01). After treatment with anti-thyroid drugs, gonadal hormone could recover without statistically difference between subjects after treatment and controls. (LH, 6.59±2.92 mIU/ml; total testosterone, 446.92±128.68 ng/dL; E2: 28.2± 7.50 pg/mL; SHBG, 51.91±29.26 nmol/L; Albumin, 4.62 ±0.21 g/dl). There were no statistically differences in the levels of bioavailable testosterone (Bio T), free testosterone (FT), follicle stimulating hormone (FSH) and inhibin B between patients before treatment, after treatment and control group. (BioT, 158.09±53.89 vs 171.3±46.44 vs 181±41.28 ng/dL; FT, 6.57±2.13 vs 6.83±1.95 vs 6.99 ±1.57 ng/dL; FSH:7.76±3.47 vs 6.88 ±3.82 vs 6.33±2.91 mIU/ml; Inhibin B, 123.32 ±61.47 vs 143.78 ± 71.47 vs 140.22 ± 67.6 pg/ml). Our results showed the hormone alteration and compensation in men with hyperthyroidism. The stability of FSH and Inhibin B level implicated fair reserve of spermatocytes (pachytene spermatocytes and round spermatids) and Sertoli cell function. The defects of sperm parameter in hyperthyroidism noted in previous studies were possibly caused by the direct effect of thyroid hormone on spermatocytes. Therefore, we will suggest that the very first step to treat hyperthyroidism-related infertility in men should be therapeutic correction of thyroid hormone levels.