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Biomedical subjects

A Cagnacci

Publications and source records attributed to A Cagnacci.

At least 55 records · Page 3Linked to original sources

Influences of melatonin on human circadian rhythms.

Administration of melatonin is useful in the treatment of desynchronized conditions. The mechanisms through which melatonin exerts its effect are not completely clear. Melatonin exerts direct effects on several biological functions, such as the regulation of body temperature, but there is no proof that these actions are important in the indirect regulation of main pacemaker activity. By contrast, it is very likely that melatonin exerts direct effects on circadian clocks, and that depending on the time of its administration/presence, it antagonizes or promotes the phase-shifting effects exerted by light. It is possible that melatonin regulates its own secretion and that its prolonged or shortened secretion in the period of the night-day transition is responsible for the lengthening or shortening, respectively, of the nocturnal melatonin rise. This possibility that needs to be confirmed by extensive studies may represent a physiological mechanism through which photoperiodic information is more rapidly and efficiently transformed by melatonin in a circadian signal to all the body.

Animals↗

Oral contraceptives and bone metabolism.

In women, the bone metabolism is markedly influenced by gonadal steroids and by their fluctuations. Indeed, estrogens influence bone metabolism by influencing endocrine and paracrine functions involved in bone remodelling. In normally cycling women, the administration of oral contraceptives does not increase bone mineral density and does not induce deleterious effects on bone. In women with ovulatory disturbances, bone turnover is increased and bone mineral density is lower than in normally cycling women. In these cases, administration of oral contraceptives is capable of blocking increased bone loss and of restoring a normal bone mineral density. Similarly, in women treated with gonadotropin releasing hormone (GnRH) analogs, the concomitant administration of oral contraceptives completely antagonizes GnRH analog-induced bone loss. The progestogenic component of oral contraceptives seems to contribute to the protective effect of estrogens on bone. Oral contraceptives are safe for bone maintenance in normal adult women, and are indeed indicated to prevent postmenopausal osteoporosis in women with ovulatory disturbances.

Adolescent↗

Biochemical aspects of hormonal contraception: effects on bone metabolism.

Both trabecular and cortical bone mineral content reduction physiologically occur during the premenopausal period and, overall, at the time of menopause. It is related to plasma estrogen fall. Several studies have examined the relationship between bone density and oral contraceptives (OCs), but their results disagree. The different results may be due to the small number of patients investigated, the different OC formulations, and to the multifactorial nature of the bone loss phenomenon. Furthermore, the use of different techniques and different sites for measuring the bone density may limit the interpretation and reproducibility of the reported findings. Our previous studies evidenced that: (1) in premenopausal (40-45 years) women (n = 26), OCs, over a period of 2 years, do not induce any change either in bone mineral density or in bone metabolism biochemical markers (osteocalcin, alkaline phosphatase, urinary hydroxyproline/creatinine ratio; and (2) independent from the therapy length, the premenopausal use of OCs does not modify the bone mineral loss in postmenopausal patients (n = 40). The present study compared, over a period of 36 months, in perimenopausal (46-53 years; follicle stimulating hormone < or = 35 mU/ml; estradiol < 50 pg/ml) women, the effect of OCs (n = 8) on bone metabolism. The results were compared with those of a matched control group (n = 9). In the treated group, a slight, though not significant, bone mass improvement was observed during the entire therapy period, whereas, in the control group, a continued and progressive bone mass loss was observed and a significant decrease was shown at the end of the observational period. Our data suggest that OCs have no significant effects on bone metabolism in women during their childbearing years. However, OCs may be beneficial in inhibiting bone reabsorption in pre- and postmenopause. Furthermore, the pill, also in virtue of its contraceptive effect, would be the first presidium in hormone therapy in the premenopause.

Alkaline Phosphatase↗

Salmon calcitonin plus intravaginal estriol: an effective treatment for the menopause.

OBJECTIVE: Intravaginal estriol (E3) effectively improves postmenopausal genito-urinary disturbances, without stimulating endometrial proliferation. The aim of the present study was to evaluate the effect of intravaginal estriol (E3) plus nasal spray salmon calcitonin (sCT), to improve neurovegetative symptoms and to prevent the decline of bone mineral density (BMD) of postmenopausal women. METHODS: Two hundred and fourteen (214) healthy postmenopausal women were treated for 12 months with: (1) E3 (0.5 mg every other day) + Ca (0.5 g/day); (2) E3 + Ca + sCT (50 IU x 2/day); (3) sCT + Ca; (4) Ca. Climacteric complaints, such as hot flushes and sweating, BMD at the distal 1/10 of the radius, analyzed by dual photon absorptiometry, urinary excretion of hydroxyproline and serum alkaline phosphatase were evaluated at baseline and every 6 months. At the same time, patient compliance and drug tolerability were evaluated. RESULTS: E3 but not sCT, improved hot flushes and sweating. E3 blunted but not completely counteracted the BMD decline observed in women treated with only Ca, and reduced urinary hydroxyproline excretion. sCT markedly increased BMD values and reduced both urinary hydroxyproline excretion and serum alkaline phosphatase. These effects were not potentiated by E3 coadministration. All treatments were well tolerated. CONCLUSIONS: Present data indicate that the combined administration of intravaginal E3 and sCT may represent an alternative therapeutic regimen for those postmenopausal women who do not accept or have contraindications to classical hormone replacement therapy.

Absorptiometry, Photon↗

The chronic administration of cabergoline normalizes androgen secretion and improves menstrual cyclicity in women with polycystic ovary syndrome.

OBJECTIVE: To investigate whether the administration of the long-lasting dopaminergic drug, cabergoline, improves endocrine and clinical features of women with polycystic ovary syndrome (PCOS). PATIENTS: Twenty-nine women participated in the study: 14 women with clinical and endocrinologic features of PCOS and 15 age- and weight-matched normal cycling women. Each subject was assigned randomly to receive either a tablet of cabergoline at the dose of 0.5 mg/wk or placebo for 4 months. Sixteen subjects (PCOS: n = 8; controls: n = 8) received cabergoline, whereas 13 (PCOS: n = 6; controls: n = 7) received placebo. INTERVENTIONS: Both before and during the 4th month of treatment, blood samples were collected every 10 minutes from 9:00 A.M. to 3:00 P.M., 3 to 7 days after spontaneous or medroxy-progesterone acetate (MPA; 5 mg daily for 5 days)-induced menses. Follicle-stimulating hormone and androgen levels were measured in the basal samples, whereas LH levels were measured in all samples. MAIN OUTCOME MEASURES: Menstrual cyclicity, LH pulsatility, and circulating levels of FSH, PRL, E2, total T, free T, androstenedione, 17 alpha-hydroxyprogesterone, DHEAS, and sex hormone-binding globulin. RESULTS: Both in controls and in PCOS-affected women, cabergoline administration blunted plasma PRL levels without affecting LH pulsatility. Androgen levels were reduced in controls and normalized in PCOS. Cabergoline, but not placebo, induced menses reappearance in amenorrheic and a normalization of menstrual cyclicity in oligoamenorrheic women with PCOS. CONCLUSIONS: The administration of cabergoline is capable to normalize androgen levels and to improve menstrual cyclicity in PCOS-affected women. Cabergoline may represent an useful treatment for menstrual irregularities of PCOS patients.

Adult↗

Melatonin in relation to physiology in adult humans.

The role exerted by melatonin in human physiology has not been completely ascertained. Melatonin levels have been measured in different physiopathological conditions, but the effects induced by melatonin administration or withdrawal have been tested only recently. Some effects have been clearly documented. Melatonin has hypothermic properties, and its nocturnal secretion generates about 40% of the amplitude of the circadian body temperature rhythm. Melatonin has sleep inducing properties, and exerts important activities in the regulation of circadian rhythms. Melatonin is capable of phase shifting human circadian rhythms, of entraining free-running circadian rhythms, and of antagonizing phase shifts induced by nighttime exposure to light. Its effect on human reproduction is not completely clear, but stimulatory effects on gonadotropin secretion have been reported in the follicular phase of the menstrual cycle. Direct actions on ovarian cells and spermatozoa have been also documented. Beside these, new important actions for melatonin may be proved. Melatonin may exert protective effects on the cardiovascular system, by reducing the risk of atherosclerosis and hypertension, and may influence immune responses. Finally, by acting as an antioxidant, melatonin could be important in slowing the processes of ageing.

Adult↗

Modification of circadian body temperature rhythm during the luteal menstrual phase: role of melatonin.

In women during early follicular phase (FP), the rise of melatonin at night accounts for 40% of the nocturnal core body temperature (Tc) decline. In seven normal-cycling women, the circadian rhythms of Tc and melatonin of the FP were compared with those of the luteal phase (LP). In addition, in both phases the Tc response to daytime melatonin administration was investigated. Melatonin levels were comparable during the two menstrual phases, but the nocturnal melatonin onset was delayed by 90 min in the LP (P < 0.01). This was accompanied by a delay of the nadir of the Tc circadian rhythm (P < 0.002), a 0.3 degrees C elevation (P < 0.005) of the mean 24-h value, and a 40% blunting (P < 0.002) of the amplitude. This attenuation of circadian Tc in LP women was replicated in two estrogen-treated hypogonadal women by the administration of medroxyprogesterone acetate. The daytime administration of melatonin (2.5 mg) decreased Tc during the FP (P < 0.01) but was ineffective in the LP. Present data indicate that in LP, in association with high progesterone levels, an attenuated and phase-delayed circadian Tc rhythm may, in part, be due to a reduced effect of melatonin.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗