Biomedical subjects

A Cagnacci

Publications and source records attributed to A Cagnacci.

At least 19 recordsLinked to original sources

PubMed1996

Spontaneous reversibility of bone loss induced by gonadotropin-releasing hormone analog treatment.

OBJECTIVE: To verify if a 6-month period of hypoestrogenism due to chronic treatment with GnRH analogue (GnRH-a) causes irreversible bone loss in young women. DESIGN: Controlled clinical study in volunteer women. SETTING: Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. PATIENTS: Twenty-eight women (mean age +/- SE 81.1 +/- 0.99 years) with endometriosis diagnosed by laparoscopy and 25 healthy, normally cycling women of the same age (28.3 +/- 1.14 years). INTERVENTIONS: In women with endometriosis, six SC implants of the GnRH-a compound, 3.6 mg goserelin acetate depot, were administered every 28 days starting within 15 days of laparoscopy. Compounds interfering with bone metabolism or hormonal formulations were not taken by control women during the entire period of the study. MAIN OUTCOME MEASURE: Evaluation of lumbar bone mineral density at the start of the study and 6, 12, and 30 months later. RESULTS: At the onset of the study, lumbar bone mineral density did not differ in women with endometriosis and control women. Lumbar bone mineral density values significantly decreased after 6 months of GnRH-a treatment. This reduction was still evident 6 months after GnRH-a interruption. However, 24 months after treatment withdrawal, bone mineral density reduction disappeared and bone mineral density values were completely superimposable (+/- O.4 percent) to those observed before treatment. In contrast, control women lumbar bone mineral density values did not change during the entire period of observation. CONCLUSIONS: These data suggest that GnRH-a treatment for 6 months is not associated with long-term effects on lumbar bone density.

Adult↗

PubMed1995

Exogenous melatonin enhances luteinizing hormone levels of women in the follicular but not in the luteal menstrual phase.

OBJECTIVE: To investigate the effect of exogenous melatonin on LH pulsatility in women during the follicular and luteal menstrual phases. DESIGN: Randomized, double-blind placebo-controlled study. PATIENTS: Normal cycling young women (25 to 35 years old). INTERVENTIONS: Each subject was admitted at the Clinical Research Center for 2 consecutive days on both the follicular and the luteal menstrual phases. On each day, at 7:00 A.M. an indwelling catether was placed in an antecubital vein for a 10 minutes blood sampling from 9:00 A.M. to 5:00 P.M. On the 2 consecutive days of both the follicular and the luteal menstrual phases, each subject randomly received either placebo or melatonin pills (1 mg at 8:00 and 0.75 mg at 10:00 and 12:00 A.M.). MAIN OUTCOME MEASURE: Luteinizing hormone pulsatility. RESULTS: The amplitude of LH pulses and mean LH levels were increased by melatonin in the follicular but not in the luteal menstrual phase. CONCLUSIONS: The stimulatory effect of exogenous melatonin on LH is modulated by the endocrine environment and selectively exerted in the follicular phase of the menstrual cycle.

Adult↗

PubMed1995

Modulation of anterior pituitary luteinizing hormone response to gonadotropin-releasing hormone by insulin-like growth factor I in vitro.

OBJECTIVE: To investigate how much insulin-like growth factor I may modulate the LH response to GnRH. DESIGN: In primary cultures of male rat anterior pituitary cells, the LH response to GnRH (10(-9) M) was evaluated after a 24-hour preincubation with medium alone, IGF-I (1, 5, 10, 15 nM), polyclonal antibody anti-IGF-I (Ab-anti-IGF-I), (1:3,000; 1:10,000), or rabbit serum (1:3,000; 1:10,000) as control. MAIN OUTCOME MEASURE: Gonadotropin-releasing hormone-induced LH release from primary cultures of male rat anterior pituitary cells. RESULTS: Insulin-like growth factor I induces a dose-dependent stimulus on the LH response to GnRH. Insulin-like growth factor I at doses of 10 and 15 nM exerted a maximal stimulus, increasing the LH response to GnRH by 30%. The Ab-anti-IGF-I at both dilutions reduced the LH response to GnRH by 30%. No effect was exerted by rabbit serum. CONCLUSIONS: Present data indicate that IGF-I may enhance the normal LH response to GnRH from rat anterior pituitary glands, suggesting important influences of this growth factor in the modulation of anterior pituitary LH release.

Animals↗

PubMed1995

Evidence that an altered prolactin release is consequent to abnormal ovarian activity in polycystic ovary syndrome.

OBJECTIVE: To investigate whether endogenous dopaminergic activity is impaired in polycystic ovary syndrome (PCOS)-affected women and is normalized by medical ovariectomy. PATIENTS: Women with PCOS untreated (n = 23) and treated for 3 months with GnRH analogue (GnRH-a) administration (n = 10) and normal cycling young women (n = 23) as controls. INTERVENTIONS: Acute blockade of dopaminergic receptors by the IV administration of 5 mg of the dopaminergic receptor blocking agent sulpiride (sulpiride test) was performed 3 to 7 days after the initiation of spontaneous menses in cycling women or medroxyprogesterone acetate-induced menses in PCOS women. In PCOS women treated with GnRH-a administration (goserelin depot, 3.6 mg SC every 28 days), the sulpiride test was repeated 10 to 15 days after the third GnRH-a administration. MAIN OUTCOME MEASURE: Basal PRL levels and PRL increase induced by sulpiride. RESULTS: Basal PRL levels and the PRL response to sulpiride were increased in women with PCOS. In women with PCOS medical ovariectomy induced by GnRH-a administration reversed to normal both basal and sulpiride-stimulated PRL levels. CONCLUSIONS: In women with PCOS the abnormal regulation of PRL and presumably of hypothalamic neurotransmitters controlling PRL secretion is not a primary alteration but it is likely dependent on abnormal ovarian functionality.

Delayed-Action Preparations↗

PubMed1995

Hypothermic effect of melatonin and nocturnal core body temperature decline are reduced in aged women.

In young humans, the nocturnal rise of the hypothermic hormone melatonin generates 40-50% of the circadian core body temperature (Tc) decline. The nocturnal Tc decline is reduced with aging in men. In this study we investigated whether a similar attenuation occurs in women and whether it is associated with a reduced serum concentration and/or action of melatonin. The circadian rhythms of melatonin and Tc (measured in the vagina) and the responses of both Tc (measured into the auricolar canal) and finger skin temperature to melatonin administration (100 mg at 0800) were investigated in two experiments involving young (22-32 yr) and aged (54-62 yr) women. In aged women, the nocturnal onset of the melatonin rise was phase advanced and Tc decline and Tc rhythm amplitude were reduced (P < 0.0005). The serum melatonin concentrations in aged women were similar to those of young women, but the melatonin capability to reduce Tc and increase skin temperature was markedly impaired. Our data show that, in women, an aging-associated reduction of temperature responses to melatonin is probably involved in inducing an attenuation of the nocturnal Tc decline and circadian Tc rhythm amplitude.

Adult↗

PubMed1995

Prolonged opioid blockade does not influence luteinizing hormone modifications of the follicular and luteal menstrual phases.

Although an acute opioid withdrawal markedly modifies LH secretion in the different phases of the menstrual cycle, whether a sustained opioid blockade imbalances spontaneous LH modifications associated with the progression of the follicular or luteal menstrual phases is presently unknown. Accordingly, normal cycling women during either the follicular (n = 14) or luteal (n = 14) menstrual phase, randomly and in double blind fashion, received either placebo (n = 7 for each phase) or 50 mg/day of the oral opioid antagonist naltrexone (n = 7 for each phase). In each subject, LH pulsatility (10-min blood drawing for 8 h) and the pituitary LH response to a 10-micrograms GnRH stimulus were investigated at baseline and on the fifth day of placebo/naltrexone administration. In the follicular phase, after placebo treatment, the number and amplitude of LH pulses did not significantly vary, whereas mean LH levels (P < 0.01) and the LH response to GnRH (P < 0.05) were significantly increased. The same occurred after naltrexone treatment, when significant increases in both mean LH levels (P < 0.02) and LH response to GnRH (P < 0.025) were observed. In the luteal phase, after placebo administration, the frequency of LH pulses and mean LH levels were not modified, but both the amplitude of LH pulses (P < 0.025) and the LH response to GnRH were reduced (P < 0.02). The same occurred after naltrexone treatment, when significant decreases in both the amplitude of LH pulses (P < 0.05) and the LH response to GnRH (P < 0.05) were observed. During both phases of the menstrual cycle, the modifications observed during naltrexone treatment were similar and not significantly different from those observed during placebo. The present data do not support important modulatory functions for endogenous opioid peptides on spontaneous LH modifications occurring with the progression of the follicular or the luteal menstrual phases.

Adult↗

PubMed1995

Melatonin enhances the luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the follicular, but not in the luteal, menstrual phase.

Exogenous melatonin enhances LH pulse amplitude and mean LH levels in women during the follicular, but not the luteal, menstrual phase. In this study we investigated whether an increased pituitary response to GnRH is involved in the stimulatory effect of melatonin. Eight normal cycling women were studied on 2 consecutive days during the follicular stage (days 4-6), and eight were studied during the luteal phase (days 19-21) of the menstrual cycle. On 2 consecutive days, each women received, randomly and in a double blind fashion, placebo or 3 mg melatonin (1 mg at 0800, 1000, and 1200 h), whereas the pituitary LH and FSH responses to GnRH were tested by the iv administration of three submaximal doses of GnRH (1 microgram at 0900 h, 5 micrograms at 1100 h, and 10 micrograms at 1300 h). In the follicular phase, melatonin administration enhanced the LH and FSH responses to all three GnRH stimuli, whereas in the luteal phase, melatonin administration was ineffective. The present data indicate that an enhancing effect of melatonin on the LH and FSH responses to submaximal GnRH stimuli is evident in the follicular, but not the luteal, phase of the menstrual cycle and infer an endocrine window for the effect of melatonin on gonadotropin secretion.

Adult↗

PubMed1995

Melatonin enhances cortisol levels in aged but not young women.

In spite of animal data showing an effect of melatonin in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, no effect of melatonin on cortisol has been evidenced in young men. Gender and aging are believed to influence the regulation of the HPA axis, and may thus modulate the melatonin effect on cortisol. In this study we investigated whether an effect of melatonin on cortisol can be observed in women of different age. Six young women in early follicular phase (22-32 years; EFW) and eight aged women in postmenopause (54-62 years; PMW) were studied. At 08.00 h on two consecutive days each woman received, randomly and in double-blind fashion, a pill of placebo or melatonin (100 mg). Serum levels of melatonin and cortisol were evaluated at 20-min intervals for 48 h. In comparison to EFW, PMW showed an earlier onset of nocturnal melatonin (p < 0.05) and cortisol rise (p < 0.01) and higher cortisol levels at lunch (p < 0.05) and early evening (p < 0.01). Melatonin administration did not modify serum cortisol levels in EFW but elicited a marked increase of daytime cortisol levels in PMW (p < 0.02). The present data reveal that in aged PMW the cortisol levels are enhanced at selected circadian times and are stimulated by melatonin.

Administration, Oral↗

PubMed1994

Prolonged opioid blockade with naltrexone and luteinizing hormone modifications in women with polycystic ovarian syndrome.

OBJECTIVE: To investigate whether enhanced LH levels of women with polycystic ovarian syndrome (PCOS) are the consequence of an absent hypothalamic opioid inhibitory control and/or an increased sensitivity of gonadotroph to GnRH, induced by sensitizing effects of circulating opioid peptides. DESIGN: Pulsatile LH secretion (10-minute sampling for 6 hours) and GnRH-stimulated (10 micrograms) LH release were investigated in 14 women with PCOS before and after the 5-day administration of placebo (n = 7) or the opioid antagonist naltrexone (50 mg/d; n = 7). Seven age- and weight-matched normal cycling women in follicular phase were used as controls. RESULTS: In comparison with normal cycling women, PCOS showed normal frequency and increased amplitude LH pulses, elevated mean LH levels, and increased LH response to GnRH. In PCOS, placebo administration was not associated with any LH modification, whereas naltrexone enhanced the frequency and decreased the amplitude of LH pulses, without modifying mean LH levels and the LH response to GnRH. CONCLUSIONS: The naltrexone-induced increment of LH frequency revealed a conserved central opioid tone in PCOS. Reduced LH pulse amplitude, induced by naltrexone, was not associated with a reduced LH response to GnRH or with a reduction in mean LH levels. Present data do not support a role for endogenous opioid peptides in the pathogenesis of increased LH levels in PCOS.

Adult↗

PubMed1994

Melatonin-induced decrease of body temperature in women: a threshold event.

Whether the biological effect of melatonin in humans is directly related to the circulating levels of the hormone, has not heretofore been investigated. In this study, we investigated whether previously described hypothermic melatonin properties are dose related. The nocturnal decline of the body temperature (BT) observed in 16 early follicular phase women, following placebo administration at 18.00 h, was compared with that observed during the preceding or following night, after melatonin suppression with the beta 1-adrenergic antagonist atenolol (100 mg). In 6 subjects (37.5%) with lower nocturnal melatonin levels (p < 0.05) atenolol induced a complete melatonin suppression and an attenuation of the nocturnal BT decline (p < 0.02), whereas in the remaining 10 subjects (62.5%) atenolol induced an incomplete melatonin suppression with no modification of the nocturnal BT decline. During a 3rd night, 2 of the 6 subjects with complete and 6 of the 10 subjects with incomplete melatonin suppression blindly received atenolol plus melatonin (1 mg at 19.30 h and 0.75 mg at 21.00 and 23.00 h). Exogenous melatonin restored the full expression of the nocturnal BT decline in the 2 subjects with complete melatonin suppression, but did not modify the BT decline in the 6 subjects with atenolol-induced incomplete melatonin suppression. Our data show that markedly, but not completely attenuated nocturnal melatonin levels are sufficient to exert maximal thermoregulatory effects, indicating rather a threshold than a dose-response effect of melatonin action on human BT.

Adult↗

PubMed1994

Insulin, insulin-like growth factor I (IGF-I) and IGF-II enhance basal and gonadotrophin-releasing hormone-stimulated luteinizing hormone release from rat anterior pituitary cells in vitro.

The role of insulin-like growth factor I (IGF-I) and IGF-II on luteinizing hormone (LH) release is still unclear. The present study was performed to investigate modifications of basal and gonadotrophin-releasing hormone (GnRH)-stimulated (10(-9) mol/l) LH release, induced by 4-h and a 24-h incubation with physiological doses of IGF-I (1, 5 and 10 nmol/l) and IGF-II (5, 10 and 15 nmol/l) in comparison with insulin (0.0017, 0.1722 and 1.722 nmol/l), from primary cultures of male rat anterior pituitary cells. Both during the 4-h and the 24-h incubation, basal and GnRH-stimulated LH release were increased by IGF-I, IGF-II and insulin in a dose-dependent fashion. Present data confirm insulin's capability of potentiating anterior pituitary LH release from dispersed rat anterior pituitary cells in vitro, and reveal similar effects for physiological doses of IGF-I and IGF-II.

Animals↗

PubMed1994

Role of goserelin-depot in the clinical management of uterine fibroids.

On 30 women suffering from uterine fibroids, the monthly subcutaneous administration of goserelin depot (3.6 mg) for 6 (n = 22) or 12 months (n = 8) induced an about 50% shrinkage of uterus and fibroid volume, and within 3 months, an increase in the haematocrit value, with no metabolic side effects or detectable bone demineralization, evaluated by single photon absortiometry at distal radius. Both uterine and fibroid volumes reversed to pretreatment values after 3 months of goserelin depot withdrawal. In comparison with untreated subjects, on another 10 patients a three month administration of goserelin depot reduced the loss of blood during the surgical removal of the uterus or fibroids. Present data indicate that goserelin depot is effective and relatively safe in the medical management of uterine fibroids. Although, goserelin depot cannot yet be proposed as a definite medical therapy, it may represent a useful instrument in the presurgical management of uterine fibroids.

Adult↗

PubMed1994

Shrinkage of pituitary PRL-secernent adenoma after short-term treatment with bromocriptine long-acting repeatable injections.

The efficacy, safety and tolerability of a single bromocriptine-LAR injection (50 mg) and of a 6 injection course at 28-day intervals, were evaluated respectively in 13 and in 9 hyperprolactinemic women with radiological signs of PRL-secreting pituitary adenoma. The long-lasting repeatable formulation of bromocriptine induced a rapid and prolonged hypoprolactinemic effect. Side effects related to central activity of the compound were observed only on the first day of compound administration in all subjects except one, whereas no modifications of cardiologic and haematologic parameters were observed. In one subject the occurrence of side effects was observed also during the 6 injection course of treatment. A significant shrinkage of pituitary adenoma was observed at the second CT scan performed in 7 of the 9 subjects treated for 6 months with bromocriptine-LAR. CT scan was not performed in one subject who achieved pregnancy after second bromocriptine-LAR injection, whereas unmodified size of pituitary microadenoma was found in one subject whose PRL secretion did not decrease during the treatment and who referred severe side effects.

Adolescent↗

PubMed1993

The effect of light on core body temperature is mediated by melatonin in women.

Acute exposure to bright light at night reduces the nocturnal decline of core body temperature (cBT) and inhibits melatonin secretion in men. Since inhibition of melatonin secretion by beta-adrenergic blockade reduces the nocturnal decline of cBT by 40% in women, experiments were performed to investigate whether the thermoregulatory effect of light is mediated by modifications of melatonin secretion in cycling women. Results show that the elevation of cBT induced by nocturnal exposure to bright light (3000 lux) can be reversed completely by circumventing the decline of serum melatonin levels with concurrent oral administration of melatonin. Our finding establishes melatonin as the mediator of the effect of light on cBT in women and provides a rationale for the use of orally administered melatonin as an aid in the reentrainment of the cBT rhythm in desynchronized conditions.

Adult↗

PubMed1992

Lack of any estrogenic effect of ipriflavone in postmenopausal women.

Estrogen replacement therapy (ERT) has been demonstrated to prevent osteoporosis in postmenopausal women (PMW). However, several contraindications exist for ERT and many PMW cannot be treated. It has also been shown that too low doses of ERT are able to exert therapeutical effects on some climacteric symptoms but not on bone and compounds exerting synergic actions with ERT on bone without effects on other organs could be useful. The isoflavone derivative, ipriflavone, seems to have this effect but data are lacking on its endocrine effect in humans; thus, this study was undertaken to clarify in PMW whether ipriflavone exerts estrogenic activity. Evaluation of LH and FSH secretion during a 24-h period was performed in a group of 15 PMW after a single oral dose of 600 or 1,000 mg of ipriflavone or placebo, and after 7, 14 and 21 days of oral treatment with ipriflavone 600 mg and 1,000 mg/daily, administered in three divided doses. LH secretion was also evaluated during naloxone infusion before and after 21 days of ipriflavone, placebo or conjugated estrogen treatment (0.625 mg/day; CE). LH response to NAL treatment was absent during ipriflavone and placebo such as it was observed before treatments. By contrast, a significant increase of LH plasma levels was measured during naloxone infusion in CE-treated women. This result demonstrates that ipriflavone is unable to exert the same effects that estrogens do in PMW. In addition, no changes like in placebo group were seen on vaginal cytology in this group of subjects after 21 days, whereas a significant increase of superficial vaginal cells was observed after 21 days of CE treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗

PubMed1992

Effect of sex steroids on body temperature in postmenopausal women. Role of endogenous opioids.

The role of endogenous opioids on the thermoregulatory effect of sex steroids was investigated in six postmenopausal women before and during treatment with transdermal 17 B-estradiol (TTS 50; 50 mcg/day) with or without vaginal progesterone (P4; 100 mg twice daily). In all the different endocrine conditions, saline or the opioid antagonist naloxone (10 mg/hr. preceded by 10 mg iv bolus) were randomly infused for 4 hrs., on two consecutive days. Measurements of body temperature (BT) variations were performed by a thermistor probe placed in the rectum. BT did not significantly vary from baseline values during saline infusion, whereas it significantly decreased during the infusion of naloxone performed, either before treatment (p less than 0.01), during TTS 50 administration (p less than 0.01), or during TTS 50 + P4 (p less than 0.025). The naloxone induced decrease of BT was greater during TTS 50 administration than before treatment (p less than 0.025). The addition of P4 to TTS 50 administration increased baseline BT of 0.4 degrees C (p less than 0.01), and reduced the ability of naloxone to reduce BT (p less than 0.01 vs. TTS 50). The hyperthermic effect of P4 was not abolished by the infusion of naloxone. Our data show that in postmenopausal women the effect of endogenous opioid peptides on BT is enhanced by estradiol and reduced by progesterone. The hyperthermic effect of progesterone does not seem to be mediated by an increased endogenous opioid activity.

Body Temperature↗

PubMed1992

Effects of low doses of transdermal 17 beta-estradiol on carbohydrate metabolism in postmenopausal women.

The impact of a 3-month continuous administration of transdermal estradiol (E2-TTS 50; 50 micrograms/day) or oral conjugated estrogen (CE; 0.625 mg/day) on glucose and lipid metabolism was investigated in two groups (n = 15/group) of postmenopausal women. Fasting levels of glucose, insulin, and C-peptide; C-peptide/insulin ratio (index of hepatic insulin clearance); and their responses to a 75-g oral glucose tolerance test (OGTT) were evaluated before and after 3 months of continuous estrogen administration. E2-TTS 50 modified carbohydrate metabolism, decreasing fasting insulin levels (P less than 0.01) and increasing the pancreatic islet response to glucose challenges, as indicated by an increased integrated value of the C-peptide curve associated with OGTT (P less than 0.05). Despite greater C-peptide secretion, integrated peripheral insulin after OGTT was decreased (P less than 0.05). The resulting increase in the integrated curve of the molar C-peptide/insulin ratio (P less than 0.01) indicated elevated hepatic insulin clearance after E2-TTS 50 administration. CE treatment did not modify carbohydrate metabolism, except for reducing fasting glucose levels (P less than 0.01). Neither therapy modified lipid metabolism, but a slight increase in circulating triglycerides (P less than 0.01) was observed during CE administration. Our data show that the addition of low doses of natural estrogens does not negatively influence glucose and lipid metabolism in postmenopausal women. By contrast, reversal of postmenopausal hypoestrogenism to early follicular phase estrogenic values with E2-TTS 50 administration seems to exert a beneficial effect on glucose metabolism by increasing hepatic insulin clearance.

Administration, Cutaneous↗

PubMed1992

Melatonin: a major regulator of the circadian rhythm of core temperature in humans.

The circadian rhythm of core body temperature (BTc), with maxima during the day and minima at night, is normally coupled with the sleep-wake cycle. Pineal melatonin secretion occurs contemporaneously during the nighttime hours and is mediated by the activation of beta-adrenergic receptors during darkness. The hypothesis that nocturnal melatonin secretion may be involved in the regulation of the human circadian BTc rhythm was examined. The temporal relationship between melatonin and the circadian BTc rhythm was characterized in 12 young women, normally entrained to the light-dark cycle. Melatonin levels were manipulated through the administration of exogenous melatonin (2.5 mg, orally) during the daytime (n = 6) or suppression of endogenous nocturnal melatonin secretion by the beta-adrenergic antagonist atenolol (100 mg; n = 6) in double blind placebo-controlled experiments conducted during 2 consecutive days. Serum melatonin levels and BTc were monitored at 20- and 10-min intervals, respectively. In a nightshift worker the temporal relationship between the circadian rhythm of melatonin and BTc was investigated before and after entrainment to a reversed wake-sleep cycle. Our data show that in normally entrained subjects, the time course and amplitude of nocturnal melatonin secretion were temporally coupled with the decline of BTc (r = 0.97; P less than 0.00001). The same occurred in the nightshift worker, both during the dissociation and after entrainment to the reversed sleep-wake cycle. Compared with placebo, administration of melatonin significantly reduced daytime BTc (P less than 0.01), and the suppression of melatonin (by atenolol) attenuated the nocturnal decline of BTc (P less than 0.01). Cosinor analysis showed that the amplitude of the circadian BTc rhythm was reduced by about 40% in response to both daytime melatonin administration (P less than 0.05) and nocturnal melatonin suppression (P less than 0.02). In conclusion, circadian rhythms of melatonin and BTc are inversely coupled. The demonstrated hypothermic properties of melatonin are accountable for the generation of at least 40% of the amplitude of the circadian BTc rhythm. Manipulation of melatonin levels might be clinically useful to resynchronize the BTc rhythm under conditions of BTc rhythm desynchronization.

Adult↗