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Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality.

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1-L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.

Bone Density↗

Pituitary down-regulation with a single depot-dose of a GnRH agonist (triptorelin) in postmenopausal women.

Gonadotropin levels were determined in 17 postmenopausal women before and after administering a single depot-dose of the GnRH agonist triptorelin. E2 levels of all samples were in the normal (low) postmenopausal range and no differences were found when the patients were grouped according to chronological age, or time after menopause. Pre-GnRH agonist levels of LH and FSH were in the normal (high) postmenopausal range. Two weeks after medication, LH and FSH had decreased to premenopausal levels (P < 0.0001). Eight weeks after medication, LH levels were still low whereas FSH levels had risen significantly again (P < 0.0001). Both LH and FSH levels, however, were still significantly below the serum concentrations before the administration of triptorelin (P < 0.0001). The pre-GnRH agonist level of FSH was significantly higher in women > 67 years old (P < 0.05), as compared to women < 67 years. Two weeks after medication both LH and FSH levels were significantly higher in women more than 15 years after menopause (P < 0.05), as compared to those < 15 years. The same was found for FSH in women > 67 years old. No further significant differences were noted. This study demonstrates a significant decrease of LH and FSH serum levels in postmenopausal women within two weeks after administration of a single depot-dose of the GnRH agonist triptorelin. After eight weeks, in contrast to premenopausal women, both LH and FSH, although rising, were still significantly suppressed.

Aged↗

The prevalence of urogenital symptoms in postmenopausal women.

Lower urogenital tract disorders, such as vaginal athropy, urethritis, dyspareunia, recurrent urinary tract infections and urinary incontinence symptoms, are more prevalent in postmenopausal women. While these disorders are attributed to the ageing process as well as estrogen deficiency, knowledge of the relationship between estrogen status and symptomatology is scarce and hard to investigate due to the complexity of the problem. Little is known about the epidemiology of urogenital symptoms and their relationship to estrogen status and treatment. Studies of the prevalence of urogenital symptoms in postmenopausal women have been rare and results divergent. Through reviewing existing literature and relating findings to our own prevalence studies of 61-, 71- and 81-year-old women, we can conclude that many of the symptoms accounted for in our study are those known to be due to the loss of estrogen and easily dealt with by estrogen therapy. However, there is a need for more adequate information about postmenopausal symptoms and the effect of estrogens, as only a minority of postmenopausal women are currently treated.

Aged↗

Genotypes of the vitamin-D-receptor gene and bone mineral density in Caucasoid postmenopausal females.

OBJECTIVE: To evaluate the relation of bone mineral density (BMD) to inherited polymorphisms within the gene coding for the vitamin D receptor (VDR) in postmenopausal women. METHODS: DNA samples from 163 post-menopausal women and from 112 controls were genotyped for common allelic determinants within the VDR gene as defined by the restriction enzyme sites for BsmI, ApaI, and TaqI. BMD was evaluated at the lumbar spine (L2-L4) by dual energy X-ray absorptiometry. Single restriction enzyme site polymorphisms as well as their joint genotypes were evaluated for their association with BMD in postmenopausal women. RESULTS: The three restriction site polymorphisms showed a close association indicating linkage disequilibrium (P < 0.0001). There was no relationship between any of the single restriction site polymorphisms and BMD. The distribution of the five most common joint genotypes among postmenopausal women and controls was similar. There was no relation of BMD and any of the five most common VDR genotype groups. Females more than 5 years after menopause had a significantly lower BMD than those less than 5 years after menopause (P < 0.001). This age-related decrease of BMD was also decernible within genotype groups. CONCLUSION: In our population, the postmenopausal period has a major influence on BMD, but BMD is not controlled significantly by any of the common allelic variations within the VDR gene.

Absorptiometry, Photon↗

Development and evaluation of an index to predict early postmenopausal bone loss.

An index to predict individual postmenopausal bone loss is presented. The index is developed by means of data from a 10-year prospective Norwegian study in which bone mass of the distal forearm was measured annually in 73 women. All the women were 47 years old and premenopausal at inclusion. Independent risk factors for postmenopausal bone loss were identified by applying multivariate regression analysis on anthropometric, biochemical, nutritional, and life-style variables measured at menopause. The analysis identified low body weight, reduced renal phosphate reabsorption, and smoking as significant independent risk factors, and by means of these three factors a predictive index for postmenopausal bone loss was developed. This index was validated by using data from a 10-year longitudinal Dutch study, in which bone mass of the proximal radius was measured annually in 86 women, aged between 49 and 57 years and perimenopausal at inclusion. We defined women with the highest index score as "high-risk persons." According to this definition approximately 25% of the perimenopausal women were classified as high-risk persons, and the estimated sensitivity/specificity/positive predictive power were 36%, 89%, and 74%, respectively, when used to select women with a postmenopausal bone loss above average. We conclude that the index may be helpful in identifying healthy perimenopausal women in whom bone mass measurements should be considered.

Female↗

Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women.

BACKGROUND: Tamoxifen is a selective estrogen-receptor modulator shown to improve several cardiovascular risk factors in postmenopausal women with breast cancer. In animal studies tamoxifen inhibits the progression of atherosclerosis. Although the presence of a history with tamoxifen treatment is related to a lower intima-media thickness (IMT) of the common carotid artery, data from controlled follow-up studies are lacking to support this observation. METHODS: We examined 14 postmenopausal women with early stage breast cancer with indication for tamoxifen treatment (20 mg/d) and 13 healthy postmenopausal women. Flow-mediated dilatation (FMD) of the brachial artery, combined carotid IMT, and aortic pulse wave were measured before and 6 months after treatment in the tamoxifen group and at the same times in the control group. RESULTS: FMD and IMT were significantly increased and decreased, respectively, in the treatment group compared to the control group (FMD: +2.2% +/- 0.9% vs +0.085% +/- 1%, P =.012; IMT: -0.088 +/- 0.03 mm vs +0.04 +/- 0.03 mm, P =.018, mean +/- standard error of the mean, treatment vs control group). These differences remained significant even when adjusted for age, duration of menopause, and cardiovascular risk factors. Low-density lipoprotein cholesterol was also significantly reduced after tamoxifen treatment. CONCLUSIONS: Tamoxifen treatment slows the progression of atherosclerosis in postmenopausal women with breast cancer as assessed by changes in carotid IMT. An improvement in endothelial function and blood lipid profile may be the reason for this beneficial effect.

Aged↗

Effect of raloxifene on aortic elasticity in healthy postmenopausal women.

BACKGROUND: The effect of raloxifene on aortic elasticity in healthy postmenopausal women is unknown. The purpose of the present study was to examine the effect of raloxifene on aortic elasticity and cardiovascular structure and function in healthy postmenopausal women. METHODS: A randomized, crossover, double-blind, placebo-controlled clinical trial was performed. Fourteen healthy postmenopausal women received treatment with raloxifene 60 mg daily and matching placebo for 8 weeks with an 8-week washout period in between the 2 treatment periods. Cardiovascular magnetic resonance imaging was used to assess ascending thoracic and abdominal aortic elasticity and cardiovascular structure and function (left ventricular volumes, ejection fraction, and mass and mitral annular displacement) before and at the end of each treatment period. RESULTS: Administration of raloxifene had no significant effect on either heart rate or systemic blood pressure. Raloxifene treatment was associated with a small decrease of the ascending aorta wall thickness (pretreatment 2.4 +/- 0.3 vs posttreatment 2.2 +/- 0.2 mm, P = .01). Consequently, there was an increase in the Young's elastic modulus after raloxifene treatment at the ascending thoracic aorta but not the abdominal aorta. There were no significant differences in aortic compliance or any cardiac indexes after raloxifene treatment. CONCLUSIONS: Raloxifene administration in healthy postmenopausal women over an 8-week period may decrease the aortic wall thickness but has no significant effects on aortic compliance or cardiac structure and function.

Aorta↗

Insulin resistance in postmenopausal women with metabolic syndrome and the measurements of adiponectin, leptin, resistin, and ghrelin.

OBJECTIVE: Metabolic syndrome (MBS) is a significant health care problem in postmenopausal women and is driven largely by obesity. We wished to assess the prevalence of insulin resistance (IR), diagnosed using practical methods, and whether several adipocyte factors (adiponectin, leptin, resistin) or the gastric peptide ghrelin, associated with cardiovascular risk, might be abnormal and may relate to IR. STUDY DESIGN: We evaluated 37 obese postmenopausal women with MBS and 34 matched obese premenopausal controls, as well as 14 non-obese premenopausal controls. We measured fasting glucose and insulin, performed 75 g 2 hr oral glucose tolerance and intravenous insulin tolerance tests to assess IR, and measured fasting lipids, adiponectin, leptin, resistin and ghrelin. RESULTS: The kinetic decline in glucose after insulin (kITT) as a marker of IR was the most frequently abnormal test (abnormal in 81%), with QUICKI, HOMA, and a modification of the Matsuda-DeFronzo index (ISIM) abnormal in 76, 73, and 68%, respectively. The GIR was abnormal in only 35% of subjects. Leptin and resistin were elevated and adiponectin and ghrelin were decreased in the postmenopausal women, compared to both groups of premenopausal controls. BMI correlated strongly with markers of insulin resistance as well as adipocytokine values. After controlling for BMI, only leptin was predictive of ISIM. CONCLUSION: Being overweight after menopause results in worsening IR and elevations in adipocytokine levels. While BMI is the most important factor, abnormal adipocytokine secretion may enhance IR and increase cardiovascular risk in postmenopausal women.

Adiponectin↗

Effects of long-term vegetarian diets on cardiovascular autonomic functions in healthy postmenopausal women.

The incidence of cardiovascular disease is higher in postmenopausal women than in premenopausal women. We hypothesized that long-term vegetarian diets might modulate cardiovascular autonomic functions measured by frequency-domain techniques in healthy postmenopausal women. A total of 35 healthy vegetarians (mean age +/- SEM 55.0 +/- 1.3 years) who had been vegetarians for > or =2 years and 35 omnivores (55.1 +/- 1.4 years) participated in this study. These subjects were all postmenopausal without hormone replacement therapy. Fluctuations in arterial blood pressure and heart rate variability were diffracted into low-frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.4 Hz) segments. Cardiovascular autonomic functions and baroreflex sensitivity were evaluated by specific frequency-domain measures. The vegetarians had statistically lower systolic and diastolic blood pressure, and lower serum total cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting blood sugar, and hemoglobin levels compared with the nonvegetarians. They also exhibited a significantly higher high-frequency power of heart rate variability and increased baroreflex sensitivity than did omnivores. No statistical differences were found in the low-frequency/high-frequency ratio or percentage of low frequency of heart rate variability between the 2 groups. In conclusion, in addition to the lower blood pressure and lipid concentrations in vegetarians, long-term vegetarian diets may facilitate vagal regulation of the heart and increase baroreflex sensitivity in healthy postmenopausal women, without increasing the sympathetic modulations of the cardiovascular system.

Autonomic Nervous System↗

Angiotensin II plays an important role in maintaining blood pressure in postmenopausal women receiving hormone replacement therapy.

BACKGROUND: We investigated the role of angiotensin (Ang) II in maintaining blood pressure (BP) by administering a small dose of candesartan, an Ang II type 1 receptor antagonist, in postmenopausal women receiving long-term hormone replacement therapy (HRT). METHODS: A single dose of 2 mg of candesartan was administered orally to 13 normotensive postmenopausal women receiving HRT (continuous combined conjugated estrogen and medroxyprogesterone acetate orally; HRT group) and 13 normotensive postmenopausal women not receiving HRT (control group). Both BP and heart rate (HR) were measured at baseline and at 1, 2, 3, 4, 5, and 6 h after administration. Plasma renin activity (PRA) and Ang I, Ang II, and bradykinin concentrations were measured at baseline and 4 h after the administration of candesartan. RESULTS: Candesartan lowered the BP and raised the HR in both groups. However, the decrease in BP was significantly greater in the HRT group than in the control group (P < .05), whereas no significant difference in the change in HR was observed between the two groups. In the HRT group, significant increases were found in PRA, Ang I, and Ang II (all P < .05) and a significant decrease in bradykinin (P < .01) with candesartan treatment. In the control group, candesartan as associated with an increase in PRA (P < .05) but not in Ang I, Ang II, or bradykinin. CONCLUSIONS: Based on our study results, Ang II plays an important role in maintaining BP in normotensive postmenopausal women receiving HRT. Maintenance of BP may be dependent on the balance between the hypertensive effect of Ang II and the hypotensive effect of bradykinin.

Administration, Oral↗

Nondipping status does not attenuate the conjugated estrogen-induced improvement in aortic stiffness in postmenopausal women with untreated hypertension.

BACKGROUND: Whether the blunted nocturnal blood pressure (BP) fall alters the potential beneficial effects of estrogen replacement therapy (ERT) on arterial elastic properties in hypertensive postmenopausal women has not been clarified. The aim of this study was to determine the potential beneficial effects of ERT on arterial elastic properties and to investigate whether a blunted nocturnal BP fall could unfavorably modify the estrogen-induced alterations of large-artery stiffness in postmenopausal women with untreated essential hypertension. METHODS: A total of 66 postmenopausal women with untreated essential hypertension underwent carotid-femoral pulse wave velocity (PWV) measurements at baseline and after 12 weeks of ERT with 0.625 mg conjugated estrogen. By 24-h ambulatory BP monitoring, women were classified according to dipping status (nondippers, n = 21; dippers, n = 45). RESULTS: The two groups were similar regarding age, body mass index, time since menopause, and lipidemic profile. Initially, nondippers compared to dippers, although they had significantly greater office systolic BP (SBP), 24-h SBP, daytime SBP and night-time SBP (by 5, 2, 3, and 19 mm Hg, respectively, P < .05 for all cases), did not differ regarding left ventricular (LV) mass index and aortic PWV (116 v 114 g/m2 and 8.40 v 7.95 cm/sec, respectively, P = NS for both cases). Use of ERT, without affecting the office SBP and DBP, reduced significantly the aortic PWV in both nondippers and dippers (by 1.28 and 1.50 cm/sec, respectively, P < .05 for both cases). However, these PWV reductions were not different between the two groups (P = NS). A multivariate analysis identified patient age and 24-h SBP as significant determinants of estrogen-induced aortic PWV reduction (P < .05). CONCLUSIONS: A blunted nocturnal BP fall does not attenuate the estrogen-induced favorable modifications of large artery elastic properties in hypertensive postmenopausal women. Whether these findings suggest that hypertensive women with ERT-induced attenuation of PWV represent a specific clinical subgroup of patients with possible ERT-associated cardiovascular benefit remains to be determined by properly randomized trials.

Aged↗

Circulating oxidized LDL is associated with parameters of the metabolic syndrome in postmenopausal women.

UNLABELLED: Oxidized low-density lipoproteins (ox-LDL) play a significant role in the development of atherosclerosis. OBJECTIVE: To investigate the relation between circulating ox-LDL and components of the metabolic syndrome (MS) in a sample of 124 postmenopausal women with varying glucose tolerance status. METHODS: This cross-sectional study included postmenopausal women not using hormone therapy. Ox-LDL concentrations were measured in plasma by a monoclonal antibody (mAb-4E6) based competition ELISA. LDL peak particle diameter (LDL-PPD) was measured by non-denaturating polyacrylamide gradient gel electrophoresis (PAGGE). Presence of the MS was determined according to the definition of the NCEP-ATPIII. RESULTS: Circulating ox-LDL concentrations were significantly associated with some factors of the MS such as triglyceride (r=0.48; p<0.0001), high-density lipoprotein cholesterol (r=-0.34; p=0.0001) and fasting plasma glucose concentrations (r=0.21; p=0.02). Ox-LDL concentrations were also associated with LDL cholesterol (r=0.54; p<0.0001), total cholesterol (r=0.48; p<0.0001), LDL apolipoprotein B (r=0.62; p<0.0001) and LDL-PPD (r=-0.18; p<0.05). Moreover, women with the MS had significantly higher ox-LDL concentrations (79.5+/-28.3 U/l) compared to women without the MS (64.2+/-19.9 U/l) (p<0.05). CONCLUSION: Ox-LDL concentrations are associated with individual components of the MS and are significantly higher in postmenopausal women with MS compared to healthy postmenopausal women.

Apolipoproteins↗

Apoptosis in raloxifene-treated postmenopausal women.

As raloxifene is a mixed estrogen receptor agonist and antagonist, it exerts different effects on apoptosis in different tissues. In this study, we aimed to evaluate apoptosis in the peripheral lymphocytes of postmenopausal women treated with raloxifene and compare it with untreated control subjects. In this way, we expected to deduce some results about the effect of raloxifene on the immune system and to serve as a guide for future studies on this newly proposed effect of a well-known agent. Twenty osteoporotic postmenopausal women treated with raloxifene for 12 months were included in this study. Another 20 osteoporotic postmenopausal women matched for age and postmenopausal years, but without any medication, were chosen as the control group. Apoptosis was evaluated using a morphological and DNA fragmentation assay, in the peripheral lymphocytes of these women. Our results revealed a decrease in the apoptosis percentages of the patients treated with raloxifene (14.6%) with respect to the control subjects (15.8%), but the difference was not statistically significant (p=0.467). This study indicated that raloxifene treatment had no apoptotic effect on peripheral human lymphocytes compared to controls.

Aged↗

Effect of zolpidem on sleep in women with perimenopausal and postmenopausal insomnia: a 4-week, randomized, multicenter, double-blind, placebo-controlled study.

BACKGROUND: Although most adults in the United States obtain less sleep than they need, women report more sleep deprivation throughout their lifetime than do men. The prevalence of self-reported sleep difficulty increases as women make the transition from the premenopausal to the postmenopausal period. OBJECTIVE: The purpose of this study was to assess the clinical efficacy and safety of zolpidem as a treatment for insomnia in perimenopausal and postmenopausal women. METHODS: Women who were perimenopausal or postmenopausal for >or=6 months, who had developed insomnia in conjunction with menopausal symptoms, and who had difficulty maintaining sleep or had nonrestorative sleep for >or=6 months were eligible for this 4-week, multicenter study. Sleep maintenance difficulty had to occur an average of >or=3 nights per week and had to be accompanied by >or=2 nocturnal hot flashes, hot flushes, or night sweats. Patients were randomized in a double-blind fashion to 1 of 2 treatment groups--zolpidem 10 mg or placebo. Capsules were provided in weekly blister cards, and patients were instructed to take 1 capsule each night at bedtime. Patients recorded estimates of their sleep quality and quantity and daytime functioning on daily morning and evening questionnaires, and made weekly global assessments of sleep. RESULTS: The study included 141 women (mean age +/- SD, 50.8 +/- 4.5 years; age range, 39-60 years). Increases in reported total sleep time were significantly greater in the zolpidem group than in the placebo group (P < 0.01) for each treatment week. Wake time after sleep onset and number of awakenings decreased significantly in the zolpidem group compared with the placebo group (P < 0.05). Each week, approximately twice as many patients in the zolpidem group as in the placebo group reported improved sleep (P < 0.001 for each week). The improvement in sleep-related difficulty with daytime functioning was significantly greater in the zolpidem group than in the placebo group (P < 0.05). The effects of zolpidem did not diminish with the duration of treatment. CONCLUSIONS: Zolpidem 10 mg/d was effective and well tolerated in the treatment of menopause-related insomnia in perimenopausal and postmenopausal women.

Adult↗

Tubo-ovarian abscesses in postmenopausal women: gynecological malignancy until proven otherwise?

OBJECTIVE: To investigate the incidence of gynecological malignancy in menopausal women who develop tubo-ovarian abscesses (TOAs), and to address the differences in presentation and underlying pathology between premenopausal and postmenopausal women with TOAs. STUDY DESIGN: In a retrospective study we included 93 patients with a diagnosis of a TOA and compared a premenopausal group (group 1) with a postmenopausal group (group 2). RESULTS: Group 1 included 76 (82%), and group 2 17 (18%) patients. Abdominal pain and pyrexia >38 degrees C were present in 93 and 74% cases of group 1, and in 71 and 41% cases of group 2 (P=0.016 and 0.019, respectively). Irregular vaginal bleeding and gross ascites were significantly more frequent in group 2. With respect to benign additional pathology we found no differences between the two groups. On the contrary a significant association between TOAs in menopause and malignancy was established. In 8 (47%) postmenopausal cases a concomitant gynecological malignancy was found including a variety of cancers. CONCLUSION: Postmenopausal women presenting with TOAs, should be thoroughly investigated to exclude a concomitant pelvic malignancy. Conservative treatment of TOAs has no place during the menopause.

Abdominal Pain↗

Assessment of DNA damage in postmenopausal women under osteoporosis therapy.

OBJECTIVE: The following study was designed to examine possible DNA damage levels in peripheral blood leukocytes, using the alkaline Comet assay, isolated from postmenopausal women undergoing osteoporosis treatment. STUDY DESIGN: Thirty-two postmenopausal women were randomized into two groups of 16. A dosage of 2.5 mg/day of tibolone (Livial) and 10mg/day of alendronate sodium (Fosamax) were administered to Group 1 over a 12-month period while Group 2 took 10 mg/day of alendronate alone over the same period. The control group consisted of 16 postmenopausal women who did not receive any treatment. Genotoxicity was assessed by the standard method of alkaline Comet assay. RESULTS: When the results of the study groups were compared with those of the control group, significant differences in terms of DNA damage levels were found (p<0.05). However, no difference was detected between Groups 1 and 2 (p>0.05). CONCLUSION: Although, no statistical difference in terms of DNA damage levels between tibolone plus alendronate as opposed to alendronate alone was found, an increase in DNA damage levels was observed in Groups 1 and 2 compared with the control group. Consequently, it can be asserted that the frequency of DNA damage in postmenopausal women with osteoporosis increases under alendronate treatment with or without tibolone.

Alendronate↗

Application of ultrasound contrast agents for the characterization of female urethral vascularization in healthy pre- and postmenopausal volunteers: preliminary report.

OBJECTIVES: Vascularization of the female urethra is an important factor contributing to the sealing effect responsible for the normal urethral closing system. The aim of this study was to assess whether contrast enhanced ultrasonography can be used to evaluate changes in urethral vascularization between pre- and postmenopausal women. METHODS: We studied the vascularization of female urethra in 11 healthy premenopausal females during the midfollicular phase of the menstrual cycle and 10 healthy postmenopausal volunteers using ultrasound contrast agents with a 2-5 MHz curved-array transducer by a translabial approach. Reperfusion curves were analyzed by a blinded investigator. Ultrasound contrast agents were measured with specifically designed software, and results were evaluated using the Mann-Whitney U-test. RESULTS: The data suggest that the enhancement characteristics of the urethra were different in pre- and postmenopausal women and that the percent of blood volume and blood flow decreased with age. No changes were observed between pre- and postmenopausal women regarding the velocity of blood flow. CONCLUSIONS: The study of female urethra vascularization by ultrasound contrast agents is safe, feasible, and noninvasive.

Adult↗

Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids.

OBJECTIVE: To evaluate the effects of a low-dose DHEA supplementation on hormonal parameters in early and late postmenopausal women. DESIGN: Prospective case study. SETTING: Postmenopausal women in a clinical research environment. PATIENT(S): Twenty postmenopausal women were divided in two groups according to age (50-55 and 60-65 years). INTERVENTION(S): All patients underwent hormonal evaluation before and at 3, 6, 9, and 12 months of therapy (25 mg/d of DHEA orally). Pelvic ultrasound examination and Kupperman score were performed before and after 3, 6, and 12 months of therapy. MAIN OUTCOME MEASURE(S): Plasma DHEA, DHEAS, estrone (E1), E2, P, androstenedione (A), T, dihydrotestosterone, 17alpha-hydroxyprogesterone (17-OHP), cortisol (F), allopregnanolone, beta-endorphin, sexual hormone-binding globulin (SHBG), LH, FSH, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) concentrations. RESULT(S): The levels of all the steroids that derive from DHEA metabolism increased in plasma with DHEA administration. Also neurosteroids (namely allopregnanolone) and endorphin showed increased plasma levels, whereas both gonadotropins were significantly reduced. Endometrial thickness did not change throughout the study period. CONCLUSION(S): Administration of low doses (25 mg) of DHEA positively modulates several endocrine parameters in early and late postmenopausal women, inducing the increase of the androgenic, estrogenic, and progestogenic milieu and reducing the climateric symptoms, similarly to estroprogestin replacement therapy. These data suggest that DHEA supplementation is a more effective replacement therapy than a simple "dietary supplement."

Age Factors↗