Effect of estradiol versus estradiol and testosterone on brain-activation patterns in postmenopausal women

OBJECTIVE: To determine the effect of estradiol and testosterone on brain-activation patterns in surgically postmenopausal women viewing erotic video clips using functional magnetic resonance imaging. DESIGN: Six women, who had undergone a bilateral oophorectomy and hysterectomy for benign disease, viewed erotic and neutral videos during functional magnetic resonance imaging while not on hormone therapy, while on estradiol therapy, and while on estradiol and testosterone therapy. Five similarly aged premenopausal women viewed the same videos. Areas of brain activation between the functional magnetic resonance imaging scans of both groups of women were compared with determine whether agonadal serum levels of sex hormones and administration of estradiol and testosterone impacted brain patterns of sexual arousal. RESULTS: When compared with premenopausal women, untreated postmenopausal women had significantly decreased areas of brain activation during both erotic and neutral stimulations. Administration of estradiol increased global brain-activation patterns during both visual stimulations, with erotic video viewing causing a limited increase in limbic system activation. Combined estradiol and testosterone therapy was associated with a greater activation of the central nervous system, with more limbic system activated during the erotic video. Brain-activation patterns of the postmenopausal women were similar to the premenopausal group only during the estradiol and testosterone treatment phase. CONCLUSIONS: Agonadal serum hormone levels result in globally decreased brain-activation patterns in postmenopausal women while viewing neutral and erotic videos. Administration of both estradiol and testosterone increase global brain activation, and both sex steroids are independently associated with enhanced limbic system response during erotic visual stimulation.     

Effects of estradiol alone or in combination with cyproterone acetate on carotid artery pulsatility index in postmenopausal women

OBJECTIVES: The incidence of cardiovascular disease (CVD) increases dramatically with the loss of ovarian function. Observational studies indicate that the risk of CVD may be reduced by up to 50% in postmenopausal women who take estrogen replacement therapy. Estrogen therapy reduces internal carotid artery pulsatility index (PI). The improvement in carotid PI following HRT has been proposed as a marker of the cardioprotective effect of estrogen therapy. Cyclical progesterone addition to ERT partially antagonizes the reduction on the carotid artery PI. As progesterone, androgens has been shown to decreases arterial vasodilatation and carotid PI. To our knowledge no information is available regarding the effect of CPA addition on the carotid artery PI in women taking estrogen replacement therapy. METHODS: We recruited a total of 30 women in postmenopause for at least 12 months and were in good health. Fifteen women were postmenopausal following surgical bilateral oophorectomy for benign condition. Fifteen postmenopausal women received estradiol valerate for 21 days and CPA (1 mg) for 10 days for 3 months (Group E/CPA). Ovarectomized women (n=15) received estradiol hemihydrate (2 mg) for 3 months (Group E). The main factor investigated was PI, an indicator of impedence to blood flow down stream. Doppler US were performed before the start and at the end of the therapy. RESULTS: The mean reductions respect to basal values were 11.5% in women treated with E and 10.8% in women treated with E/CPA. No significant difference was found between treatment values. CONCLUSIONS: The results of the present study demonstrate that cyproterone acetate addition to E do non-antagonize the effect of estrogen on carotid artery PI. The present study demonstrate that both estradiol hemihydrate and estradiol valerate plus cyproterone acetate lead to similar improvement in carotid artery; through this mechanism both treatments could potentially reduce the incidence of cerebrovascular disease in postmenopausal women.     

A short study in the treatment of hot flashes with buccal administration of 17-beta estradiol

OBJECTIVE: To assess the efficacy and safety of 17-beta estradiol buccal tablets in reducing hot flush frequency (HFF) in postmenopausal women. METHODS: Estradiol buccal tablets containing 0.05, 0.1, 0.2, or 0.4 mg or placebo were administered for 28 days to 99 postmenopausal women in a randomized, double-blind study; 19 premenopausal women were studied concurrently for comparison of laboratory data. Objective and subjective assessments of HFF were obtained along with measures of estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). RESULTS: Measurements of HFF revealed significant decreases from baseline in all estradiol groups (P < 0.01). In the 0.4 mg group, HFF decreased significantly compared to placebo (P < 0.01). All estradiol doses produced similar improvement in the vaginal maturation index. Mean serum estradiol levels increased as doses increased but were lower than in the premenopausal subjects. Mean serum FSH and LH levels decreased in all estradiol groups but not to the levels of the premenopausal subjects; the greatest decrease occurred at the two highest estradiol doses. CONCLUSION: A numerical dose-response relationship with hot flushes was seen in this pilot study comparing 0.05, 0.1, 0.2, and 0.4 mg buccal estradiol. Only 0.4 mg 17-beta estradiol significantly reduced the occurrence of hot flushes compared to placebo.     

Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women

OBJECTIVE: The purpose of this study was to investigate the association between serum adipocytokines (adiponectin, resistin, leptin, and tumor necrosis factor alpha [TNF-alpha]) and endogenous estrogen (estrone and estradiol) levels in healthy premenopausal and postmenopausal women. DESIGN: This study included 53 healthy premenopausal women, 45 healthy postmenopausal women, and 10 postmenopausal women with the metabolic syndrome who were participating in general health examinations. A secondary analysis was performed on levels of adiponectin, resistin, leptin, TNF-alpha, estrone (E1), and estradiol (E2). RESULTS: After accounting for body mass index, TNF-alpha was significantly increased (1.5+/-0.1 vs 2.0+/-0.1 pg/mL, P<0.05) in healthy postmenopausal women as compared with healthy premenopausal women, whereas leptin was decreased (5.6+/-1.1 vs 4.0+/-1.1 ng/mL). Estrogen (E1 and E2) was positively correlated with leptin in only healthy premenopausal women, whereas estrogen did not correlate with any adipocytokine in healthy postmenopausal women. In the multiple regression analysis, only leptin significantly contributed to insulin resistance. Combining healthy premenopausal and postmenopausal women, E1 correlated negatively with TNF-alpha (r=-0.23, P<0.05) and positively with leptin (r=0.35, P<0.01) and did not correlate with resistin. E2 correlated negatively with TNF-alpha (r=-0.24, P<0.05) and positively with leptin (r=0.34, P<0.01); it did not correlate with adiponectin or resistin. Leptin might stimulate the increase of plasma gonadotropin-releasing hormone levels, which could result in a positive correlation with estrogen in premenopausal women but not in postmenopausal women. CONCLUSIONS: Estrogen deficiency resulted in increased TNF-alpha levels. Serum leptin levels correlated positively with estrogen levels in premenopausal women. However, the increase in obesity in postmenopausal women increased leptin, which increases insulin resistance.     

Pharmacokinetics and pharmacodynamics of 25-mg estradiol implants in postmenopausal Mexican women

OBJECTIVE: To assess the serum concentrations of estradiol (E2), estrone (E1), gonadotrophins, sex hormone-binding globulin, and lipids, and to determine degree of symptom relief after subcutaneous implantation of 25 mg estradiol in postmenopausal Mexican women. DESIGN: Fifteen postmenopausal, hysterectomized women participated in an open, observational study. Blood samples were obtained before implantation and at regular intervals during a study period of 24 weeks. Climacteric symptoms were evaluated by means of the Greene climacteric scale. Wilcoxon's test was performed on the paired results of pre-and postimplantation values. RESULTS: Serum concentrations of E2 obtained after implantation were fairly constant, remaining within the early follicular range for the entire study period of 24 weeks, and were associated with significant symptom relief. A physiological, premenopausal E2:E1 ratio was achieved. No significant metabolic changes occurred. Side effects were estrogenic in nature and no removal of implant was required. CONCLUSIONS: Subcutaneous implantation of 25 mg estradiol results in physiological, premenopausal estrogen concentrations in most women and is associated with considerable symptom relief without inducing significant adverse metabolic effects.     

Association between menopause status and central adiposity measured at different cutoffs of waist circumference and waist-to-hip ratio

OBJECTIVE: To assess the association between menopause status and central adiposity measured using two different cutoffs of waist circumference and waist-to-hip ratio, while controlling for body mass index and other confounding factors. DESIGN: Cross-sectional study of a representative population-based sample of 358 women from Passo Fundo, Southern Brazil. Medical students performed standardized interviews and anthropometric measurements under supervision. Menopause status was categorized as premenopausal for those with no change in menstrual frequency or flow; menopause transition for those who had these changes; and postmenopausal after 12 months of amenorrhea or bilateral oophorectomy. Obesity was defined by body mass index (BMI) equal or greater than 30 kg/m, whereas central adiposity was defined as a waist circumference equal or greater than 80 or 88 cm and a waist-to-hip-ratio equal or greater than 0.80 or 0.86. RESULTS: The anthropometric assessment showed that compared with postmenopausal women, premenopausal women were taller, had a thinner waist circumference, and had a lower waist-to-hip ratio. Postmenopausal women had five times the chance of having central adiposity than premenopausal women, even after controlling for BMI and other confounding factors. Women in the menopause transition had an increased BMI, but there was no independent association with central obesity. CONCLUSION: Postmenopausal women are at greater risk of central adiposity as detected by both waist circumference and waist-to-hip ratio.     

Associations of circulating adiponectin with estradiol and monocyte chemotactic protein-1 in postmenopausal women

OBJECTIVE: The aim of the present study was to clarify the association of serum adiponectin concentrations with serum 17beta-estradiol concentrations in pre-, peri-, and postmenopausal women. In addition, the associations of serum adiponectin with serum concentrations of proinflammatory and anti-inflammatory cytokines were examined in women during the menopausal transition. DESIGN: A total of 197 women were enrolled in this study: 33 premenopausal women, 80 perimenopausal women, and 84 postmenopausal women. Serum adiponectin concentration was measured by an enzyme-linked immunosorbent assay. Serum concentrations of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha, anti-inflammatory cytokine IL-10, and the chemokines IL-8, macrophage inflammatory protein-1beta and monocyte chemotactic protein-1 were measured by using a multiplexed human cytokine assay. RESULTS: Serum adiponectin concentration showed a significant negative correlation with serum estradiol concentration (r= -0.400, P=0.001) in postmenopausal women but not in pre- and perimenopausal women, and this correlation was significant after adjustment for age and body mass index. Serum adiponectin concentration also showed a significant negative correlation with serum monocyte chemotactic protein-1 concentration (r= -0.244, P=0.05) in postmenopausal women. CONCLUSION: An increase in adiponectin level due to a decrease in estradiol results in a reduction in monocyte chemotactic protein-1 level in postmenopausal women, suggesting that adiponectin may be associated with a protective role against insulin resistance and atherosclerosis, which occur in the postmenopausal stage.     

Auditory brainstem response in postmenopausal women treated with hormone replacement therapy: a pilot study

OBJECTIVE: To research the nongenital audiological target for gonadal steroids in postmenopausal women who are treated with hormone replacement therapy. DESIGN: Fifty postmenopausal volunteers were treated with hormone replacement therapy. Women with an intact uterus had sequential weekly transdermal estradiol plus nomegestrole acetate 5 mg orally for 12 days per month or a continuous daily oral dose of conjugated estrogen 0.625 mg and medroxyprogesterone acetate 5 mg tablet. Eighteen surgically postmenopausal women received a weekly transdermal estradiol system. Twenty-five postmenopausal volunteers-5 with a natural menopause and 10 with a surgical menopause-and 20 premenopausal normally cycling women were used as a control group. Each woman performed auditory brainstem response by auditory-evoked potentials for waves I, III, and V and for interpeak I-III, I-V, and III-V intervals. RESULTS: Women who were treated with hormone replacement therapy showed wave latencies and interpeak latencies shorter than those for postmenopausal women in the control group (p < or = 0.05), overlapping those of the premenopausal women (p > 0.05). Women who were treated with estrogen replacement therapy showed shorter time latencies than those treated with combined hormone replacement therapy (p < or = 0.05). CONCLUSIONS: Our data suggest that fluctuating hormone levels cause changes in auditory brain-stem response waves, even if the exact mechanism of activity of the gonadal steroids is not clear. However, we believe that estrogen may influence the neuronal plasticity, the metabolic levels of neurotransmitters, and thus the neuronal conduction time into the audiological system.     

Menopause and the risk of coronary heart disease in women

To determine the relation of menopause to the risk of coronary heart disease, we analyzed data on a prospective cohort of 121,700 U.S. women 30 to 55 years old who were followed from 1976 to 1982. Information on menopausal status, the type of menopause, and other risk factors was obtained in 1976 and updated every two years by mailing questionnaires. Through 1982, the follow-up rate was 98.3 percent for mortality and 95.4 percent for nonfatal events. After we controlled for age and cigarette smoking, women who had had a natural menopause and who had never taken replacement estrogen had no appreciable increase in the risk of coronary heart disease, as compared with premenopausal women (adjusted rate ratio, 1.2; 95 percent confidence limits, 0.8 and 1.8). Again compared with premenopausal women, the occurrence of a natural menopause together with the use of estrogens did not affect the risk (rate ratio, 0.8, 95 percent confidence limits, 0.4 and 1.3). Women who had undergone bilateral oophorectomy and who had never taken estrogens after menopause had an increased risk (rate ratio, 2.2; 95 percent confidence limits, 1.2 and 4.2). However, the use of estrogens in the postmenopausal period appeared to eliminate this increased risk among these women as compared with premenopausal women (rate ratio, 0.9; 95 percent confidence limits, 0.6 and 1.6). These data suggest that, in contrast to a natural menopause, bilateral oophorectomy increases the risk of coronary heart disease. This increase appears to be prevented by estrogen-replacement therapy.     

Comparison of intranasal and transdermal estradiol on nasal mucosa in postmenopausal women

OBJECTIVE: To compare nasal symptomatology and function and local concentrations of estradiol (E2), estradiol receptor (ERalpha), vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20 postmenopausal women complaining of paradoxical nasal stuffiness before and after treatment with intranasal or transdermal E2. DESIGN: Twenty healthy postmenopausal women willing to start hormone therapy (HT) were allocated to one of two groups, using a computer-generated randomization list.Ten postmenopausal women were treated with transdermal 17beta-estradiol 50 microg daily plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group A). Ten postmenopausal women were treated with intranasal 17beta-estradiol 300 microg/day (one spray delivery of 150 microg per nostril) plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen fertile women undergoing nasal mucosa biopsy during plastic surgery were used as controls for the immunohistochemical evaluation (Group C).All women in groups A and B underwent evaluation of nasal stuffiness score, mucociliary transport time, rhinoscopy, and active anterior rhinomanometry at the beginning of the study and after, VIP, SP, and 6 months of HT. Nasal biopsies and evaluation of local concentrations of E2, ERalpha NPY were performed in groups A and B before and after 6 months of HT and in group C. RESULTS: Both intranasal and transdermal HT improve nasal symptomatology and nasal mucosa appearance and reduce mean mucociliary transport time. The effectiveness of intranasally administered therapy at improving nasal function is significantly better than transdermal therapy. In comparison with premenopausal controls, untreated postmenopausal women of group A and B showed significantly decreased immunopositivity for E2, ERalpha, and SP. HT induced a significant increase in E2, ERalpha, VIP, and SP and a decrease in NPY immunopositivity. Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP. CONCLUSIONS: HT improves nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered HT is more effective at improving nasal function than transdermal HT.     

Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis

OBJECTIVE: Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause. DESIGN: A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking. RESULTS: The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01). CONCLUSIONS: Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.     

Change in serum undercarboxylated osteocalcin concentration in bilaterally oophorectomized women

Objective

We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period.

Methods

The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured.

Results

Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p < 0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p < 0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different.

Conclusion

The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration.     

Effects of estrogen on proton secretion via the apical membrane in vaginal-ectocervical epithelial cells of postmenopausal women

OBJECTIVE: To understand estrogen regulation of proton (H(+)) secretion by human vaginal-ectocervical epithelial cells and the mechanisms involved. DESIGN: Primary-tertiary cultures of human normal vaginal-ectocervical epithelial cells were generated from surgical specimens of premenopausal women (aged 37-46 years) and of postmenopausal women (aged 53-65 years). Cells were grown on filters, and measurements were made of changes in extracellular pH (pHo) in the contraluminal (CL) and luminal (L) solutions 30 minutes after shifting cells to basic salt solution. RESULTS: Upon shifting cells to basic salt solution, CL-pHo decreased from 7.4 to 7.25, and was not affected by removal of intracellular estrogens or treatment with estradiol. L-pHo decreased from 7.4 to 7.05 in cells of premenopausal women, and from 7.4 to 7.20 in cells of postmenopausal women. Removal of intracellular estrogens attenuated the decrease in L-pHo in cells of premenopausal women (only to 7.20). In cells of premenopausal women stripped of estrogens, treatment with 10 nM 17beta-estradiol restored the decrease in L-pHo. In estrogen-stripped cells of postmenopausal women, treatment with estradiol augmented luminal acidification but to a lesser degree than in cells of premenopausal women (L-pHo of 7.15 vs 7.05). In cells of pre- and postmenopausal women, the addition in the L solution of bafilomycin-A(1), a specific inhibitor of the vacuolar-H(+)-ATPase (V-H(+)-ATPase), blocked the decrease in L-pHo. CONCLUSIONS: Human vaginal-ectocervical epithelial cells acidify constitutively their luminal solution, and the effect is mediated by active H(+) secretion by V-H(+)-ATPase expressed predominantly in the apical cell membrane. Estrogen deprivation attenuates, and treatment with 17beta-estradiol augments, active H(+) secretion. Finally, cells of postmenopausal women actively secrete H(+) via apically located V-H(+)-ATPase, but the effect is lesser, and estrogen failed to augment active H(+) secretion, as in cells of premenopausal women. These data suggest that in addition to hypoestrogenism, other factors of the aging process affect the capacity of vaginal-ectocervical cells to secrete acid.     

Physiological and Subjective Sexual Arousal in Pre- and Postmenopausal Women and Postmenopausal Women Taking Replacement Therapy

Twenty premenopausal, 14 postmenopausal, and 14 postmenopausal women receiving replacement estrogen therapy were studied to determine whether differences in hormone status were associated with differences in physiological and subjective sexual responses. All subjects viewed a neutral, an erotic, and a second neutral videotape while photoplethysmographic vaginal pulse amplitude was continuously recorded. Self-report ratings of sexual arousal and affective response were collected. Serum levels of testosterone, estradiol, estrone, and luteinizing hormone were obtained. The three groups did not differ in either average or maximum vaginal pulse amplitude to the videotapes nor in latency of sexual response. The postmenopausal women not taking replacement estrogen reported significantly less vaginal lubrication in response to the erotic videotape than the higher estrogen premenopausal and replacement hormone groups. Estradiol level was significantly correlated with ratings of vaginal lubrication in response to the erotic videotape but not with vaginal pulse amplitude. Results thus suggest that estrogen is important in maintaining vaginal lubrication and the perception of sexual arousal but not in determining vaginal vasocongestion.     

Ovariectomy Interferes with Proteomes of Brown Adipose Tissue in Rats

Postmenopausal women exhibit a higher prevalence of obesity due to decreased energy expenditure and increased food intake compared to their premenopausal counterparts. Brown adipose tissue (BAT) plays a key role in energy homeostasis, thus providing us with appealing therapeutic targets in obesity. However, how BAT proteomes are altered in response to low levels of estrogen remains unclear. To better understand the underlying mechanisms between the postmenopausal state and BAT proteomic changes, our study aimed to investigate the effect of ovariectomy on the BAT proteome. In this study, eight-week-old female Sprague Dawley rats were randomly allocated into bilateral ovariectomy (Ovx) and sham operation (Sham) groups. Mass spectrometry was used for proteomics assay and Ingenuity Pathway Analysis was applied to examine the differentially regulated proteins. Of the 1,412 identified proteins, 18 proteins were significantly upregulated, whereas 36 proteins were significantly downregulated in the Ovx group as compared to the Sham group. Our findings demonstrate that the proteins involved in BAT morphology, the browning of white adipose tissue, and metabolic substrates for thermogenesis were regulated by ovariectomy. The dysregulation of proteins by ovariectomy might be related to the disruption of BAT function in the postmenopausal status. Understanding how BAT proteomes are altered in response to ovariectomy may illuminate novel therapeutic strategies for the management of postmenopausal weight gain in the future.     

Effect of estradiol and exercise on lymphocyte proliferation responses in female mice

Many North American women are encouraged to take estrogen replacement therapy and to begin (or continue) physical activity during the postmenopausal years. This study investigated the effect of estradiol exposure and physical exercise on lymphocyte proliferation responses to T and B cell mitogens in female mice. Sixty C57BL/6 mice were randomized to hormone and exercise treatment conditions: hormone treatment consisted of estradiol in vivo (71.4 microg estradiol per day for 21 days) or placebo pellet following bilateral ovariectomy, or surgical sham (mice were not ovariectomized). Exercise consisted of a single forced treadmill run (26 m/min, 6 degrees slope, 90 min) or a sedentary control condition. Outcomes were thymic and splenic lymphocyte proliferation responses to the mitogens concanavalin A (ConA, 1.0 and 5.0 microg/mL concentrations) and lipopolysaccharide (LPS, 0.5, 1.0, and 2.0 microg/mL concentrations). In the thymus, there was a significant reduction of proliferation to ConA in the Ovx + E2 animals relative to the other conditions at both concentrations of mitogen. At 1.0 microg/mL concentration, there was a significant interaction of hormone and exercise treatments. Sham (control) mice given exercise had a higher proliferation response relative to sedentary counterparts, whereas E2 mice did not differ in proliferation responses, irrespective of exercise condition. In the spleen, exposure to high concentrations of estradiol was associated with reduced proliferation responses to both mitogens; there were, however, no main or interaction effects of exercise. These results suggest that high levels of estradiol exposure following ovariectomy in mice significantly reduces lymphocyte blastogenesis responses, and that thymic immunomodulation after acute exercise is masked by the hormonal effect.     

Female sex hormones and body mass in adolescent and postmenopausal Korean women.

A cross-sectional study was conducted to evaluate the relationship between body mass and serum level of female sex hormones among 153 adolescent girls, and 153 postmenopausal women in Korea. Information on lifestyles, and both menstrual and reproductive factors was collected by personal interview. Serum total estradiol (E2), progesterone (Pg), and sex hormone binding globulin (SHBG) concentrations were measured by radioimmunoassay. Multiple linear regression analysis was used to determine whether the hormonal levels would be affected by the obesity indices. Body weight and body mass index (BMI) were inversely related to SHBG level in both premenopausal (p<0.005) and postmenopausal women (p<0.005) after adjusting for age. E2 levels during any phase in premenopausal girls were not related to BMI, whereas heavier girls had significantly higher levels of late luteal-phase Pg (p<0.05). Taller postmenopausal women had lower E2 levels (p<0.05). Results on the association between SHBG and BMI are consistent with previous results in Caucasian women, and might suggest the potential role of bioavailable estradiol in breast carcinogenesis in pre- and post-menopausal women. The finding that progesterone might be related to body mass in premenopausal women should be pursued in further studies.     

Modification of serum IGF-I,IGFBPs and SHBG levels by different HRT regimens

During the menopause, levels of SHBG, IGF-I and IGFBPs are significantly modified by the use of different HRT regimens. Objective: The aim of this study is to evaluate the influence of three different HRT regimens on serum levels of SHBG, IGF-I, IGFBP-1 and IGFBP-3 in postmenopausal women. Methods: 41 postmenopausal women requesting HRT were enrolled in the study. Subjects were divided in three groups according to the therapy assigned; Group A: estradiol 2 mg/day+cyproterone acetate 1 mg/day in a cyclic sequential regimen; Group B: estradiol hemihydrate 2 mg/day plus norethisterone acetate (NETA) 1 mg/day in a continuous combined regimen; Group C: estradiol hemihydrate 1 mg/day plus NETA 0.5 mg/day in a continuous combined regimen. Blood samples were drawn before the start of hormonal treatment and after 6 months of HRT. Levels of SHBG, IGF-I, IGFBP-1 and IGFBP-3 in the serum were measured by means of a specific immunoassay. Results: In group A, a significant increase of SHBG, no change of IGFBPs and a significant decrease of IGF-I were observed; in group B and in group C, no significant variations for any of the parameters were recorded. Conclusions: The association of cyproterone acetate to oral estradiol determines a significant reduction of IGF-I levels and an increase of SHBG; nevertheless, it does not seem to influence the serum levels of the IGF-I binding proteins. The treatment with oral continuous combined estrogens plus androgenic progestins, at low doses, produces minor, not significant, changes in the circulating levels of IGF-I, SHBG and IGFBPs.     

Pharmacokinetics of estradiol valerate and medroxyprogesterone acetate in different age groups of postmenopausal women

OBJECTIVES: To study whether ageing affects the pharmacokinetics of estradiol valerate (E2V) or medroxyprogesterone acetate (MPA) in postmenopausal women. METHODS: Forty-six postmenopausal women from two essentially similar pharmacokinetic studies were divided into three age categories: under 60 years (n = 15), between 60 and 65 years (n = 18) and over 65 years (n = 13). They all were treated for 12 days or 14 days with four galenically identical tablets containing combinations of 1 mg or 2 mg E2V and 2.5 mg or 5 mg MPA. The studies followed an open, randomised cross-over design with no washout between the periods. Serum estradiol and MPA concentrations were measured at steady state on study day 12 or 14 of each period. RESULTS: No statistically significant differences were observed in the peak concentration (Cmax), time to peak (t(max)), AUC or elimination half-life for estradiol or MPA between the different age groups. In spite of the lack of statistical significance the AUC was on an average 1.6-fold and Cmax 1.40-fold higher in the oldest group of women than in the youngest group and age was found significant as a continuous variable for AUC and Cmax for MPA but not for estradiol. CONCLUSIONS: The results suggest that there would be no significant changes in the pharmacokinetics of estradiol between women under 60 and over 65 years of age. However, a significant trend towards higher MPA concentrations and bioavailability was observed with increasing age. The results suggest that from the pharmacokinetic point of view the relationship between estradiol and MPA dose to be used in elderly could be different from that in younger postmenopausal women, while no pharmacokinetic reasons to use lower estradiol doses in the elderly were observed.     

Results of the colposuspension operation in pre and postmenopausal incontinent women

OBJECTIVE: To compare the results of Burch colposuspension in premenopausal and postmenopausal women with urinary stress incontinence (USI). METHODS: A total of 85 women with urodynamic diagnosis of genuine urinary stress incontinence were divided into two groups, according to their menstrual status (premenopausal and postmenopausal group). All of them underwent the Burch colposuspension procedure. Clinical and urodynamic data were compared preoperatively and postoperatively and between the two groups. RESULTS: Cure rate was significantly higher after Burch colposuspension in the premenopausal as compared to the postmenopausal patients (90.9 vs 73.1%, respectively, P < 0.01). A significant reduction of the diurnal and nocturnal frequency and urgency was noted in both groups postoperatively. The reduction of urgency was more prominent in the premenopausal women (P < 0.001). There were no statistically significant differences between the preoperative and postoperative values of bladder capacity, residual volume, maximal voiding pressure, peak flow rate, absolute urethral length, functional urethral length, urethral pressure and maximum urethral closure pressure both preoperatively and postoperatively within the groups and between the two groups. Comparing the two groups postoperatively, the pressure transmission ratios in the postmenopausal women were found to be significantly lower in the middle two quarters of the urethra as compared to the premenopausal patients (P < 0.001). CONCLUSION: Burch colposuspension for urinary stress incontinence has better cure rate in premenopausal than in postmenopausal women. Nevertheless, the above procedure remains an acceptable method for treatment of USI in postmenopausal patients.