Plasma estradiol,free testosterone,sex hormone binding globulin binding capacity,and prolactin in benign prostatic hyperplasia and prostatic cancer

The nature of hormonal changes with age and the possible role of these changes in the development of benign prostatic hyperplasia (BPH) and prostatic cancer (PC) were studied by assaying the plasma levels of total and free testosterone (T), estradiol (E₂), prolactin, and sex hormone binding globulin binding capacity (SHBG) in 20 normal healthy men aged 40-59 years, in 30 patients with BPH aged 63-79 years, and in 30 patients with PC of similar height, weight, and age as the BPH patients. The mean E₂ was highly significantly (P < 0.0005) lower in the PC patients and in the young controls than in the BPH patients. The mean free T was significantly higher in the young controls than in the BPH patients (P < 0.025) and PC patients (P < 0.0005). The PC patients had a slightly lower (P < 0.05) mean free T and mean E₂/free T ratio than the BPH patients. The mean E₂/free T ratio was significantly higher in the BPH patients (P < 0.0005) and in the PC patients (P < 0.0025) than in the young controls. It seems possible that the observed age-dependent significant increase in plasma estrogen concentration in the BPH patients may act as a protective factor against prostatic cancer.     

Insulin resistance and sex hormone‐binding globulin are independently correlated with low free testosterone levels in obese males

Male obesity is associated with decreased testosterone levels but the pathophysiological mechanisms behind this association are not completely understood. This study aimed to investigate the impact of hyperglycaemia/insulin resistance and sex hormone‐binding globulin (SHBG) levels on testosterone levels in a population of obese men. We investigated the impact of several clinical, anthropometric and analytic measures on testosterone levels in 150 obese males. Testosterone deficiency was present in 52.0% of the enrolled patients. This percentage dropped to 17.6% when only calculated free testosterone (FT) was accounted, as SHBG levels were correlated negatively with body mass index (r = ?.20; p < .05). Older age (p < .05) and higher homoeostasis model assessment of insulin resistance (HOMA‐IR) (p < .01) and lower SHBG levels (p < .05) were independently correlated with lower FT. Weight and fasting plasma glucose lost their statistical significance after multivariate adjustment. Patients with type 2 diabetes mellitus and pre‐diabetes had lower FT than those with normal glucose tolerance (p < .05 and p < .01 respectively). Insulin resistance, and not hyperglycaemia and weight per se, seems to be the main determinant of low testosterone levels in obese males. Low SHBG levels are correlated with low FT even after HOMA‐IR adjustment. This suggests that SHBG can be associated with testosterone deficiency beyond the influence of insulin resistance unlike previously reported.     

Pretreatment plasma levels of testosterone and sex hormone binding globulin binding capacity in relation to clinical staging and survival in prostatic cancer patients

Pretreatment plasma concentrations of total testosterone (T), sex hormone binding globulin binding capacity (SHBG). T/SHBG ratio, and free testosterone (fT) were measured in 123 patients with prostatic cancer categorized into groups according to the UICC classification. The patients were randomized to orchiectomy or estrogen therapy and the mean follow-up time was 48 months. The mean plasma levels of T were higher in patients without metastases and with intracapsular cancer, but the differences were not statistically significant. The calculated ratio of T/SHBG was noticed to be significantly higher (p less than 0.05) in the M0 category. The prognostic significance of pretreatment T and, more impressively, T/SHBG ratio and fT was confirmed. Low pretreatment values indicated poorer prognosis. This study supports the view that there are differences in the pretreatment T and fT levels in prostatic cancer patients in relation to the stage of tumor and that these hormone assays could be used as prognostic factors.     

前列腺癌患者血清睾酮水平与前列腺穿刺活检阳性的相关性

目的探讨血清总睾酮水平与前列腺穿刺活检阳性之间的相关性,为临床个体化治疗方案的选择提供理论依据。方法 2015年9月至2019年3月期间在汉中市人民医院泌尿外科接受前列腺穿刺活检的患者,收集患者的年龄、血清总前列腺特异性抗原(tPSA)及性激素等相关资料,观察这些指标对前列腺穿刺活检阳性率的影响。结果在113例患者中,前列腺癌(PCa)患者检出率共89例,穿刺阳性率为78.76%。与穿刺阴性组比较,患者血清tPSA[(12.42±4.64)vs.(5.35±1.66)ng/mL,P<0.001]和催乳素水平[(8.55±2.48)vs.(6.91±1.92)ng/L,P=0.003]升高与前列腺穿刺活检阳性有关,而总睾酮激素水平下降与前列腺穿刺活检阳性有关[(12.64±3.28)vs.(16.85±3.37)nmol/L,P<0.001]。多变量分析证实tPSA[P<0.001,OR=3.383(1.924~5.342)]和血清睾酮[P=0.038,OR=1.361(1.124~1.927)]是预测前列腺穿刺活检阳性的独立预测因子。受试者工作曲线(ROC)显示tPSA水平与前列腺穿刺阳性风险呈正相关,曲线下面积(AUC)为0.989,最佳截断值为8.022,敏感度和特异度分别为87.5%和98.88%;总睾酮激素水平与前列腺穿刺阳性风险呈负相关,AUC为0.786,最佳截断值为17.85,敏感度和特异度分别为66.67%和78.65%,差异具有统计学意义(P<0.001)。结论低血清睾酮激素与前列腺穿刺检测PCa的风险有关,这些结果可能揭示了PCa与睾酮两者关系的潜在机制。     

A comparison of androgen status in patients with prostatic cancer treated with oral and/or parenteral estrogens or by orchidectomy

The effects of orchidectomy, combined oral/parenteral estrogen, and single-drug parenteral estrogen therapy on the serum levels of testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA) and its sulfate (DHAS), sex-hormone-binding globulin (SHBG), and albumin were studied in 48 patients with prostatic cancer. Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels. Oral estrogens profoundly decreased the serum levels of DHAS and, to a lesser extent, levels of DHA and of albumin, while parenteral estrogens had no effect in this respect. SHBG serum levels were highly increased by oral estrogens, slightly increased by parenteral estrogens, and unaffected by orchidectomy. The more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.     

Free testosterone in carcinoma of the prostate

Serum concentrations of testosterone (total T), sex hormone-binding globulin (SHBG), and albumin (A) have been measured, and from these values the free testosterone (free T) has been calculated in the following groups: 50 patients recalled 1-2 years after prostatectomy for benign prostatic hyperplasia (BPH); 21 patients with BPH at first presentation; and 80 patients with carcinoma of the prostate (CaP) divided into 47 without clinical or radiological evidence of metastases (Mo) and 33 with metastases (M+). The Mo patients were further subdivided by the size of the prostate. Free T showed no change with age in either of the CaP groups. In both of the BPH groups free T fell with age so that in the patients aged 65 or less it was above the mean CaP level and in patients aged 75 or more it was similar to the CaP level. SHBG rose with age so that total testosterone values were a poor guide to free T. Neither presence of metastases nor prostate size in Mo patients was related to marked differences of free T.     

Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

OBJECTIVE: Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. METHODS: Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. RESULTS: There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with newly diagnosed prostate cancer had higher serum TT (P < 0.7), ADT (P < 0.2), SHBG (P < 0.2) and lower DHEAS (P < 0.008) compared to aged matched controls. CONCLUSIONS: Serum TT, SHBG, DHEAS and ADT levels are significantly lower in Arab men compared to those reported for Caucasian men, especially in early adulthood. Arab men with newly diagnosed prostate cancer have higher circulating androgens compared to healthy controls. We suggest that low circulating androgens and their adrenal precursors in Arab men when compared to Caucasians may partially account for the relatively lower risk for prostate cancer among Arab men.     

性激素结合球蛋白在生殖医学中的应用研究进展

性激素结合球蛋白(SHBG)是一种由肝细胞合成、与类固醇激素具有高亲和力的糖蛋白,SHBG可调节体内性激素的浓度并影响其活性.临床上通过分析IVF-ET促排卵过程中患者血清SHBG水平与硫酸脱氢表雄酮(DHEA-S)、抗苗勒管激素(AMH)、体质量指数(BMI)、总睾酮(T)等的相关性,为疾病预测、临床诊断、治疗方案制...     

Time course of serum testosterone and luteinizing hormone levels after cessation of long-term luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer

INTRODUCTION: In order to elucidate the influence of hormone-releasing hormone (LH-RH) agonist therapy cessation on pituitary/testicular function and its clinical implications, we investigated prospectively hormonal (luteinizing hormone: LH; testosterone: T) responses in patients with prostate cancer who received long-term LH-RH 10 agonist therapy. PATIENTS AND METHODS: A consecutive 32 patients who had received LH-RH agonist therapy over 24 months were enrolled. As a baseline, T and LH were measured at the time of LH-RH agonist therapy cessation, monthly for 3 months, and subsequently, every 3 months. RESULTS: The median duration of LH-RH agonist therapy was 30 months (24-87 months) with median follow-up duration of 24 months following cessation. All patients had castrated T levels and suppressed LH levels at baseline. Median duration of castrated T levels following cessation was 6 months. Median time to normalization of T levels was 24 months. LH levels returned to normal within 3 months in all cases. Patients who received androgen deprivation therapy for 30 months or longer required a longer time for recovery of T levels. Patients over 65 years of age showed a statistically significant longer time for recovery of T levels (P=0.0167). CONCLUSIONS: Long-term LH-RH agonist therapy has remarkable effects on serum T level that last for a significant time after cessation, a fact that should be applied to the interpretation of both PSA and serum T levels after cessation of androgen deprivation therapy.     

The (TAAAA)n polymorphism of sex hormone‐binding globulin gene is not associated with testicular maldescent

The aim of this family‐based study was to investigate the potential association/genetic linkage of the (TAAAA)_n polymorphism of sex hormone‐binding globulin gene proximal promoter with testicular maldescent (TMD). Genomic DNA was extracted from the peripheral blood of 487 subjects (174 index families): (i) 180 children with all phenotypes of TMD, (ii) 307 parents (156 mothers and 151 fathers). Conventional polymerase chain reaction amplification products were electrophoresed on 10% nondenaturating polyacrylamide gel and visualised by silver staining. After excluding ambiguous parental–child trios and most cases of index families with missing parental genotypes, 429 individuals were left for analysis: 138 completely typed nuclear families (five included a second affected child) and five child–parent couples (one parent missing). Eight fathers presented history of TMD, that is, a total of 156 cases with TMD were analysed. Alleles were analysed with the affected family‐based control method and logistic regression‐based extension of the transmission disequilibrium test for multiallelic loci. (ΤΑΑΑΑ)_n polymorphism analysis revealed six alleles based on repeat numbers (n = 5–10). No association/genetic linkage between the (TAAAA)_n polymorphism and TMD was detected. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.     

Testosterone recovery and changes in bone mineral density after stopping long-term luteinizing hormone-releasing hormone analogue therapy in osteoporotic patients with prostate cancer

OBJECTIVE: To investigate the rate of testosterone recovery and changes in bone mineral density in patients found to be osteoporotic while receiving luteinizing hormone-releasing hormone (LHRH) analogues after changing to antiandrogen monotherapy in an attempt to reduce further demineralization. PATIENTS AND METHODS: Fifteen patients receiving LHRH analogue therapy for > or = 1 year were identified as osteoporotic by distal forearm dual X-ray densitometry. They were then converted to antiandrogen monotherapy, and prostate specific-antigen (PSA) and total testosterone monitored at 3-monthly intervals. The forearm densitometry was repeated at 1 year. RESULTS: All patients had some testosterone recovery; the mean (range) duration to initial detectable testosterone was 12.8 (6-22) months. Six patients had a normal testosterone level after a mean of 17.5 (14-30) months. In the year after stopping LHRH analogue therapy the mean bone mineral density (t-score) decreased by 7.2%. CONCLUSIONS: Osteoporotic patients, after stopping LHRH analogues, continue to have suppressed levels of testosterone which have a detrimental effect on bone mineral density. We therefore would not advocate conversion to antiandrogen monotherapy to improve bone density, and suggest alternative therapeutic intervention e.g. bisphosphonate therapy, for these patients.     

Influence of orchidectomy or oestrogen treatment on serum levels of pregnancy associated alpha 2-glycoprotein and sex hormone binding globulin in patients with prostatic cancer

Peripheral serum levels of testosterone, immnunoreactive oestrogens (E₂), FSH, LH, prolactin and growth hormone (hGH) and two steroid-sensitive proteins, 'pregnancy-associated α₂-glycoprotein' (α₂-PAG) and sex hormone binding globulin (SHBG), were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Following orchidectomy, the serum levels of testosterone and E₂ decreased whilst the levels of FSH and LH increased significantly. No changes were noted in the serum levels of α₂-PAG, SHBG or prolactin. Oestrogen treatment significantly decreased the serum levels of testosterone, FSH and LH whilst levels of α₃-PAG, SHBG and prolactin were increased significantly. Serum levels of hGH during oestrogen treatment were significantly higher than in patients subjected to orchidectomy. These data are at variance with the established dogma of the oestrogen/androgen balance as a physiological regulator or liver protein synthesis, and indicate that factors other than the endogenous steroids may be operative. hGH may play an important role in this respect.     

Kinetics of testosterone recovery in clinically localized prostate cancer patients treated with radical prostatectomy and subsequent short-term adjuvant androgen deprivation therapy

Androgen deprivation therapy (ADT) is a standard treatment for metastatic, recurrent and locally advanced prostate cancer (PCa). The aim of this study is to investigate the timing and extent of testosterone recovery in clinically localized PCa patients treated with radical prostatectomy (RP) and subsequent short-term adjuvant ADT. A total of 95 localized PCa patients underwent RP and 9-month adjuvant ADT were included in this prospective study. Serum testosterone level was measured before adjuvant ADT, at ADT cessation, and at 1, 3, 6, 9 and 12 months after cessation of ADT. A Cox proportional hazards model was used to assess variables associated with the time of testosterone normalization. The results showed that median patient age was 67 years and median testosterone level before adjuvant ADT was 361 (230–905) ng dl⁻¹. All patients finished 9-month adjuvant ADT and achieved castrate testosterone level. At 3 months after ADT cessation, testosterone recovered to supracastrate level in 97.9% patients and to normal level in 36.9% patients. The percentage of patients who recovered to normal testosterone level increased to 66.3%, 86.3% and 92.6% at 6, 9 and 12 months, respectively. Cox regression model found that higher baseline testosterone level (≥300 ng dl⁻¹) was the only variable associated with a shorter time to testosterone normalization (hazard ratio: 1.98; P = 0.012). In conclusion, in most patients, testosterone recovered to supracastrate level at 3 months and to normal level at 12 months after 9-month adjuvant ADT cessation. Patients with higher baseline testosterone level need shorter time of testosterone normalization.     

Cardiovascular and all-cause mortality in prostatic cancer patients treated with estrogens or orchiectomy as compared to the standard population

Four hundred and seventy-seven prospectively randomized patients with prostatic carcinoma were treated with a combination of intramuscular polyestradiol phosphate (PEP) and oral ethinyl estradiol, with intramuscular PEP alone, or with orchiectomy. The cardiovascular and all-cause mortality of the two estrogen therapy modalities and orchiectomy were compared with those of the Finnish male population in general. The age-standardized rate ratios (approximately relative risk) for cardiovascular mortality and for all-cause mortality were 1.51 and 2.31 in the combination estrogen therapy group, 0.17 and 1.50 in the PEP monotherapy group, and 0.78 and 1.78 in the orchiectomy group, respectively. Further mortality rates by cause for all three treatment groups were standardized for age using the age-specific person-years at risk as standard. Age-standardized mortality from cardiovascular diseases was very low in the PEP group, as compared to other treatment modalities, and the mortality rates for prostatic cancer were about equal in all three treatment groups. It is concluded that intramuscular PEP monotherapy is associated with low cardiovascular mortality and with an all-cause and prostatic cancer mortality equal to orchiectomy.     

The effects of orchidectomy, estrogens, and cyproterone acetate on plasma testosterone, LH, and FSH concentrations in patients with carcinoma of the prostate

The peripheral plasma concentrations of testosterone, luteinising hormone (LH) and follicle stimulating hormone (FSH) were determined in 46 patients (age 51-86 years) with cytologically confirmed prostatic carcinoma. Treatment consisted of subcapsular orchidectomy (15 cases) or estrogen medication (16 cases) or cyproterone acetate (15 cases). The determinations were made before and 2 weeks and 2 months after treatment was initiated. No correlation was found between the pretreatment levels of testosterone and gonadotrophins and the local extent of the primary tumor or the degree of malignancy. Nor was there any correlation between hormonal level, presence of metastases or patient age. Orchidectomy and estrogen medication both resulted in very low plasma testosterone levels, corresponding to 15% of the pretreatment values. This proportion was 28% in the group treated with cyproterone acetate. Orchidectomy was followed by significant increase in the levels of LH and FSH. Estrogen treatment resulted in suppression of the LH levels to 40% and of FSH to 14% of the pretreatment values. The corresponding decreases in response to cyproterone acetate were 65 and 35%. The results indicate that reduction in gonadotrophin secretion is the primary mechanism in the lowering of testosterone levels produced by treatment with estrogens or cyproterone acetate.     

Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3

Plasma testosterone (T) and sex hormone binding globulin (SHBG) were assayed in normal controls (N = 9) and hypothyroid patients (N = 17) receiving increasing doses of L-T4 (0.2 mg, 0.4 mg for 30 days), followed first by 30 days without medication and then by 30 days each of 0.05 mg L-T3 and 0.2 mg L-T3. Normal male controls showed a significant increase in plasma T only at high doses of either L-T4 (0.4 mg) or L-T3 (0.2 mg). A small but significant increase in plasma T levels was observed in normal female subjects at 0.4 mg of T4. In both men and women, plasma SHBG increased in a dose-dependent manner with L-T4 or L-T3 and correlated positively and significantly with serum thyroid hormone levels. Hypothyroid male subjects had significantly lower levels of plasma T (mean +/- SD) of 279 +/- 131 ng/dl as compared with normal males (431 +/- 118 ng/dl), which reached the normal range only at a relatively high dose of either L-T4 (0.4 mg) or L-T3 (0.2 mg). No significant changes in plasma T were seen in the hypothyroid female group. Basal plasma SHBG levels were significantly lower in both hypothyroid men and women and increased towards normal levels during L-T4 and L-T3 therapy, although the response to thyroid hormones was significantly lower than that of normal controls. These results indicate that thyroid hormone therapy increases plasma SHBG levels in both normal and hypothyroid patients and that this increase precedes the expected elevation of plasma T in males.     

Equivalent and sufficient effects of leuprolide acetate and goserelin acetate to suppress serum testosterone levels in patients with prostate cancer

OBJECTIVE

To compare the effects of leuprolide acetate and goserelin acetate for suppressing serum testosterone levels in Japanese patients with prostate cancer, as several recent studies suggested that serum testosterone is not always suppressed below the upper limit of the castration range in patients using luteinizing hormone‐releasing hormone (LH‐RH) agonists, especially leuprolide acetate.

PATIENTS AND METHODS

In all, 232 patients with prostate cancer, whose serum testosterone levels were measured before and during treatment using a 1‐ or 3‐monthly formulation of leuprolide or goserelin, were enrolled in a retrospective study. The mean age of the patients was 69.8 years and the mean testosterone level before the LHRH treatment was 4.54 ng/mL. The patients had their testosterone levels assessed a mean (range) of 5.4 (1–35) times during the LHRH treatment. A castrate serum testosterone level was defined as ≤0.5 ng/mL.

RESULTS

The mean maximum testosterone level during 1‐monthly leuprolide (40 patients), 3‐monthly leuprolide (68), 1‐monthly goserelin (50), or 3‐monthly goserelin (74) treatment was 0.22, 0.20, 0.19 and 0.20 ng/mL, respectively (not significant). Four patients, including two treated with 1‐monthly leuprolide, one with 3‐monthly leuprolide and one with 3‐monthly goserelin, had serum testosterone above the castrate level, with a maximum of 0.5–0.65 ng/mL. Three of these patients had elevated testosterone only once or twice during the follow‐up, and the remaining patient had serum testosterone fluctuating at 0.4–0.6 ng/mL throughout the follow‐up.

CONCLUSIONS

One‐ and 3‐monthly formulations of leuprolide and goserelin have equivalent and sufficient effects to suppress serum testosterone levels in men with prostate cancer. There were testosterone levels just outside the castrate range in a few patients during treatment.     

Suppression of plasma testosterone and prostate carcinoma size by a redox-based,brain-targeted estrogen delivery system in the rat

Studies were undertaken to examine the effects of an estradiol-chemical delivery system (E₂-CDS) or castration (CAST) on plasma testosterone (T) and growth of the Segaloff 11095 carcinoma. Fischer 344 rats were implanted subcutaneously with the Segaloff 11095 tumor and tumor growth was monitored thereafter. After optimal tumor growth, when the average tumor size was ～25 × 15 mm (length × width; 4–5 g wet weight), rats were randomized into (1) testis-intact controls; (2) CAST; (3) intact + E₂-CDS groups (rats received weekly injection of the E₂-CDS at 0.5 mg/kg). Animals were killed 7 or 14 days after the initiation of treatments. Blood and tissue samples were collected for subsequent analysis. Plasma T levels were suppressed by 98% and 97% through 14 days after CAST or E₂-CDS treatment. CAST increased plasma gonadotropin (LH) concentrations, while E₂-CDS reduced LH compared to intact control levels. E₂-CDS treatment increased plasma E₂ levels to 24 (one injection) or 75 pg/ml (two injections) at 7 or 14 days, respectively. E₂-CDS, given once a week for 2 consecutive weeks, resulted in a decreased growth of the prostate tumor by 61%, while CAST reduced the weights of these tumors by only 20%. In response to E₂-CDS (one or two injections), weights of the in situ ventral prostate and seminal vesicles were significantly reduced by 70% and 50%, respectively, in tumorbearing rats. Similarly, CAST reduced the weights of these tissues by 80% (prostate) or 52% (seminal vesicle) at 7 or 14 days after treatment. Pituitary weight increased, while testes weight decreased by 20% with two injections of E₂-CDS, compared with intact control rats. Collectively, these data indicate that E₂-CDS is effective in reducing the growth rate of prostatic tumors in the rat. © 1993 Wiley-Liss, Inc.