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.     

Effects of Carbamazepine Therapy on Serum Sex Hormone Levels in Male Patients with Epilepsy

The effects of carbamazepine (CBZ) therapy and epilepsy on sex hormone plasma levels in male patients with epilepsy were evaluated by measuring the 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) and by calculating the free androgen index (FAI) in 23 male patients with epilepsy receiving CBZ medication, in 18 untreated male patients with epilepsy, and in 19 healthy age-matched control subjects. No significant differences in the mean T or FT levels were found between the three groups, but the CBZ-treated patients had significantly higher SHBG levels and their FAI values and DHEAS concentrations were lower. The LH, FSH, PRL, or E2 levels in CBZ-treated and untreated male patients with epilepsy did not differ from the controls. CBZ monotherapy does not significantly change the serum balance of sex hormones; however, CBZ clearly affects the serum levels of SHBG and DHEAS.     

Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy

Disturbances of reproductive endocrine hormones are more often found in men with epilepsy than in the general population. There is an ongoing debate whether this can be attributed to chronic use of antiepileptic drugs or to the epilepsy itself. The aim of the present study was to evaluate the degree of endocrine disturbances in men with epilepsy compared with healthy controls, and to investigate whether there was a drug-specific effect of valproate (VPA) or carbamazepine (CBZ). Men with epilepsy, 20-40 years old, having used either VPA (n = 16) or CBZ (n = 19) as monotherapy for >2 years were included and compared with age-matched controls. Men with epilepsy (VPA + CBZ) had significantly lower FSH values and higher C-peptide values compared with controls. Regarding possible drug-specific effects, the VPA treated patients had significantly higher dehydroepiandrosterone (DHEAS) levels and lower FSH and LH concentrations compared with the controls, whereas there were no differences in testosterone, testosterone/sexhormone-binding globulin (SHBG) ratio or androstenedione levels. Men on VPA also had significantly lower free carnitine/total carnitine, which may have implications for sperm motility, and also higher insulin and C-peptide concentrations. The CBZ treated patients had significantly lower testosterone/SHBG ratio than the controls. Compared with the CBZ treated patients, men on VPA had significantly higher DHEAS concentrations and lower levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) as well as a lower free carnitine/total carnitine ratio. A marked age dependency was found in all three groups regarding several of the endocrine hormones. In conclusion, drug-specific endocrine effects of VPA and CBZ were found in men with epilepsy. Long-term VPA treatment leads to significant changes in DHEAS, FSH, LH, insulin, C-peptide and carnitine ratio. Long-term CBZ treatment leads to significant lower testosterone/SHBG ratio. A strict age matching were found to be of importance in the evaluation of endocrine function in men.     

Early hormonal changes during valproate or carbamazepine treatment: a 3-month study

BACKGROUND: Long-term treatment with valproate (VPA) or carbamazepine (CBZ) may induce reproductive endocrine disorders in patients with epilepsy. METHODS: Serum concentrations of reproductive hormones were studied in 17 women and 22 men with recently diagnosed epilepsy before they started either VPA or CBZ medication, and 1 and 3 months later. RESULTS: No weight gain or clinical signs of hormonal disorders were observed during the follow-up. The mean serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin (SHBG) increased, and dehydroepiandrosterone sulfate (DHEAS) decreased, in women starting VPA. Serum testosterone levels increased in half of the women on VPA. Serum concentrations of progesterone and dehydroepiandrosterone increased, and gonadotropins decreased, in men on VPA during the follow-up. Serum SHBG levels increased and DHEAS decreased during the first months of CBZ treatment in both sexes. In addition, the free-androgen index decreased in men after starting CBZ. CONCLUSIONS: Hormonal changes occur after only 1 month's use of VPA or CBZ. VPA-treatment seems to be associated with increased serum androgen levels, but the profile of hormonal changes appears to be different in women than in men. The use of CBZ, in turn, was associated with increased SHBG concentrations and thus with diminished sex steroid function in both sexes. The women with increased serum testosterone levels in the early phase of VPA medication may be at increased risk for VPA-related endocrine disorders later during treatment.     

Sex hormones, sexual activity and plasma anticonvulsant levels in male epileptics.

Testosterone, LH, FSH, PRL, and sex hormone binding globulin (SHBG) were measured in 72 male epileptic patients on chronic anticonvulsant drug regimes. Sexual activity was estimated and plasma anticonvulsants measured. Total testosterone (TT), LH, FSH, PRL, and SHBG were increased; free testosterone (FT) was decreased. Sexual activity appeared diminished particularly in relation to reduced FT.     

Carbamazepine, Phenytoin, Sex Hormones, and Sexual Function in Men with Epilepsy

Summary We evaluated the effects of carbamazepine (CBZ) on serum androgen levels and sexual function prospectively for 5 years in 11 men with epilepsy and in 25 patients receiving either CBZ (14 patients) or phenytoin (PHT) (11) monotherapy for >5 years. Serum sex hormone binding globulin (SHBG) levels increased and free androgen index (FAI) decreased during CBZ treatment, and these changes correlated with duration of CBZ therapy. Similarly, serum SHBG levels increased and FA1 values decreased in patients receiving PHT for >5 years. CBZ and PHT increase serum SHBG levels, leading to decreased FAI. These drugrelated hormonal changes may be the primary cause of hyposexuality common in men with epilepsy.     

Effects of Carbamazepine on Pituitary Responsiveness to Luteinizing Hormone-Releasing Hormone, Thyrotropin-Releasing Hormone, and Metoclopramide in Epileptic Patients

Pituitary responsiveness to luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and metoclopramide (MC) was studied in 40 epileptic patients (24 men and 16 women) receiving carbamazepine (CBZ) treatment and in 29 (20 men and 9 women) untreated epileptic patients. Mean basal concentration of serum LH was significantly lower in the CBZ-treated female patients than in untreated female patients. The response of LH to LH-RH was also blunted in CBZ-treated female patients. No differences were found in basal or stimulated LH levels between the two groups of male patients. Nevertheless, the mean basal concentration of serum prolactin (PRL) was lower and the response of PRL to TRH was higher in male patients treated with CBZ. No differences were found in serum levels of follicle-stimulating hormone (FSH) or in responses of FSH to LH-RH between the CBZ-treated and untreated patients. These results indicate that CBZ has effects on pituitary responsiveness.     

Sexual dysfunctions and blood hormonal profile in men with focal epilepsy

PURPOSE: To evaluate the incidence of sexual dysfunction in men with focal epilepsy and to establish their hormonal profiles. METHODS: We prospectively analyzed sexual functions and hormone blood levels in 40 male patients (age ranged from 18 to 44 years, with an average age of 27.6+/-5.6 years) with refractory focal epilepsy. We used the Czech version of the structured questionnaire entitled International Inventory of Erectile Function (IIEF) to assess the patients' sexual functions. The subscales of this questionnaire separately evaluate erectile function (IIEF I), orgasmic function (IIEF II), sexual desire (IIEF III), intercourse satisfaction (IIEF IV), and overall satisfaction with sex life (IIEF V). In all of the patients, the following blood tests were performed: quantitative assessment of blood levels of prolactin (PRL), total testosterone (total-T), free androgen index (FAI), sexual hormone-binding globulin (SHBG), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), progesterone (PRG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). All these quantitative laboratory data were correlated with other clinical variables and with the results of the IIEF. chi2 and Wilcoxon tests were used for the statistical analysis. A p-value<0.05 was considered to be statistically significant. RESULTS: At least one of the types of sexual dysfunction, as defined by IIEF (IIEF I, II, and III), was found in 22 (55%) of the 40 patients (55%). Erectile dysfunction (IIEF I) was found in six (15%) of 40 patients, orgasmic dysfunction (IIEF II) in six (15%) of 40 patients, and loss of sexual desire (IIEF III) in 16 (40%) of 40 patients. According to other subscales of IIEF, 22 (55%) of 40 patients were not satisfied with sexual intercourse (IIEF IV), and 20 (50%) of 40 patients were not satisfied with their sex livee (IIEF V). None of the subscales of IIEF was significantly correlated with the age of the patients or with the duration of epilepsy. In patients with at least one of the sexual dysfunctions (IIEF I, II, and III), we found a statistically significant increase of FSH and SHBG, and a decrease of DHEAS and FAI in comparison with those in the patients with normal sexual functions. In patients with erectile dysfunction, we found the same changes and a significant increase of E2. In patients with orgasmic dysfunction, we found a statistically significant decrease of DHEAS. In patients with dysfunction of sexual desire, we noticed a significant increase of SHBG and a decrease of DHEAS and FAI. All patients with orgasmic dysfunction were being treated with carbamazepine (CBZ) in monotherapy or combination therapy. In patients with at least one type of sexual dysfunction (IIEF I, II, and III), we found a higher proportion of valproate treatment in monotherapy or combination therapy in comparison with CBZ. CONCLUSIONS: Our study showed a relatively high incidence of sexual dysfunction and dissatisfaction with sexual intercourse and sex life, as defined by the IIEF I-V questionnaire, in men with refractory focal epilepsy. The most frequent dysfunction in these patients is the impairment of sexual desire. However, our study indicates some specific hormonal changes related to various types of sexual dysfunction that are not related to antiepileptic drug treatment.     

Serum Sex Hormones Are Altered in Patients with Chronic Temporal Lobe Epilepsy Receiving Anticonvulsant Medication

Summary: Purpose: To evaluate the changes in serum sex hormones of gonadal or adrenal origin, the gonadotropic hormones, and sex hormone-binding globulin (SHBG) in men and women with chronic temporal lobe epilepsy (TLE), who are undergoing monotherapy with carbamazepine or receiving carbamazepine in combination with other anticonvulsant drugs.
Methods: Gonadal hormones (estradiol, testosterone, free testosterone, and inhibin B), adrenal hormones [cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and 17a-hydroxyprogesterone], and gonadotropic hormones (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) were measured in 22 women and 26 men with TLE. The study also measured prolactin; human growth hormone and its major mediator, insulin-like growth factor–I; thyroid hormones (free thyroxine and free triiodothyronine); thyroid–stimulating hormone (TSH); and SHBG. The results were compared with those obtained from 60 healthy women and 106 healthy men.
Results: In the female patients, TSH, DHEAS, follicularphase LH, and luteal-phase estradiol were significantly lower than in the control groups, with prolactin and SHBG significantly higher. In the male patients, DHEAS, 17α-hydroxyprogesterone, free testosterone, inhibin B, and the testosterone LH ratio were significantly lower than in the control group, with LH, FSH, and SHBG significantly higher. Increased FSH in 31% of the men indicates an impairment of spermatogenesis; lowered inhibin B in 12% indicates an impaired Sertoli's cell function; and the decreased testosterone LH ratio in 50% indicates an impaired Leydig's cell function.
Conclusions: The case patients had endocrine disorders, mainly concerning the gonadotropic and gonadal functions in both sexes; the adrenal function, with lowered DHEAS levels in both sexes; and lowered 17α-hydroxyprogesterone levels in the men. SHBG levels were increased in patients taking anticonvulsant medications.     

Antiepileptic Drug Therapy and Sexual Function in Men with Epilepsy

Summary: Purpose: To study the effects of antiepileptic drugs (AEDs) on sex hormone levels and sexual activity in a group of men attending a hospital-based epilepsy clinic. Methods: One hundred eighteen men being treated with AED therapy, 32 with epilepsy but not receiving AEDs, and 34 controls were recruited. All subjects were aged 18–65 years. Blood (20 ml) was removed for hormone assays, after which each subject completed a validated questionnaire [Sexuality Experience Scores (Frenken and Vennix, 1981)] aimed at exploring the individuals' sexual activity and attitudes to sexual morality. Results: Men taking carbamazepine (CBZ) only had significantly higher mean sex hormone-binding globulin (SHBG) levels than the control group. The CBZ group also had a significantly lower mean DHEAS concentration than the control, untreated, and sodium valproate (VPA) monotherapy groups. The phenytoin monotherapy group (PHT) had a significantly higher mean SHBG than both the control and untreated groups, and had a significantly higher mean total testosterone (TT) value than the control untreated, CBZ, and VPA groups, and a significantly lower mean DHEAS than the controls, untreated, and VPA groups. Men receiving more than one AED had significantly higher mean SHBG concentrations compared with control, untreated, and VPA groups. In addition, the poly-therapy group's mean TT was significantly higher than the control and VPA groups, although its mean DHEAS concentration was lower than the control, untreated, and VPA groups. There were no significant differences between the study groups in mean FT, Budrostenedione (AND), or estradiol levels. But the CBZ, PHT, and polytherapy groups had significantly lower mean free and rogen index (FAI) than the controls. The CBZ group had a lower mean FAI than the VPA group. The poly-therapy group had a lower FAI than the untreated group. Sexuality Experience Scores (SES) showed that those men receiving AEDs embraced a stricter sexual morality than the controls and untreated, and expressed greater satisfaction with their marriages than the control and untreated groups. Conclusions: Seizure type did not affect SES scores. Multiple regression showed men who had received further education were less accepting of strict sexual morality.     

Effects of ECT on prolactin, LH, FSH and testosterone in males with major depressive illness

Fourteen males with major depressive illness (DSM-III) received a course of electroconvulsive therapy (ECT). Serum prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), were measured 15 minutes before and 15 minutes after each treatment. The severity of depression was assessed with the Hamilton Rating Scale for Depression (HRSD) two to three days before the first and two to three days following the last treatment. Post-ECT levels of PRL and LH were significantly higher than pre-ECT levels across every treatment. Changes in FSH and testosterone were not significant. There were no relationships between hormone levels (first versus last ECT) and severity of depression, including sexual functioning. It is argued that the relatively greater increases of LH than FSH is due to an acute antidopaminergic action of ECT which acts selectively on the secretion of the former. The blunted testosterone response to the increase of gonadotropins may be due to ECT-induced hyperprolactinemia.     

Effects of carbamazepine and oxcarbazepine on the reproductive endocrine function in women with epilepsy

PURPOSE: The aim of the study was to compare the effects of carbamazepine (CBZ) and oxcarbazepine (OXC) on the reproductive endocrine function in women with epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of reproductive dysfunction in women treated with OXC monotherapy for epilepsy has not been studied previously. METHODS: Thirty-five women with epilepsy were examined in the Department of Neurology at Oulu University Hospital. Sixteen patients were treated with CBZ monotherapy, and nineteen patients were treated with OXC monotherapy. The subjects were clinically examined, vaginal ultrasonography was performed, and serum sex hormone concentrations were measured. RESULTS: The women taking CBZ or OXC had lower serum testosterone (T) levels and lower free androgen indexes (FAIs) than the control subjects. CBZ medication was associated with increased concentrations of serum sex hormone-binding globulin (SHBG). The patients taking OXC had higher concentrations of dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the OXC-treated women. CONCLUSIONS: CBZ and OXC have different effects on the reproductive endocrine function. Although both drugs were associated with low serum T concentrations and low FAIs, only OXC was associated with a high frequency of elevated levels of A and DHEAS and with an increased prevalence of PCOs. These findings suggest that OXC may be disadvantageous for women with epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.     

托吡酯与卡马西平对成年癫痫患者甲状腺激素的影响

目的探讨托吡酯（TPM）及卡马西平（CBZ）对成年癫痫患者甲状腺激素水平的影响。方法选择新确诊的100例成年癫痫患者（50例服用TPM、50例服用CBZ）为试验组,用化学发光法测定用药前甲状腺激素水平并与40例成年健康对照进行比较；再经TPM、CBZ单药治疗3、6个月及1年后检测血中甲状腺激素水平,并与治疗前比较。结果未经治疗的癫痫患者甲状腺激素水平与正常对照组比较无显著性差异（P＞0．05）；与治疗前相比,CBZ治疗3个月、6个月及1年后的游离T4（FT4）、三碘甲状腺原氨酸（TT3）及CBZ治疗6个月及1年后的甲状腺素（TT4）显著降低（P＜0．05）,而CBZ治疗3个月的TT4与服用CBZ后各时点的游离T3（FT3）、促甲状腺素（TSH）无显著性变化（P＞0．05）；经TPM治疗后的不同时段的甲状腺激素水平与治疗前比较均无显著性差异（P＞0．05）。结论CBZ治疗可造成成年癫痫患者甲状腺激素水平的降低。癫痫本身及TPM治疗并不引起成年患者甲状腺激素水平的改变,表明TPM治疗对成年癫痫患者的甲状腺功能更安全。     

Aromatase inhibition, testosterone, and seizures

The effect of testosterone on brain excitability is unclear. The excitatory aspect of testosterone's action in the brain may be due to its conversion to estrogen via aromatase. We report herein a 61-year-old man with temporal lobe epilepsy and sexual dysfunction due to low testosterone levels. Use of an aromatase inhibitor, letrozole, normalized his testosterone level and improved his sexual functioning. Letrozole, in addition to standard antiseizure medication, was also associated with improved seizure control. This was sustained and, further, was associated with seizure exacerbation after withdrawing letrozole, and subsequent seizure improvement after restarting it. During the course of treatment, his serum testosterone level increased, sex hormone-binding globulin decreased (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels increased, while serum estradiol levels remained undetectable. Letrozole may, therefore, have produced a central alteration in the testosterone/estrogen ratio, thereby impairing estrogen-mediated feedback control of the pituitary, resulting in the observed increase in circulating LH and FSH levels. This experience suggests that aromatase inhibitors should be further investigated as a beneficial treatment modality for male patients with epilepsy.     

抗精神病药对男性精神分裂症患者垂体-性腺轴的影响

目的:研究氯丙嗪、利培酮、奎硫平及奥氮平对男性精神分裂症患者垂体性腺轴的影响。方法:88例首发男性精神分裂症患者随机分为氯丙嗪组、利培酮组、奎硫平组及奥氮平组,检测治疗前、治疗4周及8周血清促卵泡素(FSH)、黄体生成素(LH)、催乳素(PRL)、睾酮(T)的水平变化。结果:氯丙嗪组治疗8周后,血清PRL水平显著高于治疗前。利培酮组在治疗4周及8周后PRL水平均显著高于治疗前,治疗8周后T及LH水平显著低于治疗前。奎硫平组在治疗4周及8周后血清PRL、LH、T水平与治疗前比较差异均无显著性。奥氮平组治疗4周后PRL水平显著高于治疗前,治疗8周后即与治疗前差异无显著性。结论:奎硫平对垂体性腺轴激素水平无明显影响。     

A prospective study of serum sex hormones during carbamazepine therapy.

This paper reports the results of a 12-month prospective follow-up study on the effects of carbamazepine (CBZ) medication on serum sex and pituitary hormone concentrations in 21 male patients with recently diagnosed epilepsy. The results of the present study indicate that a change occurs in the androgen balance during CBZ medication in male patients with epilepsy: a rise in serum sex hormone binding globulin levels results in decreased free androgen index values, and dehydroepiandrosterone sulfate serum levels decrease. Serum testosterone and free testosterone levels remain unchanged, but estradiol levels decrease. Serum basal prolactin (PRL) levels remain unchanged, but the PRL responses to thyrotropin-releasing hormone and metoclopramide increase slightly during the first year of CBZ medication. Basal and stimulated serum gonadotropin levels remain unchanged. The clinical consequences of these hormonal changes during CBZ medication call for further studies.     

Menstrual Disorders in Women with Epilepsy Receiving Carbamazepine

Summary: We measured concentrations of serum sex hormones and sex hormone binding globulin (SHBG) in relation to regularity of the menstrual cycles in 8 women before carbamazepine (CBZ) treatment was initiated and after 1 and 5 years of CBZ therapy. In addition, we evaluated menstrual cycle regularity and related endocrine changes in 56 women receiving CBZ treatment for >5 years. Serum SHBG levels increased, and serum concentrations of 17β-estradiol (estradiol) and estradiol/SHBG ratio decreased during CBZ treatment. Two of the 8 patients (25%) in the prospective study group developed menstrual irregularities during the first 5 years of therapy. In the cross-sectional study group of patients treated with CBZ for >5 years, the frequency of menstrual disturbances was also 25.0% (14 of 56 patients). Concentrations of serum sex hormones and SHBG were measured in 13 women with menstrual disorders and in 11 randomly selected women with regular cycles. In most cases, menstrual disorders were associated with increased serum SHBG and decreased serum estradiol levels and low estradiol/SHBG ratio. Long-term CBZ treatment results in increased serum SHBG levels and decreased estradiol effect, which correlate with the frequency of menstrual disorders in CBZ-treated women with epilepsy.     

Role of the septum on LH, FSH and prolactin secretion in male rats

Serum concentrations of luteinizing hormone (LH) follicle-stimulating hormone (FSH), prolactin (PRL) and testosterone were measured by radioimmunoassay in male Wistar rats:

1. (a) Four days after a septal lesion (n = 19) and

2. (b) Just following electrical stimulation of the septum (n = 15). Septal lesions induced a significant decrease in serum LH (16.37 ± 2.01 vs. 30.27 ± 2.08 ng/ml; p < 0.001) and testosterone concentrations (0.53 ± 0.05 vs. 1.01 ± 0.14 ng/ml; p < 0.02). No significant changes were observed for FSH or PRL levels. Electrical septal stimulation induced an increase in serum levels of LH (211.5 ± 46.4 vs. 29.6 ± 11.5 ng/ml; p < 0.01) and FSH (703 ± 83 vs. 378 ± 57 ng/ml;p < 0.01), without changes in PRL or testosterone concentrations. From these data we conclude that in male rats the septum may play a role in the mechanisms controlling gonadotropins release by the anterior pituitary gland.

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.     

Circadian patterns of rat anterior pituitary and target gland hormones in serum: determination of the appropriate sample size by statistical power analysis

(1) Experiments were performed to ascertain circadian fluctuations in the serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T), growth hormone (GH), thyroid stimulating hormone (TSH), and corticosterone in rats. (2) Serum LH, TSH, T and corticosterone varied throughout the 24-hr period, but the magnitude of change for LH, TSH and T was small compared with the range of individual animals' hormone concentrations at a given time point. (3) Statistical power analyses were performed on the LH, TSH, and corticosterone data in order to determine retrospectively the sample size necessary to reduce the possibility of a Type II (beta) statistical error to an acceptable level. (4) The results of these analyses indicate that many similar studies already published used too few animals and thus were biased toward not rejecting the null hypothesis.