Inhibin A and B in peri- and postmenopause

Objective: The aim of the study was to investigate the origin of inhibin A and B during the last years of the reproductive age and after menopause by measuring their levels in the ovarian and peripheral venous blood. Methods: The study population consisted of 43 women, aged 42–69 years (mean 50), who underwent hysterectomy with ovarian removal for a benign disease. A total of 24 of them were in follicular phase, 11 in luteal phase, and eight were postmenopausal. Peripheral and ovarian venous blood was collected for measurement of inhibin A and B. In addition, sex steroid hormone and gonadotropin levels were measured. Results: Ovarian venous inhibin B correlated significantly with ovarian estradiol secretion (r=0.5, P=0.001). The levels of inhibin B were significantly higher in the ovarian vein than in the peripheral vein (P=0.006). The highest inhibin B concentrations were detected in the mid-proliferative (mid-follicular) phase (median 31.6 pg/ml range 25.9–47.9). In postmenopausal women, inhibin B was not detectable. No correlation between FSH and ovarian inhibin B was found. Inhibin A rose rapidly in late proliferative (late follicular) phase (median 28.5, range <2–51.8) and dominated in the circulation throughout the luteal phase (median 20.9, range 8.8–60). For inhibin A, no concentration gradient existed between the ovarian and peripheral vein. Unlike inhibin B, inhibin A was detectable in ovarian and peripheral blood in postmenopausal women. A significant negative correlation between ovarian and peripheral inhibin A and FSH was found (r=−0.386, P=0.015; r=−0.345, P=0.034, respectively). Conclusion: Inhibin B correlates with ovarian estradiol secretion and seems to reflect follicular function. Inhibin A dominates in circulation during the luteal phase but is detectable at low concentrations both in follicular phase and even in postmenopause. Our findings suggest that inhibin A may play a role in FSH suppression in the female reproduction. In addition to the ovary, there may be extragondal source(s) of inhibin A.     

Effect of hormone replacement therapy on serum levels of tumor markers in healthy postmenopausal women

Objective: The effect of hormone replacement therapy (HRT) on serum levels of tumor markers is barely defined. The aim of this study was to evaluate the effect of HRT on levels of tumor markers CA 125, CA 15-3, CA 19-9, CEA and -FP. Methods: Retrospective analysis of prospectively collected data in healthy postmenopausal women under oral estrogen replacement therapy (ERT, conjugated equine estrogen (CEE) 0.625 mg (n=21) or estradiol 2 mg (n=31)), and continuous combined estrogen and progesterone regimen (HRT, CEE 0.625 mg plus medroxyprogesterone acetate 2.5 mg (n=34) or estradiol 2 mg plus norethisterone acetate 1 mg (n=37)). One hundred and twenty-three healthy women among a sampled population of 654 postmenopausal patients with complete records, initial normal tumor marker levels, and at least 1 year of follow-up were included into the study. Tumor markers were measured with 1-year interval. Results: Fifty-two (41.5%) patients were under ERT and 71 (58.5%) were under combined HRT. The number of months since menopause, age and age at menopause did not influence tumor marker levels at first admission. All of the tumor marker levels were in normal range after 1 year. Pretreatment CA 125 II, CA 15-3 and CEA levels were significantly low (median and range) 5.0 (1.0–11.8) versus 7.45 (1.0–18.1) U/ml for CA 125, 27.05 (7.3–37.5) versus 32.6 (12.5–37.9) U/ml for CA 15-3, 0.88 (0.58–2.8) versus 1.34 (0.53–2.41) ng/ml for CEA in women with hysterectomy when compared to women without hysterectomy. There was no effect of ERT on CA 125 II, CA 19-9, CEA and -FP levels. E2 led to a significant decrease in post-treatment CA 15-3 levels [32.9 (8.1–34.9) vs. 18.1 (6.7–31.4); P<0.001]. CA 125 levels were only significantly reduced in hysterectomised women using continuously combined HRT [7.9 (2.6–17.7) vs. 5.6 (1.3–19.2) for CEE+MPA, and 7 (1–18.1) vs. 5.8 (1.8–17.4) for E2+NETA; P<0.05]. There was a small, but not significant, increase in CA 125 levels in women under ERT. Conclusion: Although there was a statistically significant decrease in CA 15-3 levels in current E2 and E2+NETA users, and a decrease in CA 125 levels in combined regimens, this change is clinically not relevant in healthy postmenopausal women. This data will be useful for the caregivers in the management and follow-up of cancer survivors who preferred replacement therapy as the only treatment of their postmenopausal symptoms.     

Plasma leptin levels in obese and non-obese postmenopausal women before and after hormone replacement therapy

Objective: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. Methods: premenopausal women with normal cycles (n=30; mean ages, 35.4±8.3 years) and postmenopausal women (n=45; mean ages, 49.5±4.7 years) were randomly selected. Women were classified as obese (BMI>27 kg/m²) and as non-obese (BMI<27 kg/m²). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. Results: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18.60±5.0; 3.67±2.44 ng/ml, respectively, P<0.001). Obese premenopausal women (n=15) had significantly higher plasma leptin levels (24. 60±7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n=15; 12.50±4. 63 ng/ml) (P<0.001). Although there was no significant difference in the plasma leptin levels between obese (n=25) and non-obese (n=20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P<0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05±10.53; 14.78±6.76 ng/ml, respectively, P<0.001). Conclusion: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT.     

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study

Objectives: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. Methods: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45–58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50.8±2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. Results: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50–1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22–0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39–0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09–0.69). Compliance with HRT was 65% after five years. Conclusions: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.     

Effect of hormone replacement therapy on lipids in perimenopausal and early postmenopausal women

Objective: To determine the effects of oral sequential hormone replacement therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women. Methods: We performed a single-center, randomized, placebo-controlled trial. The trial was double blind with respect to 17β-estradiol/desogestrel (17β-E-D) and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A total of 125 healthy perimenopausal and early postmenopausal women, aged 43–58 years, were recruited from the general population in Zoetermeer, the Netherlands. The intervention consisted of 6 months treatment with 1.5 mg 17β-estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight fasting blood samples were obtained in which lipids were determined. We used linear regression analysis to calculate differences in mean change from baseline in lipids in the active treatment groups compared to placebo. Results: In both treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)-cholesterol (17β-E-D: −7.8% and CEE-N: −8.4%) and lipoprotein(a) (17β-E-D: −11.7% and CEE-N: −28.3%) were found compared to placebo. Apolipoprotein A1 (17β-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17β-E-D: 6.4% and CEE-N: 8.0%) significantly increased compared to placebo. No significant changes were found in the other lipids. Mean changes from baseline in total cholesterol, LDL-cholesterol and apolipoprotein B were significantly more pronounced in postmenopausal women compared to perimenopausal women, adjustment for age-differences did not change the results. Conclusion: Treatment of perimenopausal and early postmenopausal women with 17β-E-D or CEE-N changes their lipid-profile in a potentially anti-atherogenic direction. Changes appear to be more pronounced in postmenopausal women compared to perimenopausal women.     

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.     

A comparison of the central effects of different progestins used in hormone replacement therapy

Objective: To evaluate the central effect exerted by different progestins used for hormone replacement therapy. Methods: Randomised, placebo-controlled study. One hundred-twenty postmenopausal women on continuous hormonal replacement therapy with transdermal estradiol (50 μg per day) associated, for 10 days every 28 days, with four different progestins: dydrogesterone (DYD; 10 mg per day; n=20), medroxyprogesterone acetete (MPA; 10 mg per day; n=20), nomegestrol acetate (NMG; 5 mg per day; n=20) or norethisterone acetate (NETA; 10 mg per day; n=20). Other 40 women, 10 for each treatment group, were used as controls and were monitored for a single cycle of 28 days during the administration of transdermal estradiol plus placebo. Morning basal body temperature (BBT) was monitored for 28 days. Anxiety, by the state-trait anxiety inventory, and depression, by the self-evaluation depression scale of Zung, were evaluated just prior to and in the last 2 days of the 10-day progestins adjunct. Results: All progestins except DYD increased (P<0.0001) BBT by 0.3–0.5 °C. Anxiety was decreased by DYD (−2.3+1.1; P<0.01) and MPA (−1.5+0.5; P<0.01), but not by NMG or NETA. Depression did not significantly increase during progestins and actually decreased during MPA (−3.0+0.7; P<0.01). Only the effect of DYD on anxiety and that of MPA on depression were significant versus the control group (P<0.05). Conclusions: Different progestins exert different central effects. DYD has the peculiarity of not increasing BBT and of decreasing anxiety, which is also decreased by MPA. Depression is not negatively affected by the tested progestins and it may be ameliorated by MPA. The present data may help to individualise the progestin choice of hormone replacement therapy.     

Effect of estrogen replacement therapy on natural killer cell activity in postmenopausal women

Objective: To evaluate the impact of menopause and estradiol substitution on natural killer cell activity. Methods: Natural killer cell activity and antibody-dependent cellular cytotoxicity were measured in peripheral blood of 53 postmenopausal and 20 premenopausal women in an interval of 3 weeks. Postmenopausal patients were randomly assigned to receive either estradiol valerate (2 mg daily) orally (n = 18), estradiol (50 μg/24 h) transcutaneously (n = 18) or no substitution (n = 17), and the testing was repeated 3 weeks later. Results: Natural killer cell activity but not antibody-dependent cellular cytotoxicity was significantly (P < 0.01) higher in unsubstituted postmenopausal compared to premenopausal subjects. Natural killer cell activity decreased both in orally and transcutaneously estradiol-treated patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]% P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution: 60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to peripheral blood mononuclear cells of untreated postmenopausal women in vitro had no influence upon natural killer cell activity. Conclusion: Postmenopausal women receiving no estrogen replacement exhibited an increased natural killer cell activity which decreased during estrogen substitution.     

Effects of estrogen on susceptibility to oxidation of low-density and high-density lipoprotein in postmenopausal women

Objective: To investigate the effects of estrogen on the susceptibility to oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in postmenopausal women. Methods: A total of 23 postmenopausal women were treated with 0.625 mg of conjugated equine estrogen daily for 3 months. Blood samples were obtained before and after therapy. Plasma levels of total cholesterol and triglyceride and the concentrations of cholesterol, triglyceride, phospholipid in LDL and HDL were determined enzymatically and the levels of apolipoprotein A-I, A-II in HDL and apolipoprotein B in LDL were measured by turbidimetric immunoassay. The isolated LDL and HDL were incubated at 37°C for 24 h with CuSO₄ 5 μmol/l and the lipid peroxide concentration of LDL and HDL was measured. Results: Estrogen significantly reduced the plasma level of total cholesterol and significantly increased the plasma level of triglyceride. The LDL concentrations of cholesterol, phospholipid and apolipoprotein B were significantly decreased following estrogen therapy. The triglyceride level of LDL did not change significantly. The HDL concentrations of cholesterol, triglyceride, phospholipid and apolipoprotein A-I and A-II were all significantly elevated after estrogen therapy. Estrogen significantly inhibited the peroxidation of LDL at 50–2000 μg of LDL protein (14.17±4.17–11.49±1.42 nmol/200 μg of LDL protein, P<0.001) and of HDL (4.49±1.74–3.37±1.24 nmol/200 μg of HDL protein, P<0.03) induced by their incubation in the presence of CuSO₄. Conclusions: Estrogen inhibited the susceptibility of LDL and HDL to oxidative modification and favorably affected lipid metabolism by reducing the number of LDL particles and increasing the number of HDL particles in plasma that were resistant to oxidation.     

Effect of menopause on low-density lipoprotein oxidation: is oestrogen an important determinant?

Objectives: Significantly increased risk for developing cardiovascular disease in post-menopausal women is linked with the fall of oestrogen. Although supraphysiological levels of oestrogen may inhibit oxygen free radical mediated low-density lipoprotein (LDL) oxidation, the effect of physiological level of oestrogen on LDL oxidation is unknown. Methods: The present study compared oxidizability of LDL in healthy pre- and post-menopausal women by using a commonly employed copper ion-dependent method. Results: Pre-menopausal women (n=20, mean age 27) had significantly higher serum oestradiol level (576±109 pmol/l) in comparison to post-menopausal women (n=23, mean age 51, oestradiol 64±18 pmol/l, P<0.001). The oxidation of LDL in two groups was not different by measuring either the lag phase of conjugated dienes formation (54±12 vs. 55±14 min, P>0.05) or the generation of thiobarbituric acid reactive substances over 4 h of oxidation. The major lipid soluble antioxidant in LDL, vitamin E (determined as -tocopherol) is similar in two groups (2.34±0.48 vs. 2.40±0.56 nmol/mg LDL, pre- and post-menopausal subjects, respectively, P>0.05). Linear regression analysis found a weak but significant correlation between LDL vitamin E level and oxidizability of LDL in both groups but did not show effect of serum oestradiol levels. Conclusion: The results suggest that physiological levels of oestrogen may not be able to affect in vitro LDL oxidation.     

Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women

Objective: To analyse the interest of baseline levels and short-term (3-months) changes in serum osteocalcin (BGP), serum bone-specific alkaline phosphatase (BALP) and urinary C-telopeptide of type I collagen/creatinine ratio (U-CTX) to predict 3-years changes in bone mineral density (BMD) and spinal deformity index (SDI) in postmenopausal osteoporotic women. Methods: Data were derived from a cohort of 603 osteoporotic women corresponding to the placebo arm of a 3-years prospective, double-blind study. Results: Baseline values of BALP, BGP and U-CTX were negatively and significantly correlated with baseline spinal BMD. Significant correlations were also observed between the changes in BMD observed after 36 months at the spine and baseline BALP (r=0.20, P=0.0001), BGP (r=0.09, P=0.05) and U-CTX (r=−0.11, P=0.02). At 3 years, 71 women (15.9%) showed an increase in their SDI, corresponding to the occurrence of at least one new vertebral deformity. Baseline values of the four bone turnover markers (BTM) were not significantly related to the occurrence of new vertebral deformities. However, when considering the changes in the BTM observed after 3-months of follow-up, BGP (P=0.003) and U-CTX (P=0.047) were identified as significant predictors of an increase of SDI. The associated odds ratios (95% confidence interval (CI)) were 10.922 (2.218–53.78) for unit changes of log BGP and 1.369 (1.003–1.867) for unit changes of log U-CTX. The relative risk (RR) (IC 95%) of having a new vertebral fracture over 36 months was 0.31 (0.15–0.65) when being in the lowest quartile of 3-months changes in BGP as compared with the highest. Conclusion: We conclude that two sequential measurements of BGP and U-CTX performed at 3-months intervals could be of interest to identify postmenopausal osteoporotic women with the highest risk to present new vertebral deformities.     

Transvaginal color Doppler and CA125 as tools in the differential diagnosis of postmenopausal ovarian masses

Objective: To evaluate whether transvaginal color Doppler and CA125 are valid in differentiating malignant from benign postmenopausal ovarian masses. Methods: Sixty-two women with ovarian masses were studied with transvaginal color Doppler ultrasound before surgery. Serum CA125 levels were also measured. Resistance index (RI) and pulsatility index (PI) were calculated from the waveforms generated from blood flow within the ovary. Results: Benign tumors had a significantly higher pulsatility index (mean 1.23 ± 1.02; range 0.65–2.99) and resistive index (mean 0.78 ± 0.22; range 0.5–1.1) than did malignant tumors. However some overlap in individual values for benign and malignant lesions was found. RI and PI sensitivity were significantly higher than those with CA125 (P < 0.05). Blood flow was detectable by color Doppler imaging in 95% of cases with malignant masses. Conclusion: Doppler sonographic evaluation of resistance and pulsatility indexes in the vessels of ovarian masses together with CA125 increased the sensitivity of prediction of malignancy for pelvic masses, but further work is needed before the validity of these factors is proved.     

Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures

Objective: This work was carried out in order to investigate possible relationships between bone turnover rate, as evaluated by bone biomarkers and skeletal mass, as evaluated by bone mineral density (BMD). Method: Fifty-eight normal women and 30 female patients with osteoporotic fractures were enrolled. Three groups were defined: (1) fertile subjects (n=24), mean age 33.7±8.1 years; (2) postmenopausal women (n=32, including 11 patients with fractures) whose BMD values, in terms of T score, were less than −2.5 S.D. below the young adult mean obtained in our laboratory (mean age 61.7±7.9 years; and years since menopause (ysm), 12.6±8.3); (3) postmenopausal women (n=32, including 19 patients with fractures) whose BMD values in terms of T score, were below −2.5 S.D. (mean age 62.9±8.6 years; and ysm 15.9±9.0). Groups II and III characterised, by inclusion criteria, by significant different mean BMD values, were similar as far as chronological and menopausal age were considered. Metabolic tests included a short urine collection to determine calcium, hydroxyproline, cross-linked N-telopeptides of type I collagen (NTx) and creatinine (Cr); half-way through this collection, a blood sample was taken for the measurement of total alkaline phosphatase activity (ALP) and tartrate-resistant acid phosphatase activity (TRAP). BMD at lumbar spine was evaluated. Results: There were significant differences amongst the three groups in mean ALP (P<0.001, by analysis of variance) TRAP (P<0.006) and NTx/Cr (P<0.001) values, but not as far as mean values of calcium/Cr or hydroxyproline/Cr ratios were concerned. Considering the group as a whole, there were significant inverse correlations between NTx/Cr, ALP, TRAP and BMD controlling for both age (r=−0.392, P<0.001; r=−0.447, P<0.001 and r=−0.327, P<0.002, respectively) and ysm (r=−0.374, P<0.001; r=−0.474, P<0.001 and r=−0.333, P<0.002). Conclusions: Our results indicate, that, even after controlling for both ageing and oestrogen status, there is an inverse relationship between bone mass (that at a given time represents the balance of all previous metabolic events) and a biochemical marker (which reflects bone turnover at the time of examination). These findings are in line with the belief that increased bone turnover should be regarded as a risk factor for osteoporosis. Furthermore, our results indicate that, unless there is no increase of hepatic isozyme, total ALP still maintains a possible role as a first analysis to evaluate bone turnover before requesting markers with greater specificity, sensitivity but also more expensive and whose analysis is sometimes time-consuming.     

The impact of hormonal therapy for infertility on the age at menopause

Objectives: To look for possible association between past history of ovulation induction and age at menopause. Design: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. Patients: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. Results: The age at the final menstrual bleeding was 46.4±5 in the study group, and 50±4 for the control group (P<0.001). This difference was most prominent for women who had induction of ovulation prior to age 35 years: they entered menopause at age 43.8±5 years. Smoking had a weak effect on the age at menopause (48.5±4 for current, vs. 49.9±4 for non- or past-smokers; P<0.03). Conclusions: This retrospective and preliminary study raises the question whether hormonal manipulations and ovarian over-stimulation during fertility treatments could be a risk factor for premature menopause.     

Effects of continuous and cyclic nasal calcitonin administration in ovariectomized women

The aim of the present study was to assess the effects of continuous and cyclic salmon calcitonin (sCT) administration in the prevention of the rapid bone loss that follows ovariectomy in humans. Patients who had undergone bilateral ovariectomy 10–30 days previously received either calcium supplementation alone (500 mg/day, n = 12) or such supplementation together with nasal sCT (200 IU/day) according to a continuous (n = 20) or a cyclic (3 months on, 1 month off) regimen (n = 16) for 2 years. In the calciumonly-treated subjects urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels showed a substantial increase (P < 0.01) 6 months after surgery, while radial bone density was found to have decreased significantly (P < 0.01). The patterns of biochemical markers in the sCT-treated groups indicated that nasal sCT can positively uncouple the two bone remodelling processes without inducing any significant change in radial bone density over a 2-year period. No differences were observed between the two sCT-treated groups. These results demonstrate that the rapid bone loss that follows ovariectomy can be prevented by either cyclic or continuous nasal sCT administration. Thus, cyclic nasal sCT represents an attractive alternative for the prevention of osteoporosis in postmenopausal women with contraindications to oestrogen replacement therapy.     

Dietary flour supplementation decreases post-menopausal hot flushes: Effect of soy and wheat

Plants contain compounds with oestrogen — like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30–70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively <0.001 for both) with a significant rapid response in the soy flour group in 6 weeks (P < 0.001) that continued. Menopausal symptom score decreased significantly in both groups (P < 0.05). Urinary daidzein excretion confirmed compliance. Vaginal cell maturation, plasma lipids and urinary calcium remained unchanged. Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group.     

Phenotype of apolipoprotein E influences the lipid metabolic response of postmenopausal women to hormone replacement therapy

Objectives: We investigated whether the phenotype of apolipoprotein E (apo E) would influence the response of postmenopausal Japanese women to hormone replacement therapy (HRT). Methods: We measured the plasma levels of lipoprotein and apolipoprotein in 242 postmenopausal women at baseline and again after 12 months of HRT. Patients were divided into three groups according to apo E phenotype: E2+ (E2/2 and E2/3, n=21), E3/3 (n=176), E4+ (E3/4 and E4/4, n=45). Results: We found that the E4+ group had the highest levels of total and low density lipoprotein (LDL) cholesterol and apolipoprotein B, being significantly higher than in the E2+ group at baseline. The plasma levels of total and LDL cholesterol showed a significant decrease only in the E2+ and E3/3 groups after 12 months of HRT (E2+ group, total cholesterol −8.9% and LDL cholesterol −21.5%; E3/3 group, total cholesterol −2.9% and LDL cholesterol −9.5%). No significant difference in the reduction of total and LDL cholesterol was found in the E4+ group. Other lipid parameters did not differ in the three groups. Conclusions: These data show that the apo E phenotype influenced the response of lipid metabolism in postmenopausal women to HRT, especially in the reduction of LDL cholesterol. Therefore, apo E phenotyping may be important in predicting the cholesterol-lowering effect of HRT.     

Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women

Objectives: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma β-endorphin (β-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n=6). Methods: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an 2 presinaptic agonist for adrenergic system, (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E₁) and estradiol (E₂) levels were evaluated before and after treatment, while plasma β-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. Results: Basal plasma β-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E₁ and E₂ significantly increased after treatment. The clonidine test induced a significant increase of plasma β-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GH levels increased both before and after treatment. Conclusions: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary β-EP to clonidine, an 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary β-EP secretion.     

Hormone replacement therapy improves arterial stiffness in normotensive postmenopausal women

Objectives: Aortic stiffness, determined by the pulse wave velocity (PWV), is an independent marker of cardiovascular risk. PWV is mainly influenced by age-associated alterations of arterial wall structure and blood pressure (BP). To determine the impact of hormone replacement therapy (HRT) on arterial compliance in normotensive, postmenopausal women, we examined the effects of HRT on PWV. Methods: Fifty-six postmenopausal women aged 50–70 years were recruited into the present retrospective study from the patients visiting our menopause clinic. Twenty-seven women who were prescribed HRT (14 on estrogen alone and 13 on estrogen plus progestogen) for several months to 6 years and an age-matched group of 29 women not on HRT were studied (Study 1). Nine postmenopausal women were also studied before and at 4 weeks of the treatment of estrogen replacement therapy (ERT) (Study 2). Brachial to ankle PWV (baPWV), which is correlated with aortic PWV, was determined using an automatic device, BP-203PRE. Results: In Study 1, PWV was significantly correlated with age in both groups (controls: r=0.392, P=0.035; HRT group: r=0.471, P=0.013), and HRT significantly lowered the PWV value at all ages examined (Mean±S.D. of baPWV in controls: 1382.2±114.1; HRT: 1245.3±124.8, P=0.0001). In Study 2, baPWV decreased significantly after ERT (P<0.05), without a significant change in systolic BP (P=0.851). Conclusions: Estrogen appears to improve arterial compliance independently of BP within 4 weeks.     

Hormone replacement therapy, C-reactive protein, and fibrinogen in healthy postmenopausal women

Objective: To investigate short-term and long-term effects of combined hormone replacement therapy (HRT) on C-reactive protein (CRP) and fibrinogen plasma concentrations in healthy postmenopausal women. Methods: In this cross-sectional study 241 healthy postmenopausal women were enrolled. A total of 81 women were receiving the following treatments for 3 months; transdermal 17β-estradiol (17β-E₂)+medroxyprogesterone acetate (MPA) (n=21), oral 17β-E₂+norethisterone acetate (NETA) (n=27), and conjugated equine estrogens (CEE)+MPA (n=33). The same combined therapies were implemented in another 58 women for 12 months; transdermal 17β-E₂+MPA (n=10), oral 17β-E₂+NETA (n=16), and CEE+MPA (n=32). Control group included 102 healthy postmenopausal women not receiving HRT. The effect of the type and the duration of HRT regimens on plasma levels of CRP, fibrinogen and lipids were investigated. Results: Median CRP concentrations were significantly higher in women receiving oral 17β-E₂+NETA (P=0.037) and CEE+MPA (P=0.0001) for 3 months than in women taking the same types of HRT for 12 months and of those were not on HRT. Median CRP levels were similar in women taking transdermal 17β-E₂+MPA for 3 and 12 months, compared with controls. Fibrinogen levels were not different between nonusers and any group of HRT users. Conclusions: These elevated levels of CRP, which appears very recently as a crucial marker for cardiovascular disease, may be responsible for the early increased cardiovascular risk after starting oral combined HRT. But this increased risk in the early period seems to decrease with long-term use. Transdermal 17β-E₂+MPA had insignificant effect on CRP both in short-term or in long-term use.