1,720,974 research outputs found
Aerodiol: the efficacy and tolerability of intranasal estrogen administration. An overview
No full textEstrogen supplementation, given mainly by oral or transdermal route has been shown to decrease climacteric symptoms, bone turnover, prevent postmenopausal bone loss, and significantly reduce fracture risk in both early and late postmenopausal women. Estrogens exert their principal biological effects through the actions on 2 different intracellular estrogen receptor (ER) proteins, ERa and ERb. These receptors, are completely distinct in their action. However, regardless the type of receptor involved, the response induced through the action of ER induction can be dependent also on the total dose exposure rather than estradiol concentrations at subsaturating levels. The nasal route is an effective and well-established route of drug delivery. Nasal administration produces a pulsed profile of plasma estradiol, with plasma levels rising rapidly and returning to pre-administration levels within 12 h (fall to 10% of their peak level within approximately 2 h). As a consequence, daily intranasal administration results in a pulse-like estrogen profile, rather than the relatively sustained serum levels attained with both oral and transdermal administration. In addition, exposure obtained with a single dose is compared with the exposure obtained with the same total dose given as 2 divided doses administered 12 h apart. It's known that different route of administration exert different biological and clinical RESULTS: In the years, several clinical studies have demonstrated the efficacy and safety of intranasal estradiol in the treatment of climacteric symptoms, compared with other routes of estrogen administration. Interestingly, intranasal therapy also showed a lower tendency to stimulate endometrial proliferation than the oral route, with a high incidence of atrophic endometrium maintained during the long-term study. The reduced level of stimulation of the reproductive organs produced by Aerodiol compared with oral estradiol therapy of equivalent efficacy on climacteric symptoms may be related to the pulsed kinetic profile of estradiol exposure that occurs with the intranasal route. Improvement of climacteric symptoms observed with nasal estradiol administration is comparable to that seen with transdermal or oral estrogens. A similar reduction in Kupperman Index or in the number of hot flushes was reported over a 6-month period with results similar to those of several studies performed with transdermal patches delivering estradiol or with conjugated equine estrogen. Different routes of administration may exert different results in terms of compliance, biological and clinical effects even if long term clinical trials are needed for demonstrating it. The pulsed kinetics of Aerodiol may exert less side effects in terms of coagulation cascade activation and a favourable lipid profile with less mammary tissue stimulation. These aspects became of paramount importance since the recent publication of 2 trials, Women Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS), regardless their important population selection bias and uncertain results, left important consequences in terms of HRT indication and use for both women and clinicians. In conclusion, Aerodiol introduces the new concept of pulsed estrogen therapy. Pulsed estrogen therapy is safe, well accepted and highly efficient in alleviating postmenopausal symptoms and prevent postmenopausal bone loss. Aerodiol therapy demonstrated also a lower stimulation of reproductive tissues (endometrium, breast) compared with the equivalent oral therapy, with important repercussion for future HRT strategies
Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists.
No full textIn a double-blind, placebo controlled study, ipriflavone (600 mg/day, T.D.D.) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with the gonadotropin hormone-releasing hormone agonist (Gn-RH-A) leuproreline acetate, 3.75 mg every 30 days for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma osteocalcin levels showed a significant (P < 0.01 and P < 0.05, respectively) increase, whereas spine bone density and total body bone density significantly (P < 0.001 and P < 0.05, respectively) decreased after 3 and 6 months of GnRH-A administration. Conversely, in the ipriflavone-treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medically induced hypogonadism
Longitudinal evaluation of perimenopausal femoral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism.
No full textTo characterize the pattern of biochemical markers of bone metabolism and femoral bone mineral density in eumenorrheic and oligomenorrheic perimenopausal women, and assess the effects of a low-dose oral contraceptive (OC) on bone metabolism and femoral bone density, bone biochemical markers and femoral bone density (measured at the neck, Ward's triangle and trochanter regions) were evaluated in a longitudinal 2-year follow-up study. The study was conducted in healthy, normally menstruating perimenopausal women (n = 18), perimenopausal oligomenorrheic women (n = 18), and perimenopausal oligomenorrheic women treated with an OC containing 20 microg ethinylestradiol plus 0.15 mg desogestrel (n = 19). The results were analyzed by factorial or repeated measures analysis of variance, as appropriate. During the observation period, in normally menstruating women there were no changes in the menstrual cycle, plasma FSH and estradiol levels, biochemical markers of bone turnover or femoral bone density. In oligomenorrheic untreated women an increase in cycle length with a concomitant decrease in plasma estradiol and an increase in plasma FSH levels were found (p < 0.05). In this group a significant increase in urinary excretion of hydroxyproline and in plasma osteocalcin levels with a concomitant significant decrease in femoral bone density (p < 0.05) occurred. In OC-treated women, osteocalcin plasma levels and urinary excretion of hydroxyproline significantly (p < 0.05) decreased, leading to a significant (p < 0.05) increase in femoral bone density. It is concluded that perimenopausal OC administration can avoid the increase in bone turnover and the decrease in femoral bone density due to the perimenopausal impairment of ovarian function
The relative contributions of menopause and aging to postmenopausal reduction in intervertebral disk height
No full textAIM:
To evaluate, in a population of normal women, the effects of aging and menopause on the height of intervertebral discs by measuring the intervertebral disk space, between the 12th thoracic and 4th lumbar vertebrae, by dual-energy X-ray absorptiometry (DXA).
MATERIALS AND METHODS:
The study was conducted on 2455 consecutive women attending our Department, from whom 464 normal women were selected. The measurement was validated utilizing a spine phantom.
RESULTS:
The phantom mean intervertebral disk space was 0.44 cm, with a coefficient of variation of 1.4%. The coefficients of variation in premenopausal, early postmenopausal and elderly women were 2.2, 2.0 and 6.0%, respectively. Values of intervertebral disk space were stable from age 20 to 50 years, thereafter showing a significant (p < 0.05) decrease, negatively correlated with both age and years since menopause (p < 0.0001). In postmenopausal women younger than 60 years, a correlation (p = 0.042) was evident between intervertebral disk space and years since menopause, but no correlation was evident with age. In women over 60 years, no correlations were found between intervertebral disk space and either age or years since menopause. In three groups of age-matched women (47.5 +/- 1.5 years, n = 39 in each group), intervertebral disk space was significantly (p < 0.0001) lower in postmenopausal than in both premenopausal and perimenopausal women.
CONCLUSION:
The DXA measurement of intervertebral disk space is precise. After menopause, intervertebral disk space shows a progressive decrease that almost entirely occurs in the first 5 - 10 years since menopause, suggesting that the estrogen decrease may rapidly change connective tissue metabolism in the intervertebral disks
Effects of low-dose continuous combined conjugated estrogens and medroxyprogesterone acetate on menopausal symptoms, body weight, bone density, and metabolism in postmenopausal women.
No full textOBJECTIVE:
The purpose of this study was to determine the effects of a low dose of conjugated equine estrogens and medroxyprogesterone acetate plus calcium supplementation on bone density, metabolism, body weight, and symptoms in young postmenopausal women.
STUDY DESIGN:
Sixty postmenopausal women, aged 45 to 56 years, were randomized in an open-label, 2-year trial that compared treatment with low-dose continuous combined hormone replacement therapy that contained 0.3 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate plus 1000 mg of calcium per day or treatment with 1000 mg of calcium per day alone. Menopausal symptoms were evaluated for the first 12 weeks of the study; bleeding profiles, bone mineral density, bone turnover, and body weight were assessed for 24 months.
RESULTS:
After 24 months, we evaluated 15 subjects in the control group (with a 50% drop-out rate) and 23 patients (with a 23% drop-out rate) in the low-dose continuous combined hormone replacement therapy group. Low-dose continuous combined hormone replacement therapy was effective in reducing menopausal clinical symptoms and provided a favorable bleeding profile and minimal side effects. In comparison with basal values, bone mineral density significantly (P <.05) increased by 2.72% +/- 0.3% in the low-dose continuous combined hormone replacement therapy group and decreased by 7.9% +/- 0.8% (P <.05) in the control group after 24 months, with parallel changes in bone metabolism marker action. In the control group, body mass index significantly (P <.05) increased from baseline value with a weight gain of 3%; in the low-dose continuous combined hormone replacement therapy group, the body mass index did not change after 24 months of treatment, and the 1.3% gain in body weight was not significant.
CONCLUSION:
Low-dose continuous combined hormone replacement therapy can alleviate subjective symptoms and minimize body transformations that are associated with early menopause and provide an effective protection against the activation of bone turnover and osteoporosis
Quantitative bone ultrasonometry in climacteric women
No full textQuantitative bone ultrasound (QUS) measurement is an emerging technique in the assessment of osteoporosis risk. In this study, bone mineral density (BMD) (mg/cm2) of lumbar vertebrae, neck, Ward's triangle and trochanter were measured by DXA and the phalanx amplitude dependent speed of sound (AD-SOS) was measured by QUS in climacteric (n = 1025) women. The relationship between AD-SOS and BMD values at different skeletal sites was significant, even if the analysis showed poor correlation coefficients. These data seem to indicate that QUS can detect bone characteristics in addition to density. The AD-SOS was higher in premenopausal than in perimenopausal women. The AD-SOS further decreases in postmenopausal women without hormone replacement. The age at menopause is relevant for predicting the AD-SOS in the postmenopausal years. Conversely, the maintenance of a regular menstrual function is associated with higher AD-SOS. Thus, the early impairment and cessation of ovarian function can lead to an earlier and/or sharper decline in bone homeostasis that can be detected by QUS. In conclusion, AD-SOS is a valuable index in detecting menopausal bone loss, and could be used for the patient follow-up during menopausal transition and in therapeutic trial
Effects of combined low dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density and metabolism in postmenopausal women.
No full textOBJECTIVES:
To assess the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in early postmenopausal women treated with combined ipriflavone and low dose conjugated estrogens.
METHODS:
Bone biochemical markers and vertebral bone density were evaluated in a longitudinal, comparative, 2 year study conducted in postmenopausal women treated with sole calcium supplementation (500 mg/day), or with either ipriflavone (IP) at the standard dose (600 mg/day) plus the same calcium dose, low dose conjugated estrogens (CE) (0.3 mg/day) plus calcium, or low dose IP (400 mg/day) plus low dose CE (0.3 mg/day) plus calcium. The results were analyzed by repeated measures analysis of variance, as appropriate.
RESULTS:
No modifications of both urinary excretion of hydroxyproline and plasma osteocalcin levels were observed in calcium and in CE-treated women, while vertebral bone density significantly decreased (P < 0.0001) in both groups. In IP or IP + CE-treated women, plasma osteocalcin did not show any modification, while urinary hydroxyproline showed a significant (P < 0.05) decrease, that paralleled a significant (P < 0.05) increase in vertebral bone density.
CONCLUSION:
Postmenopausal IP administration, at the standard dose of 600 mg/day, can prevent the increase in bone turnover and the decrease in bone density that follow ovarian failure. The same effect can be obtained with the combined administration of low dose (400 mg/day) IP with low dose (0.3 mg/day) CE
Hormone replacement therapy in perimenopause: effect of a low dose oral contraceptive preparation on bone quantitative ultrasound characteristics.
No full textOBJECTIVES:
Our aim was to assess the effects of a combined oral contraceptive (OC) preparation on bone quantitative ultrasound and biochemical markers of bone metabolism in perimenopausal women.
DESIGN:
Bone biochemical markers and bone quantitative ultrasound were evaluated in a longitudinal 2-year follow-up study conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrheic women, and age-matched oral contraceptive-treated women (20 micrograms of ethinyl estradiol plus 0.15 mg desogestrel). The results were analyzed by factorial or repeated-measures analysis of variance, as appropriate.
RESULTS:
In normal women, there were no significant modifications in menstrual cycle, plasma FSH and estradiol levels, biochemical markers of bone turnover, and bone quantitative ultrasound. Conversely, in oligomenorrheic women, an increase in the cycle length with a concomitant rise in circulating plasma FSH and parallel decrease of plasma estradiol levels was evident. In this group, an increase in both urinary excretion of hydroxyproline and plasma osteocalcin levels paralleled a decrease in bone quantitative ultrasound. In perimenopausal OC-treated women, the pattern of osteocalcin and urinary excretion of hydroxyproline showed a slight decrease, whereas bone quantitative ultrasound did not show any significant modification.
CONCLUSION:
Perimenopausal OC administration can prevent the increase in bone turnover and the decrease in bone quantitative ultrasound that follow the perimenopausal impairment of ovarian function
A longitudinal evaluation of the effect of two doses of tibolone on bone density and metabolism in early postmenopausal women
No full textTibolone, a steroid with tissue-specific activities, can reduce the bone resorption that takes place after the menopause. The present calcium-controlled, 2-year study aimed to evaluate the effect of two doses of oral tibolone, 1.25 mg and 2.5 mg, on bone loss in early postmenopausal women. The subjects were randomly allocated to one of the three groups, namely tibolone 2.5 mg (n = 30), tibolone 1.25 mg (n = 30) and a control group (n = 30). All subjects received 1000 mg of calcium per day. In the control group, vertebral and femur bone mineral density (BMD) decreased significantly (p < 0.05) after 12 and 24 months. In both tibolone groups, vertebral and femur BMD increased significantly (p < 0.05) increased after 12 and 24 months. In the control group, bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin levels) remained constant, while in both tibolone groups these markers showed similar significant decreases (p < 0.05) after 12 and 24 months. After 24 months, body weight increased in the control group (p < 0.05), while smaller increments were evident in the tibolone groups. Symptom scores in the control group did not show any significant modification during the study. In contrast, the administration of 2.5 mg tibolone was significantly (p < 0.05) effective in reducing hot flushes and other symptoms. The tibolone 1.25 mg group yielded similar results (even if it was proportionally less efficient) to the higher dose. It is concluded that tibolone is effective, even at lower doses, in relieving climacteric symptoms and preventing a decrease in spine and femur BMD in early postmenopausal women
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