High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood.

AIM: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34-40. METHODS: We studied 27 subjects born at Uppsala University Hospital in 1975-1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within ±1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries. RESULTS: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher. CONCLUSION: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight.

Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia.

OBJECTIVE: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt-1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt-1, PlGF and the sFlt-1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE. METHODS: Serum sFlt-1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22-MHz) ultrasonography in 55 women at PE diagnosis and in 64 women with normal pregnancy at a similar gestational age, with reassessment at 1 year postpartum. RESULTS: During pregnancy, higher levels of sFlt-1, lower levels of PlGF, a thicker intima, a thinner media and a higher I/M ratio of the CCA were found in women with PE vs controls (all P < 0.0001). Further, sFlt-1 and the sFlt-1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all P < 0.0001). At 1 year postpartum, levels of sFlt-1 and the sFlt-1/PlGF ratio had decreased in both groups; however, their levels in the PE group were still higher than in the controls (P = 0.001 and < 0.0001, respectively). Levels of sFlt-1 and the sFlt-1/PlGF ratio remained positively correlated with intima thickness and I/M ratio at 1 year postpartum. CONCLUSIONS: Higher sFlt-1 levels and sFlt-1/PlGF ratio in women with PE were positively associated with signs of arterial aging during pregnancy. At 1 year postpartum, sFlt-1 levels and the sFlt-1/PlGF ratio were still higher in the PE group and were associated with the degree of arterial aging. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Thicknesses of individual layers of artery wall indicate increased cardiovascular risk in severe pre-eclampsia.

OBJECTIVE: To assess whether thicknesses of the intima and media in the common carotid artery (CCA) and the intima/media ratio (I/M) indicate an increased cardiovascular risk in non-pregnant women with a history of previous severe pre-eclampsia. METHODS: Thicknesses of the CCA intima and media layers were measured using non-invasive high-frequency (22 MHz) ultrasound in 42 women with a history of severe pre-eclampsia and 44 women with previous normal pregnancy. RESULTS: Women with a history of severe pre-eclampsia had a thicker CCA intima and a higher I/M than had women with previous normal pregnancy, also after adjustment for mean arterial pressure, body mass index and CCA intima-media thickness (IMT) (all P < 0.0001). CCA-IMT did not differ significantly between groups. In receiver-operating characteristics curve analysis, intima thickness and I/M clearly discriminated between women with and those without previous pre-eclampsia (area under the receiver-operating characteristics curve (AUC), 0.98 and 0.93), whereas CCA-IMT did not (AUC, 0.52). CONCLUSIONS: CCA individual intima and media thicknesses as well as I/M, but not CCA-IMT, reflect the known increased long-term cardiovascular risk of pre-eclampsia. Estimation of individual CCA layers using high-frequency ultrasound appears preferable to measuring CCA-IMT for investigating arterial effects and the increased cardiovascular risk in women with a history of severe pre-eclampsia.

Increased carotid intima thickness and decreased media thickness in premenopausal women with systemic lupus erythematosus: an investigation by non-invasive high-frequency ultrasound.

OBJECTIVE: To determine whether high-frequency ultrasound (US) yielding separate assessments of intima and media thickness gives additional information about the vascular morphology compared with the total common carotid artery intima-media thickness (CCA-IMT). METHODS: Using a 22 MHz US instrument, we determined the near-wall CCA-IMT, the intima and media layers, and the intima/media (I/M) ratio in 47 premenopausal women with systemic lupus erythematosus (SLE), 20 healthy women, and 17 postmenopausal women (mean ages 37, 40, and 69 years, respectively). RESULTS: In SLE, the carotid intima was thicker (0.19 ± 0.04 vs. 0.12 ± 0.02 mm), the media thinner (0.45 ± 0.12 vs. 0.68 ± 0.24 mm), the I/M ratio higher (0.45 ± 0.17 vs. 0.20 ± 0.07) (all p < 0.0001), and the CCA-IMT lower (0.64 ± 0.13 vs. 0.80 ± 0.25 mm, p < 0.01) compared to age-matched controls. The SLE patients had a thicker carotid intima compared to the postmenopausal women (0.19 ± 0.04 vs. 0.14 ± 0.03 mm, p < 0.0001) and a similar I/M ratio. CONCLUSION: Separate assessment of carotid artery wall layers demonstrated a thicker intima, thinner media, and a higher I/M ratio in women with SLE compared to healthy controls and indicated an artery wall status in SLE comparable to 30-years-older healthy women. Separate estimates of carotid intima and media layers may be preferable to CCA-IMT in SLE patients.

Endometrial safety of ultra-low-dose Vagifem 10 microg in postmenopausal women with vaginal atrophy.

OBJECTIVE: The objective of the study was to evaluate the endometrial safety of a 10 microg estradiol vaginal tablet in the treatment of vaginal atrophy in postmenopausal women. METHODS: A total of 336 healthy, non-hysterectomized, postmenopausal women (age 59.5 +/- 6.16 years, 9.4 +/- 5.9 years from last menses) were treated with a 10 microg estradiol vaginal tablet for 12 months (once daily for 2 weeks and then twice weekly for 50 weeks). Endometrial histology was analyzed at baseline and at the end of the trial. RESULTS: Of the 336 enrolled subjects, 292 (86.9%) completed the 52-week study. All 336 subjects received an endometrial biopsy at baseline, and 283 had biopsy results at week 52, when 258 out of the 283 biopsy samples were classified as 'atrophic' or 'inactive' endometrium. There were 21 with 'no tissue' despite a repeat biopsy attempt to obtain endometrial tissue, one had insufficient tissue with endometrial thickness >4 mm, one was 'weakly proliferative' and two revealed polyps. No cases of endometrial hyperplasia or endometrial cancer were reported. The mean endometrial thickness decreased from 2.04 mm (n = 334) from study start to 1.94 mm (n = 293) after 52 weeks, and the estradiol levels remained at the low postmenopausal level. CONCLUSIONS: After 12 months of treatment with the 10 microg estradiol vaginal tablet, there was no suggestion of endometrial stimulation and no cases of endometrial hyperplasia or cancer reported. This study provides reassuring data on the endometrial safety of treatment with the 10 microg estradiol vaginal tablet for 1 year in a large group of postmenopausal, non-hysterectomized women with vaginal atrophy.

Placental dysfunction in Suramin-treated rats--a new model for pre-eclampsia.

Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of placental dysfunction and pre-eclampsia. This study was carried out to evaluate if inhibited angiogenesis by Suramin injections in early pregnancy may cause a condition resembling pre-eclampsia in rats. Rats of two different Sprague-Dawley strains, U and H, were given intraperitoneal injections of Suramin or saline in early pregnancy. The outcome of pregnancy was evaluated on gestational day 20. Suramin injections caused increased blood pressure and decreased renal blood flow in the U rats. In both rat strains Suramin decreased the placental blood flow and caused fetal growth retardation. In both strains the placental concentration of the isoprostane 8-epi-PGF2alpha was increased, indicating oxidative stress. The serum concentration of Endothelin-1 was increased in the U rats. The U strain had a lower basal placental blood flow, and the effects of Suramin were more pronounced in this strain. We conclude, that Suramin injections to pregnant rats cause a state of placental insufficiency, which partly resembles human pre-eclampsia. The induction of this condition is at least partly mediated by oxidative stress, and is subject to varied genetic susceptibility.

An open, randomized, controlled study of transdermal hormone replacement therapy on the rate of bone loss in primary biliary cirrhosis.

OBJECTIVES: The prevalence of osteoporosis amongst patients with primary biliary cirrhosis (PBC) is high and may be a serious clinical problem. Hormone replacement therapy (HRT) is effective in preventing bone loss but has not been evaluated in randomized trials in PBC. The primary aim was to study the effect of transdermal HRT in combination with daily vitamin D and calcium supplementation on bone loss compared with vitamin D and calcium supplementation only in postmenopausal women with PBC. The secondary aim was to study the safety of transdermal HRT. SUBJECTS/INTERVENTIONS: Eighteen females with PBC were randomized to receive 2 years therapy with either (i) transdermal oestradiol 50 microg 24 h(-1) two times per week + medroxyprogesterone 2.5 mg day(-1) + alfacalcidol 0.25 microg day(-1) and calcium 1 g day(-1) or (ii) alfacalcidol 0.25 microg day(-1) and calcium 1 g day(-1). Dual-energy X-ray absorptiometry for measurement of bone mineral density (BMD) and sampling of blood and serum for measurements of biochemical markers of liver function was performed before, during and at the end of treatment. RESULTS: BMD increased significantly at the lumbar spine (P < 0.05) and the femoral neck (P < 0.05) in the HRT group whereas no significant change was found in the control group. One oestrogen-treated patient was excluded after 1 year because of deteriorating, but reversible, aminotransferases. Dropout frequency because of nonliver-related causes was higher in the HRT group. Otherwise, no difference with respect to adverse liver reactions was found between the groups. CONCLUSION: Transdermal HRT increases BMD in PBC patients with few severe side effects related to the liver.

Lipids and antioxidative effects of estradiol and sequential norethisterone acetate treatment in a 3-month randomized controlled trial.

OBJECTIVE: To determine the influence of hormone replacement therapy on serum lipids and antioxidative factors associated with the risk of coronary heart disease. METHODS: The effect of a sequential estradiol-norethisterone acetate regimen or placebo on lipid metabolism, antioxidative variables and fatty acid composition in serum was measured during the peak-estrogen phase in a randomized, double-blind, placebo-controlled study of 42 healthy postmenopausal women for 3 months. RESULTS: Active treatment significantly reduced lipoprotein(a) by 15% (p = 0.005, compared with placebo), low-density lipoprotein (LDL) cholesterol by 10% (p = 0.005) and the LDL cholesterol/high-density lipoprotein (HDL) cholesterol ratio by 11% (p = 0.016). Serum triglycerides increased by 21% (p = 0.045). No effect was observed on HDL cholesterol, on apolipoproteins apo A(1) or apo B, or on non-esterified fatty acids in serum. No treatment effect was seen in the proportions of monounsaturated and polyunsaturated fatty acids. The concentration of malondialdehyde in serum did not change with the estrogen-progestin treatment. CONCLUSIONS: This sequential estrogen-progestin therapy has a beneficial effect on apolipoprotein(a) and LDL cholesterol, but no effect on non-esterified fatty acids or the level of lipid peroxidation products in serum.

Ambulatory morning growth hormone concentrations increase in men and decrease in women with age.

A remarkable 80-fold difference in median growth hormone (GH) values in young adult men and women was recently found in a study of sera taken in ambulatory state in the morning, after overnight fasting. In this study, the effect of ageing on morning ambulatory GH levels was investigated in 254 apparently healthy men, 21-75 years of age, and 40 women, 21-85 years. Furthermore, the effect of oestradiol on morning GH values was studied in 19 postmenopausal women, 51-79 years, treated with subcutaneous implants of 17beta-oestradiol (E2). The sera were analysed for GH, sex hormone-binding globulin (SHBG), E2, and in the men, also for testosterone (T). The morning GH levels increased (p<0.0001) with age in a group of 195 men of 41-75 years. After adjustment for age, an inverse correlation (p <0.05) was found between the levels of GH and free androgen index (T/SHBG) and a direct correlation between GH and SHBG. These relationships were more pronounced before the age of 60 than after. In the women, the GH levels decreased (p<0.01) with age and the gender difference of median values was reduced from 102-fold at younger age, 21-39 years, to 12-fold in elderly individuals, 60-75 years. In the E2-treated postmenopausal women, the morning GH values were similar to those of an untreated control group, indicating that the decrease with age in the morning GH levels in women is not a result of lower oestrogen levels alone. The gender difference in median ambulatory morning GH values decreased from 102-fold at a mean age of 25 years to 12-fold at a mean age of 68 years owing to opposite changes with age in men and women: an increase in men and a decrease in women.

Validation of in vivo noninvasive high-frequency ultrasonography of the arterial wall layers.

To validate estimates of the arterial wall thickness and its separate layers, 19 superficial (7 femoral and 12 cutaneous) arteries were transcutaneously sonographed in 13 anaesthetized pigs with a high-resolution equipment fitted with a 25 MHz frequency probe. Means of ultrasonographic estimates of each wall layer were compared with those obtained from microscopy of the respective arterial specimens taken after the pigs were sacrificed. For all vessels combined, Spearman-rank correlation tests between ultrasonography and histology estimates were significant for total arterial wall thickness (r(s) = 0.78; p =.0001) but not for the separate layers. For the cutaneous arteries, a significant correlation was found for total arterial wall thickness (r(s) = 0.69; p =.01) and media layer (r(s) = 0.76; p =.004). The method seems to give valid estimates of both total arterial wall and media thickness in superficial arteries, but to be less accurate for estimate the adventitia and intima layers.

Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo.

RATIONALE: It is well established that serotonin reuptake inhibitors (SRIs) are effective for the treatment of premenstrual dysphoria (PMD), but the receptor subtype(s) mediating this effect of serotonin have yet not been identified. OBJECTIVE: In this trial, the possible efficacy of buspirone, a partial 5HT1A receptor agonist, and nefazodone, a combined SRI and 5HT2 receptor antagonist, was evaluated in women with PMD. METHODS: After a three-menstrual-cycle screening phase, patients were randomised to buspirone (n=19), nefazodone (n=22) or placebo (n=22). During the first two treatment cycles, patients were taking the drug during the luteal phase only (mean +/- SD daily dose of buspirone: 21 +/- 6 mg; nefazodone: 228 +/- 54 mg). During the subsequent two cycles, the medication was taken each day of the menstrual cycle (mean daily dose of buspirone: 27 +/- 10 mg; nefazodone: 304 +/- 95 mg). RESULTS: With respect to self-rated global improvement, buspirone (P<0.001) but not nefazodone was significantly superior to placebo. While buspirone appeared to reduce self-rated irritability (visual analogue scale) more effectively than placebo, other self-rated symptoms did not differ markedly between the groups. The side-effects were mild, and sexual dysfunction was not significantly more common in patients given buspirone or nefazodone than in those given placebo. CONCLUSION: It is suggested that buspirone is mildly effective for premenstrual irritability. In patients experiencing sexual dysfunction when treated with an SRI, buspirone may be a useful alternative.

Serum lipid profile improved by ultra-low doses of 17 beta-estradiol in elderly women.

To determine whether ultra-low doses of estradiol (E(2)) affect the serum lipid profile in elderly women, we analyzed changes in serum lipids and lipoproteins in 70 healthy women, 60 yr and older, randomly assigned to parenteral E(2) (7.5 microg per 24 h) delivered by a vaginal ring (Estring; Pharmacia-Upjohn, Malmö, Sweden) or no treatment for 12 months. Baseline serum estrone sulfate (E1S), but not E(2) or serum FSH, was negatively associated with serum total cholesterol (P = 0.026), low-density lipoprotein (LDL) cholesterol (P = 0.053), and apolipoprotein B levels (P = 0.023). Compared with no treatment, Estring treatment yielded nonsignificant increases within the normal postmenopausal range in serum E1S (+16%) and E(2) (+13%), but significantly reduced serum LDL cholesterol by 7.6% (-0.32 mmol/L; 95% confidence interval, -0.58, -0.07; P = 0.014) and LDL to high-density lipoprotein (HDL) ratio by 7.3% (-0.19 mmol/L; 95% confidence interval, -0.44, -0.06; P = 0.030). In Estring users values were significantly reduced in total cholesterol (by 4%), LDL cholesterol (by 7%), LDL to HDL ratio (by 7%), and apolipoprotein B (by 4%), and significantly increased in serum HDL triglyceride (by 25%) but not triglycerides. No significant changes were found in the untreated group. There was a significant interaction between age and both baseline serum E(2)/sex hormone-binding globulin (P = 0.006) and sex hormone-binding globulin (P = 0.009) and a marginal interaction between age and E1S (P = 0.083) with regard to effects on changes in LDL cholesterol levels during Estring treatment. We conclude that ultra-low doses of E(2), which previously were considered to have only local effects, may improve serum lipid profile in elderly women with a pattern and magnitude similar to that reported after conventional estrogen doses or first-generation lipid-lowering agents. The reduction in LDL cholesterol tended to be greater with a combination of high age and low baseline levels of biologically active estrogens.

Carotid vascular resistance in long-term estrogen users.

OBJECTIVE: To compare carotid vascular resistance in long-term estrogen users with that of age-matched nonusers. METHODS: Pairwise comparisons between 18 long-term users of 17beta-estradiol (E2) implants (mean age 67.8 years, mean duration of treatment 18.8 years, range 5.8-33.9 years) and 18 age-matched (+/- 2 years) nonusers. We used color Doppler ultrasound to assess pulsatility index (PI) and resistance index (RI) in common, external, and internal carotid arteries. RESULTS: Estrogen users compared with age-matched nonusers had significantly lower mean values for common carotid RI, -4%; -0.04 (95% confidence interval [CI] -0.07, -0.03, P =.036) and marginally significant for PI, -12%; -0.25 (95% CI -0.54, 0.04, P =.087). Differences in external and internal carotids were smaller and insignificant. Age was a determinant of internal carotid vascular resistance in estrogen users and nonusers. Increasing pairwise differences in external carotid vascular resistance with advancing age (r = 0.55; P =.02), with magnitudes of mean group differences indicate a modest but true effect of long-term estrogen therapy on vascular resistance in common carotids, less in external, and negligible in internal carotid arteries. The study had an 80% power to detect a 10% mean difference (0.08 units) in common carotid RI at the 5% level. The standard deviation was considerably lower for estimates of RI than for PI. CONCLUSION: Long-term estrogen therapy was associated with minor reduction of vascular resistance in common carotid, less in external, and negligible in internal carotid arteries. Effects on carotid vascular resistance do not seem to be a major mechanism in the long-term protective effect of estrogen therapy on cardiovascular risk.

Risk of myocardial infarction after oophorectomy and hysterectomy.

To determine the risk of developing a first myocardial infarction after a hysterectomy and/or oophorectomy. Case-cohort analysis performed among 17,126 women in the Uppsala Health Care Region of Sweden, who had undergone a hysterectomy and/or oophorectomy in 1965 to 1983. Record linkage was used for follow-up and medical records to ascertain the actual history of oophorectomy. Risk estimates were calculated by relating the observed number of cases in the cohort to that expected on the basis of incidence rates in the population. Overall, 214 cases of myocardial infarction were observed. In premenopausal women a bilateral oophorectomy alone tended to increase the relative risk 1.6; 95% CI 0.8-3.1, but this operation combined with hysterectomy increased the risk only among those aged 50 and over at surgery. Hysterectomy at premenopausal age or unilateral oophorectomy did not alter the risk of myocardial infarction. In naturally menopausal women, hysterectomy-mainly for uterine myoma-was associated with a four-fold increase in relative risk (3.8; 95% CI 1.9-7.8). Hysterectomy for treatment of myoma performed after a natural menopause is linked to an excess risk for myocardial infarction. Bilateral oophorectomy before menopause may increase the risk of myocardial infarction.

Postmenopausal hormone therapy and risk of cardiovascular disease and hip fracture in a cohort of Swedish women.

Postmenopausal estrogen use is associated with a reduced risk of heart disease and hip fracture; in observational studies, different behaviors among hormone users and nonusers may partially explain these results. We examined risk of cardiovascular disease and hip fracture with medium-potency compared with low-potency or short-term estrogen use, and the effect of added progestin, among 9,236 women in Uppsala, Sweden, who responded to a mailed questionnaire in 1987-1988. Using population registries, we identified 213 cases of myocardial infarction, 289 strokes, and 114 hip fractures from 1987-1995. We found a reduced risk of myocardial infarction for medium-potency compared with low-potency or short-term estrogen use (relative risk = 0.75, 95% confidence interval (CI) = 0.56-0.99), with a similar decrease in the subgroup that took estrogens with progestin (RR = 0.69, 95% CI = 0.45-0.90). There was no relation of medium-potency estrogen to stroke (RR = 0.91, 95% CI = 0.71-1.17, and RR = 0.81, 95% CI = 0.61-1.10 for the subgroup taking progestin), and no effect of duration on either heart disease or stroke. We observed a reduction in hip fractures for medium-potency use (RR = 0.65, 95% CI = 0.45-0.95), and for use of combined estrogen-progestin therapy (RR = 0.64, 95% CI = 0.41-1.00). These data support a decreased risk of heart disease and hip fracture for medium-potency estrogen use alone or with progestin; self-selection to hormone use cannot explain these reductions.

Pregnancy-related back and pelvic pain and changes in bone density.

OBJECTIVE: To elucidate whether there is an association between pregnancy-related back and pelvic pain and changes in bone density. METHODS: In this prospective cohort study, bone density was measured in the distal and ultra-distal forearm at 12 and 35 weeks of pregnancy and at 5 months post partum. The location and degree of any back or pelvic pain was registered. The patients were classified into four subgroups on the basis of presence or absence of disabling pain in late pregnancy and presence or absence of pain at 5 months' follow-up. Forty-nine women participated. RESULTS: Bone density decreases during pregnancy and lactation. Trabecular bone is mainly lost during pregnancy and cortical bone during lactation. No association between back or pelvic pain during pregnancy and bone loss was found. Between 35 weeks of pregnancy and 5 months post partum, bone loss in all the women was estimated as 1.1% of cortical bone (p < 0.001) and 0.6% of trabecular bone (n.s.). During the same period five women with mild pain during pregnancy and pain at follow-up lost 3.9% of cortical bone (p=0.043) and 5.3% of trabecular bone (p=0.043). Although this bone loss was significant compared to the other subgroups, the small study size does not permit general conclusions to be drawn from this finding. CONCLUSION: The results indicate that bone density decreases during pregnancy and lactation. The decrease in bone density was not associated with back or pelvic pain during pregnancy. It remains unclear whether bone loss is associated with back and pelvic pain during lactation.

In vitro evaluation of aromatase enzyme in granulosa cells using a [11C]vorozole binding assay.

An in vitro method for measuring aromatase cytochrome P450 enzyme (P450AROM) in human granulosa cells (GC) has been developed, based on binding of the 11C-labeled aromatase inhibitor vorozole. GC were obtained following superstimulation during in vitro fertilisation. The method revealed a binding affinity (Kd) of 0.4 nM and a maximum binding (Bmax) at 11 fmol/4000 cells which is equal to 1.6 million binding sites per cell. Linear Scatchard plots indicated a single type of binding site. P450AROM concentrations measured by [11C]vorozole binding correlated positively with aromatisation of [1beta-3H]androst-4-ene-3,17-dione measured as [3H]water release, and a positive association was also found with the ovarian in vivo response to follicle-stimulating hormone (FSH) stimulation expressed as 1000 times the ratio of the number of oocytes recovered from a patient and the total dose of recombinant FSH administered. Frozen cells could be used for P450AROM quantitation, provided the correct freezing procedure was used. Quantitation of P450AROM, based on binding of [11C]vorozole is an accurate and sensitive in vitro method, which might be extended to the measurement of aromatase expression by a noninvasive technique in the intact ovary in vivo using positron emission tomography.

Performance in functional balance tests during menopausal hormone replacement: a double-blind placebo-controlled study.

BACKGROUND AND PURPOSE: Recent studies have indicated that oestrogens might have an effect on postural control. The purpose of this study was to investigate the short-term effect of hormone replacement therapy (HRT) on postural control in menopausal women and to analyse the correlation between sway velocity measures and results of functional balance tests. SUBJECTS: 100 menopausal women who were randomized to receive either HRT or placebo for three months were included in the study. METHOD: The balance function was measured with nine different static and dynamic functional balance tests. The sway velocities were measured on a computerized force platform. RESULTS: No significant differences were found between the two groups in the results of the functional balance tests after the three-month placebo-controlled period or in the changes over time. However, some significant improvements occurred within both groups over this three-month period. The correlations between different sway velocities and the results of the functional balance tests were all very low (r < 0.35). CONCLUSION: It can not be concluded that HRT had a positive effect on the performance in the functional balance tests, as some improvement occurred in both groups. The low correlations indicate that the sway velocity and functional balance tests measure different aspects of balance function.

Ultrasonographic blood flow measurement in the carotid arteries in postmenopausal women.

OBJECTIVES: The aim of the present study was to evaluate blood flow in postmenopausal women on hormone replacement therapy (HRT) compared to controls. Blood flow was ultrasonographically measured in the great arteries of the neck instead of in the vessels of the internal genital organs. METHODS: Fifty healthy women with climacteric complaints, at least 6 months postmenopausal, participated in the study. They were randomly divided into two groups. One group received 2 mg estradiol (E2) for 12 days, continued with 2 mg E2 and 1 mg norethisterone acetate for 10 days, followed by 1 mg E2 for 6 days, cyclically during 6 months. The other group received placebo tablets the first 3 months and the same HRT as the first group for the last 3 months. Blood flow was measured ultrasonographically by color flow pulsed Doppler in the common (CCA), internal (ICA) and external (ECA) carotid arteries, before the start of the study, after 3 and 6 months of therapy. RESULTS: CCA and ICA, both low resistance vessels, and ECA, a high resistance vessel, and their waveforms were identified. Pulsatility index did not decrease statistically significant (p > 0.05) in any of the great vessels during 6 months of HRT in this study. There were no differences in blood flow between the HRT-treated group compared to control group during 3 months of therapy, except for the right ECA (p = 0.04). CONCLUSION: The difference in blood flow and wave-forms of the major arteries of the neck were clearly shown, but HRT did not have any important impact on the blood flow in this study. No difference was shown concerning blood flow between the two groups of postmenopausal women, on active therapy or placebo.