EFFECTS OF ETHINYLOESTRADIOL ON PLASMA LEVELS OF PITUITARY GONADOTROPHINS, TESTICULAR STERIODS AND SEX HORMONE BINDING GLOBULIN IN NORMAL MEN

Daily measurements of plasma FSH, LH, prolactin, testosterone, 17β-oestradiol and sex hormone binding globulin (SHBG) activity were made in eight healthy, normal men during treatment with oral ethinyloestradiol (EE₂) in a dose of 30 μg/day for 5 days following a 5-day control period. No significant changes in plasma levels of FSH and prolactin during oestrogen treatment occurred. In contrast, plasma concentrations of both LH and testosterone showed a biphasic pattern. Following an initial suppression during the first 3 days of oestrogen treatment both LH and testosterone increased again to baseline values despite continuation of oestrogen administration. The secondary rise of both hormones was associated with (and probably resulted from) a nearly 100% increase in the plasma concentration of SHBG binding activity, and hence reduction of free testosterone index (FTI). Unlike testosterone, plasma 17β-oestradiol during EE₂ administration did not show a biphasic pattern, but a progressive decline that was positively correlated with the fall in FTI. The rapidity of onset and magnitude of the observed rise in SHBG levels emphasizes the need for measurement of this binding protein (or the free testosterone fraction) in studies on feedback regulation of gonadotrophins employing exogenous EE₂ in human males. The observed increase of SHBG to supraphysiological values suggests that currently employed EE₂ doses in such studies may be less ‘physiologic’ than is often assumed.     

男性Graves病患者唾液睾酮及血清性激素水平的变化

本文观察了20例男性Graves病患者抗甲状腺药物治疗前后的唾液睾酮及血清中几种性激素水平的变化,并与年龄、性别相配对的20例健康者进行了比较分析。患者治疗前唾液睾酮水平明显低于正常,治疗后显著上升,与血T_3、T_4的变化呈负相关;治疗前血总睾酮、雌二醇、LH及FSH显著高于正常,治疗2个月后除雌二醇外均随T_3、T_4的下降而下降。本文结果支持唾液睾酮不受SHBG的影响,提示Graves病患者游离睾酮减低。     

THE INFLUENCE OF BROMOCRIPTINE ON SERUM LEVELS OF GROWTH HORMONE AND OTHER PITUITARY HORMONES AND ITS METABOLIC EFFECTS IN ACTIVE ACROMEGALY

The effect of treatment with bromocriptine for 12--18 months on serum GH and metabolic responses was studied in sixteen patients with active acromegaly. Of this group ten patients showing a sustained GH reduction of more than 50% during an 8 h bromocriptine test, proved to be responsive to long-term therapy. In the responding patients GH levels decreased to 38% of the pretreatment level after 12 months of therapy. A dose higher than 10 mg did not produce a significantly greater effect. Prolactin and LH levels decreased in all patients, FSH levels showed a significant rise. Testosterone levels in the male patients increased significantly, indicating that the state of hypogonadism can at least be partially reversed. The GH levels became normal in only one patient. We conclude that the role of bromocriptine in acromagaly is limited and selective pituitary operation and/or irradiation is preferred as definitive treatment in most patients.     

NORMAL NEONATAL SURGE OF GONADOTROPHINS AND SEX STEROIDS IN INFANTS OF MEN WITH ISOLATED HYPOGONADOTROPHIC HYPOGONADISM

The inheritance of isolated hypogonadotrophic hypogonadism (IHH) is not fully determined. Although men with this diagnosis can be treated to induce fertility, it is not known whether their offspring will inherit the hormonal deficiency. We evaluated the hypothalamic-pituitary-gonadal axis in nine children (born to men with IHH) during the first few months of life. This axis normally shows activation in infancy similar to that which occurs at puberty. Luteinizing hormone (LH) releasing hormone stimulated a peak LH response in excess of prepubertal levels (39.0 +/- 11 mIU/ml [mean +/- SD]). Testosterone in males (6.2 +/- 2.8 nmol/l and oestradiol in two of the females (320 and 100 pmol/l) were also in excess of prepubertal levels. These infants of men with IHH showed no evidence of inheriting hypogonadotrophic hypogonadism. While further studies will be conducted at the usual age of puberty to confirm spontaneous activation of the hypothalamic-pituitary-gonadal axis, our studies suggest that it may be possible to assess the integrity of this axis at a much younger age.     

EFFECTS OF HEROIN ADDICTION ON THYROTROPHIN, THYROID HORMONES AND PROLACTIN SECRETION IN MEN

Pituitary-thyroid function in male heroin addicts and addicts after abstinence (ex-addicts) was studied and compared with that of healthy euthyroid men. In heroin addicts the increases in circulating total thyroxine and triiodothyronine levels were accompanied by an increase in the thyroid hormone uptake test. These changes may reflect a quantitative increase in thyroxine binding globulin. Reverse triiodothyronine concentrations in heroin addicts were normal. The thyrotrophin-releasing hormone elicited a diminished thyrotrophin response in heroin addicts which was significantly different from that in control subjects and ex-addicts. An elevation of serum prolactin was noted in heroin addicts, while ex-addicts had normal levels. Gradual recovery of pituitary-thyroid function occurred after heroin withdrawal.     

COMPARISON OF THE EFFECT OF APOMORPHINE AND l-DOPA ON SERUM GROWTH HORMONE LEVELS IN NORMAL MEN

Apomorphine hydrochloride (0.75 mg s.c.) has been compared with L-dopa (500 mg p.o.) in their effects on growth hormone secretion in a double blind cross-over study involving nine healthy men. Apomorphine increased serum GH levels above 10 ng/ml in all nine subjects 30-60 min after injection. In contrast, only six of these subjects showed a similar elevation with L-DOPA and in only three had the level increased above 6 ng/ml by 60 min. One subject failed to respond to L-dopa and in two others the peak was less than 6 ng/ml. GH levels were significantly higher at 30, 45 and 60 min following apomorphine than following L-dopa. Apomorphine-induced GH release was not related to changes in serum cortisol or blood sugar. Benztropine mesylate (1 mg i.m.) had no effect on apomorphine-induced GH release. These results suggest: (a) apomorphine may have advantages over L-dopa as a provocative agent to assess GH secretory capacity; (b) a dopaminergic mechanism subserves GH secretion; (c) cholinergic mechanisms do not antagonize dopaminergic-related GH release.     

EFFECT OF ACUTE AND CHRONIC NEUROLEPTIC THERAPY ON SERUM PROLACTIN LEVELS IN MEN AND WOMEN OF DIFFERENT AGE GROUPS

A single fasting level of serum prolactin was measured in each of sixty control subjects and eighty-three psychiatric patients of both sexes who had been on neuroleptic therapy for 2-4 weeks (acute treatment) or at least 5 years (chronic treatment) and who were aged either 17-45 or 48-85 years. All groups of patients had significantly higher mean prolactin levels than controls. Gender, age group of women, and exposure to acute or chronic treatment were significant variables determining the magnitude of neuroleptic-induced elevation of prolactin. In some of the groups, dose, duration of chronic therapy, and concomitant administration of anticholinergic drugs also influenced prolactin levels. Whereas all acutely treated women had prolactin values above the control range, one out of twelve (8.3%) of the women aged 17-45 years and six out of fourteen (42.9%) of the women aged 48-85 years who were under chronic treatment had normal values. Normal prolactin levels were also found in five out of sixteen (31.2%) of the acutely treated and nine out of twenty-four (37.5%) of the chronically treated men aged 17-85 years.     

DOSAGE-RELATED EFFECTS OF DANAZOL ON SEX HORMONE BINDING GLOBULIN AND FREE AND TOTAL ANDROGEN LEVELS

Danazol is known to cause marked suppression of sex hormone binding globulin (SHBG) levels in plasma and to increase the proportion of plasma testosterone unbound to protein but the effect on the concentration of total and free testosterone is unclear. Twenty-five patients with endometriosis were treated daily for 6 months with doses of danazol ranging from 50 to 600 mg. The fall in SHBG and rise in percent free testosterone was dose-related during the early part of treatment. Suppression of total testosterone and 5 alpha-dihydrotestosterone levels occurred and was probably due to increases in metabolic clearance rates. The observed fall in androstenedione levels was related to the incidence of menstrual abnormality, suggesting that this might be due to reduced ovarian activity. The concentration of free testosterone increased by a factor of two in the first week but subsequently returned to levels of between 25 and 50% above pretreatment levels. This pattern of changes may be due to the rise in metabolic clearance rates being dependent on induction of enzymes of androgen metabolism.     

慢性胃病中几种胃肠激素水平的改变和意义

本文用RIA法测定352例胃镜病理诊断的胃十二指肠病患者之胃液,血清表皮生长因子（EGF），生长抑素（SS）和胃泌素（GAS）水平。结果表明，胃液EGF水平在胃癌明显升高，在消化性溃疡降低；血清SS及GAS水平在各种胃十二指肠病中均显著高于正常对照，溃疡病的血清SS和GAS水平呈负相关趋势。各种胃病血清SS水平相近，胃液SS水平胃癌显著高于良性胃病，且胃癌胃液SS显著高于其血清SS水平。幽门螺杆菌（HP）感染不影响溃疡病的血清GAS和SS水平及慢性浅表性胃炎的血清SS水平，HP感染严重时慢性萎缩性胃炎的血清SS水平显著升高。     

缬沙坦对高血压病患者血清Ⅲ型前胶原水平及左室舒张功能的影响

目的评价缬沙坦对高血压病患者血清Ⅲ型前胶原(PCⅢ)水平及左室舒张功能的影响.方法测定分析18例无左室肥厚的高血压病患者(NLVH组)、16例伴左室肥厚的高血压病患者(LVH组)缬沙坦治疗前、后血清PCⅢ水平及左室舒张功能指标的变化,并与15例健康人(正常对照组)进行比较.分析血清PCⅢ水平与血浆血管紧张素Ⅱ(AngⅡ)的相关性.结果二组高血压病患者血清PCⅢ水平均高于正常对照组,其增高程度与左室舒张功能指标E/A比值呈显著负相关(r=-0.8257,P＜0.05),与血浆AngⅡ水平无明显相关性(r=0.3362,P＞0.05).缬沙坦治疗后二组血压和血清PCⅢ水平均较治疗前显著降低(P均＜0.05),左室舒张功能指标E峰峰值增高、E/A比值增大(P＜0.05),A峰峰值降低(P＜0.05).LVH组的左室重量指数(LVMI)明显下降(P＜0.05).结论高血压病患者血清PCⅢ水平增高,左室舒张功能下降,缬沙坦可降低血清PCⅢ水平,改善左室舒张功能.     

HYPERPROLACTINAEMIA AND HYPOGONADISM IN MEN: RESPONSE TO EXOGENOUS GONADOTROPHINS

Three male patients with pituitary tumours and marked hyperprolactinaemia were investigated. Their prolactin (PRL) levels ranged from 210 to 2500 ng/ml. The subjects had clinical and laboratory characteristics of hypogonadotrophic hypogonadism. All were treated with human chorionic gonadotrophin (HCG) and in one subject human menopausal gonadotrophin (HMG) was given in addition. In all three patients, despite the persistence of hyperprolactinaemia, serum testosterone had risen to normal levels within 4--17 days after starting HCG. Despite the normal testosterone level, impotence persisted in two patients and the third had persistently decreased libido. The hypogonadism in these patients may be related to an absolute reduction in gonadotroph number secondary to destruction by tumour mass. Alternatively, hyperprolactinaemia may inhibit the synthesis or release of the gonadotrophins or LHRH. Despite hyperprolactinaemia, pharmacological doses of HCG induced testosterone secretion in all these three subjects.     

RESPONSE OF PERIPHERAL SERUM SEX STEROIDS AND SOME OF THEIR PRECURSORS TO A SINGLE INJECTION OF hCG IN ADULT MEN

Nine healthy men were given a single intramuscular injection of 5000 iu of human chorionic gonadotrophin (hCG). Peripheral blood samples were serially collected up to 7 days after the injection, and the sera were analysed for hCG and eight steroids hCG reached a maximum, 130·13 (SEM) iu/l, at 8 h and declined thereafter with a half-life of about 24 h. Testosterone and 17-hydroxyprogester-one were elevated at 2 h, to 132·11% and 169·32%, respectively, when compared with the 0 h levels. It is to be observed, however, that in saline injected control men (n= 6) an early increase in serum testosterone was also observed. When compared with the saline-injected controls, the first significant elevation in testosterone was obtained not earlier than at 12 h, and the maximum was seen at 96 h (239·23% of controls). Correspondingly, the first significant elevation of 17-hydroxyprogesterone was seen at 8 h and the maximum at 36 h (296·44%) after the hCG injection. The maximum concentration of serum oestradiol was also found at 36 h (230·15%). The patterns of response in serum levels of androstenedione, and, to a lesser extent, in those of 5α-dihydrotestosterone, were similar to those of testosterone. Progesterone levels decreased during days 3–7 after the hCG injection, and no clear changes were seen in the peripheral serum concentrations of pregnenolone and androsterone. The -24 and -12 h control samples displayed a diurnal rhythmicity for progesterone, androstenedione, testosterone and androsterone; the 08.00 h levels being significantly higher than those at 20.00 h. Our results show that, in the adult, human testicular androgen biosynthesis responds relatively slowly to additional gonadotrophic stimulation. The late peak of peripheral serum testosterone level after the hCG injection and the stimulatory sequence of its precursor steroids suggest that the side chain cleavage of C₂₁ steroids, beyond 17 α-hydroxylation, may be a critical step in the human testicular androgen response to this gonadotrophin. The clear increase in serum oestradiol during the hCG stimulation points out the potential importance of endogenous oestrogens in testicular endocrine function.     

老年男性2型糖尿病患者性激素变化4年随访

目的探讨老年男性2型糖尿病患者性激素水平的变化。方法分析2000年及2004年住本院有完整病史资料的老年男性糖尿病患者,在4年中性激素水平的变化,并与同期住院的无糖尿病病史老年患者进行比较。两组患者均排除原发性急慢性肝肾疾病、急慢性感染、免疫系统疾病以及恶性肿瘤等疾病。结果2000年,糖尿病组血清睾酮(T),雌二醇(E2)、促黄体生成素(LH)和促卵泡生成素(FSH)水平分别为14.75±6.60nmol/L,203.95±109.90pmol/L,11.15±6.07U/L和23.09±13.81U/L。非糖尿病组为17.33±6.76nmol/L,162.84±95.43pmol/L,8.99±5.33U/L和18.04±9.50U/L。2004年,糖尿病组性激素水平为12.08±6.31nmol/L,264.62±124.19pmol/L,13.44±6.54U/L和25.99±13.30U/L;非糖尿病组为18.06±7.30nmol/L,167.71±78.09pmol/L,9.57±6.12U/L和18.20±9.49U/L。2000年与2004年比较,糖尿病组血清T水平下降,E2、LH和FSH水平均升高,存在统计学差异。非糖尿病组2000年与2004年比较,血清T、E2、LH和FSH均无显著性差异。两组比较,2000年糖尿病组较非糖尿病组,血清T水平下降,E2、LH和FSH均升高,有显著性差异;四年以后,两组患者的性激素水平差异更为显著。2000年和2004年,糖尿病组中血糖控制者的血清T水平均较控制不良者低,而E2、LH和FSH均无显著性差异。结论老年男性2型糖尿病患者存在性激素水平紊乱,并随着病程的延长有加剧的趋势。     

SERUM INHIBIN LEVELS DURING THE PERIOVULATORY INTERVAL IN NORMAL WOMEN: RELATIONSHIPS WITH SEX STEROID AND GONADOTROPHIN LEVELS

Inhibin is a gonadal glycoprotein believed to be important in the regulation of pituitary FSH secretion and/or to function as a paracrine factor within the ovary and testis. We studied serum levels of inhibin, oestradiol (E2), progesterone (P), FSH and LH during the periovulatory interval in order to determine whether there is differential control of sex steroid and inhibin secretion by the mature follicle and the emerging corpus luteum. Seven normal cyclic women were admitted 3-4 days prior to midcycle and blood samples drawn every 3 h for 5-7 days. Serum E2, P, FSH, LH and inhibin were measured by radioimmunoassay. Data were normalized around the peak LH value (0 h). Serum E2 and inhibin rose in parallel (r = 0.92, P less than 0.001) between -69 and -18 h, E2 reached a peak of 1296 +/- 154 (mean +/- SEM) pmol/l at -18 h, then fell to 1050 +/- 139 pmol/l at 0 h. Serum inhibin, on the other hand, continued to rise to a peak of 837 +/- 95 U/l at -6 h, fell to 455 +/- 48 U/l at +45 h, then rose again. On average, the peak inhibin level occurred 10.4 +/- 5.1 h after the peak E2 (P less than 0.05). Inhibin levels were positively correlated with both serum LH and FSH between -24 and +24 h (P less than 0.01). Serum E2 was negatively correlated with LH, FSH and inhibin between -24 and 0 h (P less than 0.01). Serum P levels increased from 1.8 +/- 0.3 nmol/l at -24 h to 14.3 +/- 1.0 nmol/l at +60 h. Serum inhibin was positively correlated with serum P from -24 to 0 h (P less than 0.01) and +45 to +60 h (P less than 0.01), but was inversely correlated from 0 to +45 h (P less than 0.01). We conclude that the maturing follicle secretes both E2 and inhibin in parallel until -18 h, at which time the process of luteinization is initiated by the onset of the midcycle LH surge, as evidenced by the rise in P. E2 secretion then falls while inhibin secretion rises, indicating different regulation of secretion of these two hormones by the maturing follicle. Furthermore, the close positive correlation between inhibin and gonadotrophin levels around midcycle suggests that FSH and/or LH stimulate inhibin secretion and that the presumed negative feedback effect of inhibin on FSH secretion is overcome at this time. After midcycle, inhibin secretion initially falls, then rises, while P rises progressively.(ABSTRACT TRUNCATED AT 400 WORDS)     

HYDROTESTOLACTONE LOWERS SERUM OESTRADIOL AND PRL LEVELS IN NORMAL MEN: EVIDENCE OF A ROLE OF OESTRADIOL IN PRL SECRETION*

The effect on serum PRL levels of lowering serum oestradiol (E₂) concentration by short-term administration of an aromatase activity inhibitor, hydrotestolactone (HT), was studied in six healthy male subjects. After HT administration serum E₂ levels decreased from 68 ± 5±8 to 26 ± 2±5 pmol/1 (mean ± SE, P < 0±05). These E₂ changes were accompanied by a significant decrease in mean 2-h PRL levels from 11±2 ± 2±1 to 6±5 ± 1±6 ng/ml mean ± SE, P < 0±05). The evaluation of individual percentage change from basal concentrations showed a varying decrease in all subjects. These findings suggest that under physiological conditions E₂ may be one of the factors which control blood PRL concentrations in men.     

EFFECT OF METOCLOPRAMIDE ON SERUM PROLACTIN LEVELS IN HUMANS

The effect of acute and chronic administration of metoclopramide on serum prolactin levels in normal subjects was studied. Metoclopramide 10 mg i.v. induced a prompt rise in serum prolactin levels in all subjects. At 180 min the levels remained high. Prolactin levels were markedly elevated during a 5 day course of treatment with metoclopramide in six subjects. It is suggested that metoclopramide could be used in the functional exploration of the hypothalamic-pituitary axis.     

BIOACTIVE AND IMMUNOREACTIVE FSH IN SERUM OF NORMAL AND OLIGOSPERMIC MEN

In men suffering from idiopathic oligospermia and azoospermia the hypothesis was tested that decreased spermatozoa production could be due in part to inadequate hormonal stimulation of spermatogenesis. In 53 healthy male subjects with normal spermatozoa production (n = 10), varying degrees of oligospermia (n = 40), and azoospermia (n = 3), serum immunoreactive LH, testosterone (T), and oestradiol (E2), and immunoreactive and bioactive FSH concentrations were determined. FSH bioactivity was estimated using the rat granulosa cell aromatase bioassay. Mean LH, T, and E2 levels were similar in the control group (spermatozoa concentration greater than 40 x 10(6)/ml) compared with men exhibiting mild (10-20 x 10(6)/ml), moderate (5-10 x 10(6)/ml), or severe oligospermia (1-5 x 10(6)/ml), and in the azoospermia group. An inverse correlation was found between immunoreactive FSH levels and spermatozoa concentration (P less than 0.05), with elevated levels (twofold increase) of FSH in the combined severe oligospermia and azoospermia (P less than 0.01) groups. Moreover, augmented (P less than 0.01) bioactive FSH levels were also observed in this group of patients. The mean bioactive to immunoreactive FSH ratio was also negatively correlated with sperm counts (P less than 0.005). In addition, T/LH ratios were inversely correlated with immunoreactive (P less than 0.05) and bioactive (P less than 0.05) FSH, which may indicate that altered Leydig cell function is involved in the augmented secretion of FSH. The data presented in this study indicate that immunoreactive FSH, as measured in oligospermia and azoospermia, does not exhibit decreased bioactivity.     

EFFECT OF THE COMBINATION OF DEXAMETHASONE AND SODIUM IPODATE ON SERUM THYROID HORMONES IN GRAVES'' DISEASE

To investigate the effect of the combination of dexamethasone (Dex) and sodium ipodate (SI) on hyperthyroidism, we studied 24 patients with typical Graves' disease, divided into four groups of six persons each. Three groups (Study I) were studied acutely (24 h) to determine the effects of Dex (5 mg every 12 h intramuscularly), SI (one oral dose of 3 g) and both drugs at the same doses, upon T4, T3, and rT3 at 0900 h before therapy was started and 24 h later. The group on Dex and that on SI had a similar T3 decrement of 25.9 +/- 4.0% and 35.8 +/- 5.0%, respectively, (P less than 0.05), whereas the effect of both drugs combined was greater (64.2 +/- 3.6%; P less than 0.01, Dex, and P less than 0.01, SI, respectively). The increment of rT3 was markedly greater in those patients on SI than in those on Dex (561.3 +/- 149.2% and 58.9 +/- 11%, respectively, P less than 0.025). A fourth group (Study II) was studied for seven days while receiving both Dex (1 mg orally three times per day) and SI (500 mg orally three times per day). Both T4 (from 18.8 +/- 1.1 to 13.1 +/- 1.1 micrograms/dl, P less than 0.02) and T3 (from 593 +/- 41 to 136.3 +/- 12.7 ng/dl, P less than 0.001) decreased at day 8. The initial brisk increment of rT3 at 24 h (808 +/- 149%, P less than 0.005) then diminished concomitantly with the fall of its precursor, T4.(ABSTRACT TRUNCATED AT 250 WORDS)     

老年男性骨密度的增龄改变与骨代谢有关激素的相关性研究

目的探讨老年男性增龄与骨密度(BMD)及骨代谢有关激素的关系。方法123例老年男性按年龄分成3组,分别测定骨密度及血清甲状旁腺素(PTH)、睾酮(T)、雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)并进行比较。结果老年男性BMD随增龄而减少,在股骨近端和髋关节处更为明显(P<0.05),在腰椎不确定;老年男性T、E2处于低水平,而FSH、LH及PTH随增龄而增高,FSH更为明显(P<0.05)。结论随着增龄,老年男性MBD下降,T、E2水平低下,而FSH、LH和PTH水平增高。提示体内骨代谢有关激素的变化,可能是老年男性骨质疏松症发病的重要机制之一。