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.

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.

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.

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.

Serum allopregnanolone levels in pregnant women: changes during pregnancy, at delivery, and in hypertensive patients.

Allopregnanolone is a neuroactive steroid measurable in peripheral circulation. The aim of the present study was to investigate the presence and the possible changes in serum allopregnanolone and progesterone levels in pregnant women during gestation, at delivery, and in patients with chronic hypertension, with or without superimposed preeclampsia. We also evaluated allopregnanolone in cord blood. Three groups of pregnant women were studied: 1) healthy controls followed longitudinally throughout gestation (n = 14); 2) at vaginal or cesarean delivery (n = 66); and 3) with chronic hypertension (n = 12), with (n = 7) or without (n = 5) superimposed preeclampsia. Allopregnanolone and progesterone levels were measured in maternal and cord serum by RIA. In healthy pregnant women, serum allopregnanolone and progesterone levels progressively increased throughout gestation. Whereas no changes were found at vaginal delivery, serum allopregnanolone and progesterone levels were significantly lower at delivery by emergency cesarean section (P < 0.01). Umbilical cord serum allopregnanolone and progesterone levels in emergency cesarean were significantly lower than those found at vaginal delivery (P < 0.01). Patients with chronic hypertension, with or without superimposed severe preeclampsia, showed serum allopregnanolone levels significantly higher than those of healthy women at the same gestational age (P < 0.01). In conclusion, maternal serum allopregnanolone levels increased during normal gestation were lower in women who underwent emergency cesarean and higher in patients with chronic hypertension, with or without preeclampsia. Because allopregnanolone is active on the central nervous system and in the control of systemic blood pressure, an involvement of this neurosteroid in the adaptive processes induced by pregnancy is suggested.

Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences.

Allopregnanolone is a neuroactive steroid involved in modulating behavioral functions, stress, and neuroendocrine axes in rats. Changes in plasma allopregnanolone levels throughout the menstrual cycle have been reported in healthy women, but there exists no information on the possible gender or age-related changes or on the source(s) of circulating allopregnanolone. The aim of the present study was to assess serum allopregnanolone concentrations according to gender, menstrual cycle, age, and menopause in normal men and women; serum progesterone (P) and dehydroepiandrosterone (DHEA) levels were evaluated in the same specimens. In addition, the possible source of circulating allopregnanolone in fertile women was investigated by using stimulatory and inhibitory endocrine tests acting on the ovary and/or adrenal cortex. The present study included 189 fertile women, 112 postmenopausal women, and 46 men. Serum steroid levels were determined after extraction, using specific RIAs. Allopregnanolone levels in fertile women in the follicular phase were similar to those in age-matched men; no significant difference was found between fertile women in the follicular phase and postmenopausal women. The highest levels were found in fertile women during the luteal phase (P < 0.01). An age-related decrease was observed in men (P < 0.01), but not in women. P and DHEA levels were significantly higher in women than in men and were higher in fertile women than in postmenopausal women (P < 0.01). Both P and DHEA showed an age-related decrease in men and women (P < 0.01). Serum allopregnanolone and P, but not DHEA, significantly increased in response to a GnRH test, whereas corticotropin-releasing factor and ACTH tests elicited a significant increase in allopregnanolone, P, and DHEA levels (P < 0.01). The suppression of adrenal steroidogenesis by dexamethasone markedly reduced both allopregnanolone and DHEA serum levels (P < 0.01). In conclusion, the present study demonstrated that although men show an age-related decrease, serum allopregnanolone levels in women do not change with age and correlate with P levels during the menstrual cycle and in response to endocrine tests. Ovary and adrenal cortex may be major sources of circulating allopregnanolone in fertile women.

Signal-averaged P-wave duration and risk of paroxysmal atrial fibrillation in hyperthyroidism.

The onset of atrial fibrillation (AF) in hyperthyroid patients constitutes an unfavorable clinical event associated with high risk of cardiovascular complications, occurring in approximately one fifth of patients. Therefore, it is advantageous to define noninvasive markers that may identify patients at risk. The high-resolution, signal-averaged electrocardiogram was used to evaluate the relation between P-wave duration and occurrence of paroxysmal AF in a group of 50 patients with hyperthyroidism, of whom 24 had a history of paroxysmal AF and 26 did not. Filtered signal-averaged P-wave duration was measured over an average of 300 beats/patient while in sinus rhythm, both at the time of first diagnosis of hyperthyroidism and after restoration of euthyroidism by medical treatment. The 24 patients with paroxysmal AF had significantly greater P-wave duration than the 26 patients without it (135 +/- 7 vs 124 +/- 9 ms; p = 0.001). A P-wave duration cut-off value of 130 ms held specificity, sensitivity, and positive predictive accuracy values of 79%, 85%, and 83%, respectively. Of several variables, multivariate analysis showed P-wave duration to be the only independent variable significantly associated with the occurrence of paroxysmal AF. Thus, the high-resolution signal-averaged electrocardiogram may be a useful noninvasive clinical tool for the identification of electrical instability associated with paroxysmal AF in hyperthyroid patients.

Allopregnanolone concentrations and premenstrual syndrome.

OBJECTIVE: To evaluate basal allopregnanolone and progesterone in both phases of the menstrual cycle in women suffering from premenstrual syndrome (PMS) and their response to a GnRH test. DESIGN: We selected 56 women (28 patients with PMS and 28 controls) aged between 18 and 32 years. Blood samples were drawn in both follicular and phases. Twenty-eight women (14 patients with PMS and 14 controls) underwent a GnRH test in the luteal phase. METHODS: We evaluated allopregnanolone by RIA, using a specific antibody. Serum progesterone and oestradiol were determined using a commercially available RIA kit. RESULTS: Luteal phase allopregnanolone concentrations were significantly lower in patients with PMS than in controls. Progesterone concentrations were significantly lower in patients with PMS in both the follicular and the luteal phase. Serum oestradiol concentrations were in the normal range in both groups of women, although slightly greater in those with PMS. Allopregnanolone and progesterone responses to a GnRH test were significantly blunted in women with PMS. CONCLUSIONS: Diminished concentrations of allopregnanolone and progesterone, its precursor, and a blunted response to the GnRH test lead us to hypothesise that patients with PMS may suffer from an inadequate production of ovarian neuroactive steroids, especially in the luteal phase. This would lead to an impaired anxiolytic GABA(A)-mediated response in stressful physiological and psychological conditions, and may in part explain various psychoneuroendocrine symptoms that arise during PMS.

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

OBJECTIVE: Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. DESIGN: We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. METHODS: We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. RESULTS: Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). CONCLUSIONS: In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Allopregnanolone and dehydroepiandrosterone response to corticotropin-releasing factor in patients suffering from Alzheimer's disease and vascular dementia.

OBJECTIVE: Neurosteroids have been suggested to be involved in the regulation of cognitive performances. A major neurosteroid gamma-aminobutyric acid (GABA) agonist is allopregnanolone: the main source of circulating allopregnanolone is the adrenal cortex. Studies indicated that a disturbance of the central regulation of the hypothalamic-pituitary-adrenocortical axis occurs in both senile (Alzheimer's disease: AD) and vascular dementia (VD). DESIGN: The aim of the present study was to evaluate the levels of circulating allopregnanolone, dehydroepiandrosterone (DHEA) and cortisol and their response to corticotropin-releasing factor (CRF) test in AD and VD. METHODS: Three groups of 12 subjects were included in the study: AD, VD and age-matched control subjects. CRF test was performed in all subjects and allopregnanolone, DHEA and cortisol levels were measured every 15min for 2h. RESULTS: Mean +/- s.e.m. allopregnanolone and DHEA basal levels were significantly lower in AD and VD than in controls, while cortisol levels were significantly higher than in controls (P<0.01). Allopregnanolone and DHEA levels increase in response to CRF test in all subjects but the area under curve (AUC) in patients was significantly lower than in controls (P<0.01). Cortisol secretion appeared to be very sensitive in response to CRF stimulation: in fact, cortisol response to CRF test in AD and VD subjects was higher (both as AUC and as % max increase) than in controls (P<0.01). CONCLUSIONS: The present study firstly showed that allopregnanolone levels are reduced both in AD and in VD and that dementia has a preserved stimulated response of allopregnanolone to CRF. Overall, however, the total response of allopregnanolone to CRF remains reduced in respect to controls. Further studies are necessary for a better understanding of the role of neurosteroids in the regulation of cognitive function.

Highly specific polyclonal antisera against estriol: cross-reactivity restriction following affinity chromatography.

An immunosorbent technique was developed to attenuate cross-reactivity of a polyclonal antiserum against a 4(2) (rho-carboxyphenylazo)-1,3,5[10]-estratrien-3,16 alpha,17 beta-triol-bovine serum albumin conjugate. The chromatographic separation of antiserum through stationary phases having either rho(carboxymethyl)phenylazo-phenol or rho(carboxymethyl)-phenylazo-2-naphthol side residues reduced the antiserum avidity, while increasing the apparent antiserum affinity and decreasing the residual cross-reactivities against heterologous ligands. The highly specific antiserum obtained allowed the development of a competitive binding assay over an extended analytical range, which opens up the possibility of direct measurement of estriol from the early pregnancy to delivery. The significance of the attenuation of antiserum cross-reactions after affinity chromatography is discussed with reference to epitope-paratope interaction in the case of small endogenous molecules like estrogens.

Relevance of oestrone presentation to the specificity of the elicited antisera, as revealed by affinity separation.

Polyclonal antisera raised against two different azobenzoyl-oestrone derivatives were analysed to investigate both the latency/intensity relationship of the immune response and the influence of antigen presentation on the specificity of the antisera elicited. Elongation of the azo-bridge of the hapten ([p(carboxyphenyl)-azo]-1,3,5[10]- oestratrien-3 ol-17 one) with a short aliphatic chain (4-amino-n-butyric acid) resulted in a marginal increase in the antibody yield, without affecting the time required to attain the maximum titre. The increased flexibility and mobility of the extended azo-bridge was shown to result in the appearance of antisera which cross-reacted with oestrogens with D ring structures different to that of oestrone. Antiserum fractionation by affinity chromatography through a stationary phase exposing the carrier protein determinants, as modified by the addition of the coupling bridge and the phenol ring, resulted in a reduction in its specificity. These findings are discussed with regard to the phenomena underlying the specificity of a polyclonal antiserum.

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.

Neuropeptides, neurotransmitters, neurosteroids, and the onset of puberty.

Puberty results from withdrawal of the "gonadostat" mechanisms and from increased gonadotropin sensitivity to GnRH. It has been hypothesized that GnRH release may be modulated by a non-steroid-mediated mechanism. Modifications of neuropeptides, neurotransmitters, and neurosteroids may underlie the onset of pubertal processes. Neuropeptides mainly involved in the control of GnRH release are opioids, neuropeptide Y (NPY), galanin, and corticotropin-releasing factor (CRF), whereas neurotransmitters are noradrenaline, dopamine, serotonin, melatonin and gamma-aminobutyric acid (GABA). Norepinephrine, epinephrine, and dopamine stimulate GnRH, whereas the effect of serotonin on hypothalamic-pituitary-ovarian axis seems to be norepinephrine-mediated. Neurosteroids are steroid hormones that bind to the GABA-A receptor, synthesized in the brain de novo or from blood-borne precursors. DHEA, a GABA-A antagonistic neurosteroid, and allopregnanolone, a GABA-A agonistic neurosteroid, may be important in the onset of gonadarche. In conclusion, the onset of puberty derives from the complex interplay among neuropeptides, neurotransmitters, and neurosteroids that occurs in the awakening of hypothalamic-pituitary-ovarian axis.

Endocrinological and clinical investigations in post-menopausal women following administration of vaginal cream containing oestriol.

The maturation value (MV), cervical mucus parameters (ferning, Spinnbarkeit), oestrone (E1), oestradiol (E2), oestriol (E3), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyrotropin (TSH), growth hormone (GH), sex hormone binding globulin (SHBG), corticosteroid binding globulin (CBG) and thyroxin-binding globulin (TBG) were determined in 11 post-menopausal women presenting with vaginal atrophy prior to, and following, treatment with Ovestin vaginal cream containing 0.5 mg/day of E3 for 8 wk. In 6 of the patients E3 was measured during frequent plasma sampling on days 1, 21 and 56; in the same patients and on the same days TRH-stimulated PRL, TSH and GH levels were estimated. While the therapy induced a sharp rise in the MV, there was a moderate effect on ferning/Spinnbarkeit. Baseline E3 rose from undetectable levels to a mean value of 86.8 pmol/l at day 21. E3 levels achieved during frequent plasma sampling were higher on day 1 than on days 21 and 56 - a decline of the areas under the response curves being significant (P2-sided = 0.03). There was a slight suppression of FSH and LH. No changes in the circulating levels of E1, E2, SHBG, CBG, TBG, PRL, TSH and GH were seen. TRH-stimulated PRL, TSH and GH levels remained unaffected. Clinical effect was excellent and no untoward effects were reported.

A group-comparative study of effects of Ovestin cream versus Premarin cream in post-menopausal women with vaginal atrophy.

Fourteen post-menopausal women with vaginal atrophy applied, intravaginally, Ovestin cream (0.5 mg oestradiol/day; 7 patients) or Premarin cream (1.25 mg conjugated oestrogens/day; 7 patients) for 3 wk. Effects on plasma E1, E2, E3, FSH, LH, PRL, TRH-stimulated PRL release, SHBG, and on maturation value (MV), ferning (F) and spinnbarkeit (S) were studied. Endometrial biopsies at pre-treatment and at 2 wk were obtained from 2 patients from each group. Premarin induced a significant and progressive rise in E1 and E2 levels and in SHBG, whereas Ovestin induced no changes. Both creams increased E3 slightly and suppressed FSH and LH, Premarin suppression of FSH and LH being significantly greater. No significant changes in PRL or TRH-stimulated PRL release occurred with either cream. A similar, marked rise in the MV occurred, but the effect of Premarin on F and S was significantly greater. Endometrium remained atrophic in the 2 Ovestin-treated patients, but moderate proliferation occurred in the 2 Premarin-treated patients. The data showed Ovestin cream to be superior to Premarin cream because of the absence of undesirable effects on E1 and E2 levels and the subsequent changes in SHBG and endometrium.

Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women.

OBJECTIVES: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma beta-endorphin (beta-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n = 6). METHODS: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an alpha 2 presinaptic agonist for adrenergic system (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E1) and estradiol (E2) levels were evaluated before and after treatment, while plasma beta-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. RESULTS: Basal plasma beta-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E1 and E2 significantly increased after treatment. The clonidine test induced a significant increase of plasma beta-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GM levels increased both before and after treatment. CONCLUSIONS: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary beta-EP to clonidine, an alpha 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary beta-EP secretion.