1,720,985 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
The HRT misuse and osteoporosis epidemic: a possible future scenario
No full textRecent controversies with hormone replacement therapy (HRT) have caused much concern in women and their health-care providers. As a result, the number of HRT users in the USA has fallen dramatically. Consequently, the potential HRT-induced reduction in fracture risk is lost so that, in the next few years, we can expect an excess of 43,008 fractures per year in women aged 65 - 69 years. In addition, the recent evidence on the merits of early initiation of HRT on cardiovascular disease risk and neurocognitive function and the effect of type and combination of hormones on breast cancer risk now require an urgent review by the regulatory authorities of their recommendations about HRT
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
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
Clinical usefulness of endometrial screening by ultrasound in asymptomatic postmenopausal women
No full textOBJECTIVE:
The aim of the present study was to evaluate the clinical usefulness of routine use of endometrial ultrasound in asymptomatic, bleeding-free postmenopausal women.
METHODS:
We retrospectively reviewed the data of 850 postmenopausal women subjected to hysteroscopy, focusing our attention on those cases (148) with an ultrasound indication of endometrial thickening.
RESULTS:
In 850 postmenopausal women, we identified 27 (3.2%) endometrial adenocarcinomas. In these subjects, the indication for office hysteroscopy was abnormal uterine bleeding in 24 (24/27; 88.9%) cases; pathological pap smear with abnormal endometrial cells in 2 (2/27; 7.4%) cases and thickened endometrium upon transvaginal ultrasound (tvUS) only in one (1/27; 3.7%) patient. On the other hand, 148 hysteroscopies were performed on the basis of the tvUS indication in otherwise asymptomatic (bleeding free) postmenopausal women; only 1(0.7%) of these presented an adenocarcinoma.
CONCLUSION:
Our findings show that the use of tvUS as a screening tool for endometrial pathology in asymptomatic postmenopausal women generates 93.2% false positive results, so that most of these women undergo this second level invasive procedure uselessly. Our data suggest that, in asymptomatic postmenopausal women, endometrial ultrasound evaluation is not worthwhile as a screening tool, such as it is considered in common clinical practice. The present results call for a larger prospective trial to further elucidate this controversial issue
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
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
Effects of oral contraceptives on bone mineral density
No full textOsteoporosis 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
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