Clinical and hormonal aspects of male hypogonadism in myotonic dystrophy

In order to study male hypergonadotropic hypogonadism as completely as possible, and to evaluate its possible effects on muscle atrophy and sexuality, RIA or IRMA methods were used to measure the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, total (T) and free (FT) testosterone, estradiol (E), dihydrotestosterone (DHT), sex hormone binding globulin (SHBG), androstenedione (A) and 17-OH-progesterone (17-OH-P) in 29 patients with myotonic dystrophy (MD). The mean hormonal levels ±SD were: LH 8.0±4.4 mIU/ml, FSH 17.4±11.5 mIU/ml, A 200±130 ng/dl (all higher than in controls); T 406±290 ng/dl, FT 22.7±7.0 pg/ml, DHT 55.5±29.7 ng/ml (all lower than in controls). The low FT and DHT levels (never previously studied in MD) confirm the androgenic deficiency. The high androstenedione levels and low testosterone concentrations suggest defective enzyme 17-dehydrogenase. The duration of the disease correlated with both testosterone (r=–0.56) and FT levels (r=–0.59), showing that hypogonadism tends to worsen progressively. When the patients were divided into three groups on the basis of the severity of muscle involvement (A, B and C), LH and FSH levels were higher in group C (more severe disease) than in group A, respectively 9.3±4.7 and 20.6±12.3 mIU/ml versus 4.8±0.9 and 8.4±3.8, p<0.03; T levels were lower in group C than in group A, 337.3±263.4 ng/dl versus 649.7±320.3 (p<0.03); however, there was no significant difference in the FT levels of the three groups, which may imply that hypogonadism is unlikely to have a direct effect on muscle atrophy. About 25% of our patients were impotent; these subjects had higher LH and FSH (p<0.001) and lower FT levels than the patients who were not impotent (p<0.03). However, hypogonadism may not be the only cause of impotence as all of the impotent patients belonged to group C and had a very high (CTG)n triplet expansion. We hypothesise that hypogonadism and sexual impairment could be partially due to a muscle cell alteration: i.e. a dysfunction of both the testicular peritubular myoid cells and of the corpus cavernosum smooth muscle.The financial support of Theleton (Grant No. 640) is gratefully acknowledged.     

Estrogen positive feedback on LH secretion in transsexuality

In order to test the hypothesis whether there is variation in hormonal levels or response to hormonal manipulation that could permit a distinction between heterosexuals and transsexuals, we designed the following protocol: Six male-to-female (m-to-f) transsexuals, six heterosexual control females and six female-to-male (f-to-m) transsexuals were given estradiol benzoate (E2B) (4.5 micrograms/kg/12 hr) for five days. In the female population, E2B treatment was initiated on day 5 of the menstrual cycle. In all the subjects blood luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol-17 beta (E2) and testosterone (T) levels were measured twice daily. Additionally, LH and FSH responses to LHRH (100 micrograms iv) stimulation prior to and on day 5 of the E2B treatment were evaluated. In the m-to-f transsexuals, T levels decreased sharply and progressively during estrogen treatment, along with a fall in LH and FSH levels. The magnitude of the LH and FSH responses to LHRH stimulation also decreased following estrogen administration. In the heterosexual female controls and in the f-to-m transsexuals, estrogen administration increased LH levels to a minimum of 100% above initial values from day 3 onwards. Interestingly, the magnitude of the LH increase in the f-to-m transsexuals was greater than that of the heterosexual female controls. In both groups, LHRH stimulation resulted in a greater LH response compared to that prior to estrogen treatment. Our present observations, based on blood hormonal levels and responses to hormonal manipulations do not permit a distinction between heterosexual females and f-to-m transsexuals. There was no convincing evidence for the existence of a positive estrogen feedback on LH secretion in m-to-f transsexuals. These results contradict some of the reported hypotheses concerning hormonal alterations in these individuals.     

Differential response to estrogen challenge test in women with and without premenstrual dysphoria

This study tested the hypothesis that brain sensitivity to normal fluctuations in gonadal hormones is increased in women with premenstrual dysphoria. For this purpose, the effect of a common gonadal hormonal challenge on the sensitivity of the brain was investigated in 13 women with premenstrual dysphoria and 12 asymptomatic controls. The estrogen challenge test, comprising estradiolbenzoate 0.04 mg/kg, was given as an intramuscular gluteal injection between 0700 and 1000h on day 3 or 4 of the menstrual cycle; blood was sampled at 0, 0.6, 6.5, 24, 32, 48, 56, 72, 96, 120, and 144h and analyzed for estradiol, FSH and LH. Serum estradiol levels after the injection and the corresponding FSH responses were similar between the study groups; however, the LH responses were significantly different. Women with premenstrual dysphoria had a relatively stronger negative feedback response (p=0.014) up to the point of nadir LH levels (maximal negative feedback), but displayed higher LH levels at the nadir (p=0.01), more LH surge-like reactions (p=0.047), and a 50% higher area under the curve (AUC) for LH (p=0.03) than controls. The LH response in women with premenstrual dysphoria was related to the VAS-rated symptoms; the negative increment (AOC) correlated to luteal phase "bloating" (r(s)=0.73; p=0.0069) whereas the AUC of LH correlated to "irritability" (r(s)=0.58; p=0.040). A significant interaction term between study group and changes in LH during the negative feedback phase (32-0h), with regard to luteal phase "irritability" was found (test for interaction p=0.005). For the premenstrual dysphoria group, ratings of "depressed mood"were related to baseline FSH levels (r(s)=0.60; p=0.034), and to the AUC of FSH during the negative feedback phase (r(s)=0.58; p=0.043). Women with premenstrual dysphoria displayed a gonadotrophin response to estradiol challenge that differed from that of controls, and was correlated to symptom severity.     

Congenital cerebellar hypoplasia and hypogonadotropic hypogonadism

The association of cerebellar ataxia and non-neurological syndromes is a well known phenomenon. A 20-year-old male patient presented with a longstanding and non-progressive ataxia. Magnetic resonance examination revealed marked inferior vermian-cerebellar hypoplasia. He also showed a hypogonadism with low serum gonadotropin and prolactin levels. Chronic pulsatile gonadotropin-releasing hormone (GnRH) administration resulted in a small non-pulsatile luteinizing hormone (LH) increase and no follicle-stimulating hormone (FSH) elevation. This hormonal pattern suggests a primary deficiency of the gonadotroph and lactotroph cells, rather than a hypothalamic lesion. This is the first report where cerebellar hypoplasia of congenital origin is associated with hypogonadotropic hypogonadism. Because of consanguinity, autosomal recessive transmission is considered.     

Effects of estrogen and progesterone on plasma gonadotropins and on catecholamine levels and turnover in discrete brain regions of ovariectomized rats.

Estradiol benzoate (EB) was administered, either alone or followed 48 h later by progesterone to ovariectomized rats. Plasma gonadotropins (FSH and LH) and steady state levels of norepinephrine (NE) and dopamine (DA) in 17 individual brain nuclei were assayed. In addition, catecholamines were measured after administration of the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in order to assess hormonal influences on turnover. Treatment with EB, which lowered plasma FSH and LH, reduced the depletion of NE produced by alpha-MT in the lateral septum, interstitial nucleus of the stria terminalis, and central gray catecholamine area, and reduced the depletion of DA in the nucleus of the tractus diagonalis. EB enhanced NE depletion in the periventricular and anterior hypothalamic nuclei, and raised steady state levels of NE in the medial amygdaloid nucleus. These effects were reversed by subsequent treatment with progesterone, which stimulated FSH and LH release. EB plus progesterone enhanced the alpha-MT-induced depletion of NE over that observed with EB alone in the arcuate nucleus, and similarly enhanced DA depletion in the interstitial nucleus of the stria terminalis. EB plus progesterone prevented the depletion of NE by alpha-MT in the paraventricular and ventromedial nuclei, and also lowered resting NE levels in the paraventricular nucleus. The results suggest that catecholamine neurons in several discrete brain regions participate in the stimulatory and inhibitory feedback effects of ovarian hormones on gonadotropin secretion, and perhaps also on the hormonal induction of sexual receptivity.     

Evaluation of pituitary and thyroid hormones in patients with subarachnoid hemorrhage due to ruptured intracranial aneurysm

It is well known that the central nervous system (CNS) influences the pituitary hormone secretions and that diseases of CNS are frequently associated with an altered endocrine function. The aim of this study has been the evaluation of the serum concentrations of the pituitary and thyroid hormones in a series of patients with subarachnoid hemorrhage due to a ruptured cerebral aneurysm. Thirty-five patients (23 females and 12 males), aged 51.9 +/- 13.3 years on the mean were admitted. They were evaluated to assess the clinical severity of the subarachnoid hemorrhage by Hunt & Hess scale: nine patients were in the grade I, 14 in the grade II, and 12 in the grade III. Blood samples were obtained between 8:00 and 9:00 a.m. and serum hormones were measured by commercial kits (IRMA or MEIA methods). Cortisol serum levels (normal range (NR) = 5 to 18 micro g/dL) were increased in all the patients (mean +/- standard deviation = 31.4 +/- 12.4 micro g/dL). Mean prolactin levels (NR < 20 ng/mL) were 18.6 +/- 17.1 ng/mL and five patients (14.2%) had levels higher than normal. FSH and LH levels were normal according to age and sex: men: FSH = 4 +/- 2.9 mUI/mL (NR = 1 to 10.5 mUI/mL); LH = 6.1 +/- 6.3 mUI/mL (NR = 2 to 12 mUI/mL); premenopausa women: FSH = 2.5 +/- 1.5 mUI/mL (NR = 2.4 to 9.3 mUI/mL); LH 3.9 +/- 5.1 mUI/mL (NR =2 to 15 mUI/mL); post- menopausal women: FSH = 48.3 +/- 18.5 mUI/mL (NR =31 to 134 mUI/mL); LH = 29 +/- 13.8 mUI/mL (NR =16 to 64 mUI/mL). Mean TSH levels were 3.9 +/- 5.2 micro UI/mL (NR =0.5 to 4.7 micro UI/mL) and five patients (14.2%) had levels higher than normal. Mean triiodothyronine levels (T3) were 66.4 +/- 18.7 ng/dL (NR = 45 to 137 ng/dL) and five patients (14.2%) had levels lower than normal (33.8 +/- 9 ng/dL). Mean thyroxine levels (T4) (NR= 4.5 to 12.5 micro g/dL) were 7.4 +/- 1.7 micro g/dL and two patients (5.6%) had levels lower than normal. Thyroglobulin and microsomal antibodies were not detectable. CONCLUSIONS: In the first 24 hours following ictus, the hormonal changes may be due to the stress produced by the intracranial bleeding; thyroid hormone alterations suggest that patients with subarachnoid hemorrhage might have an euthyroid sick syndrome.     

Increasing hypothalamic nucleobindin 2 levels and decreasing hypothalamic inflammation in obese male mice via diet and exercise alleviate obesity-associated hypogonadism

To explore the role of nesfatin-1 in regulating male reproductive function during energy balance variation, we employed an obese mouse model which was first induced by a high-fat diet (HFD) and followed by interventions of a normal diet (ND) and/or moderate exercise, and then serum reproductive hormones of male mice, hypothalamic nucleobindin 2 (NUCB2)/nesfatin-1, inflammatory factors, and gonadotropin-releasing hormone (GnRH) levels were tested. Our findings showed that both serum nesfatin-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels and hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels were reduced, whereas, the mRNA and protein levels of hypothalamic tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, inhibitor kappa B kinase β (IKKβ), and nuclear factor (NF)-κB were increased in obese male mice. Diet, exercise, and diet combined with exercise interventions reversed the decreases in serum nesfatin-1, FSH, LH, and T levels; increased hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels; and reduced hypothalamic TNF-α, IL-1β, IKKβ, and NF-κB levels. These changes were accompanied by reduced adiposity, and these effects were more obvious in the diet combined with exercise group. Overall, our findings suggested that the hypogonadotropic hypogonadism associated with obesity may be induced by reduced hypothalamic NUCB2/nesfatin-1 levels, which attenuated the stimulatory effect on GnRH directly or indirectly by suppressing its anti-inflammatory effect in the brain. Diet and/or exercise interventions were able to alleviate the hypogonadotropic hypogonadism associated with obesity, potentially by increasing hypothalamic NUCB2/nesfatin-1 levels.     

Twice daily dosing of aspirin improves platelet inhibition in whole blood in patients with type 2 diabetes mellitus and micro- or macrovascular complications

The efficacy of low-dose aspirin in type 2 diabetes mellitus (T2DM) has been questioned. We tested if twice daily dosing of aspirin would be more effective in T2DM, possibly due to increased platelet turnover. A randomised cross-over study compared 75 mg aspirin OD, 75 mg BID and 320 mg OD (≥ 2 week treatment periods) in 25 patients with T2DM and micro- or macrovascular complications. Platelet responses were examined by impedance aggregometry (WBA) and the IMPACT-R aspirin test in whole blood, light transmittance aggregometry in platelet-rich plasma (LTA), and urinary 11-dehydro-thromboxane B2 (TxM). Aspirin 75 mg BID decreased arachidonic acid (AA)-induced WBA compared to 75 mg OD (9.7 ± 4.5 vs. 12.6 ± 3.5 ohm; p = 0.003) or to 320 mg OD (11.5 ± 4.2 Ohms; p = 0.049). WBA responses to collagen were similarly attenuated by BID or high dosing (by 12-14%; p = 0.02 for both). The IMPACT-R showed a better response to 75 mg BID compared to 75 mg OD (p = 0.049), but not to 320 mg OD. AA-induced aggregation by LTA was <6.5% on all occasions, with no differences between aspirin dosages. TxM was reduced after 320 mg OD (p = 0.002), but not 75 mg BID (p = 0.07). Reticulated platelets were highly correlated with mean platelet volume (MPV; r2 = 0.74, p<0.0001). Both markers for platelet turnover were correlated with AA-induced WBA, but neither identified patients who benefited from BID dosing dependably. In conclusion, twice daily dosing improved laboratory responses to aspirin in high risk T2DM patients. Studies of whether BID dosing of aspirin can improve clinical outcomes in such patients are of interest.     

Gonadal steroid and gonadotropin response to dexamethasone: A study in sexual dysfunction and normal controls

Summary Numerous investigations have reported an alteration of hormonal response to dexamethasone in depressive disorder. No such data are available in psychogenic sexual dysfunction. Pre- and postdexamethasone levels of testosterone, estradiol, LH and FSH were studied in 20 male patients with sexual dysfunction and 20 male healthy controls. Dexamethasone had no influence on testosterone, estradiol, LH and FSH in normal controls. The patients showed an increase in testosterone and LH but not in FSH levels in the morning after dexamethasone administration. When compared with basal levels, the increase in postdexamethasone levels in sexual dysfunction was significant for testosterone (T) but not for LH (LH). The altered gonadal steroid and gonadotropin response to dexamethasone in sexual dysfunction might be due to disturbances of dexamethasone metabolism and glucocorticoid receptor density comparable to similar findings in depressive disorder.     

Skeletal muscle involvement in myotonic dystrophy type 2. A comparative muscle ultrasound study

This study determines the presence and extent of muscle changes in 31 myotonic dystrophy type 2 (DM2) patients detected by muscle ultrasound. Results were compared to 31 adult-onset myotonic dystrophy type 1 patients (DM1) and healthy controls. Furthermore, we tested the hypothesis that structural muscle changes correlate with age, quantitative muscle force and serum creatine kinase in both disorders. In DM2 all seven examined muscles (right masseter muscle, right and left biceps brachii, right and left forearm flexors, right rectus femoris, and left tibialis anterior muscle) showed increased mean echo intensities (p ≤ 0.001). Atrophy of the masseter muscle and rectus femoris were both found in 23% of DM2 patients. Muscle thickness was significantly more decreased in the elbow flexors in DM2 compared to DM1. Echo intensity sum score correlated positively with age in DM2 (r=0.57, p=0.001) and negatively with muscle force (r=0.36, p=0.048). We conclude that all tested muscles are affected and structurally abnormal in DM2 patients. Proximal arm muscles are more affected in DM2 compared to DM1, which corresponds to clinical findings.     

Some hormones secretion and personality in anorexia nervosa syndrome

The relationship between plasma leptin, some hormones (GH, IRI, IGF-1, DHEA-S, LH, FSH, T, E2, TSH, fT3, fT4), glucose level, personality dispositions and adipose tissue content in 22 women with anorexia nervosa were evaluated. Some personality features as: defensiveness, domination and aggression necessities, high self-control, bad self-estimation, retiring, expectation of custody--correlated with some hormones (LH, E2, IGF-1, fT3, F, T) and leptin level. The ascertained relationships suggest that still unexplained causes generate simultaneous disturbances in the endocrine and psychic processes in central nervous system of anorexia nervosa patients. Probably hormonal and neurotransmitter derangement are the adaptive changes allowing longer survival, as the low leptin secretion in the severest undernutrition states is.     

Evaluation of Endocrine Profile,Hypothalamic–Pituitary–Testis Axis and Semen Quality in Multiple Sclerosis

Several endocrine and sexual disturbances have been demonstrated in multiple sclerosis (MS) patients of both sexes. The endocrine profile, hypothalamic–pituitary–testis (HPT) axis and semen quality were evaluated in male patients with MS. A total of 68 male MS patients aged 18 years or older were recruited. Forty‐eight age‐matched healthy male volunteers served as controls. All subjects underwent complete physical examination and routine semen analysis. Two blood samples were drawn from each participant at 15‐min intervals for the determination of the resting levels of: luteinising‐hormone (LH), follicle‐stimulating hormone (FSH), prolactin, testosterone, oestradiol and sex hormone binding globulin. The HPT axis was assessed using gonadotrophin‐releasing hormone (GnRH) and human chorionic gonadotrophin tests. The mean basal serum levels for LH, FSH and testosterone in MS patients were significantly lower than the mean for normal controls (P = 0.01). The injection of GnRH analogue did not yield a significant increase in FSH and LH levels in the MS patients compared to normal controls (P = 0.001). Total sperm count, sperm motility and percent normal sperm morphology were lower in MS patients compared to controls. MS subjects with progressive disease had higher and more severe HPT axis abnormalities than that for patients with relapsing remitting MS. Most subjects with MS have hypogonadotrophic hypogonadism state and fertility impairment. It appears that the damage to HPT axis is both in pituitary and testicular levels. Further studies are needed to better elucidate the underlying pathophysiology of HPT axis dysregulation.     

Effects of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) on GH, LH, prolactin, FSH, and TSH secretion in rats with and without morphine.

Plasma concentrations of GH, LH, prolactin, FSH, and TSH were evaluated in adult rats after administration of Tyr-MIF-1. Male rats were killed 0, 15, 30, and 60 min after Tyr-MIF-1 (0.02, 0.2 and 2.0 mg/kg) and ovariectomized females 15 min after injection of the peptide (0.2 and 2.0 mg/kg). The effect of Tyr-MIF-1 on pituitary hormonal secretion in morphine-treated ovariectomized rats also was studied. After 15 min, Tyr-MIF-1 (0.2 mg/kg) increased plasma concentrations of LH in males (p less than 0.05) and, at 2.0 mg/kg, in ovariectomized rats (p less than 0.05). Tyr-MIF-1 (0.2 mg/kg) decreased plasma concentrations of GH as compared with diluent at 15 min in males (p less than 0.05) but was ineffective in ovariectomized females not receiving morphine. Plasma concentrations of prolactin, FSH, and TSH remained unchanged both in males and in ovariectomized females by any of the administered doses of the peptide at any of the times tested. When administered to ovariectomized rats injected earlier with morphine sulfate, Tyr-MIF-1 (0.2 and 2.0 mg/kg) reduced (p less than 0.05) the effect of morphine (5 mg/kg) on GH secretion and tended (p = 0.061) to partially inhibit the effect of morphine (10 mg/kg) on prolactin secretion at a dose of 2.0 mg/kg. The decrease in plasma concentrations of TSH after morphine at a dose of 10 mg/kg (p less than 0.001) remained unaffected by any of administered doses of Tyr-MIF-1. The results suggest that Tyr-MIF-1 may affect the regulation of the secretion of some anterior pituitary hormones.     

Studies using releasing factors in Klinefelter's Syndrome: The responses of LH and FSH to luteinizing hormone-releasing hormone and of prolactin and TSH to thyrotropin-releasing hormone before and after testosterone

(1) During an investigation of their pituitary function, the TSH prolactin (PRL) and gonadotropin, (LH, FSH) response to TRH was measured in four patients with documented euthyroid Klinefelter's syndrome. (2) In all four patients, the serum testosterone was low, the gonadotropins were elevated and thyroid antibodies undetectable. (3) The identical study was repeated after each patient had received intramuscular testosterone cypionate 200 mg bi-weekly for three doses. This raised the serum testosterone at least four-fold. (4) Basal TSH was normal in all four patients but its response to TRH was blunted (mean peak TSH 9.6 μU/ml), compared with normal controls (mean peak TSH 18 μU/ml). Following testosterone this response to TRH was further suppressed to a mean peak of 3.4 μU/ml TSH. (5) Basal PRL levels were also normal and the mean peak response to TRH, 28 ng/ml. When repeated after testosterone, TRH produced a mean peak PRL of 58 ng/ml. (6) LH and FSH, both elevated basally, did not change with TRH administration, but both were stimulated by LHRH 100 μg i.v., LH briskly, FSH more variably. (7) FSH was suppressed sharply but LH only partially with testosterone therapy. (8) Our studies indicate that the TSH response to TRH in Klinefelter's syndrome is blunted and further suppressed with short term testosterone replacement. The PRL response to TRH under these same circumstances, however, is enhanced. Previous reports of abnormal LH feedback control are confirmed. (9) Klinefelter's syndrome is associated with subtle abnormalities in hypothalamic pituitary regulation not expected in typical primary hypogonadism.     

Pulsatile LH secretion in women with premenstrual syndrome (PMS): evidence for normal neuroregulation of the menstrual cycle.

The premenstrual syndrome (PMS) has been proposed to result from excessive exposure to and/or withdrawal of brain opioid activity during the luteal phase. Because hypothalamic opioids are believed to modulate GnRH secretion, in part under the influence of ovarian steroids, we performed longitudinal studies of gonadotropin and ovarian steroid secretion across ovulatory, symptomatic cycles of 17 PMS patients and 8 normal volunteers. Pulsatile LH secretion was measured every 10 min for 8 hr at times when central opioid activity was expected to be low (early follicular phase), high (mid-luteal phase; ML), and declining (late luteal phase). In both subject groups, a cycle-phase effect was observed for LH pulse frequency (p = < 0.001) and amplitude (p = 0.002), and for the transverse mean concentrations of LH (p = 0.05), FSH (p < = 0.001), estradiol (E2) (p = < 0.001) and progesterone (P) (p = < 0.001). ML P secretion in PMS patients was pulsatile, and mean concentrations (over 30-60 min) were similar to those of normal controls. The changes in pulsatile LH secretion across the cycle were not different in the PMS patients compared to the normal women, though mean FSH in the ML phase was higher in the PMS group (p = < 0.05). The similar changes in luteal LH pulse frequency fail to provide evidence that GnRH secretion is impaired, thus challenging the view that the neuroregulation of the menstrual cycle in women with PMS is markedly altered.     

Erectile dysfunction in diabetes mellitus contributes to poor quality of life

Erectile dysfunction (ED) is seen in a large number of male patients with diabetes mellitus (DM). However, little is known about the impact of ED on quality of life (QoL) of DM patients. To study the QoL of men with type 2 diabetes mellitus (T2DM) and ED and compare the same for men with DM without ED 63 patients of DM with ED were compared with 30 matched patients (on sociodemographic and clinical profile, rating on depression and anxiety) of DM without ED on QoL measures using WHO-QoL-Bref. Patients with ED had poorer QoL in all domains (except the physical domain); however, the differences between the two groups were significant only for the environmental domain. ED contributes to poorer QoL in patients with diabetes mellitus.     

Effects of Carbamazepine on the Hypothalamic-Pituitary-Gonadal Axis in Male Patients with Epilepsy: A Prospective Study

The effects of carbamazepine (CBZ) monotherapy on serum sex hormone levels and on pituitary responsiveness to various stimuli were evaluated in a prospective study with 21 male patients with epilepsy. The serum levels of testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and dehydroepiandrosterone sulfate (DHEAS) were assayed, and the free androgen index (FAI) values were calculated for each patient before and after 2-month CBZ treatment. The pituitary PRL, LH, and FSH responses to luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and metoclopramide (MC) were also measured before and after CBZ treatment. The baseline serum hormone and SHBG levels were measured and the FAI values calculated in 16 healthy male control subjects of similar age. The mean E2 level was higher in patients before CBZ treatment than in control subjects, and untreated patients had greater variances for FAI values, PRL levels, and LH levels than control subjects. No other significant differences were found between untreated patients and control subjects. The FAI values and DHEAS levels of patients decreased during 2-month treatment with CBZ. The PRL response to MC was higher after CBZ treatment than before. The baseline levels of other hormones and SHBG, as well as the LH and FSH responses to LH-RH, remained unaltered. The results indicate that during the first 2 months of CBZ treatment the androgen balance in male epileptic patients changes: Serum DHEAS levels and FAI values decrease, although FT levels remain unchanged. The clinical relevance of these hormonal changes is obscure.     

精神分裂症患者性激素与认知功能的关系

目的:探讨精神分裂症患者性激素与认知功能的关系。方法:精神分裂症患者95例,使用利培酮治疗6周,分别于治疗前和治疗后进行雌二醇(E2)、孕酮(Prog)、睾酮(T)、催乳素(PRL)、促卵泡激素(FSH)、黄体生成素(LH)检测、简明精神病评定量表(BPRS)评定和瑞文标准推理测验。结果:男性患者的E2、T、FSH、LH水平与瑞文测验正确题数、知觉辨别、类同比较、比较推理、系列关系正确题数均正相关;治疗后E2、T水平不再与瑞文推理测验相关。女性患者的E2、Prog、T、FSH、LH水平与瑞文测验正确题数、智商数、类同比较、比较推理、系列关系、抽象推理正确题数均正相关;治疗后E2、LH水平仍与瑞文测验正确题数、智商数、类同比较、比较推理、系列关系、抽象推理正确题数正相关,T水平与瑞文测验正确题数及所有因子正确题数负相关。结论:男女精神分裂症患者性激素对认知功能有不同影响。     

Hormonal changes in cerebral infarction in the young and elderly

Fifty-one patients with CCT verified cerebral infarction were submitted to serum and CSF radioimmunoassay of FSH, LH, estradiol (E2), progesterone, testosterone, cortisol and T4. The results were compared to those of 82 matched controls. Our findings suggest that (1) high serum E2 is a risk factor of stroke in males; (2) low serum T4 is a risk factor in males; (3) serum testosterone is reduced in acute stroke in males confirming that it is stress sensitive; (4) serum LH was higher in hypertensive thrombotic males when compared to normotensive ones, and (5) FSH, LH, E2 and T4 are undetectable in CSF of patients and controls.     

Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease

The objective was to describe the indices of platelet aggregation and activation in a large cohort of diabetic patients with coronary artery disease (CAD). Recently, a number of observations have indicated that patients with diabetes mellitus (DM) exhibit persistent platelet activation, and low response after antiplatelet therapy, although no randomized data exist. We sought to define the baseline platelet biomarkers, and the patterns of response to aspirin and clopidogrel therapy in DM versus non-diabetic patients. Secondary post-hoc analyses were made of platelet activity biomarkers in the dataset which consisted of patients with documented CAD (n = 822), including those with DM (n = 257). Patients with DM exhibited higher baseline platelet activity by adenosine diphosphate (ADP)- (p = 0.0002), and collagen-induced (p = 0.03) aggregometry; Ultegra- (p = 0.0001), and PFA-100 (p = 0.02) analyzers; and expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (p = 0.01), glycoprotein (GP) IIb/IIIa antigen (p = 0.001), and activity (p = 0.02), vitronectin receptor (p = 0.03), P selectin (p = 0.02), and intact epitope of PAR-1 thrombin receptor (p = 0.02). Antiplatelet response after clopidogrel in diabetics was impaired when compared with non-diabetics. In conclusion, diabetic patients exhibit high pretreatment platelet activity, and do not respond well to the available antiplatelet regimens when compared with similar patients without DM. The clinical implications of these findings are unknown but are potentially important. Considering worsened outcomes in this high-risk population, clinical trials in DM are urgently needed in order to define the optimal degree of platelet inhibition and suitability for more aggressive antiplatelet regimens.