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Biomedical subjects

Marco Gambacciani

Publications and source records attributed to Marco Gambacciani.

At least 19 recordsLinked to original sources

Effect of climacteric transition and hormone replacement therapy on body weight and body fat distribution.

In the present study we evaluated the effects of climacteric modifications on body weight and fat distribution. From women attending a menopause clinic we selected 2175 untreated, normal healthy women who were divided into three groups: premenopausal (n = 540), perimenopausal (n = 750) and postmenopausal (n = 885), and compared them with 354 postmenopausal women receiving different forms of hormone replacement therapy (HRT). The total body fat tissue mass and distribution were analyzed using dual-energy X-ray absorptiometry. Body weight and body mass index (BMI) were significantly higher in perimenopausal and postmenopausal than in premenopausal women. Mean total body fat and fat as a percentage of soft tissue were significantly (p < 0.05) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. Fat tissue and regional fat tissue as a percentage of total fat tissue were higher in the trunk (p < 0.0001) and arms (p < 0.0001) in perimenopausal and postmenopausal than in premenopausal women. In postmenopausal women, leg fat tissue was significantly (p < 0.05) lower than in premenopausal and perimenopausal groups. Total body and leg lean tissue were significantly lower (p < 0.05) in postmenopausal than in premenopausal and perimenopausal women. In age-matched women with similar BMI, total body fat as a percentage of soft tissue was significantly (p < 0.001) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. As for body fat distribution, fat as a percentage of total fat tissue was significantly higher in the trunk (p < 0.0001) region in perimenopausal and postmenopausal women compared with the premenopausal group. In the legs, fat as a percentage of total fat tissue was significantly higher (p < 0.05) in the premenopausal than in the postmenopausal group. In the arms a slight but not significant (p < 0.18) difference was shown in fat distribution between the three untreated groups. In age-matched HRT-treated postmenopausal women, the fat tissue was similar to that in the premenopausal group. The present results confirm that endocrine changes during the menopausal transition, rather than the aging process, are related to changes in body weight and fat distribution. Perimenopausal and postmenopausal women show a shift to a central, android fat distribution that can be counteracted by HRT.

Adult↗

Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density.

OBJECTIVES: To evaluate the pattern of mineral density in eumenorrhoic and oligomenorrhoic perimenopausal women, and assess the effects of different low dose oral contraceptives (OC) on bone metabolism and spine bone density. METHODS: Spine bone density was evaluated in a longitudinal 2-year follow-up, randomized, unblinded, uncontrolled clinical trial conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrhoic women and in perimenopausal oligomenorrhoic women treated with an oral contraceptive containing 20 microg ethinyl estradiol plus 0.15 mg desogestrel, 0.100 mg levonorgestrel, 0.75 mg of gestodene (n=15 in each group). The results were analyzed by factorial or repeated measures analysis of variance, as appropriate. RESULTS: During the observation period, in normal menstruating women there were no changes in menstrual cycle, plasma FSH and estradiol levels, and spine bone density. In oligomenorrhoic untreated women an increase in cycle length, with a concomitant decrease in plasma estradiol and an increase in plasma FSH levels were evidenced (p<0.05). In this group a significant decrease in bone density (p<0.05) occurred. In OC-treated women, a significant (p<0.05) increase in bone density was observed, with no differences among different groups. CONCLUSION: Different progestins used in OC preparations do not modify the bone sparing effect of perimenopausal OC administration avoiding the decrease in bone density.

Adult↗

Different effect of hormone replacement therapy, DHEAS and tibolone on endothelial function in postmenopausal women with increased cardiovascular risk.

Menopause is associated with an increased cardiovascular risk and with a decrease in endothelial function. Hormone replacement therapy (HRT) improves endothelial function in post-menopausal women (PMW) without established atherosclerosis. New alternative treatments, among which tibolone (T) and DHEAS have been suggested to reduce postmenopausal cardiovascular risk. Although, in vitro animal studies have suggested that T and DHEAS improve endothelial function, their effect in humans has never been tested. The aim of the present study was to compare the effects of HRT (continuous combined 0.625 mg conjugated equine estrogen plus 2.5 mg/d medoxyprogesterone) DHEAS and T on endothelium-dependent flow-mediated vasodilatation (FMD), plasma nitrite, nitrate and endothelin-1 levels in 16 PMW with increased cardiovascular risk in a double-blinded, double-crossover study. Women were randomized and treated for 4 weeks with HRT, T or DHEAS. Brachial artery diameter, FMD, endothelin-1 and plasma nitrite and nitrate levels were measured at baseline and after each treatment phase. Brachial artery diameters remained unchanged after each treatment phase. HRT significantly improved FMD compared to both baseline and to T and DHEAS therapies while no effect of T or DHEAS on FMD was noted. In conclusion, HRT, but neither T nor DHEAS, improves endothelial function and reduces plasma levels of endothelin-1 in PMW at risk of CAD.

Brachial Artery↗

Effects of low-dose, continuous combined hormone replacement therapy on sleep in symptomatic postmenopausal women.

Sleep disturbances in peri- and postmenopausal women may result from hormonal changes, vasomotor symptoms, and possibly psychological factors. Hormone replacement therapy (HRT) seems to diminish the disruption of sleep in climacteric women. The aim of this study was to determine the effects of a low dose of conjugated equine estrogens (CE) in combination with different progestins (LD-HRT) and evaluate differences between regimens on sleep in symptomatic postmenopausal women. Postmenopausal women were recruited and assigned to calcium-vitamin (control group) or to LD-HRT with 0.3mg of CE associated with a daily administration at bedtime of a progestin (2.5 mg MPA, CE + MPA, n = 20), or 100 mg natural micronized progesterone (CE + P, n = 20). Subjective symptoms were evaluated by the Greene climacteric scale, and by a visuanalogic graduated scale (0-10) at baseline and after 4, 8, and 12 weeks of study. Greene's scores for the control group were similar to those in LD-HRT group at baseline, and showed no significant modification at all subsequent measurements. Conversely, in LD-HRT group, a significant (P < 0.05) reduction in the scores of all Greene's domains was evident versus corresponding baseline and control group values. Conversely, in LD-HRT group, a significant (P < 0.05) reduction in the scores of all Greene's domains was evident with no difference in the scores of the two treated group. Both CE + MPA and CE + P significantly (P = 0.05) reduced the HF and sleep visuanalogic score in comparison to the control group. The score of sleep was significantly (P = 0.05) lower in the CE + P group in comparison to that measured in the CE + MPA group. No significant correlation between sleep and vasomotor score was found. In conclusion, low estrogen dose may have a value in the treatment of menopausal women in which sleep disturbances may be a symptom of estrogen deprivation. Low-dose estrogen associated with low-dose micronized progesterone may especially benefit women who complain of disturbed sleep.

Contraceptive Agents, Female↗

Quantitative ultrasound (QUS) of bone in the management of postmenopausal women.

OBJECTIVES: Postmenopausal osteoporosis is becoming a major problem for healthcare institutions as it has a growing social and economic impact. The incidence of osteoporotic fractures is constantly increasing due to the increase in life expectancy. The gynaecologist plays an important role in establishing a "biological zero" in each perimenopausal patient, and controlling the rate of bone loss during postmenopausal period. RESULTS: Dual energy X-ray absorptiometry (DXA) has been widely used for the diagnosis and management of osteoporosis and represents a strong risk factor for fractures, but it presents several limitations with regards to diagnosis, treatment follow-up and differential diagnosis of secondary osteoporosis. In these last years quantitative ultrasound (QUS) technique has been introduced for the evaluation of bone status in postmenopausal women and several in vitro and clinical studies have demonstrated the reliability of the examination in terms of: reproducibility, evaluation of fracture risk, treatment follow-up, differential diagnosis. QUS has proven to be equally capable in the prediction of future osteoporosis related fractures in comparison to DXA. Large-scale cross-sectional and longitudinal studies have demonstrated the applicability of QUS in screening the female population during the climacteric period. QUS technique seems to be very efficient in identifying "fast losers", identifying subjects at risk for osteoporosis requiring second-level investigation (DXA, X-ray), diagnosing secondary osteoporosis. CONCLUSION: If QUS is used in a systematic and rational manner in clinical practice, it is a valid technique for the prevention of osteoporosis in postmenopausal women.

Bone and Bones↗

New HRT options for the treatment of menopausal symptoms and the maintenance of quality of life in postmenopausal women.

Quality of life (QoL) is an important aspect that reflects the way people feel and function. The assessment of QoL quality of life is an essential tool for estimating the efficacy of any therapy in different pathophysiological conditions. In normal, healthy women, the perception of QoL can be significantly modified during the peri/postmenopausal period. Conventional HRT improves not only symptoms, but also QoL. Selection of patients, as well as the choice of a personalized HRT in terms of doses, types, routes of administration, and combination, are the keys to optimize the benefits and reduce the risks. One type of HRT cannot fit all populations of postmenopausal women. The safety and the benefit/risk ratios reported for the standard higher doses used in the past, as well as in the HERS and WHI trials, cannot vaguely be referred to different preparations, and particularly to newer HRT schedules with lower dosages. The demonstration of efficacy of lower-dose HRT provides important information for the treatment of the postmenopausal syndrome. Lower-dose HRT (as 0.3 mg/d of conjugated estrogens) minimizes the side effects and is likely to improve compliance to the treatment. The choice of lower estrogen doses may at least in part reduce the potential risks of postmenopausal hormone use, while maintaining the benefits of conventional HRT.

Dose-Response Relationship, Drug↗

Effects of oral contraceptives on bone mineral density.

Osteoporosis is a major health problem that leads to a high incidence of spine, radial, and hip fractures. It is now well recognized that a chronically hypoestrogenic state increases bone turnover that, in turn, causes a critical decrease in bone mineral density (BMD), an important determinant of fracture risk. During the premenopausal period, hypogonadism can have deleterious effects on skeletal health by reducing peak bone mass or inducing precocious bone loss. In young women, hypothalamic amenorrhea, caused by gonadotropin-releasing hormone pulsatility dysregulation, is often associated with bone loss. Although the relationship between hypothalamic amenorrhea and bone density is not completely understood, the most plausible intervention for this disorder at the moment seems to be the use of hormone replacement. Oral contraceptives are associated with an improvement in BMD if assumed upon the onset of anovulatory cycles and, therefore, estrogen deficiency, but confer no benefit in healthy women with normal ovarian function. In perimenopausal oligomenorrheic women, the use of oral contraceptives seems to have bone-sparing effects. In conclusion, the protective role of oral contraceptives on bone density is biologically plausible, since this treatment represents a replacement therapy with continuous exposure to exogenous estrogens.

Bone Density↗

Postmenopausal femur bone loss: effects of a low dose hormone replacement therapy.

OBJECTIVES: Previous studies indicate that low-dose hormone replacement therapy (LD-HRT) can relieve vasomotor symptoms and prevent spine bone loss. METHODS: In the present study, we evaluated the effects of a low dose of conjugated equine estrogens (CEE; 0.3 mg) associated with different progestins in continuous combined scheme [2.5 mg of medroxyprogesterone acetate (n=25), 5 mg dydrogesterone (n=27), 2.5 mg nomegestrol (n=11)] as single group, on femur bone mineral density (BMD) and bone metabolism in young postmenopausal women (<or=56 years). All women were supplemented with 1 g of calcium per day, and compared with women treated with 1 g of calcium per day alone (control group, n=15). There were no significant differences in age, body mass index (BMI), hormone values, bone metabolism markers and femur BMD in the treatment and control groups before the study. RESULTS: In calcium-treated women serum plasma osteocalcin (BGP) and hydroxyproline/creatinine urinary excretion (OHP/Cr) remained stable during all the observation period. In this group, femoral neck, Ward's triangle and trochanter BMD showed a progressive and significant (P<0.05) decrease. In the LD-HRT group, a significant (P<0.05) decrease in serum BGP and OHP/Cr was observed. In these women, the values of these markers of bone turnover at 36 months were significantly (P<0.01) different from those of calcium-treated women. During the LD-HRT administration, all BMD measures did not show any significant modifications. In these women, treated with LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women in all the femur sites of measurements. In the control group, BMI significantly (P<0.05) increased from baseline value with a weight gain of 3%, while in the LD-HRT group, BMI did not change after 36 months of treatment and the 1.3% gain in body weight was not significant. LD-HRT was effective in reducing menopausal clinical symptoms and provided a favorable bleeding profile, and minimal side effects. CONCLUSION: LD-HRT was effective in reducing menopausal clinical symptoms and minimal and transient side effects were reported. In addition, the 0.30 mg/day of CEE, in addition to a proper calcium supplementation, irrespective of the progestin used, can provide effective protection against activation of bone turnover and femur osteopenia.

Drug Therapy, Combination↗

Effects of low-dose, continuous combined estradiol and noretisterone acetate on menopausal quality of life in early postmenopausal women.

OBJECTIVES: To describe the effects of low dose hormonal replacement therapy (LD-HRT) on quality of life in early postmenopausal women, since the postmenopausal estrogen deprivation in mid age women often brings along a series of changes and symptoms, which may greatly affect quality of life. METHODS: Fifty normal postmenopausal women were recruited and randomly treated with LD-HRT, 17beta-estradiol (1 mg/day) and norethisterone acetate (0.5 mg/day) (LD-HRT) or calcium supplement (controls). No significant differences in age, age at menopause, the presence of chronic diseases and socio-economic status were present in the two groups. The Women's Health Questionnaire (WHQ), a validated quality-of-life instrument for perimenopausal and postmenopausal women, was administered at baseline and after 6 and 12 weeks of treatment in both groups. RESULTS: At baseline no significant differences in WHQ scores were present in the two groups. In the control group the scores in all different areas showed no significant modification either after 6 and 12 weeks of observation. Conversely, the LD-HRT group showed a significant decrease in the scores of vasomotor symptoms, somatic symptoms, anxiety/fear, depressed mood and sleep problem items. No effects on memory/concentration and menstrual symptoms areas were evident. CONCLUSION: Although quality of life is also and may be mainly influenced by socio-economic and cultural factors, LD-HRT definitively can improve not only vasomotor symptoms, but also more general aspects of physical and psychological well-being of symptomatic postmenopausal women.

Drug Administration Schedule↗

Dydrogesterone does not reverse the effects of estradiol on endothelium-dependant vasodilation in postmenopausal women: a randomised clinical trial.

OBJECTIVES: The purpose of this study was to evaluate endothelium-dependent flow-mediated dilation (FMD) in the brachial artery and the plasma levels of endothelin-1 in postmenopausal women at risk for coronary artery disease before and after treatment with both estradiol and estradiol plus dydrogesterone. METHODS: Sixteen postmenopausal women (PMW) (mean age 58+/-9 years) with more than two risk factors for coronary artery disease, were randomized to receive either oral estradiol (2 mg) for 28 days or oral estradiol (2 mg) for 14 days and oral estradiol (2 mg) and dydrogesterone (10 mg) for 14 days, in a double-blind, placebo-controlled, single cross-over study. Patients were crossed-over the complementary treatment 7 days after completing the first treatment. The study of forearm blood flow and the measurement of plasma endothelin-1 levels was carried out before and after each treatment. RESULTS: Estradiol significantly increased FMD as compared to baseline; the addition of dydrogesterone did not affect the effect of estradiol on FMD. Similarly reactive hyperemic flow increased after estradiol alone or in association with dydrogesterone compared to baseline. Plasma levels of endothelin-1 were significantly reduced by estradiol both when administered alone or in association with dydrogesterone. CONCLUSIONS: Hormone replacement therapy with estradiol and dydrogesterone improves endothelial function and reduces plasma levels of endothelin-1 in PMW at risk for coronary artery disease.

Cross-Over Studies↗

Hormonal influence on the central nervous system.

Sex steroids play a very important role in female neurobiology. Postmenopausal gonadal hormone withdrawal seem to be of critical importance in mood disorders, reduced libido and cognitive disturbances, which accompany this phase of a woman's life. Clinical studies have demonstrated that central nervous system (CNS) effects of estrogens are not only limited to resolution of vasomotor instability, they are extended to psychological disturbances like depression, behavioral changes and cognitive dysfunction. Progestins, on the other hand, may have variable effects on the brain, occasionally inducing dysphoric mood and altered behavior. Although their use in hormone replacement therapy (HRT) is widely debated, androgens may help resolve changes in libido experienced by many women after the menopause. It is still, however, difficult to draw guidelines on the use of HRT and postmenopausal CNS disorders as studies present up to date have been carried out with different kinds of molecules and routes of administration. Further studies are required in order to explain the specific role of endogenous and exogenous sex steroids on the CNS.

Central Nervous System↗