Higher uric acid levels are associated with better functional recovery in elderly patients receiving cardiac rehabilitation.

BACKGROUND AND AIMS: Whether uric acid (UA) serves as risk factor for cardiovascular diseases or as antioxidant defense has not yet been completely clarified. In this study we investigated the effects of UA on functional recovery in patients receiving cardiac rehabilitation. METHODS AND RESULTS: 306 patients, 209 men and 97 women, age range 25-87 years (mean 68 ± 11), performed the 6-min walk test (6mWT) before and after the rehabilitation, and the increase in walking distance was considered as the outcome measure of the study. Baseline UA serum levels ranged from 1.0 to 10.9 mg/dL (mean 5.2 ± 1.7). As there was a significant (p = 0.005) age*UA levels interaction, patients were divided into two subgroups, less then 65 years (n. 103, 68 men and 35 women, mean age 56 ± 9) and 65 years or more (n. 203, 141 men and 62 women, mean age 74 ± 5). After adjusting for relevant confounders, higher UA levels remained independent positive predictors of the increase in walking distance in older (p < 0.001) but not in younger patients (p = 0.807). CONCLUSIONS: Our findings show an independent association of higher UA levels with better functional recovery after cardiac rehabilitation selectively in elderly patients, suggesting that higher UA levels might reflect the decline in antioxidant defenses that occurs with advancing age. Future studies aimed at understanding the several contradictions concerning UA should, probably, address the issue within this perspective.

Polycystic ovary syndrome: brain-derived neurotrophic factor (BDNF) plasma and follicular fluid levels.

Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age. Features of PCOS are hyperandrogenism, chronic anovulation and polycystic ovaries on ultrasonography. Follicle development is a complex and carefully orchestrated phenomenon, involving gonadotropins and a rapidly expanding list of other intraovarian regulators, such as brain-derived neurotrophic factor (BDNF). The aim of this study is to evaluate BDNF in plasma and in follicular fluid in women affected by PCOS and in normal menstruating women. In PCOS patients the BDNF levels in plasma and in follicular fluid are higher than values obtained in healthy controls. Therefore we can hypothsize that high levels of luteinizing hormone, probably increase the secretion of BDNF in PCOS patients.

Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality.

BACKGROUND: Sexual desire is affected by endocrine and psychosocial factors. Menopausal hormonal changes are relevant to the causes of sexual dysfunction during reproductive aging. AIM: To evaluate the effects of different types of hormonal replacement therapy (HRT) on sexual function, frequency of sexual intercourse, and quality of relationship in early postmenopausal women. We recruited 48 healthy postmenopausal women aged 50-60 years (mean age 54.5 ± 3.3 years). Women with climacteric symptoms were uniformly randomized into three groups receiving either dehydroepiandrosterone (DHEA 10 mg) daily, or daily oral estradiol (1 mg) plus dihydrogesterone (5 mg), or daily oral tibolone (2.5 mg) for 12 months. Women who refused hormonal therapy were treated with oral vitamin D (400 IU). Efficacy was evaluated using the McCoy Female Sexuality Questionnaire before treatment and after 12 months. We evaluated the hormonal profile before treatment and after 3, 6 and 12 months. RESULTS: The groups receiving DHEA or HRT reported a significant improvement in sexual function compared to baseline (p < 0.001 and p < 0.01, respectively) using the McCoy total score. The quality of relationship was similar at baseline and after 3, 6 and 12 months of treatment. There were significant increases in the numbers of episodes of sexual intercourse in the previous 4 weeks in women treated with DHEA, HRT and tibolone in comparison with the baseline value (p < 0.01, p < 0.05, p < 0.01, respectively). No changes in the McCoy score occurred in women receiving vitamin D. CONCLUSIONS: Daily oral DHEA therapy at the dose of 10 mg, HRT and tibolone all provided a significant improvement in comparison with vitamin D in sexual function and in frequency of sexual intercourse in early postmenopausal women.

Daily variation of brain-derived neurotrophic factor and cortisol in women with normal menstrual cycles, undergoing oral contraception and in postmenopause.

BACKGROUND: Plasma brain-derived neurotrophic factor (BDNF) levels are associated with the hormonal status of women. Moreover, the suprachiasmatic nucleus appears to be implicated in the modulation of BDNF central levels. We aimed to investigate whether BDNF circadian rhythms exist in women and if there is a relationship with cortisol circadian rhythmicity. Moreover, we aimed to establish whether the hormonal status influences BDNF diurnal variations. METHODS: A total of 30 women were studied: 10 fertile ovulatory women, 10 women undergoing oral contraceptive (OC) therapy and 10 post-menopausal women. Basal BDNF and estradiol levels were assayed in blood samples collected after overnight fasting at regular intervals (08:00, 12:00, 16:00, 20:00, 24:00). BDNF and cortisol levels were measured in samples collected during the follicular and luteal phases in ovulatory women and once a month in OC and post-menopausal women. RESULTS: Luteal BDNF levels were significantly higher than follicular levels in fertile women (P < 0.001). In OC women, BDNF levels were similar to the follicular BDNF levels, whereas in post-menopausal women, they were significantly lower (P < 0.001). BDNF showed a diurnal rhythm in the follicular phase and in women undergoing OC, although the diurnal rhythm was blunted in the luteal phase. In post-menopausal women, BDNF and cortisol levels significantly decreased during the day. CONCLUSIONS: BDNF has a diurnal variation in women that is somewhat analogous to cortisol variation; however, the amplitude of the variation in BDNF levels appears to be influenced by ovarian function. Interactions between BDNF, the hypothalamus-pituitary-adrenal axis and sex steroids might play a critical role in the human homeostasis and adaptation.

Central modifications of allopregnanolone and beta-endorphin following subcutaneous administration of Nestorone.

The aim of the present study was to evaluate the potential action of Nestorone (alone or in combination with estradiol valerate) on the level of allopregnanolone and of the opioid beta-endorphin in selected brain areas. Wistar ovariectomized rats were given 0.05 mg/(kg day) of estradiol valerate (E2V) or subcutaneous Nestorone at three dose levels: low dose (10 microg/(kg day)), antiovulatory dose (50 micro/(kg day)) and high dose (250 microg/(kg day)) with and without E2V. E2V therapy reversed the reduction of allopregnanolone and beta-endorphin induced by ovariectomy anywhere was analyzed except for the adrenal gland. Nestorone showed no effect on allopregnanolone concentration in serum or any part of the brain tissue when given alone while it had a synergistic increasing effect in allopregnanolone concentration in some parts of the brain (hippocampus, hypothalamus, anterior pituitary and serum) when given at high dose of 250 microg/(kg day) in combination with E2V. At lower doses it possesses a synergistic effect with E2V only in the hippocampus (at 50 microg/(kg day)) and in the anterior pituitary (at 10 and 50 microg/(kg day)). Nestorone administered alone at any dose led to significant increase in beta-endorphin levels in the hippocampus only while, in the high dose group, there was a significant increase in endorphin levels in anterior pituitary and hypothalamus in addition to hippocampus as compared to ovariectomized control rats. In addition, only the highest dose of Nestorone added to estrogen increased beta-endorphin levels of hippocampus and plasma. Thus the lower doses of Nestorone alone or in combination with estrogen do not seem to exert any great effect on both allopregnanolone and beta-endorphin. It is only the highest dose of Nestorone that increases allopregnanolone and beta-endorphin levels in selected brain areas, which are the hippocampus, the hypothalamus, the anterior pituitary and serum/plasma. This suggests that Nestorone at the antiovulatory dose levels may not alter the positive effects of estrogen treatment on mood and behaviour.

Eating habits in elderly diabetic subjects: assessment in the InCHIANTI Study.

BACKGROUND AND AIMS: Nutritional therapy is a cornerstone of the treatment of type 2 diabetes. The aim of this study was to assess differences in dietary habits between subjects with and without known type 2 diabetes. METHODS AND RESULTS: In a sample of 1242 predominantly elderly subjects enrolled in the InCHIANTI study, total energy and macronutrient intake was assessed cross-sectionally using the EPIC self-reported questionnaire. Results were compared in subjects with (N=109) and without known diabetes, and differences were adjusted for age, sex, and reported comorbidities. Subjects with known diabetes reported a significantly lower (p<0.001) total energy and soluble carbohydrate intake in comparison with the rest of the sample (1793+/-481 vs 2040+/-624 kCal/day, and 66.9+/-22.3 vs. 93.5+/-34.9 g/day, respectively). Conversely, consumption of total and saturated fats, dietary fibres and proteins was not significantly different. CONCLUSION: Known diabetes is associated with a reduction of soluble carbohydrate consumption and total energy intake without any further modification of dietary habits. These data suggest that the diagnosis of diabetes could induce some changes in nutritional style. However, corrections in dietary habits do not appear to be consistent with current guidelines and recommendations.

Brain derived neurotrophic factor circulating levels in patients undergoing IVF.

PURPOSE: The aim of the study was to measure circulating BDNF levels, a neurotrophin recently identified in the ovary, in parallel with estradiol, to verify if assessing this factor could add any predictive value to the outcome of in vitro fertilization. METHODS: Blood sampling for BDNF and estradiol was performed in 23 subjects undergoing IVF on day 1 (D1), day 8 (D8), day of HCG administration (DHCG) and day of oocyte retrieval.(DOR). RESULTS: There was a positive correlation between BDNF and estradiol throughout the stimulation cycle in all subjects. In both pregnant and nonpregnant patients, the values of BDNF grew significantly only between D8 and DHCG and remained constant until DOR. Between-group comparisons showed no statistically significant differences in both BDNF and estradiol values throughout the IVF cycle. CONCLUSION: Although BDNF plasma concentrations are not seemingly predictive of IVF outcome, this neurotrophin is highly correlated to estradiol levels and seems to be an important factor especially in the periovulatory period.

Progesterone and progestins: effects on brain, allopregnanolone and beta-endorphin.

The increased use of hormonal therapies over the last years has led to improve the knowledge of pharmacological, biochemical and metabolic properties of several progestins and their effects in target tissues, such as the central nervous system. Progesterone and synthetic progestational agents are able to modulate the synthesis and release of several neurotransmitters and neuropeptides in response to specific physiological and pathological stimuli. While these actions may relay on differential activation of progesterone receptor or recruitment of intracellular pathways, some of the differences found between synthetic progestins may depend on the specific conversion to neuroactive steroids, such as the 3-alpha, 5-alpha reduced metabolite, allopregnanolone. This is a potent endogenous steroid that rapidly affects the excitability of neurons and glia cells through direct modulation of the GABA-A receptors activity exerting hypnotic/sedative, anxiolytic, anaesthetic and anticonvulsive properties. Estrogens increase the CNS and serum levels of allopregnanolone and the addition of certain but not all synthetic progestins determines a further increase in allopregnanolone levels, suggesting that the metabolism into this reduced product is related to the chemical structure of progestin molecule used. In addition, depending on specific progestin molecule used, different interaction are found with the estradiol-induced beta-endorphin synthesis and release, showing that diverse progestins have specific and divergent actions on the opiatergic system. These results highlight the concept that natural and synthetic progesterone receptor agonists may systematically induce different biological actions in CNS. This may have far-reaching implications for the clinical effects and related indications of each compound.

Tibolone, transdermal estradiol or oral estrogen-progestin therapies: effects on circulating allopregnanolone, cortisol and dehydroepiandrosterone levels.

The aim of the present study was to evaluate, in healthy postmenopausal women, the impact of tibolone (2.5 mg), transdermal estradiol (50 microg) (TE) and different oral estrogen-progestin regimens, conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (5 mg) (CEE + MPA) and estradiol (2 mg) plus norethisterone acetate (1 mg) (E2 + NETA) on circulating estradiol, progesterone, allopregnanolone, cortisol and dehydroepiandrosterone (DHEA) levels. Blood samples were collected before and after 1, 3, 6 and 9 months of treatment in 85 postmenopausal women. Estradiol levels increased (p < 0.001) in the TE, CEE + MPA and E2 + NETA groups after 1 month of therapy, but did not change in the tibolone group during the entire follow-up period. Both E2 + NETA and tibolone treatments induced an increase in progesterone levels (p < 0.05) after 1 year of therapy. Allopregnanolone levels showed an increase in all estrogen-based groups, being significant after 3 months of treatment (p < 0.01). Patients receiving tibolone showed a significant increase in allopregnanolone levels at 3 months (p < 0.05), but lower than in the other groups. Cortisol levels decreased significantly in the TE and CEE + MPA groups after 6 months and 12 months of treatment, respectively. Neither tibolone nor E2 + NETA treatments modified circulating cortisol levels. DHEA levels significantly (p < 0.05) decreased after 6 months of TE or estrogen-progestin therapies independently of the presence or the type of progestin used. In contrast, DHEA remained stable throughout the 12 months of treatment with tibolone. The increase of allopregnanolone, a steroid with sedative and anxiolytic properties, in response to these different treatments could underlie, at least in part, the central effects that hormone replacement therapy and tibolone have on anxiety, mood and behavior. Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the androgen deficiency syndrome in postmenopausal women.

Disadaptive disorders in women: allopregnanolone, a sensitive steroid.

Allopregnanolone, a neurosteroid acting as a potent anxiolytic agonist of the gamma-aminobutyric acid A receptor, has been shown in animal models to modify its concentrations at central and peripheral levels according to the estrous cycle. Moreover, it modulates behavioral and biochemical responses to acute and chronic stress, anxiety, depression, aggressiveness, convulsions, anesthesia, sleep, memory, pain and feeding. These observations suggest that fluctuations of allopregnanolone might be involved in the development, course and prognosis of some mental disorders in humans. This has been hypothesized for depressive disorders, premenstrual dysphoria, anorexia and bulimia nervosa and Alzheimer's disease, where increased, decreased or dysregulated secretion of the main neurosteroids and their metabolites has been observed. Women show a marked gender-related sensitivity to disadaptive disorders. In addition to the well-studied role of sex steroids in modulating mood and behavior, a putative involvement of neurosteroid fluctuations, and in particular of allopregnanolone, has recently been hypothesized. In fact, several paraphysiological events and various disadaptive disorders in women are associated with modifications of circulating levels of this neurosteroid that might associated with a certain vulnerability to an altered adaptation to stressful life events.

Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency.

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25 mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while beta-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment. The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and beta-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain. In conclusion, the present study demonstrates that 25 mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.

Clinical, biochemical and therapeutical aspects of amiodarone-induced hypothyroidism (AIH) in geriatric patients with cardiac arrhythmias.

The clinical features and the laboratory aspects of the amiodarone-induced hypothyroidism (AIH) in the elderly as well as the effects of amiodarone treatment in aged AIH people have not yet been well clarified. In the present paper, we evaluated 18 subjects of both sexes (7 females, 11 males), aged 65-83 years, affected by AIH, recruited in Central Tuscany, Italy. The patients were divided in two subsets on the basis of thyroid stimulating hormone (TSH) values: mild (TSH < 20 mU/l; Group A, n=11) and severe (TSH > 20 mU/l; Group B, n=7) hypothyroid patients. On the basis of clinical features, hypothyroidism was diagnosed only in two patients (out of Group B). Concerning the hormonal pattern, we found that free tetraiodothyronine (fT4) levels were significantly lower than the normal range only in Group B subjects; TSH and thyroglobulin were higher than normal in both groups; free triiodothyronine (fT3) were always in the normal range. Thyroid autoantibodies were found positive only in one patient out of Group A and in two patients out of Group B. In 5/18 patients T4 substitutive therapy was rapidly assigned, because of severe degree of hypothyroidism. In the remaining 13/18 patients, we evaluated the clinical behavior of AIH. After additional cardiac evaluation, amiodarone was withdrawn in 5/13 patients: during follow-up period (4-10 months) four patients became quickly euthyroid while one worsened. In 8/13 patients, amiodarone treatment had to be carried on; during follow-up (2-48 months), four patients remained mildly hypothyroid, while other four patients became severely hypothyroid. In conclusion, in amiodarone treated elderly people, diagnosis of hypothyroidism is reliable only on the basis of high values of TSH; clinical features and fT3 serum levels never enable diagnosis.

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.

High serum allopregnanolone levels in girls with precocious puberty.

Allopregnanolone, a circulating neuroactive steroid hormone, is involved in the modulation of behavioral functions, stress, and the neuroendocrine axis. The aim of this study was to evaluate serum allopregnanolone concentrations in girls with central precocious puberty (n = 12), girls with normal pubertal development at the same pubertal stage (n = 17), and prepubertal girls (age-matched; n = 16). Gonadotropin and steroid hormones (allopregnanolone, cortisol, dehydroepiandrosterone sulfate, and E2) were assessed in all patients. GnRH and ACTH stimulation tests were performed in all girls with central precocious puberty and in some pubertal controls. Basal allopregnanolone levels in girls with central precocious puberty were significantly higher than in normal controls (P < 0.01). Allopregnanolone levels increased significantly after GnRH and ACTH stimulation tests (P < 0.05) both in girls with central precocious puberty and in those with normal pubertal development. There was no difference found between the peak values. In conclusion, our study shows that allopregnanolone is hypersecreted in central precocious puberty, confirming a pubertal stage-related increase in its levels during normal pubertal development. The increase in serum allopregnanolone after GnRH and ACTH stimulation tests demonstrates that both adrenal cortex and gonads are sources of this neuroactive steroid.

Neuroendocrine effects of raloxifene hydrochloride in postmenopausal women.

Raloxifene is a selective estrogen modulator able to exert an estrogen-like action on some target tissues and a specific antiestrogenic action on the uterus and breast. In ovariectomized rats, it has been shown to stimulate the beta-endorphin and allopregnanolone concentrations of the anterior and neurointermediate pituitary lobes, the hypothalamus and the hippocampus. The present study aimed to evaluate, in 12 healthy postmenopausal women, the effect of 60 mg/day raloxifene hydrochloride administration for 6 months on plasma beta-endorphin and allopregnanolone levels, and on the dynamic changes of both beta-endorphin and allopregnanolone secretion after the administration of: (1) clonidine, an alpha 2-presynaptic adrenergic agonist; (2) naloxone, an opioid receptor antagonist; and (3) fluoxetine, a serotonin selective reuptake inhibitor. The administration of raloxifene significantly increased both circulating beta-endorphin and allopregnanolone concentrations, at both the third and sixth months of treatment (p < 0.01). Clonidine, fluoxetine and naloxone administration before therapy was not able to stimulate the release of beta-endorphin, but the response was completely restored after raloxifene administration. Before therapy, clonidine and naloxone tests were accompanied by a significant rise in allopregnanolone secretion; the same changes were observed after raloxifene administration, but with significantly higher allopregnanolone concentrations at each time considered. While the fluoxetine test before therapy failed to increase the release of allopregnanolone, the same test after 6 months of raloxifene administration was characterized by a significant release of allopregnanolone at 60 and 90 minutes. The present data indicate that raloxifene has an estrogen-like effect on neuroendocrine pathways in postmenopausal women.

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

OBJECTIVE: To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. DESIGN: Controlled clinical study. SETTING: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. PATIENT(S): Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. INTERVENTION(S): Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). MAIN OUTCOME MEASURE(S): Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). RESULT(S): Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. CONCLUSIONS: Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

Circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in women with partial epilepsy in the postcritical phase.

PURPOSE: Several lines of evidence indicate that there exists a relation between ovarian hormones and epilepsy. Estrogens decrease seizure threshold and increase brain excitability, whereas progesterone has an inhibitory effect and reduces epileptiform activity. Recently considerable interest has turned to neuroactive steroids, a group of progesterone metabolites, as endogenous modulators of excitability of the central nervous system (CNS). Their ability to alter neuronal firing rapidly occurs through interaction with gamma-aminobutyric acid (GABA) A receptor complex. In a previous experience, serum allopregnanolone (3alpha-OH-5alpha-pregnan-20-one) levels were measured in 15 women with partial epilepsy in the intercritical phase, and no significant differences were found between patients and control subjects. METHODS: To find out if there are changes in serum allopregnanolone levels after epileptic seizure, blood samples were drawn immediately, 15 min, and 6 h after a seizure in seven fertile females with partial epilepsy. RESULTS: The most interesting finding is that allopregnanolone increases in serum during the first 15 min after partial seizures (p < 0.05) and decreases after 6 h. CONCLUSIONS: These data are consistent with a role for allopregnanolone in the control of neuronal excitability and seizures.

Plasma levels of neuroactive steroids are increased in untreated women with anorexia nervosa or bulimia nervosa.

OBJECTIVE: Animal data suggest that neuroactive steroids, such as 3alpha,5alpha-tetrahydroprogesterone (3a,5a-THP), dehydroepiandrosterone (DHEA), and its sulfated metabolite (DHEA-S), are involved in the modulation of eating behavior, aggressiveness, mood, and anxiety. Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders characterized by abnormal eating patterns, depressive and anxious symptoms, enhanced aggressiveness, and endocrine alterations. Previous studies reported decreased blood levels of DHEA and DHEA-S in small samples of anorexic patients, whereas no study has been performed to evaluate the secretion of these neuroactive steroids in BN as well as the production of 3alpha,5alpha-THP in both AN and BN. Therefore, we measured plasma levels of DHEA, DHEA-S, 3alpha,5alpha-THP and other hormones in patients with AN or BN and explored possible relationships between neuroactive steroids and psychopathology. METHOD: Ninety-two women participated in the study. There were 30 drug-free AN patients, 32 drug-free BN patients, and 30 age-matched, healthy control subjects. Blood samples were collected in the morning for determination of hormone levels. Eating-related psychopathology, depressive symptoms, and aggressiveness were rated by using specific psychopathological scales. RESULTS: Compared with healthy women, both AN and BN patients exhibited increased plasma levels of 3alpha,5alpha-THP, DHEA, DHEA-S, and cortisol but reduced concentrations of 17beta-estradiol. Plasma testosterone levels were decreased in anorexic women but not in bulimic women. Plasma levels of neuroactive steroids were not correlated with any clinical or demographic variable. CONCLUSIONS: These findings demonstrate increased morning plasma levels of peripheral neuroactive steroids in anorexic and bulimic patients. The relevance of such hormonal alterations to the pathophysiology of eating disorders remains to be elucidated.